bluuebunny/crossref_metadata_2025 huggingface dataset:
The Future of FDI: Achieving the Sustainable Development Goals 2030 through Impact Investment
Authors: Suehrer Juri
Published: September 2019

Publicized as a global call for action in 2015, the United Nations General Assembly passed a resolution on the Sustainable Development Goals 2030 (SDGs). Before issuing the SDGs in 2015, the United Nations Conference on Trade and Development (UNCTAD) has already identified in 2014, as part of their World Investment Report, that especially developing countries are facing an estimated USD 2.5 trillion funding gap annually in the efforts to achieve the SDGs. Yet, the investment opportunities and challenges for investors, when contributing to the closure of this funding gap while benefiting from its economic potential have not been widely discussed. Despite that Foreign Direct Investments (FDI) are a key driver to sustainable economic growth and prosperity of a nation, policies and a holistic framework linking the 2030 Agenda to actionable investment opportunities for private investors are missing. Furthermore, a global platform capturing, channeling and promoting investment projects aiming to achieve the SDGs through impact investment has not been established. Utilizing global financial resources more effectively while developing new approaches and tools to promote impact investments, which demonstrate the benefits for investors to tap into the funding gap of the 2030 Agenda, will have the potential to significantly shape and influence the future of FDI.
Dos and Don'ts in Export Transactions: A Practitioner's Guide for SMEs?
Authors: Oberle Claudia , Ponterlitschek Lars
Published: September 2019

Being successful in export business transactions constitutes a great challenge for export newcomers. Entering a new foreign market, export newcomers must take into consideration many additional risks and pitfalls even if they are world‐class in their technology field in their domestic market. Besides the knowledge of common risks and pitfalls, experience in international project management is a must!Good contracts are to be carefully drafted, especially key project execution issues like timeschedules, starting point of deadlines, scope of supplies and services and its limits. If this is properly done, contracts may be used like a checklist for project execution and help the exporter to provide evidence on their contractual performance at any stage.Besides project execution topics, financial risk management has to be taken into account. Although – very hopefully ‐ not needed, legal / legal enforcement issues need to be drafted equally cautiously. Small and medium‐sized companies are well advised to organize expertise and support, if needed.
Neuronal p38α mediates age‐associated neural stem cell exhaustion and cognitive decline
Authors: Moreno‐Cugnon Leire , Revuelta Miren , Arrizabalaga Olatz , Colie Sandra , Moreno‐Valladares Manuel , Jimenez‐Blasco Daniel , Gil‐Bea Francisco , Llarena Irantzu , Bolaños Juan Pedro , Nebreda Angel R. , Matheu Ander
Published: September 2019

Neuronal activity regulates cognition and neural stem cell (NSC) function. The molecular pathways limiting neuronal activity during aging remain largely unknown. In this work, we show that p38MAPK activity increases in neurons with age. By using mice expressing p38α‐lox and CamkII‐Cre alleles (p38α∆‐N), we demonstrate that genetic deletion of p38α in neurons suffices to reduce age‐associated elevation of p38MAPK activity, neuronal loss and cognitive decline. Moreover, aged p38α∆‐N mice present elevated numbers of NSCs in the hippocampus and the subventricular zone. These results reveal novel roles for neuronal p38MAPK in age‐associated NSC exhaustion and cognitive decline.
Voluntary Chronic Heavy Alcohol Consumption in Male Rhesus Macaques Suppresses Cancellous Bone Formation and Increases Bone Marrow Adiposity
Authors: Kahler‐Quesada Arianna M. , Grant Kathleen A. , Walter Nicole A. R. , Newman Natali , Allen Matthew R. , Burr David B. , Branscum Adam J. , Maddalozzo Gianni F. , Turner Russell T. , Iwaniec Urszula T.
Published: September 2019

Background

Chronic heavy alcohol consumption is an established risk factor for bone fracture, but comorbidities associated with alcohol intake may contribute to increased fracture rates in alcohol abusers. To address the specific effects of alcohol on bone, we used a nonhuman primate model and evaluated voluntary alcohol consumption on: (i) global markers of bone turnover in blood and (ii) cancellous bone mass, density, microarchitecture, turnover, and microdamage in lumbar vertebra.

Methods

Following a 4‐month induction period, 6‐year‐old male rhesus macaques (Macaca mulatta, n = 13) voluntarily self‐administered water or ethanol (EtOH; 4% w/v) for 22 h/d, 7 d/wk, for a total of 12 months. Control animals (n = 9) consumed an isocaloric maltose–dextrin solution. Tetracycline hydrochloride was administered orally 17 and 3 days prior to sacrifice to label mineralizing bone surfaces. Global skeletal response to EtOH was evaluated by measuring plasma osteocalcin and carboxyterminal collagen cross‐links (CTX). Local response was evaluated in lumbar vertebra using dual‐energy X‐ray absorptiometry, microcomputed tomography, static and dynamic histomorphometry, and histological assessment of microdamage.

Results

Monkeys in the EtOH group consumed an average of 2.8 ± 0.2 (mean ± SE) g/kg/d of EtOH (30 ± 2% of total calories), resulting in an average blood EtOH concentration of 88.3 ± 8.8 mg/dl 7 hours after the session onset. Plasma CTX and osteocalcin tended to be lower in EtOH‐consuming monkeys compared to controls. Significant differences in bone mineral density in lumbar vertebrae 1 to 4 were not detected with treatment. However, cancellous bone volume fraction (in cores biopsied from the central region of the third vertebral body) was lower in EtOH‐consuming monkeys compared to controls. Furthermore, EtOH‐consuming monkeys had lower osteoblast perimeter and mineralizing perimeter, no significant difference in osteoclast perimeter, and higher bone marrow adiposity than controls. No significant differences between groups were detected in microcrack density (2nd lumbar vertebra).

