bluuebunny/crossref_metadata_2025 huggingface dataset:
9 Property Law Issues
Authors: John McGhee
Published: May 2022

This chapter explores the potential for forfeiture of a company's leases due to a CVA's proposal or approval, particularly Landlord CVAs. Landlord CVAs are popular as they enable tenant companies to mitigate or restructure leasehold obligations such as liabilities in paying rent. The proviso for re-entry or forfeiture clause indicates the landlord's right to forfeit being expressly granted by leases. The chapter explains the Debenhams case to expound on the concept of restricting the right of forfeiture. The availability and terms of relief depend on whether or not the CVA changed any covenants which were grounds of forfeiture such as non-payment of rent.
Extra-contractual Civil Liability (Tort Law) and Compliance
Authors: Sester Peter
Published: May 2022

This chapter will focus on tort law but also introduce the topic of compliance. For the purpose of this book compliance is understood in a procedural manner. Under this approach, compliance is about the creation, implementation, and supervision of procedural rules adopted by organizations to measure operational results and avoid costs caused by the violation of laws, regulations, internal rules on risk management, soft law, and the predominant moral and ethical standards of society. The provisions of the Brazilian Civil Code on extra-contractual civil liability (tort law) have been inspired by French law. Therefore, that comparison will be emphasized. Although liability normally requires fault, strict liability has been fostered by the legislator over the decades. The chapter will focus on those issues of classical tort law and strict liability that are important for risk analyses conducted prior to investing and deal making. It will also discuss the issue of piercing the corporate veil.
Public Procurement and Concessions
Authors: Sester Peter
Published: May 2022

The Brazilian public administration is an important customer of private companies. Together, the Federal Union, the Brazilian states, and the municipalities are by far the largest counterparty for the construction and facility management sector. Furthermore, the current government is promoting privatization, thereby creating opportunities for foreign investors, especially in the energy and aviation sector (airport privatization). Therefore, this chapter is very important for investors. It will focus on public procurement and contracts between private parties and units of the public administration. This specific area of the law, termed administrative law is not yet codified. Instead, it consists of a rather fragmented bundle of laws with an overlapping scope of application. However, two pillars stand out: the Public Procurement Act and the General Concession Act. Under the CFRB the acquisition of almost all goods and services needed by the public administration requires a public call for tender. Therefore, the recently revamped Public Procurement Act will be discussed extensively. The second key focus of this chapter is administrative contract law and its new provisions on risk allocation.
6 Corporate Actions Processing: Bridging the Gap Between Issuer and Investor
Authors: Thomas Keijser
Published: May 2022

This chapter explains the lifecycle of securities, wherein issuers and investors must effectively liaise with regard to the rights attached to securities and other rights concerning general meetings, distribution of income, and provision of information. It talks about the complication of processing corporate actions when an intermediated chain is involved and typically composed of several actors. It also analyzes the discrepancy between who is legally entitled to the rights attached to the securities and who is economically entitled to these rights. The chapter explores bottlenecks in the intermediated system and ways to address them in relation to different types of corporate actions, which includes voting rights, income payments, and the provision of information. It highlights possible solutions on the gap between issuer and investor that is compatible across borders, such as a cross-border investor being able to exercise rights in the same way as a domestic investor can.
10 Crypto Securities and Other Digital Assets: Aspects of Substantive and Regulatory Law
Authors: Thomas Keijser
Published: May 2022

This chapter reviews the dematerialization of securities that has been the dominant topic in securities law and regulation since the paper crunch in the late 1960s. It discusses common issues in the substantive legal framework for digital securities, including an overview over the regulation of digital securities. It also talks about the blockchain or distributed ledger technology (DLT), which refers to a group of technologies that have a database that is shared across a network of multiple sites and participants within a network that have their own identical copy of the ledger. The chapter looks at the security and accuracy of the assets stored in the ledger that are maintained by using crypto technologies. It refers to blockchain as one of the several possible data structures in a DLT system that is characterized by the fact that its entries are combined in blocks.
11 Conflict-of-Laws Rules
Authors: Thomas Keijser
Published: May 2022

