bluuebunny/crossref_metadata_2025 huggingface dataset:
Underground and Over the Sea: More Community Prophylactics in Europe, 1100-1600
Authors: Geltner G , Weeda Claire
Published: February 2021

Public health historians have repeatedly shown that the theory, policy, and practice of group prophylactics far predate their alleged birth in industrial modernity, and regularly draw on Galenic principles. While the revision overall has been successful, its main focus on European cities entails a major risk, since city dwellers were a minority even in Europe’s most urbanised regions. At the same time, cities continue to be perceived and presented as typically European, which stymies transregional and comparative studies based at least in part on non- or extra-urban groups. Thus, any plan to both offer an accurate picture of public health’s deeper past and fundamentally challenge a narrative of civilizational progress wedded to Euro-American modernity (“stagism”) would benefit from looking beyond cities and their unique health challenges. The present article begins to do so by focusing on two ubiquitous groups, often operating outside cities and facing specific risks: miners and shipmates. Evidence for these communities’ preventative interventions and the extent to which they drew on humoral theory is rich yet uneven for Europe between the thirteenth and sixteenth centuries. Methodological questions raised by this unevenness can be addressed by connecting different scales of evidence, as this article demonstrates. Furthermore, neither mining nor maritime trade was typically European, thus building a broader base for transregional studies and comparisons.
Do Economic Crises Trigger Treaty–Based Investor–State Arbitration Disputes?
Authors: Bellak Christian , Leibrecht Markus
Published: February 2021

The number of investor–state arbitration disputes has increased to more than 1000 to date, but their determinants are still not fully understood. We argue that in the wake of severe macroeconomic turmoil—economic crisis—policymakers have strong incentives to implement regulatory changes, even if these allegedly breach protection standards are provided by International Investment Agreements (IIAs). We base our empirical analysis on a unique country-dyadic dataset containing 961 investor–state arbitration claims over the 1987–2017 period. Our findings support the results of the related literature, which stresses the importance of good governance for avoiding arbitration cases. In contrast to this literature, we provide robust evidence consistent with a positive statistical association of economic crises and the number of investor–state arbitration disputes. Our investigation suggests that governments risk paying compensation to foreign investors for their actions in times when public regulation is needed in other areas. This may warrant a reconsideration of economic emergency measures of governments and the national security clause in International Investment Agreements in the current reform debate.
Is Article 8(3) EUTMR applicable only to identical marks and identical goods? ‘No’, says the Court of Justice
Authors: Martin Stefan , Boyd Jonathan
Published: February 2021

Court of Justice of the European Union, MINERAL MAGIC/MAGIC MINERALS BY JEROME ALEXANDER et al, C-809/18 P, EU: C:2020:902, 11/11/2020

The Court of Justice provides clear guidance on the test to be applied under Article 8(3) of the EU Trade Mark Regulation 2017/1001 (‘EUTMR).
Developing a nomogram for predicting intravesical recurrence after radical nephroureterectomy: a retrospective cohort study of mainland Chinese patients
Authors: Lai Shicong , Long Xingbo , Wu Pengjie , Liu Jianyong , Seery Samuel , Hou Huimin , Liu Ming , Li Yuan , Wang Jianye
Published: February 2021

Objective

To evaluate the role of Ki-67 in predicting subsequent intravesical recurrence following radical nephroureterectomy and to develop a predictive nomogram for upper tract urothelial carcinoma patients.

Methods

This retrospective analysis involved 489 upper tract urothelial carcinoma patients who underwent radical nephroureterectomy with bladder cuff excision. The data set was randomly split into a training cohort of 293 patients and a validation cohort of 196 patients. Immunohistochemical analysis was used to assess the immunoreactivity of the biomarker Ki-67 in the tumor tissues. A multivariable Cox regression model was utilized to identify independent intravesical recurrence predictors after radical nephroureterectomy before constructing a nomographic model. Predictive accuracy was quantified using time-dependent receiver operating characteristic curve. Decision curve analysis was performed to evaluate the clinical benefit of models.

Results

With a median follow-up of 54 months, intravesical recurrence developed in 28.2% of this sample (n = 137). Tumor location, multifocality, pathological T stage, surgical approach, bladder cancer history and Ki-67 expression levels were independently associated with intravesical recurrence (all P < 0.05). The full model, which intercalated Ki-67 with traditional clinicopathological parameters, outperformed both the basic model and Xylinas’ model in terms of discriminative capacity (all P < 0.05). Decision-making analysis suggests that the more comprehensive model can also improve patients’ net benefit.