Conclusions

Voluntary chronic heavy EtOH consumption reduces cancellous bone formation in lumbar vertebra by decreasing osteoblast‐lined bone perimeter, a response associated with an increase in bone marrow adiposity.
Concordance of Self‐ and Partner‐Reported Alcohol Consumption Among Couples Experiencing Intimate Partner Violence in Zambia
Authors: Kane Jeremy C. , Murray Sarah M. , Vinikoor Michael J. , Greene M. Claire , Fine Shoshanna L. , Paul Ravi , Murray Laura K.
Published: September 2019

Background

Hazardous alcohol use is a predictor of intimate partner violence (IPV), and both are increasingly prevalent in sub‐Saharan Africa. The accurate measurement of alcohol consumption is therefore critical in IPV intervention studies that target hazardous drinking. Collecting a collateral report in addition to self‐report is one convergent validity approach to improve alcohol measurement. We investigated concordance between self‐ and partner‐reported alcohol use among women who reported recent IPV and their male partners in Zambia.

Methods

Data were from the baseline of a randomized IPV intervention trial of 247 heterosexual couples in which a woman has reported recent IPV and her male partner has recent hazardous alcohol use. Both partners completed the Alcohol Use Disorders Identification Test (AUDIT) in reference to their own drinking and in reference to their partner's drinking. We calculated percent agreement across a range of outcomes: any use, quantity, frequency, and hazardous use. We also compared self‐ and partner‐reported AUDIT scores using t‐tests.

Results

Concordance was poor across most outcomes. Percent agreement with respect to the women's drinking ranged from 60% to 65% across outcomes and with respect to the men's drinking from 51% to 89%. Women's average partner‐reported AUDIT score (20.7) was statistically significantly (p < 0.0001) higher than men's average self‐reported score (15.8).

Conclusions

In contrast to collateral report studies conducted in the United States, concordance between self‐ and partner‐reported alcohol consumption was poor among families experiencing IPV in Zambia. Given the possible biases associated with self‐reported alcohol use, findings suggest that a convergent validity approach is useful in this research context.
Measuring Trade Profile with Granular Product‐Level Data
Authors: Kim In Song , Liao Steven , Imai Kosuke
Published: September 2019

The product composition of bilateral trade encapsulates complex relationships about comparative advantage, global production networks, and domestic politics. Despite the availability of product‐level trade data, most researchers rely on either the total volume of trade or certain sets of aggregated products. In this article, we develop a new dynamic clustering method to effectively summarize this massive amount of product‐level information. The proposed method classifies a set of dyads into several clusters based on their similarities in trade profile—the product composition of imports and exports—and captures the evolution of the resulting clusters over time. We apply this method to two billion observations of product‐level annual trade flows. We show how typical dyadic trade relationships evolve from sparse trade to interindustry trade and then to intra‐industry trade. Finally, we illustrate the critical roles of our trade profile measure in international relations research on trade competition.
Automated diagnosis and quantitative analysis of plus disease in retinopathy of prematurity based on deep convolutional neural networks
Authors: Mao Jianbo , Luo Yuhao , Liu Lei , Lao Jimeng , Shao Yirun , Zhang Min , Zhang Caiyun , Sun Mingzhai , Shen Lijun
Published: September 2019

Background

The purpose of this study was to develop an automated diagnosis and quantitative analysis system for plus disease. The system provides a diagnostic decision but also performs quantitative analysis of the typical pathological features of the disease, which helps the physicians to make the best judgement and communicate the decisions.

Methods

The deep learning network provided segmentation of the retinal vessels and the optic disc (OD). Based on the vessel segmentation, plus disease was classified and tortuosity, width, fractal dimension and vessel density were evaluated automatically.

Results

The trained network achieved a sensitivity of 95.1% with 97.8% specificity for the diagnosis of plus disease. For detection of preplus or worse, the sensitivity and specificity were 92.4% and 97.4%. The quadratic weighted k was 0.9244. The tortuosities for the normal, preplus and plus groups were 3.61 ± 0.08, 5.95 ± 1.57 and 10.67 ± 0.50 (104 cm−3). The widths of the blood vessels were 63.46 ± 0.39, 67.21 ± 0.70 and 68.89 ± 0.75 μm. The fractal dimensions were 1.18 ± 0.01, 1.22 ± 0.01 and 1.26 ± 0.02. The vessel densities were 1.39 ± 0.03, 1.60 ± 0.01 and 1.64 ± 0.09 (%). All values were statistically different among the groups. After treatment for plus disease with ranibizumab injection, quantitative analysis showed significant changes in the pathological features.