This chapter highlights the vast majority of transactions in securities held with an intermediary that take place in an international context. It cites the Hague Convention of 5 July 2006 on the Law Applicable to Certain Rights in Respect of Securities Held with an Intermediary (HSC), which has been drafted to clarify the law applicable to a situation involving intermediated securities. It also defines the scope of the application and examines the choice-of-law rule set out in the HSC. The chapter discusses the factors that are not relevant to determining the applicable law and deals with the protection of third-party rights under the HSC, which may be compromised in case of a change of law or the opening of insolvency proceedings. It analyzes the relationships between the HSC and the UNIDROIT instruments for intermediated securities.
Creation of Agency
Authors: Munday Roderick
Published: May 2022

This chapter reviews the agreement between a principal and his agent that can be either express or implied as the great majority of agency agreements are contractual. It discusses contractual agencies wherein consideration must be present, and the agent must be under an enforceable obligation to do what is promised. It also examines how gratuitous agents may possess rights against their principals, notably the right to be indemnified for losses and expenses incurred in the course of their agency. The chapter describes the right to an indemnity as a normal incident of agency that exists independently of any contract between principal and agent. It cites Lord Pearson’s Garnac Grain, wherein he considered what evidence a court might look at in order to determine whether the parties could be taken to have consented to an agency.
Apparent Authority
Authors: Munday Roderick
Published: May 2022

This chapter highlights apparent authority or ostensible authority, which arises when a third party is induced to enter into a transaction with a principal by a party that appears to have authority to act but who in fact lacks such authority. It describes actual authority as a legal relationship between principal and agent that is created by a consensual agreement to which they alone are parties. It also talks about the illusion that can be created by the principal misrepresenting to third parties that the agent enjoys authority to perform certain acts. The chapter explains how apparent authority can arise in a variety of circumstances, suggesting that an agent may come to have apparent authority in several broad categories of situation. It refers to a principal that allows his agent to continue to appear as his agent after the agency has been terminated.
Legal Relations between Principal and Agent: Duties the Agent Owes to His Principal
Authors: Munday Roderick
Published: May 2022

This chapter considers the agent as both a contracting party and a fiduciary that owes strict equitable obligations to the principal arising out of the special position of trust in which the law of agency places him. It cites Turpin v Bilton, where an agent breached his principal’s instructions to arrange insurance for the ship. It also highlights an agent’s authority that will be governed by the exact terms of the agreement with the principal. The chapter explains how the agent cannot be expected to carry out instructions that would be null and void at common law or under statute. It discusses Ireland v Livingston, wherein an agent who will not be held liable to his principal for breach of their contract of agency.
Carriage of Goods by Sea
Authors: Girvin Stephen
Published: May 2022

This book provides an extensive comparative analysis of the carriage of goods by sea, examining the principles, regulation, responsibilities, obligations, and immunities within this area of English law in a single volume. The book covers a broad range of subjects in this area of shipping law. These include an essential overview of the business of shipping, a core group of chapters on different functions of bills of lading and other documents of carriage, the international and domestic regulation of carriage, an analysis of the major conventions (the Hague, Hague-Visby and Hamburg Rules, and the Rotterdam Rules), as well as the shippers’ responsibilities, both at common law and under the international conventions. Later chapters are concerned with the obligations of the carrier, and the rights and immunities of the carrier, again at common law, and under the international conventions. The book concludes by examining charterparties, as well as including chapters on frustration and damages. This third edition provides updates on new bills of lading, major Commonwealth developments impacting on the law in this field, and UK Supreme Court decisions including Volcafe Ltd v Compania Sud Americana de Vapores SA (Trading as CSAV) [2018] UKSC 61, The Ocean Victory [2017] UKSC 35, and The Kos [2012] UKSC 17. It also includes a new chapter relating to damages.
The Carrier’s Obligations under the Hague, Hague-Visby, and Rotterdam Rules
Authors: Girvin Stephen
Published: May 2022

This chapter examines the carrier’s obligations under the Hague, Hague-Visby, and Rotterdam Rules. These include the issue of bills of lading, seaworthiness, and care of cargo. Article III, rule 3 of the Hague and Hague-Visby Rules provides that: ‘After receiving the goods into his charge the carrier or the master or agent of the carrier shall, on demand of the shipper, issue to the shipper a bill of lading’. Article III, rule 1 of the Hague and Hague-Visby Rules states that: ‘The carrier shall be bound before and at the beginning of the voyage to exercise due diligence to (a) make the ship seaworthy; (b) properly man, equip and supply the ship; (c) and make the holds, refrigerating and cool chambers, and all other parts of the ship in which goods are carried, fit and safe for their reception, carriage and preservation’. Meanwhile, article III, rule 2 states that: ‘Subject to the provisions of Article IV, the carrier shall properly and carefully load, handle, stow, carry, keep, care for and discharge the goods delivered’.
Liens
Authors: Girvin Stephen
Published: May 2022