Conclusions

This new model, which intercalates the Ki-67 biomarker with traditional clinicopathological factors, appears to be more sensitive than nomograms previously tested across mainland Chinese populations. The findings suggest that Ki-67 could be useful for determining risk-stratified surveillance protocols following radical nephroureterectomy and in generating an individualized strategy based around intravesical recurrence predictions.
Temporal-dependent effects of DNA degradation on frozen tissues archived at −80°C
Authors: Soniat Taylor J , Sihaloho Hendra F , Stevens Richard D , Little Todd D , Phillips Caleb D , Bradley Robert D
Published: February 2021

Frozen tissues, associated with natural history and biological collections, historically have been archived at temperatures between −20°C and −80°C. More recently, the availability of liquid nitrogen systems has enabled the storage of tissue samples (biobanking) at temperatures as low as −196°C. Currently, it is not known how the degree of coldness (e.g., −80°C or −196°C) or longevity (time in storage) impacts preservation of tissue samples. To examine the effects of long-term storage (−80°C and −196°C) on DNA degradation, tissue samples (muscle and liver) archived for 30, 20, 10, or 1 years were obtained from the Natural Science Research Laboratory at Texas Tech University. The integrity of DNA (measured as molecular weight and fragment length) extracted from samples was determined using automated DNA isolation methods followed by microfluidic distribution measurement. DNA distributions were compared using measures of central tendency, a regression-based molecular mass profile, and as a latent variable in a structural equation model. Muscle samples consistently outperformed liver samples in terms of quality of DNA yield. Also, muscle samples exhibited a significant linear relationship with time in which older samples were more degraded than were recent samples. The signal for a temporal effect on DNA was strongest when considering a latent variable of DNA quality based on mode and kurtosis; 37% of the variation in the latent variable was explained by variation in units of time. More recent time points tended to be more similar, but the temporal effect on the latent variable remained strong even when the oldest samples were removed from the analysis. In contrast, integrity of DNA from liver samples did not have a significant linear relationship with time; however, in some years they exhibited non-normally distributed DNA quality metrics that may have reflected sensitivity of liver tissue to degradation during specimen preparation, DNA extraction, or archive parameters. Results indicated that tissue type and temporal effects influenced rates of DNA degradation, with the latter emphasizing the long-term value of biobanking at the coldest temperatures possible (liquid nitrogen storage) to mitigate degradation of biological samples of ever-increasing scientific value.
Application of deproteinized bovine bone mineral as proangiogenic scaffold for alveolar bone formation in beagle dogs
Authors: Ogasawara Keita , To Masahiro , Liu Yu-Hao , Okudera Toshimitsu , Nakamura Takatsuna , Matsuo Masato
Published: February 2021

Alveolar bone repair after tooth extraction is essential after oral surgeries. Various grafting materials are used to promote the regeneration of lost alveolar bone. This study analysed the morphological features of the tissue regeneration process using deproteinized bovine bone mineral (DBBM). DBBM was used to densely fill the extraction sockets in beagle dogs. Following resin casting of the vasculature, stereomicroscopy and scanning electron microscopy were used to observe blood vessels and hard tissues in haematoxylin and eosin-stained sections on postoperative days 14, 30 and 90 in conjunction with vascular endothelial growth factor (VEGF) immunostaining to evaluate alveolar bone vascularization. On day 14 post-operation, the DBBM granules tightly filled the extraction sockets, maintained alveolar margin height and formed a scaffold for aiding angiogenesis and new bone formation. On day 30, new bone formation was observed around the DBBM granules. By day 90, bone tissue regeneration progressed in both groups but was more pronounced in the DBBM group. Alveolar margin height was maintained in the DBBM group throughout the study. Furthermore, VEGF expression in the DBBM group was detected around newly formed bone. We conclude that DBBM acts as a suitable scaffold for new bone generation, as well as angiogenesis around healing alveolar bone, and that it has the potential to play a key role in vascularization and bone formation.
The Road Back Home is Never Long: Refugee Return Migration
Authors: Zakirova Komila , Buzurukov Bilol
Published: February 2021

The current paper, building on qualitative research for refugees’ return migration, endeavours to provide an empirical evaluation of return migration. More specifically, this study focuses on the effect of political and economic stimuli on refugees’ choice to return. We conducted a quantitative analysis using a negative binomial model with fixed effects on a longitudinal dataset for more than 150 countries for the period 1991–2018. Our results reveal that the strongest predictors of return migration are political factors. Notably, a reduction in human rights violations, the elimination of genocides/politicides, the termination of wars and peace agreements are the most influential variables. Economic incentives are relatively weak, indicating that economic motives are not the principal factor for refugee returnees’ decision-making. The most robust economic covariate, educational access, is a conglomerate of economic and social factors; consequently, it is more influential within its group.
Ethylene activation of carotenoid biosynthesis by a novel transcription factor CsERF061
Authors: Zhu Kaijie , Sun Quan , Chen Hongyan , Mei Xuehan , Lu Suwen , Ye Junli , Chai Lijun , Xu Qiang , Deng Xiuxin
Published: February 2021