Conclusions

Our system achieved high accuracy of diagnosis of plus disease in retinopathy of prematurity. It provided a quantitative analysis of the dynamic features of the disease progression. This automated system can assist physicians by providing a classification decision with auxiliary quantitative evaluation of the typical pathological features of the disease.
Novel role of Tieg1 in muscle metabolism and mitochondrial oxidative capacities
Authors: Kammoun Malek , Piquereau Jerome , Nadal‐Desbarats Lydie , Même Sandra , Beuvin Maud , Bonne Gisèle , Veksler Vladimir , Le Fur Yann , Pouletaut Philippe , Même William , Szeremeta Frederic , Constans Jean‐Marc , Bruinsma Elizabeth S. , Nelson Holte Molly H. , Najafova Zeynab , Johnsen Steven A. , Subramaniam Malayannan , Hawse John R. , Bensamoun Sabine F.
Published: September 2019

Aim

Tieg1 is involved in multiple signalling pathways, human diseases, and is highly expressed in muscle where its functions are poorly understood.

Methods

We have utilized Tieg1 knockout (KO) mice to identify novel and important roles for this transcription factor in regulating muscle ultrastructure, metabolism and mitochondrial functions in the soleus and extensor digitorum longus (EDL) muscles. RNA sequencing, immunoblotting, transmission electron microscopy, MRI, NMR, histochemical and mitochondrial function assays were performed.

Results

Loss of Tieg1 expression resulted in altered sarcomere organization and a significant decrease in mitochondrial number. Histochemical analyses demonstrated an absence of succinate dehydrogenase staining and a decrease in cytochrome c oxidase (COX) enzyme activity in KO soleus with similar, but diminished, effects in the EDL. Decreased complex I, COX and citrate synthase (CS) activities were detected in the soleus muscle of KO mice indicating altered mitochondrial function. Complex I activity was also diminished in KO EDL. Significant decreases in CS and respiratory chain complex activities were identified in KO soleus. 1H‐NMR spectra revealed no significant metabolic difference between wild‐type and KO muscles. However, 31P spectra revealed a significant decrease in phosphocreatine and ATPγ. Altered expression of 279 genes, many of which play roles in mitochondrial and muscle function, were identified in KO soleus muscle. Ultimately, all of these changes resulted in an exercise intolerance phenotype in Tieg1 KO mice.

Conclusion

Our findings have implicated novel roles for Tieg1 in muscle including regulation of gene expression, metabolic activity and organization of tissue ultrastructure. This muscle phenotype resembles diseases associated with exercise intolerance and myopathies of unknown consequence.
Effect of Genetic and Nongenetic Factors on the Clinical Response to Mineralocorticoid Receptor Antagonist Therapy in Egyptians with Heart Failure
Authors: Sarhan Neven M. , Shahin Mohamed H. , El Rouby Nihal M. , El‐Wakeel Lamia M. , Solayman Mohamed H. , Langaee Taimour , Khorshid Hazem , Schaalan Mona F. , Sabri Nagwa A. , Cavallari Larisa H.
Published: September 2019

This prospective cohort study evaluated the association between the renin angiotensin aldosterone system genotypes and response to spironolactone in 155 Egyptian patients with heart failure with reduced ejection fraction (HFrEF). Genotype frequencies for AGT rs699 were: CC = 16%, CT = 48%, and TT = 36%. Frequencies for CYP11B2 rs1799998 were: TT = 33%, TC = 50%, and CC = 17%. After 6 months of spironolactone treatment, change in the left ventricular ejection fraction (LVEF) differed by AGT rs699 (CC, 14.6%; TC, 7.9%; TT, 2.7%; P = 2.1E‐26), and CYP11B2 rs1799998 (TT, 9.1%; TC, 8.7%; CC, 1.4%; P = 0.0006) genotypes. Multivariate linear regression showed that the AGT rs699 and CYP11B2 rs1799998 polymorphisms plus baseline serum potassium explained 71% of variability in LVEF improvement (P = 0.001), 63% of variability in serum potassium increase (P = 2.25E‐08), and 39% of the variability in improvement in quality of life (P = 2.3E‐04) with spironolactone therapy. These data suggest that AGT and CYP11B2 genotypes as well as baseline serum K are predictors of spironolactone response in HFrEF.
What Determines China's Grain Imports and Self‐sufficiency? The Role of Rising Domestic Costs and Varying World Market Prices
Authors: Yu Wusheng , Li Tianxiang , Zhu Jing
Published: September 2019

China's grain sectors have faced unprecedented challenges in recent years as the ever‐increasing and historically high level of grain output has failed to reduce grain imports. On the contrary, high grain imports and high domestic stock have accompanied historically high domestic output, a situation dubbed the “triple high” phenomenon in current policy discussion. This paper explores the role of widening domestic–world market price gaps in determining the triple high phenomenon. Unlike earlier studies that relied on production capacities, this paper argues that domestic production and demand (hence imports) are functions of domestic and world market prices and proposes an analytical framework to explicitly capture such price gaps under restricted trade linkages in general equilibrium. Following this approach, a set of price scenarios for the 2011–2020 period are constructed and simulated in a computable general equilibrium model. Results from the core scenarios, in which recent domestic and world market price trends are assumed to continue, suggest that further widening price gaps would substantially increase grain imports and reduce domestic output (by 60 million tons) and self‐sufficiency ratios from base levels. In the alternative scenarios with larger (smaller) price gaps, we find higher (lower) imports and larger (smaller) decreases in domestic output and self‐sufficiency ratios. Such results provide important policy implications as China's agricultural policy undergoes significant adjustment.
Difference in pressure‐formed mouthguard thickness according to the laminate procedure
Authors: Mizuhashi Fumi , Koide Kaoru
Published: September 2019

Aim

Mouthguard thickness influences the preventive effects against dental and oral injury. The aim of this study was to examine the difference in pressure‐formed mouthguard thickness according to the laminate procedure used.