This chapter addresses liens, the classic definition of which is that ‘a lien is a right in one man to retain that which is in his possession belonging to another, till certain demands of him the person in possession are satisfied’. This definition, however, explains the basis for the common law (or possessory) lien. There are three other types of lien in English law. These are statutory liens, equitable liens, and maritime liens. Maritime liens are particularly important. The main characteristic is that maritime liens are non-possessory and attach to the property from the moment the particular cause of action arises. The chapter then looks at liens at common law, before considering express contractual liens over cargo in bills of lading and charterparties. It also studies liens over sub-freights and cesser clauses.
Securities and Derivatives Central Counterparties in the EU
Authors: Zebregs Bas , de Serière Victor
Published: May 2022

This chapter provides a general introduction to the relevant international standards and their transposition into the regulatory framework for the clearing sector in the European Union. It summarizes the applicable regulations established by the European Market Infrastructure Regulation (EMIR) of 2012 and related legal instruments. Specifically, the chapter analyses the applicable licensing and governance requirements, requirements pertaining to restricting and managing conflicts of interests, the outsourcing of certain activities and, in particular, the applicable prudential requirements for the management of losses and liquidity shortfalls and relevant conduct-of-business rules. All of these are broadly in line with the CPSS-IOSCO principles for market infrastructures of 2012. The chapter then turns to a closer look at the relevant investor protection rules established by MiFID II and the corresponding Markets in Financial Instruments Regulation (MiFIR). Of particular relevance within the European framework are issues relating to the segregation and portability of client assets.
Central Counterparties Insolvency and Resolution in the United States
Authors: Skeel David
Published: May 2022

This chapter addresses how, unlike in the European Union, the US legislation thus far has not established a bespoke regime for the management of central counterparty (CCP) failures. This leaves considerable uncertainty as to whether, and how, the reformed regulatory environment created by the post-financial crisis Dodd-Frank Act would respond to failures in the sector. While Title VIII of the Dodd-Frank Act has empowered the Financial Stability Oversight Council (FSOC) to designate clearinghouses as systemically important, it has been questioned whether the so-called 'Orderly Resolution Authority', a process for the resolution of failing systemically important financial institutions established by Title II of the Dodd-Frank Act, would apply—and, even if it did, would provide adequate solutions. The procedures and tools included in Title II hardly would fit, leaving room for the application of ordinary bankruptcy procedures. However, neither liquidation under Chapter 7 nor reorganization under Chapter 11 of the US Bankruptcy Code can be expected to be very helpful in the case of a clearinghouse failure, which essentially leads to a high level of reliance on the clearinghouses' risk mitigation and loss management arrangements contractually agreed with their respective members.
Swaps Client Clearing in the United States
Authors: Patel Nihal S
Published: May 2022

This chapter discusses the US legal regime system for customer clearing of swaps more than ten years after the adoption of Dodd-Frank Act and its related clearing mandates. Trading mandates have been implemented in numerous jurisdictions and clearing services have expanded significantly. However, in the years since implementation, this push has been accompanied by a great deal of rethinking. Market participants and observers have found new and different risks associated with clearing vis-à-vis bilateral trading. In addition, competitive balances in the derivatives markets have shifted, in significant part due to the implementation of regulatory reform. The chapter provides a critical overview of the legal infrastructure for swap clearing in the United States and considers ways in which the Commodity Futures Trading Commission regime could be approved, while taking the overall governmental desire to promote clearing as a given. It then takes a particular look at recent CFTC proposals to address US client access to clearing overseas and finally considers some of the macro-level trends in client clearing—in particular, the ongoing consolidation taking place among firms in the client clearing business—and whether and how regulators should address these changes.
Historical Evolution of Bank Capital Requirements in the European Union
Authors: Gortsos Christos V
Published: May 2022