Chromoplast-specific lycopene β-cyclase (LCYb2) is a critical carotenogenic enzyme, which controls the massive accumulation of downstream carotenoids, especially provitamin A carotenoids, in citrus. Its regulatory metabolism is largely unknown. Here, we identified a group I ethylene response factor, CsERF061, in citrus by yeast one-hybrid screen with the promoter of LCYb2. The expression of CsERF061 was induced by ethylene. Transcript and protein levels of CsERF061 were increased during fruit development and coloration. CsERF061 is a nucleus-localized transcriptional activator, which directly binds to the promoter of LCYb2 and activates its expression. Overexpression of CsERF061 in citrus calli and tomato fruits enhanced carotenoid accumulation by increasing the expression of key carotenoid pathway genes, and increased the number of chromoplasts needed to sequester the elevated concentrations of carotenoids, which was accompanied by changes in the concentrations of abscisic acid and gibberellin. Electrophoretic mobility shift and dual-luciferase assays verified that CsERF061 activates the promoters of nine other key carotenoid pathway genes, PSY1, PDS, CRTISO, LCYb1, BCH, ZEP, NCED3, CCD1, and CCD4, revealing the multitargeted regulation of CsERF061. Collectively, our findings decipher a novel regulatory network of carotenoid enhancement by CsERF061, induced by ethylene, which will be useful for manipulating carotenoid accumulation in citrus and other plants.
Recent advances in peptide signaling during Arabidopsis root development
Authors: Jeon Byeong Wook , Kim Min-Jung , Pandey Shashank K , Oh Eunkyoo , Seo Pil Joon , Kim Jungmook
Published: February 2021

Roots provide the plant with water and nutrients and anchor it in a substrate. Root development is controlled by plant hormones and various sets of transcription factors. Recently, various small peptides and their cognate receptors have been identified as controlling root development. Small peptides bind to membrane-localized receptor-like kinases, inducing their dimerization with co-receptor proteins for signaling activation and giving rise to cellular signaling outputs. Small peptides function as local and long-distance signaling molecules involved in cell-to-cell communication networks, coordinating root development. In this review, we survey recent advances in the peptide ligand-mediated signaling pathways involved in the control of root development in Arabidopsis. We describe the interconnection between peptide signaling and conventional phytohormone signaling. Additionally, we discuss the diversity of identified peptide–receptor interactions during plant root development.
Natural ultraviolet radiation exposure alters photosynthetic biology and improves recovery from desiccation in a desert moss
Authors: Ekwealor Jenna T B , Clark Theresa A , Dautermann Oliver , Russell Alexander , Ebrahimi Sotodeh , Stark Lloyd R , Niyogi Krishna K , Mishler Brent D
Published: February 2021

Plants in dryland ecosystems experience extreme daily and seasonal fluctuations in light, temperature, and water availability. We used an in situ field experiment to uncover the effects of natural and reduced levels of ultraviolet radiation (UV) on maximum PSII quantum efficiency (Fv/Fm), relative abundance of photosynthetic pigments and antioxidants, and the transcriptome in the desiccation-tolerant desert moss Syntrichia caninervis. We tested the hypotheses that: (i) S. caninervis plants undergo sustained thermal quenching of light [non-photochemical quenching (NPQ)] while desiccated and after rehydration; (ii) a reduction of UV will result in improved recovery of Fv/Fm; but (iii) 1 year of UV removal will de-harden plants and increase vulnerability to UV damage, indicated by a reduction in Fv/Fm. All field-collected plants had extremely low Fv/Fm after initial rehydration but recovered over 8 d in lab-simulated winter conditions. UV-filtered plants had lower Fv/Fm during recovery, higher concentrations of photoprotective pigments and antioxidants such as zeaxanthin and tocopherols, and lower concentrations of neoxanthin and Chl b than plants exposed to near natural UV levels. Field-grown S. caninervis underwent sustained NPQ that took days to relax and for efficient photosynthesis to resume. Reduction of solar UV radiation adversely affected recovery of Fv/Fm following rehydration.
Cartel Damages
Authors: Veljanovski Cento
Published: February 2021

This book represents a comprehensive, practical guide on the law, economics, and measurement of cartel damages under UK and European competition laws. It draws together the most recent research on cartels, economic analysis, empirical techniques, case law, and legislation to examine how the quantification of losses suffered by those harmed by a cartel are, and could be, applied under European and UK competition laws. Written with the practitioner in mind, the book displays a rigorous yet pragmatic approach to the subject. Detailed discussions of leading cases complement the treatment of the application of economic theory and empirical techniques in competition law and litigation. Three appendices provide the reader with quick reference guides to statistics on European Commission Cartel Decisions (1999 to 2019), Bank of England ‘base rate’ (1980 to 2019), and where to find key documents and information. The book is a practical guide to issues of increasing importance and relevance in competition law.
Establishing a Cartel Exists
Authors: Veljanovski Cento
Published: February 2021

This chapter examines the first step in any damage claim, which is to establish the existence of a cartel or, more precisely, an infringement of Article 101(1) TFEU. The claimant will typically rely on an infringement decision of a competition authority to bring a follow-on action. Without an infringement decision, proving that a cartel exists will be difficult. This is because cartels operate in secrecy, rarely leave a paper trial, and potential claimants have no right to inspect the internal documents and emails of firms they suspect are colluding. As such, competition authorities use leniency programmes to detect cartels, which offer reduced fines and other protections to encourage whistleblowing and cooperation. In addition, economic theory and statistical techniques can assist in the detection of cartels. This will become a more prominent feature of cartel enforcement in the future as competition authorities become less reliant on leniency programmes.
Damages
Authors: Veljanovski Cento
Published: February 2021