Materials and methods

The materials used were mouthguard sheets of 2.0‐mm and 3.0‐mm ethylene vinyl acetate, and pressure formed using a pressure former. Two forming conditions for laminated mouthguards were examined: the condition 23P used the 2.0‐mm sheet as the first layer and 3.0‐mm sheet as the second layer. The condition 32P used the 3.0‐mm sheet as the first layer and 2.0‐mm sheet as the second layer. The first layer was trimmed to cover only the anterior region; then, the second layer was formed over the first layer. Mouthguard thickness was measured at the labial surface of the central incisor, buccal surface of the first molar, and occlusal surface of the first molar. Statistical analysis was performed by two‐way analysis of variance and Bonferroni method to analyze the differences in thickness by measurement region of mouthguards and forming conditions.

Results

Mouthguard thickness differed in different regions of the central incisors and the first molars (P < .01). The thickness at the labial surface of the central incisor became statistically significantly larger on the 32P condition than that on the 23P condition (P < .01). The thickness at the buccal surface and the occlusal surface of the first molar became statistically significantly larger on the 23P condition than that on the 32P condition (P < .01).

Conclusions

The thicknesses of the labial surface of the central incisor became larger when the sheet thickness of the first layer was larger.
Novel Medications for the Treatment of Migraine
Authors: Ceriani Claire E. J. , Wilhour Danielle A. , Silberstein Stephen D.
Published: September 2019

Objective

To describe the new classes of medication for headache management and their roles in clinical practice.

Background

Calcitonin gene‐related peptide (CGRP) is a key component in the underlying pathophysiology of migraine. Research focused on targeting CGRP for headache treatment has led to the development of entirely new classes of medications – the gepants and the CGRP monoclonal antibodies (mAbs) – for both acute and preventive treatment. A third class, the ditans, is being developed to target the 5‐HT1Freceptor to provide acute treatment without vasoconstrictive effects.

Methods

This article reviews the pathophysiology of migraine that has led to these new pharmacologic developments. Available information from randomized controlled trials, abstracts, press releases, and relevant preclinical studies is summarized for each class of medications.

Results

At the time of this writing, one ditan has been submitted to the U.S. Food and Drug Administration (FDA) for approval. One gepant is anticipated to be submitted within the first quarter of 2019, and others are in clinical trials. Three CGRP mAbs have been FDA approved and are now available in clinical practice, and a fourth was submitted in the first quarter of 2019.

Conclusions

The development of new migraine‐specific classes of medications provides more treatment options for both acute and preventive treatment of migraine.
Reduced Visual Quality of Life Associated with Migraine is Most Closely Correlated with Symptoms of Dry Eye
Authors: Ozudogru Seniha , Neufeld Anastasia , Katz Bradley J. , Baggaley Susan , Pippitt Karly , Zhang Yue , Digre Kathleen B.
Published: September 2019

Background and Objective

Patients with migraine frequently report ocular or visual symptoms including aura, photophobia, and eye pain. Using validated instruments, our group previously reported that due to these symptoms, patients have marked reductions in visual quality of life. In chronic migraine, these reductions can be as substantial as those reported for other neuro‐ophthalmic diseases such as multiple sclerosis with optic neuritis and idiopathic intracranial hypertension. Because the instruments take several different dimensions into account, we were unable to determine which ocular symptom(s) contributed to reduced visual quality of life. The purpose of this investigation was to attempt to determine which ocular symptom(s) were driving the observed reduction in visual quality of life.

Methods

We designed a cross‐sectional survey‐based study to assess visual quality of life, headache impact, aura, dry eye, and photophobia in migraine patients. Subjects were recruited from the Headache Clinic and General Neurology Clinic at a tertiary teaching hospital. Subjects completed validated questionnaires including: The visual functioning questionnaire‐25 (VFQ‐25), the headache impact test (HIT‐6), the visual aura rating scale (VARS), the ocular surface disease index (OSDI), and the Utah photophobia score (UPSIS‐17). Associations between VFQ‐25 and OSDI, VFQ‐25 and VARS, VFQ‐25 and UPSIS‐17, HIT‐6 and OSDI, HIT‐6 and VARS, and HIT‐6 and UPSIS‐17 were calculated.

Results

Of the 62 patients who completed all questionnaires, 17 had episodic migraine and 45 had chronic migraine. Twenty‐three patients experienced aura and 39 did not report aura. The most striking correlations were observed between the VFQ‐25 and the OSDI (−0.678; P < .001), between the HIT‐6 and UPSIS‐17 (0.489; P < .001), and between the HIT‐6 and OSDI (0.453; P < .001).

Conclusions

Dry eye seems to be the most important symptom that reduces visual quality of life and worsens headache impact. This symptom may be a form of allodynia, a well‐known feature of chronic migraine. Photophobia appears to have modest effects on headache impact. In the future, we hope to determine whether treatment of dry eye symptoms can improve visual quality of life and reduce headache impact.
Partnerships for safe care: A meta‐narrative of the experience for the parent of a child with Intellectual Disability in hospital
Authors: Mimmo Laurel , Woolfenden Susan , Travaglia Joanne , Harrison Reema
Published: September 2019

Objective

To systematically identify and synthesize peer‐reviewed qualitative evidence of the parental experience of hospitalization with a child with Intellectual Disability.

Search strategy

Key words, synonyms and MeSH subject headings that related to the three key concepts of parental experience, children with Intellectual Disability and hospital settings were applied to six electronic databases: Medline, CINAHL, Embase, PsycINFO, Scopus and Web of Science. Titles and abstracts of publications between January 2000 and February 2019 were screened for relevance.