This chapter provides an overview of the historical evolution of bank capital requirements and capital adequacy legislation in the European Union (EU) under the influence of international financial standards. It begins by reviewing bank capital adequacy requirements within the system of prudential banking regulation and dealing with the various sources of negative externalities in the banking system, the components of the so-called ‘bank safety net’. The chapter then looks at the international financial standards developed by the Basel Committee on Banking Supervision (BCBS) until the outbreak of the recent (2007–2009) Global Financial Crisis (GFC) and their impact on the shaping of the relevant EU banking legislation. It also traces the migration in 2010 from the so-called ‘Basel II’ capital adequacy framework to the ‘Basel III’ regulatory framework, before considering its incorporation into EU law in the context of the Banking Union. The emphasis is mainly placed on the basic provisions of the two legislative acts of the European Parliament and of the Council: the Capital Requirements Regulation (CRR) and the Capital Requirements Directive (CRD IV). Finally, the chapter studies the most recent (June 2020) amendments of the former legislative acts implemented amidst the current pandemic crisis.
The Definition of Common Equity Tier 1 Capital and of Contingent Capital
Authors: Lamandini Marco , Muñoz David Ramos
Published: May 2022

This chapter discusses the interpretation and application of Common Equity Tier 1 (CET1) and Contingent Capital requirements. The path towards Basel III was marked by the 2007–2009 financial crisis, which prioritised the need to enhance soundness, at the expense of clarity and simplicity. Capital rules now have a more restrictive definition of ‘capital’, but also introduce new ratios, such as the equity capital ratio, and the ‘core capital’ ratio, plus the new measures of contingent capital, and the leverage ratio. They all have complicated the definition of what ‘solvency’ means. The chapter then differentiates between Tier 1 and Tier 2 capital, before considering the challenge of setting the optimal minimum requirements. It also defines CET1 capital in Capital Requirements Regulation (CRR) and CRR II and CET1 capital instruments. Finally, the chapter looks at the role of the European Banking Authority (EBA) in terms of CET1 instruments, before focusing on Contingent Convertible Bonds (CoCos). Under Basel III, CoCos must be deeply subordinated, perpetual, and must pay non-cumulative coupons out distributable profits, payable at the discretion of the issuer.
The Construction of the Total Risk Exposure Amount and the Relationship with the Combined Buffer Requirements
Authors: Joosen Bart PM
Published: May 2022

This chapter focuses on the total risk exposure amount (TREA) and on the leverage ratio (LR). It begins by introducing the different concepts of an institution’s capital, before discussing the TREA in the Capital Requirements Regulation (CRR), including the most significant changes introduced by the CRR II. The chapter then analyses the relationship between the TREA and the different additional buffer requirements set out in the fourth Capital Requirements Directive (CRD IV). The TREA is also the denominator of the ratios of these different additional buffers. Finally, the chapter looks into the LR. Contrarily to the capital ratio, the LR is a non-risk weighted capital measure. The binding LR which requires institutions to maintain at least Tier 1 (T1) capital of 3% of their non-risk weighted assets is a new ratio introduced by CRR II. An additional ratio will apply for global systemic important institutions (G-SIIs).
The Definition of Default, Loss Distribution, Expected and Unexpected Loss, and Provisioning in the Context of Credit Risk
Authors: Joosen Bart PM
Published: May 2022

This chapter evaluates the principles for assessing credit risk, the consequences this has for capital requirements, and the fundamental approach that is chosen for all banks in this area. Absorbing losses is one of the functions of bank capital. As regards the credit risk concerning the bank’s exposures, it can generally be argued that banks will suffer losses on their credit portfolios due to counterparties failing to pay interest, the principal or costs incurred by the bank and attributable to the relevant loans. Banks will by nature always be faced with such losses, the only question of when they will occur, and their magnitude is an issue that will have to be dealt with in the context of credit risk management. The chapter then differentiates between manifest losses, expected losses, and unexpected losses. It also looks at the capital conservation buffer (CCB) introduced by Basel III; the definition of default in European banking law; and credit risk adjustments. Finally, the chapter considers the revisions to Capital Requirements Regulation (CRR) to address non-performing exposures.
Credit Risk Weighting—SA and IRB Approaches
Authors: Joosen Bart PM
Published: May 2022