This chapter assesses damages actions for competition infringement. The Damages Directive sets out a common legal basis across the EU for the right of those harmed by a competition infringement to sue and quantification of damages. It has been transposed into the UK and incorporated as Schedule 8A of the Competition Act 1989. The Damages Directive gives the national courts the power to estimate the overcharge; requires the European Commission to issue guidelines on the quantification of overcharges and on ‘pass-on to’; and advises that the national courts can request assistance from a willing national competition authority where appropriate to determine quantum. In English law, the position is that damages are compensatory and aim to place the victim in the position they would have been had they not been injured so far as monetary compensation can. There are several heads or types of damages that have so far been claimed: overcharge damages; lost volume or lost profit damages; run-on damages; umbrella damages; cost-based damages; future losses, lost chance, and lost opportunity damages; and aggregate damages in collective actions.
Cost-based Approaches
Authors: Veljanovski Cento
Published: February 2021

This chapter studies the cost-based and margin approaches, which are attractive to courts because they rely on actual data and are easily understood. There are several variants. The simplest version is to collect data on the cartel’s avoidable, marginal, or average costs, and add to this a competitive or pre-cartel margin to determine ‘but for’ prices. If the cartel’s prices are found to exceed the prices calculated using the firm’s marginal costs plus a competitive margin, the difference is regarded as the overcharge. This approach is attractive because it is based on the defendant’s cost data, the prices charged by the defendant, and evidence of what might be regarded as a reasonable or competitive mark-up on these costs. More recently, the English courts have adopted pure cost-based approaches which treat cost as a proxy for benefits or to take account of cost inefficiencies and cost savings during the cartel period.
The Foundations of International Investment Law
Authors: Salacuse Jeswald W
Published: February 2021

This chapter examines the state of international investment law that exists in the absence of an applicable treaty, as that law remains an important foundation for the international law governing investments. One of the purposes of law is to protect the legitimate interests of persons, groups, and states, and to provide a mechanism for resolving disputes when those interests are in conflict. In any international investment transaction, there are three primary parties in interest: the investor, the host country in which the investment is made, and the home country of the investor. Each party ordinarily uses laws and legal devices to advance its perceived interests. The chapter then explores the sources of international law, as well as customary international law and general principles of law governing international investment. It also looks at customary international law on expropriation and breach of state contracts.
A History of International Investment Treaties
Authors: Salacuse Jeswald W
Published: February 2021

This chapter traces the history and considers the purposes and consequences of the movement by states to negotiate investment treaties. In the post-colonial era of nationalizations and contract renegotiations, the economic facts of life in host countries struggled against the form of various legal commitments made to foreign investors. To change the dynamics of this struggle so as to protect the interests of their companies and investors, capital-exporting countries began a process of negotiating international investment treaties that, to the extent possible, would be: (1) complete; (2) clear and specific; (3) uncontestable; and (4) enforceable. These treaty efforts took place at both the bilateral and multilateral levels, which, though separate, tended to inform and reinforce each other. As a result of this process, a widespread treatification of international investment law took place in a relatively short time. By the end of the second decade of the twenty-first century, foreign investors in many parts of the world were protected primarily by international treaties rather than as previously by customary international law alone. For all practical purposes, treaties have become the fundamental source of international law in the area of foreign investment.
The Interpretation of Investment Treaties
Authors: Salacuse Jeswald W
Published: February 2021

This chapter discusses the interpretation of investment treaties. Treaty interpretation is never easy, but the task of interpreting investment treaties is rendered particularly difficult by two factors: first, the generality and vagueness of many of the terms used in their texts, such as ‘fair and equitable treatment’, ‘full protection and security’, and ‘expropriation and measures tantamount to expropriation’ which reasonable persons may interpret differently. Although investment treaties have not traditionally defined these terms, some of the more recent international investment agreements, perhaps influenced by disputed arbitral decisions, have sought to provide more or less detailed definitional provisions for the often-contested important terms they employ. The second interpretational difficulty arises from the factual and legal complexity of the investment transactions and relationships to which investment treaties are applied. As a result of these complexities, arbitral tribunals and lawyers must devote significant effort and time to give meaning to words that at first glance appear simple but usually are not. The chapter then provides guidance on treaty interpretation. The basic rules of investment treaty interpretation are found in Articles 31, 32, and 33 of the Vienna Convention on the Law of Treaties (VCLT).
Investment Promotion, Facilitation, Admission, and Establishment
Authors: Salacuse Jeswald W
Published: February 2021

This chapter assesses investment promotion, facilitation, admission, and establishment. International law recognizes that by virtue of its sovereignty a state has the right to control the entry and exit of persons and things into and from its territory and also to regulate the activities of nationals or foreign persons and companies within that territory. A corollary of that principle is that a state is not required to allow foreign nationals or companies to establish or acquire an enterprise or investment within its territory. With respect to foreign investment, states have complete legislative jurisdiction to determine to what extent foreign nationals and companies may undertake investments, which sectors and industries they may or may not enter, and whether or not they must fulfil additional conditions in order to undertake and operate an investment within state territory. Numerous factors have shaped individual countries' attitudes towards foreign investment and investment treaty negotiations. One of the traditional aims of the investment treaty movement has been to reduce these internal barriers to foreign investment, particularly through treaty provisions on investment promotion, admission, and establishment. The second decade of the twenty-first century witnessed a growing emphasis in both international discussions and a few treaties on a new concept: foreign investment facilitation.
General Treatment Standards
Authors: Salacuse Jeswald W
Published: February 2021