Inclusion criteria

Empirical qualitative research involved participants aged 0‐18 years, involved children with Intellectual Disability, involved participants hospitalized as an in‐patient and involved participants focused on parent perspective.

Data extraction and synthesis

Data were extracted and synthesized using a meta‐narrative approach.

Results

Eleven publications met the inclusion criteria. Data synthesis revealed three research traditions contributing to this meta‐narrative: Paediatric Nursing Practice, Intellectual Disability Healthcare and Patient Experience. A total of five themes were identified: (a) being more than a parent, (b) importance of role negotiation, (c) building trust and relationships, (d) the cumulative effect of previous experiences of hospitalization and (e) knowing the child as an individual.

Discussion and conclusion

This review presents a working model for professional‐parent partnership for the safe care of children with Intellectual Disability in hospital. Shifting paediatric healthcare to whole of hospital/multidisciplinary models of care that centre on the child will necessitate partnerships with the parent to identify and manage the needs of the child with Intellectual Disability, in order to achieve safe and equitable care for these children.
Daptomycin‐resistant Staphylococcus aureus clinical isolates are poorly sensed by dendritic cells
Authors: Patton Timothy , Jiang Jhih‐Hang , Lundie Rachel J , Bafit Mariam , Gao Wei , Peleg Anton Y , O'Keeffe Meredith
Published: September 2019

Methicillin‐resistant Staphylococcus aureus (MRSA) presents an increasing threat to public health, with antimicrobial resistance on the rise and infections endemic in the hospital setting. Despite a global research effort to understand and combat antimicrobial resistance, less work has focused on understanding the nuances in the immunopathogenesis of clinical strains. In particular, there is a surprising gap of knowledge in the literature pertaining to how clinical strains are recognized by dendritic cells (DCs). Here, we show that the activation of DCs is compromised in response to MRSA strains resistant to the last‐line antibiotic daptomycin. We found a significant reduction in the secretion of proinflammatory cytokines including tumor necrosis factor‐α, interleukin‐6, regulated upon activation, normal T cell expressed, and secreted and macrophage inflammatory protein‐1β, as well as decreased expression of CD80 by DCs responding to daptomycin‐resistant MRSA. We further demonstrate that this phenotype is coincident with the acquisition of specific point mutations in the cardiolipin synthase gene cls2, and, partly, in the bifunctional lysylphosphatidylglycerol flippase/synthetase gene mprF, which are genes that are often mutated in clinical daptomycin‐resistant strains. Therefore, throughout infection and antibiotic therapy, MRSA has the capacity to not only develop further antibiotic resistance, but also develop resistance to immunological recognition by DCs, because of single amino acid point mutations occurring under the selective pressures of both host immunity and antibiotic therapy. Understanding the diversity of clinical MRSA isolates and the nuances in their immune recognition will have important implications for future therapeutics and the treatment of these infections.
Regulatory B cells: Development, phenotypes, functions, and role in transplantation
Authors: Alhabbab Rowa Y. , Nova-Lamperti Estefanía , Aravena Octavio , Burton Hannah M. , Lechler Robert I. , Dorling Anthony , Lombardi Giovanna
Published: September 2019

The interest in regulatory B cells (Bregs) began in the 1970s with the evidence that B cells could downregulate the immune system by the production of “inhibitory” antibodies. Subsequently, a series of results from different studies have emphasized that B cells have antibody‐independent immunoregulatory functions. Since then, different subsets of B cells with regulatory functions and their development and mechanisms of action have been identified both in human and in animal models of inflammation, transplantation, and autoimmunity. The present review outlines the suggested pathways by which Bregs develop, describes the different subsets of Bregs with their phenotypes and function as well as their role in transplantation, highlighting the differences between human and animal studies throughout.
Session Ii: Capitalism and Social Insurance
Authors: Fox Merritt , Gordon Jeff
Published: September 2019

In what Jeff Gordon describes as “the great risk shift,” large U.S. companies have responded during the last 50 years to the forces of globalization and increased pressure from investors by transferring the risks associated with product and worker obsolescence from their shareholders to their employees. Layoffs have generally meant very large, if not complete, losses of “firm‐specific investments” by displaced employees. And the problem is especially troubling in the U.S., where the employees of large companies lose not only their jobs and income streams, but also often their connection to their social network, to the entire system of social welfare and insurance that tends to be provided by large companies and the workplace.

While applauding corporate retraining programs, Gordon suggests that individual company efforts are likely to be overwhelmed by the demand for such services. The solution accordingly lies in the form of government‐provided social insurance—in programs that, whether orchestrated and funded at the state or federal level, provide the most cost‐effective government “match” designed to ensure the preservation of human potential and lifetime earnings power of employees.
Session IV: The Law, Corporate Governance, and Economic Justice
Authors: Strine Leo , Talley Eric , Roe Mark , Fisch Jill , Kogut Bruce
Published: September 2019

The Chief Justice of the Delaware Supreme Court begins by invoking the New Deal, and expressing admiration for the way its goals and some of its social programs have been put into practice by Northern European social democracies. Most important are their protections for workers and the unemployed—protections the Judge finds deplorably absent in U.S. law and corporate labor practices. Nevertheless, when contemplating how corporate boards in the U.S. might respond to the growing demand for U.S. public companies to address social problems like the environment and economic inequality, the Delaware judge falls back on the prescription of Adolph Berle, who, though one of the framers of the New Deal, insisted that companies “stick to their knitting” by putting shareholders first as the only way of ensuring the accountability of corporate managements and boards.