This chapter traces the evolution of the Basel Committee on Banking Supervision (BCBS) standards in respect of credit risk. The First Basel Capital Accord of 1988 (Basel I) introduces uniform rules for the minimum capital that banks must hold in light of the risks that banks run in the credit business. Basel II codifies a number of rules that had been adopted since the adoption of Basel I in 1988. With regard to the weighting of the credit risk for (on) balance sheet items, banks can apply two methods, the Standard approach (SA) and the internal models method (Internal Ratings-Based Approach, ‘IRB’). The original foundations of the SA as laid down in Basel I of 1988 underpinned the risk weighting of credit risk exposures for about 30 years. However, the fundamental turn in the approach to risk weighting of the various exposure classes as a result of Basel III-Reform brought about major changes for European banks applying the SA. No less fundamental are the changes introduced for banks applying the IRB approach as a result of Basel III-Reform.
Capital Treatment of Securitizations
Authors: Joosen Bart PM
Published: May 2022

This chapter addresses the prudential treatment of securitisation transactions. It focuses on the various facets of the prudential treatment from a perspective of European regulated credit institutions in the various roles and capacities banks may play or assume in securitisation transactions. Firstly, for banks acting as originator or original lender, provided strict conditions are met, a securitisation transaction may result in an off-balance sheet treatment for prudential purposes, in other words assets forming part of the securitisation transaction are no longer part of the assets held by banks for which risk weights must be calculated. Secondly, from the perspective of banks investing in securitisation positions, such positions may obtain lower risk weights if they meet certain conditions. Thirdly, banks may act as sponsor in connection with Asset Backed Commercial Paper (ABCP) transactions, therefore fulfilling a pivotal role in managing the liquidity of the ABCP conduit. Finally, securitisation positions held by banks within the treasury function may be comprised in the liquidity buffer in order to meet the liquidity management rules. The chapter looks at the development of the regulatory framework for securitisations in the Basel Committee on Banking Supervision (BCBS), as well as the adoption of the Basel capital standards and the Significant Risk Transfer (SRT) rules in Europe.
Position Risk and Market Risk Measures Fundamental Review of the Trading Book
Authors: Cherubini Umberto
Published: May 2022

This chapter describes the concept of market risk measures, starting with a review of the long-standing debate on risk measures. It provides an overview of the main structure and (non-quantitative innovations) that will be introduced by the Fundamental Review of the Trading Book (FRTB) from the point of view of a ‘quant’. The chapter then looks at the quantitative procedures required to compute the capital charge for both the standardised and the internal model, before discussing the question that risk factors are prices, the regulatory prescriptions to define whether the prices observed are sufficiently transparent to deem the risk factors ‘modellable’, and how to address the other risk factors (Non Modellable Risk Factors). It also considers backtesting and profits and loss (P&L) attribution, and the degree of association between prices used in trading and risk management. Finally, the chapter examines the pros and cons of the new standards, the increase in regulatory costs, and the prospects of choice in the banking systems, before assessing the transposition of the Basel soft law into regulations such as the Capital Requirements Regulation (CRR) and CRR II.
The ECB Guide to Internal Liquidity Adequacy
Authors: Singh Dalvinder
Published: May 2022

This chapter analyses the European Central Bank Guide to Internal Liquidity Adequacy (ECB ILAAP Guide), which aim to introduce safeguards against liquidity contingency risk from a crisis prevention perspective. While the strategic direction of liquidity management resides with a bank’s management body, it requires delegation down to technical experts to ensure it is operationalized as efficiently as possible. The chapter argues that the crisis prevention narrative is delegated to banks to discharge their obligation in bank supervision so as to minimize the asymmetry of information problems created by their business and improve the way they manage adverse scenarios and the risks to depositors, markets, and supervisory authorities. The ECB ILAAP Guide is simply one component of a complex web of supervisory instruments and tools for banks’ liquidity management. In view of this, it is also important to consider the European Banking Authority (EBA) findings on internal governance from its convergence assessment. The chapter considers how these inform various decision-making processes within the Single Supervisory Mechanism (SSM) such as the work of the Joint Supervisory Teams (JSTs) and Supervisory Review and Evaluation Process (SREP), as the ECB ILAAP Guide specifically emphasizes the traditional qualitative approach to the supervision of liquidity management.
Aboveground plant-to-plant electrical signaling mediates network acquired acclimation
Authors: Szechyńska-Hebda Magdalena , Lewandowska Maria , Witoń Damian , Fichman Yosef , Mittler Ron , Karpiński Stanisław M
Published: May 2022