This chapter addresses the general standards of treatment in investment treaties. General treatment standards consist of two types: (a) absolute standards, which are not contingent upon specified factors, happenings, or government behaviour towards other investors or persons; and (b) relative standards, which are dependent upon the host government's treatment of other investments or investors. The chapter discusses the absolute and relative general treatment standards used most frequently in international investment treaties. These include full protection and security, fair and equitable treatment, minimum treatment according to international law, most-favoured-nation treatment, and national treatment. That these standards exist in one form or another in most investment treaties gives the treaties a strong similarity. It must also be acknowledged, however, that not all treaties include all of these general standards and that significant differences exist in the way individual treaties articulate them.
Protection Against Expropriation, Nationalization, and Dispossession
Authors: Salacuse Jeswald W
Published: February 2021

This chapter examines the investment treaty protections against expropriation, nationalization, and dispossession. Because the investment treaty movement arose during a period when many expropriations and nationalizations had taken place and states exhibited significant disagreement about the applicable international law, one of the primary goals of capital-exporting countries in promoting investment treaties was to protect their investors and investments from acts of expropriation, nationalization, and dispossession by host governments. As a result, virtually all investment treaties contain a provision concerning the expropriation or nationalization of covered investments; however, the nature of those provisions, their scope, and the limitations they place on governmental action, vary among treaties. The chapter then examines the scope of coverage of expropriation provisions as they apply to direct and indirect takings of investor property by a state. It also considers the various conditions and limitations that treaties place upon such state actions, including the obligation to pay compensation.
The Consequences of Treaty Violations
Authors: Salacuse Jeswald W
Published: February 2021

This chapter assesses the consequences of treaty violations. As a general rule, investment treaties do not specifically state the consequences of a state's breach of treaty provisions. In fact, many, if not most investment treaties make no reference at all to the obligation of an offending state to pay compensation or make reparation to investors injured by a breach. While investment treaties generally do not specify rules on damages for failure to respect their provisions, they nearly always provide that tribunals are to decide disputes not only in accordance with the applicable treaty provisions but also in accordance with ‘the relevant principles of international law’, ‘the general principles of international law’, or ‘the applicable principles of international law’. Thus, all investment treaties stipulate that international law, customary international law, or some variation of that formulation is the source of law that tribunals are to apply in deciding the issues that they confront, which of course includes compensation for investments that have been injured by a contracting state's failure to respect treaty provisions. In order to determine the value of the loss to an injured investment, one must have recourse to valuation techniques drawn from the science of finance.
The Genesis of Termination
Authors: Stannard John E , Capper David
Published: February 2021

This chapter explains how English law got to the point it is at now where it treats breach of condition and fundamental breach as the grounds on which a contract may be terminated. It differentiates between conditions and warranties. Breach of condition is where a contractual term of sufficient importance to justify the non-breaching party terminating the contract is breached. Breach of warranty is where the non-breaching party is only permitted an action for damages. The chapter then assesses the concepts of frustration and frustrating breach, and traces the history of the development of the law on frustration. A contract is frustrated when some unforeseeable supervening event occurs that without the fault of either party essentially destroys the bargain they have made. Where a contract is frustrated, both parties are released from their obligations of future performance.
Applications for Prompt Release of Vessels and Crews
Authors: Kittichaisaree Kriangsak
Published: February 2021

This chapter looks at applications for prompt release of vessels and crews detained after violating laws and regulations of a coastal State. Pursuant to Article 292(1) of the 1982 United Nations Convention on the Law of the Sea (UNCLOS), the International Tribunal for the Law of the Sea (ITLOS) has default jurisdiction over prompt release applications, unless the parties otherwise agree. The parties must be States Parties to UNCLOS and have not agreed to submit the question of release from detention to any other court or tribunal within ten days from the time of detention. Article 112 of the ITLOS Rules adds, inter alia, that ITLOS shall give priority to applications for release of vessels or crews over all other proceedings before ITLOS. In its judgment, ITLOS must determine in each case whether or not the allegation made by the applicant that the detaining State has not complied with a provision of UNCLOS for the prompt release of the vessel or the crew upon the posting of a reasonable bond or other financial security is well founded. If ITLOS decides the allegation is well founded, it shall determine the amount, nature, and form of the bond or financial security to be posted for the release of the vessel or the crew.
Responsible Practice or Restricted Practice? an Empirical Study of the Use of Clinical Guidelines in Medical Negligence Litigation
Authors: Samanta Ash , Samanta Jo , Beswick Joanne
Published: February 2021