Harvard Law's Mark Roe responds with a defense of corporate America against the charge of corporate short‐termism by noting that, although U.S. capital expenditures have declined in the past 15–20 years, corporate investment in R&D and other intangible assets have both grown sharply. Corporate distributions in the form of dividends and stock buybacks are rising, but so have the net borrowings of the companies making the distributions, leaving the cash balances of U.S. companies also near record levels. And the remarkably high valuations of successful high tech companies are themselves forceful rebuttals of the idea that pressure from the stock market for current earnings is a serious deterrent to investment and innovation.

The University of Pennsylvania's Jill Fisch follows Roe's dismissal of the short‐termism argument with even more forceful questioning of whether corporate America in fact has a major governance problem. U.S. companies have been taking voluntary measures to address environmental problems—in some cases even in the face of federal deregulatory initiatives—and many have raised their workers’ wages, without any challenges (and often with encouragement) from their shareholders. And echoing Justice Strine's concerns, Fisch also ends up questioning the premise that companies can be asked to define a single social purpose (other than maximizing shareholder value) that would be appropriate for, and end up satisfying, all their different stakeholders.

Columbia Business School's Bruce Kogut closes with the suggestion that our greatest problems today may be coming not from the shortsightedness and other failings of corporations and corporate law, but from “deep distrust of the competence of the state.” Kogut's main prescription is that to take advantage of the enormous potential gains from effective arm's‐length collaboration between business and the public sector, governments at all levels should find ways to strike “Coasian bargains” with the private sector that makes the best possible uses of the core competencies and resources of each.
EVA, not EBITDA: A New Financial Paradigm for Private Equity Firms
Authors: Stewart Bennett
Published: September 2019

Private equity firms have boomed on the back of EBITDA. Most PE firms use it as their primary measure of value, and ask the managers of their portfolio companies to increase it. Many public companies have decided to emulate the PE firms by using EBITDA to review performance with investors, and even as a basis for determining incentive pay. But is the emphasis on EBITDA warranted?

In this article, the co‐founder of Stern Stewart & Co. argues that EVA offers a better way. He discusses blind spots and distortions that make EBITDA highly unreliable and misleading as a measure of normalized, ongoing profitability. By comparing EBITDA with EVA, or Economic Value Added, a measure of economic profit net of a full cost‐of‐capital charge, Stewart demonstrates EVA's ability to provide managers and investors with much more clarity into the levers that are driving corporate performance and determining intrinsic market value. And in support of his demonstration, Stewart reports the finding of his analysis of Russell 3000 public companies that EVA explains almost 20% more than EBITDA of their changes in value, while at the same time providing far more insight into how to improve those values.
Elevated hsa‐miR‐590‐3p expression down‐regulates HMGB2 expression and contributes to the severity of IgA nephropathy
Authors: Zhai Yaling , Qi Yuanyuan , Long Xiaoqing , Dou Yanna , Liu Dong , Cheng Genyang , Xiao Jing , Liu Zhangsuo , Zhao Zhanzheng
Published: September 2019

Peripheral blood mononuclear cells (PBMCs) play important roles in the pathogenesis of IgA nephropathy (IgAN). Our study aimed to provide a deep understanding of IgAN and focused on the dysregulation of hsa‐miR‐590‐3p and its target gene HMGB2 in PBMCs. Three gene expression profile datasets (GSE14795, GSE73953 and GSE25590) were downloaded from the GEO database. The DEGs (differentially expressed genes)‐miRNA network that was associated with IgAN was constructed by Cytoscape, and HMGB2 and hsa‐miR‐590‐3p were selected for further exploration. The dual‐luciferase reporter system was utilized to verify their interaction. Then, the expression levels of HMGB2 and hsa‐miR‐590‐3p in PBMCs were detected by qPCR in another cohort, and the correlation of their expression levels with the clinical pathological manifestations and serum Gd‐IgA1(galactose‐deficient IgA1) levels was also investigated. HMGB2 was identified as the target gene of hsa‐miR‐590‐3p. Furtherly, the elderly patients had higher HMGB2 expression levels than the expression levels of the younger patients. As the serum creatinine, serum BUN levels increased, the expression of HMGB2 decreased; Besides, the HMGB2 expression was positively correlated with serum complement 3(C3) levels, and it also had a negative correlation with the diastolic blood pressure, but not reach statistical significance. What is more, both hsa‐miR‐590‐3p and HMGB2 expression had a slight correlation tendency with serum Gd‐IgA1 levels in the whole population. In conclusion, HMGB2, the target gene of hsa‐miR‐590‐3p, was identified to correlate with the severity of IgAN, and this provides more clues for the pathogenesis of IgAN.
Retracted: INPP1 up‐regulation by miR‐27a contributes to the growth, migration and invasion of human cervical cancer
Authors: Li Pu , Zhang Qiaoge , Tang Hua
Published: September 2019