Systemic acquired acclimation and wound signaling require the transmission of electrical, calcium, and reactive oxygen species (ROS) signals between local and systemic tissues of the same plant. However, whether such signals can be transmitted between two different plants is largely unknown. Here, we reveal a new type of plant-to-plant aboveground direct communication involving electrical signaling detected at the surface of leaves, ROS, and photosystem networks. A foliar electrical signal induced by wounding or high light stress applied to a single dandelion leaf can be transmitted to a neighboring plant that is in direct contact with the stimulated plant, resulting in systemic photosynthetic, oxidative, molecular, and physiological changes in both plants. Furthermore, similar aboveground changes can be induced in a network of plants serially connected via touch. Such signals can also induce responses even if the neighboring plant is from a different plant species. Our study demonstrates that electrical signals can function as a communication link between transmitter and receiver plants that are organized as a network (community) of plants. This process can be described as network-acquired acclimation.
Neuroanatomical correlates of working memory performance in Neurofibromatosis 1
Authors: Sawyer Cameron , Green Jonathan , Lim Ben , Pobric Gorana , Jung JeYoung , Vassallo Grace , Evans D Gareth , Stagg Charlotte J , Parkes Laura M , Stivaros Stavros , Muhlert Nils , Garg Shruti
Published: May 2022

Introduction

Neurofibromatosis 1 (NF1) is a single-gene disorder associated with cognitive impairments, particularly with deficits in working memory. Prior research indicates that brain structure is affected in NF1, but it is unclear how these changes relate to aspects of cognition.

Methods

29 adolescents aged 11-17 years were compared to age and sex-matched controls. NF1 subjects were assessed using detailed multimodal measurements of working memory at baseline followed by a 3T MR scan. A voxel-based morphometry approach was used to estimate the total and regional gray matter(GM) volumetric differences between the NF1 and control groups. The working memory metrics were subjected to a principal component analysis (PCA) approach.

Results

The NF1 groups showed increased gray matter volumes in the thalamus, corpus striatum, dorsal midbrain and cerebellum bilaterally in the NF1 group as compared to controls. Principal component analysis on the working memory metrics in the NF1 group yielded three independent factors reflecting high memory load, low memory load and auditory working memory. Correlation analyses revealed that increased volume of posterior cingulate cortex, a key component of the default mode network (DMN) was significantly associated with poorer performance on low working memory load tasks.

Conclusion

These results are consistent with prior work showing larger subcortical brain volumes in the NF1 cohort. The strong association between posterior cingulate cortex volume and performance on low memory load conditions supports hypotheses of deficient DMN structural development, which in turn may contribute to the cognitive impairments in NF1.
Erroneous Pressure Reading from an Unpowered Intra-aortic Balloon Pump: Case Report
Authors: Belway Dean , Corrigan Andrea , Manchuk Derek , Bittira Bindu
Published: May 2022

Intra-aortic balloon pump (IABP) technology is an established treatment modality for patients with acute cardiac failure. Advances in IABP technology have simplified use and reliability such that electromechanical malfunctions are relatively rare. We present a case of an unanticipated pressure output signal from a powered off Cardiosave IABP console resulting in an erroneous mean arterial blood pressure waveform being displayed during cardiopulmonary bypass. The patient suffered no ill effects and made a full recovery. As a result of this incident, our policies have been revised to ensure that all patients with an IABP brought to the operating room for surgery have at least two arterial lines, one of which is not off the IABP, to prevent future occurrences.
A wireless ultrasound patch detects mild-to-moderate central hypovolemia during lower body negative pressure
Authors: Kenny Jon-Émile S. , Elfarnawany Mai , Yang Zhen , Eibl Andrew M. , Eibl Joseph K. , Kim Chul-Ho , Johnson Bruce D.
Published: May 2022

BACKGROUND

We have developed a wireless, wearable Doppler ultrasound system that continuously measures the common carotid artery Doppler pulse. A novel measure from this device, the Doppler shock index, accurately detected moderate-to-severe central blood volume loss in a human hemorrhage model generated by lower body negative pressure. In this analysis, we tested whether the wearable Doppler could identify only mild-to-moderate central blood volume loss.