In medical negligence litigation, the standard for breach of duty is measured against the Bolam test which reflects accepted practice. Despite protracted debate and common law development, the Bolam standard remains the touchstone for litigation in this area. Clinical guidelines (CGs) are statements based upon best available medical evidence and are designed to facilitate clinical decision-making to optimise outcomes thereby reflecting expected practice. Nevertheless, there is little research that considers how CGs engage in litigation and their influence on judicial reasoning. Given the increasing pressures on the NHS amid rising costs of litigation, these are important issues. This study provides an original contribution to the literature on CGs in determining breach of duty in law. Using a mixed methods’ approach, data from multiple sources have been gathered and analysed to assess the use of CGs by lawyers and the courts thereby adding to the discourse on the judicial shift away from deference to Bolam. It concludes by offering a conceptual basis for the use of CGs within a framework for reasonableness and promotes their principled use while avoiding constraints on expert testimony, experience, and exercise of clinical discretion. This study has relevance for academics, legal and medical practitioners, and policy makers.
The role of DNA polymerase ζ in benzo[a]pyrene-induced mutagenesis in the mouse lung
Authors: Ishii Yuji , Takasu Shinji , Grúz Petr , Masumura Kenichi , Ogawa Kumiko , Nohmi Takehiko , Umemura Takashi
Published: February 2021

DNA polymerase zeta (Polζ) is a heterotetramer composed of the catalytic subunit Rev3l, Rev7 and two subunits of Polδ (PolD2/Pol31 and PolD3/Pol32), and this polymerase exerts translesion DNA synthesis (TLS) in yeast. Because Rev3l knockout results in embryonic lethality in mice, the functions of Polζ need further investigation in vivo. Then, we noted the two facts that substitution of leucine 979 of yeast Rev3l with methionine reduces Polζ replication fidelity and that reporter gene transgenic rodents are able to provide the detailed mutation status. Here, we established gpt delta mouse knocked in the constructed gene encoding methionine instead of leucine at residue 2610 of Rev3l (Rev3l L2610M gpt delta mice), to clarify the role of Polζ in TLS of chemical-induced bulky DNA adducts in vivo. Eight-week-old gpt delta mice and Rev3l L2610M gpt delta mice were treated with benzo[a]pyrene (BaP) at 0, 40, 80, or 160 mg/kg via single intraperitoneal injection. At necropsy 31 days after treatment, lungs were collected for reporter gene mutation assays. Although the gpt mutant frequency was significantly increased by BaP in both mouse genotypes, it was three times higher in Rev3l L2610M gpt delta than gpt delta mice after treatment with 160 mg/kg BaP. The frequencies of G:C base substitutions and characteristic complex mutations were significantly increased in Rev3l L2610M gpt delta mice compared with gpt delta mice. The BaP dose–response relationship suggested that Polζ plays a central role in TLS when protective mechanisms against BaP mutagenesis, such as error-free TLS, are saturated. Overall, Polζ may incorporate incorrect nucleotides at the sites opposite to BaP-modified guanines and extend short DNA sequences from the resultant terminal mismatches only when DNA is heavily damaged.
Structural determinants of the IRF4/DNA homodimeric complex
Authors: Sundararaj Srinivasan , Seneviratne Sandali , Williams Simon J , Enders Anselm , Casarotto Marco G
Published: February 2021

Interferon regulatory factor 4 (IRF4) is a key transcription factor (TF) in the regulation of immune cells, including B and T cells. It acts by binding DNA as both a homodimer and, in conjunction with other TFs, as a heterodimer. The choice of homo and heterodimeric/ DNA interactions is a critical aspect in the control of the transcriptional program and cell fate outcome. To characterize the nature of this interaction in the homodimeric complex, we have determined the crystal structure of the IRF4/ISRE homodimeric complex. We show that the complex formation is aided by a substantial DNA deformation with co-operative binding achieved exclusively through protein–DNA contact. This markedly contrasts with the heterodimeric form where DNA bound IRF4 is shown to physically interact with PU.1 TF to engage EICE1. We also show that the hotspot residues (Arg98, Cys99 and Asn102) contact both consensus and non-consensus sequences with the L1 loop exhibiting marked flexibility. Additionally, we identified that IRF4L116R, a mutant associated with chronic lymphocytic leukemia, binds more robustly to DNA thereby providing a rationale for the observed gain of function. Together, we demonstrate key structural differences between IRF4 homo and heterodimeric complexes, thereby providing molecular insights into IRF4-mediated transcriptional regulation.
COVID-19 Testing Results by HIV Status, March–July 2020, Chicago, USA
Authors: Pyra Maria , Rusie Laura , Houlberg Magda , Balthazar Christopher , Montgomery Jerome , Hotton Anna , Yang Wenho , Betanzos Mateo , Green Maya , Schneider John
Published: February 2021

The role of HIV in coronavirus disease 2019 acquisition is not yet understood. Among 1862 patients, including 349 people with HIV—with most of these being virally suppressed and 308 having recently used pre-exposure prophylaxis—we compared rates of positive polymerase chain reaction results. Positivity was higher among people with HIV (10.6%) compared with HIV-negative patients (7.1%) but was not significant in adjusted models.
Comparison of All-Cause Mortality Between Individuals With COVID-19 and Propensity Score–Matched Individuals Without COVID-19 in South Korea
Authors: Oh Tak Kyu , Song In-Ae , Song Kyoung-Ho , Jeon Young-Tae
Published: February 2021

Background

We compared all-cause mortality between individuals in South Korea with and without coronavirus disease 2019 (COVID-19) using propensity score (PS) matching.