Inositol polyphosphate‐1‐phosphatase (INPP1) is an enzyme that is responsible for glycolysis and lipid metabolism. Here, we discovered that INPP1 expression was up‐regulated in CC tissues compared to that in adjacent normal tissues by RT‐qPCR. Inositol polyphosphate‐1‐phosphatase overexpression promoted and INPP1 knockdown suppressed cell viability, cellular migration/invasion and EMT in CC cells. To explore the mechanism of dysregulation, INPP1 was predicted to be a target of miR‐27a, and a pmiRGLO dual‐luciferase reporter assay showed that miR‐27a bound to the 3′ UTR of INPP1. RT‐qPCR revealed that miR‐27a was also up‐regulated and had a positive correlation with INPP1 expression in CC tissues. Furthermore, shR‐INPP1 could favour the malignant phenotype reversion induced by miR‐27a, suggesting that miR‐27a up‐regulates INPP1 to promote tumorigenic activities. Altogether, our findings show that the up‐regulation of INPP1 by miR‐27a contributes to tumorigenic activities and may provide a potential biomarker for CC.
Influence of hydrology on water quality and trophic state of irrigation reservoirs in Sri Lanka
Authors: Nadarajah Sareeha , Wijenayake W. M. H. Kelum , Amarasinghe Upali S.
Published: September 2019

Many reservoirs provide multiple benefits to people around the world, in addition to primary uses such as irrigation. Thus, reservoir management should address their multiple uses. The water quality of ten irrigation reservoirs in Sri Lanka was examined in the present study with the objective of better understanding the effects of hydrological regimes on reservoir water quality and trophic state. Basic limnological parameters pertinent to the nutrient loads to, and trophic state of, the reservoirs were collected from June 2013 to February 2016. The sampling period was arbitrarily divided into two periods of approximately similar duration (period 1 = June 2013–September 2014; period 2 = October 2014–February 2016) to investigate whether or not there was a seasonal variation in the water quality parameters. Although temporal and spatial variations were observed, most water quality parameters were within the levels acceptable for drinking water standards. The 10 reservoirs were also ordinated by principal component analysis (PCA) on the basis of the water quality parameters of the two sampling periods in a two‐dimensional score plot. Reservoirs in the first principal component (PC1) axis were represented by negative scores attributable to the dissolved oxygen concentration and pH and, to a lesser extent, by electrical conductivity and chlorophyll‐a concentration. Positive scores in PC1 were represented by reservoirs with a score loading attributable to alkalinity, nitrate concentration, Secchi depth, temperature and seston weight and, to a lesser extent, from the total phosphorus concentration. There was a significant negative correlation of PC1 scores with relative reservoir water‐level fluctuation (RRLF; the ratio of mean reservoir water‐level amplitude to mean reservoir depth). Furthermore, Carlson's trophic index also were influenced by RRLF, although not by hydraulic retention time (HRT), indicating allochthonous nutrient inputs into the irrigation reservoirs were mainly governed by RRLF, but not by HRT. Thus, the results of the present study provide useful insights into achieving desirable reservoir water quality through the manipulation of the hydrological regime.
Loss of wbpL disrupts O‐polysaccharide synthesis and impairs virulence of plant‐associated Pseudomonas strains
Authors: Kutschera Alexander , Schombel Ursula , Wröbel Michelle , Gisch Nicolas , Ranf Stefanie
Published: September 2019

Despite its importance for membrane stability and pathogenicity of mammalian pathogens, functions of the O‐polysaccharide (OPS) of lipopolysaccharide (LPS) remain unclear in plant‐associated bacteria. Genetic information about OPS biosynthesis in these bacteria is largely missing. Genome analysis of various plant‐associated Pseudomonas strains revealed that one of the two known OPS biosynthesis clusters from Pseudomonas aeruginosa PAO1, the common polysaccharide antigen (CPA) gene cluster, is only conserved in some strains of the Pseudomonas fluorescens group. For the O‐specific antigen (OSA) biosynthesis cluster, the putative genomic position could be identified, but orthologues of most functional important OSA biosynthesis enzymes could not be detected. Nevertheless, orthologues of the glycosyltransferase WbpL, required for initiation of CPA and OSA synthesis in P. aeruginosa PAO1, could be identified in the analysed Pseudomonas genomes. Knockout mutations of wbpL orthologues in Pseudomonas syringae pv. tomato DC3000 (Pst) and Pseudomonas cichorii ATCC10857/DSM50259 (Pci) resulted in strains lacking the OPS. Infection experiments of Arabidopsis thaliana plants revealed a reduced entry into the leaf apoplast after spray inoculation and a reduced apoplastic amplification of Pst ∆wbpL. Stab and spray inoculation of lettuce (Lactuca sativa) leaves with Pci ∆wbpL causes reduced infection symptoms compared to the wild‐type strain. Furthermore, swarming motility was reduced in ∆wbpL mutants of Pst and Pci. This might be a possible reason for reduced bacterial titres after surface inoculation and reduced bacterial amplification in the plant. Our results imply that the presence of lipopolysaccharide OPS is required for efficient host colonization and full virulence of plant‐pathogenic Pseudomonas bacteria.
Major exopolysaccharide, EPS I, is associated with the feedback loop in the quorum sensing of Ralstonia solanacearum strain OE1‐1
Authors: Hayashi Kazusa , Senuma Wakana , Kai Kenji , Kiba Akinori , Ohnishi Kouhei , Hikichi Yasufumi
Published: September 2019

The Gram‐negative soil‐borne bacterium Ralstonia solanacearum first infects roots of host plants and then invades xylem vessels. In xylem vessels, the bacteria grow vigorously and produce exopolysaccharides (EPSs) to cause a wilt symptom on host plants. The EPSs are thus the main virulence factors of R. solanacearum. The strain OE1‐1 of R. solanacearum produces methyl 3‐hydroxymyristate as a quorum‐sensing (QS) signal, and senses this QS signal, activating QS. The QS‐activated LysR‐type transcriptional regulator PhcA induces the production of virulence‐related metabolites including ralfuranone and the major EPS, EPS I. To elucidate the function of EPS I, the transcriptomes of R. solanacearum strains were analysed using RNA sequencing technology. The expression of 97.2% of the positively QS‐regulated genes was down‐regulated in the epsB‐deleted mutant ΔepsB, which lost its EPS I productivity. Furthermore, expression of 98.0% of the negatively QS‐regulated genes was up‐regulated in ΔepsB. The deficiency to produce EPS I led to a significantly suppressed ralfuranone productivity and significantly enhanced swimming motility, which are suppressed by QS, but did not affect the expression levels of phcA and phcB, which encode a methyltransferase required for methyl 3‐hydroxymyristate production. Overall, QS‐dependently produced EPS I may be associated with the feedback loop of QS.
Vitamin K2 immunosuppressive effect on pediatric patients with atopic dermatitis
Authors: Xu Wencheng , Meng Kehan , Wu Hongguang , Miura Taro , Suzuki Shunsuke , Chiyotanda Masako , Tanaka Sachiko , Sugiyama Kentaro , Kawashima Hisashi , Hirano Toshihiko
Published: September 2019

Background

Over 20 kinds of steroids, tacrolimus ointments, and cyclosporine capsules are usually recommended for the treatment of atopic dermatitis (AD), depending on the symptoms of patients. However, several side effects sometimes occur with the extensive use of these agents for the treatment of pediatric AD patients. The purpose of this study was to explore whether vitamin K2 could be a new immunosuppressive candidate for pediatric patients with AD.

Methods

The immunosuppressive efficacy of vitamin K2 was evaluated through a cell‐culture procedure using mitogen‐activated peripheral blood mononuclear cells (PBMCs) obtained from pediatric AD patients.

Results

The mean (SD) IC50 value of vitamin K2 for the proliferation of concanavalin A‐activated PBMCs was 15.37 (30.05) μmol/L, while the value for tacrolimus was 0.10 (0.28) ng/mL (0.12 (0.35) nmol/L). There was a significant correlation between the IC50 values for vitamin K2 and those for tacrolimus (P = 0.0001, r = 0.8871). However, there was no significant correlation between the IC50 values of vitamin K2 and those of cyclosporine A or methylprednisolone. A significant correlation between the IC50 values of vitamin K2 or tacrolimus and blood eosinophil counts (P = 0.0099, r = 0.7086 and P = 0.0032, r = 0.7722, respectively) was observed.

Conclusion

Vitamin K2‐inhibited T‐cell mitogen stimulated proliferation of PBMCs from pediatric AD patients in a dose‐dependent manner. The PBMCs from pediatric AD patients were more sensitive to the immunosuppressive efficacy of vitamin K2 than the PBMCs from healthy subjects. The individual immunosuppressive pharmacological efficacy of vitamin K2 and of tacrolimus could be inferred from the blood eosinophil count of pediatric AD patients.
The Interplay of Empathy and Individualism in Support for Social Welfare Policies
Authors: Feldman Stanley , Huddy Leonie , Wronski Julie , Lown Patrick
Published: September 2019

Public support for government welfare programs is grounded in two potentially conflicting factors: a belief in individualism which undermines support for welfare assistance and the capacity for empathy which potentially enhances support. However, empathy is an expensive psychological commodity subject to pervasive up‐ and down‐regulation. This article examines the degree to which a belief in individualism affects the expression of compassionate support for a person in need among those with the capacity for empathy. In two online survey experiments, empathic ability powerfully increases support for a welfare recipient and social welfare policies when it does not conflict with individualism. But, empathic ability decreases compassion and support for government welfare among strong individualists. Evidence that individualists down‐regulate empathy for someone in need of government assistance is consistent with the conservative view that welfare promotes dependency and undermines individual agency. In contrast, charitable assistance is not associated with long‐term dependency, and we find that empathy is up‐regulated by strong individualists to generate charitable support for the same individual to whom they denied government assistance. The up‐ and down‐regulation of empathy in response to someone in need of government welfare helps illuminate the sharp divisions over social welfare policy among the American public.
Modelling the Socio-Economic Determinants of Fertility: A Mediation Analysis using the Parametric g-formula
Authors: Bijlsma Maarten J. , Wilson Ben
Published: September 2019

Theories predict that the timing of childbearing and number of children born are determined by multiple socio-economic factors. Despite this, many methods cannot investigate the interrelationships between these determinants, including the direct and indirect influence that they have on fertility over the life course. Here we use the parametric g-formula to examine the interdependent influences of time-varying socio-economic processes—education, employment status and partnership status—on fertility. To demonstrate this approach, we study a cohort of women who were born in the UK in 1970. Our results show that socio-economic processes play an important role in determining fertility, not only directly but also indirectly. We show that increasing attendance in higher education has a largely direct effect on early childbearing up to age 25 years, resulting in a substantial increase in childlessness. However, childbearing at later ages is dominated by an indirect effect of education on fertility, via partnership status and employment status, that is twice as large as the direct effect. We also use the g-formula to examine bias due to unobserved heterogeneity, and we demonstrate that our results appear to be robust. We conclude that the method provides a valuable tool for mediation analysis in studies of interdependent life course processes.