Methods

This population-based cohort study used data from the National Health Insurance Service COVID-19 cohort database. In the database, we included individuals (COVID-19 patients, control population, and test-negative individuals) aged 20 years or older, regardless of hospitalization. The primary end point was all-cause mortality between January 1, 2020, and August 27, 2020.

Results

A total of 328 374 adults were included in the study: 7713 and 320 660 in the COVID-19 group and the control group. After PS matching, a total of 15 426 individuals (7713 per group) were included in the analysis. All-cause mortality was 3.2% (248/7713) and 1.6% (126/7713) in the COVID-19 group and the control group, respectively. In Cox regression analysis after PS matching, the risk of death in the COVID-19 group was twice as high (hazard ratio, 2.00; 95% CI, 1.61–2.48; P < .001) as that in the control group. Among patients aged ≥60 years, the COVID-19 group had a 2.32-fold higher all-cause mortality compared with the control group, while statistically significant differences were not observed in the age groups 20–39 years (P = .339) and 40–59 years (P = .562).

Conclusions

In South Korea, all-cause mortality was twice as high among individuals with COVID-19 as among those with similar underlying risks, primarily because of the elevated COVID-19-associated mortality in those aged ≥60 years. Our results highlight the need for prevention of COVID-19 with respect to mortality as a public health outcome.
Geochemical Distinction Between Altered Oceanic Basalt- and Seafloor Sediment-Derived Fluids in the Mantle Source of Mafic Igneous Rocks in Southwestern Tianshan, Western China
Authors: Ma Li-Tao , Dai Li-Qun , Zheng Yong-Fei , Zhao Zi-Fu , Fang Wei , Zhao Kai , Xiao Yilin , Tong Fengtai
Published: February 2021

The role of subducting oceanic crust-derived fluids in generating mafic arc magmatism has been widely documented. However, the subducting oceanic crust is generally composed of basaltic igneous crust and seafloor sediment, which may give rise to different compositions of liquid phases causing metasomatism of the mantle wedge. Because of the similarity in enrichment of fluid-mobile incompatible elements in the two sources of subduction zone fluids, it has been a challenge to distinguish between them when studying the products of mafic arc magmatism. This difficulty is overcome by a combined study of whole-rock Li isotopes and zircon O isotopes in addition to whole-rock major-trace elements and Sr–Nd–Hf isotopes in Late Paleozoic mafic igneous rocks from southwestern Tianshan in western China. Zircon U–Pb dating yields consistent ages of 313 ± 3 Ma to 305 ± 1 Ma for magma crystallization. The mafic igneous rocks exhibit arc-like trace element distribution patterns and depleted whole-rock Nd–Hf isotopes but slightly high (87Sr/86Sr)i ratios of 0·7039– 0·7057. They also show positive zircon εHf(t) values and slightly higher zircon δ18O values of 5·2–7·6‰. There are covariations of whole-rock Sr isotopes with Th/La and Rb/Nb ratios, indicating a contribution from terrigenous sediment-derived fluids to their mantle source in addition to basaltic igneous crust-derived fluids. Based on the slightly higher zircon δ18O values but variably lower whole-rock δ7Li values of -0·8 to 3·5‰ for the target rocks than those of mantle respectively, both altered oceanic basalt- and terrigenous sediment-derived fluids are identified in the mantle source of these mafic igneous rocks. Model calculations for trace elements and Sr–Nd–Li isotopes further confirm that the geochemical compositions of these mafic igneous rocks can be explained by chemical reaction of depleted MORB mantle peridotite with the mixed fluids to generate ultramafic metasomatites at subarc depths. Therefore, chemical metasomatism of the mantle wedge is a key mechanism for the incorporation of crustal components into the source of arc-like mafic igneous rocks above oceanic subduction zones.
Hexose transporter CsSWEET7a in cucumber mediates phloem unloading in companion cells for fruit development
Authors: Li Yaxin , Liu Huan , Yao Xuehui , Wang Jiang , Feng Sheng , Sun Lulu , Ma Si , Xu Kang , Chen Li-Qing , Sui Xiaolei
Published: February 2021

In the fleshy fruit of cucumbers (Cucumis sativus L.), the phloem flow is unloaded via an apoplasmic pathway, which requires protein carriers to export sugars derived from stachyose and raffinose into the apoplasm. However, transporter(s) involved in this process remain unidentified. Here, we report that a hexose transporter, CsSWEET7a (Sugar Will Eventually be Exported Transporter 7a), was highly expressed in cucumber sink tissues and localized to the plasma membrane in companion cells of the phloem. Its expression level increased gradually during fruit development. Down-regulation of CsSWEET7a by RNA interference (RNAi) resulted in smaller fruit size along with reduced soluble sugar levels and reduced allocation of 14C-labelled carbon to sink tissues. CsSWEET7a overexpression lines showed an opposite phenotype. Interestingly, genes encoding alkaline α-galactosidase (AGA) and sucrose synthase (SUS) were also differentially regulated in CsSWEET7a transgenic lines. Immunohistochemical analysis demonstrated that CsAGA2 co-localized with CsSWEET7a in companion cells, indicating cooperation between AGA and CsSWEET7a in fruit phloem unloading. Our findings indicated that CsSWEET7a is involved in sugar phloem unloading in cucumber fruit by removing hexoses from companion cells to the apoplasmic space to stimulate the raffinose family of oligosaccharides (RFOs) metabolism so that additional sugars can be unloaded to promote fruit growth. This study also provides a possible avenue towards improving fruit production in cucumber.
The Impact of Lockdown on Police Service Calls During the COVID-19 Pandemic in China
Authors: Dai Mengliang , Xia Yiwei , Han Rongxu
Published: February 2021

Police service calls have been studied widely in the Western context, but they are rarely discussed in the Chinese context. For the context of this study, it is important to note that the Chinese authorities implemented the strictest lockdown after the COVID-19 pandemic began. Drawing on the data from a county-level city in Hubei province, this study examines changes in the quantity and nature of 110 service calls before, during, and after the COVID-19 pandemic lockdown. The results indicate that the average weekly call numbers before and after the lockdown were higher than during the lockdown. Meanwhile, different call types produced different patterns, though the weekly call totals decreased during the lockdown. There was a significant decrease in crime, traffic, and dispute calls, but a substantial increase in calls related to domestic violence, public security, and other issues. Changes in the frequency of different call types pose challenges to police departments. These findings will have implications for deploying police forces and allocating resources within the pandemic crisis in particular.
The first-order symmetry operator on gravitational perturbations in the 5D Myers–Perry spacetime with equal angular momenta
Authors: Tsuchiya Masataka , Houri Tsuyoshi , Moon Yoo Chul
Published: February 2021

It has been revealed that the first-order symmetry operator for the linearized Einstein equation on a vacuum spacetime can be constructed from a Killing–Yano 3-form. This might be used to construct all or part of the solutions to the field equation. In this paper, we perform a mode decomposition of a metric perturbation on the Schwarzschild spacetime and the Myers–Perry spacetime with equal angular momenta in 5 dimensions, and investigate the action of the symmetry operator on specific modes concretely. We show that, on such spacetimes, there is no transition between the modes of a metric perturbation by the action of the symmetry operator, and it ends up being the linear combination of the infinitesimal transformations of isometry.
No indigenous peoples left behind on the rolling out of COVID-19 vaccines: considerations and predicaments
Authors: Sarmiento Philip Joseph D , Serrano Jose P , Ignacio Ria P , Cruz Arlan E dela , De Leon Jonald C
Published: February 2021

In recent correspondences, authors emphasized the need to consider vulnerable groups such as migrants, refugees, prisoners, and persons with disabilities in the interventions and plans of government and health authorities in combatting coronavirus disease 2019 (COVID-19). This paper discusses the urgent call for government and health authorities to ensure that indigenous peoples, being distinct ethnic communities, are included in the rolling out of COVID-19 vaccines with considerations to their unique culture, beliefs and traditions.
Clinical impact of myositis-specific autoantibodies on long-term prognosis of juvenile idiopathic inflammatory myopathies: multicentre study
Authors: Yamasaki Yuichi , Kobayashi Norimoto , Akioka Shinji , Yamazaki Kazuko , Takezaki Shunichiro , Nakaseko Haruna , Ohara Asami , Nishimura Kenichi , Nishida Yutaka , Sato Satoshi , Kishi Takayuki , Hashimoto Motomu , Mori Masaaki , Okazaki Yuka , Kuwana Masataka , Ohta Akiko
Published: February 2021

Objectives

This study aimed to investigate the clinical characteristics, treatment and prognosis of juvenile idiopathic inflammatory myopathies (JIIM) in Japan for each myositis-specific autoantibody (MSA) profile.

Methods

A multicentre, retrospective study was conducted using data of patients with JIIM at nine paediatric rheumatology centres in Japan. Patients with MSA profiles, determined by immunoprecipitation using stored serum from the active stage, were included.

Results

MSA were detected in 85 of 96 cases eligible for the analyses. Over 90% of the patients in this study had one of the following three MSA types: anti-melanoma differentiation-associated protein 5 (MDA5) (n = 31), anti-transcriptional intermediary factor 1 alpha and/or gamma subunits (TIF1γ) (n = 25) and anti-nuclear matrix protein 2 (NXP2) (n = 25) antibodies. Gottron papules and periungual capillary abnormalities were the most common signs of every MSA group in the initial phase. The presence of interstitial lung disease (ILD) was the highest risk factor for patients with anti-MDA5 antibodies. Most patients were administered multiple drug therapies: glucocorticoids and MTX were administered to patients with anti-TIF1γ or anti-NXP2 antibodies. Half of the patients with anti-MDA5 antibodies received more than three medications including i.v. CYC, especially patients with ILD. Patients with anti-MDA5 antibodies were more likely to achieve drug-free remission (29 vs 21%) and less likely to relapse (26 vs 44%) than others.

Conclusion

Anti-MDA5 antibodies are the most common MSA type in Japan, and patients with this antibody are characterized by ILD at onset, multiple medications including i.v. CYC, drug-free remission, and a lower frequency of relapse. New therapeutic strategies are required for other MSA types.