METHODS

Eleven healthy volunteers were recruited and studied in a physiology laboratory at the Mayo Clinic. Each participant underwent a lower body negative protocol in duplicate. Carotid Doppler measures including Doppler shock indices were compared with blood pressure and the shock index for their ability to detect both 10% and 20% reductions in stroke volume.

RESULTS

All carotid Doppler measures were better able to detect diminishing stroke volume than either systolic or mean arterial pressure. Falling carotid artery corrected flow time and rising heart rate/corrected flow time (DSIFTc) were the most sensitive measures for detecting 10% and 20% stroke volume reductions, respectively. The area under the receiver operator curves (AUROCs) for all shock indices was at least 0.86; however, the denominators of the two Doppler shock indices (i.e., the corrected flow time and velocity time integral) had AUROCs ranging between 0.81 and 0.9, while the denominator of the traditional shock index (i.e., systolic blood pressure) had AUROCs between 0.54 and 0.7.

CONCLUSION

The wearable Doppler ultrasound was able to continuously measure the common carotid artery Doppler pulse. Carotid Doppler measures were highly sensitive at detecting both 10% and 20% stroke volume reduction. All shock indices performed well in their diagnostic ability to measure mild-to-moderate central volume loss, although the denominators of both Doppler shock indices individually outperformed the denominator of the traditional shock index.

LEVEL OF EVIDENCE

Diagnostic test or criteria; Level III.
The impacts of the processing levels on testing effect
Authors: Sun Jian , Liu Yi , Guo Chunyan
Published: May 2022

The testing effect refers to that retrieval practice enhances memory retention more than restudying does. A few previous studies have demonstrated that initial tests could improve memory by increasing recollection, and the depth of encoding could influence the degree of recollection and familiarity involved in retrieval process. The present study aimed to investigate whether the testing effect would be affected by the processing levels. Behavioral results revealed a significant testing effect in the shallow-processing condition, but not in the deep processing. Then, an event-related potential (ERP) experiment was conducted, showing that FN400 that represents familiarity occurred in the testing and restudying conditions with both processing levels, whereas the parietal old/new effect that indicates recollection only did not exist in the restudying with shallow-processing level. These findings revealed that the testing effect would be affected by the processing levels, and the underlying mechanism may be that tests could promote memory by enhancing recollection, which was involved in the deep rather than shallow-processing level during retrieval process. The practical meaning of the present study is that we can use tests to improve memory in a better and more efficient way.
Oddball-irrelevant visual stimuli cross-modally attenuate auditory mismatch negativity in rats
Authors: Shiramatsu Tomoyo Isoguchi , Mori Kanato , Ishizu Kotaro , Takahashi Hirokazu
Published: May 2022

Objective

To elaborate the recent theory of prediction models of the brain in light of actual neural activities, it is important to investigate the cross-modal interactions in the context of prediction construction. To this end, in this study, we assessed whether cross-modal disturbances would result in the attenuation of mismatch negativity in anesthetized animal models.

Methods

A surface electrode array recorded neural activities from the visual and auditory cortices of rats under isoflurane anesthesia, during an auditory oddball paradigm over the course of three audiovisual sequences. In the audiovisual sequences, the visual stimuli were simultaneously presented with the first, second, or third standard before the deviants.

Results

The interrupting visual stimuli decrease the amplitude of mismatch negativity in the auditory and visual cortices. In addition, the correlation coefficients between the amplitude of middle-latency potential for the interrupting visual stimuli and the amplitude of mismatch negativity to the following auditory deviant stimuli were smaller when the visual stimuli were presented alongside the third standards from the deviants.

Conclusion

Such attenuation in mismatch negativity has been often associated with a top-down mechanism and the present anesthesia selectively attenuates top-down transmission. Taken together, our study’s findings indicate that the cross-modal disturbances on prediction and deviation detection may also be mediated by bottom-up mechanisms, as well as previously reported top-down mechanisms.
The limited place in cognitive space
Authors: Hodgetts Carl J. , Hahn Ulrike
Published: May 2022

The idea that objects can be represented within multi-dimensional ‘cognitive spaces’ remains popular within psychology and neuroscience, and yet the restrictive topology of such spaces is seldom considered. Here, we show that it is possible, even within a simple set of items, to break such models by imposing neighbourhood relations that are incompatible with a purely spatial representation. These results highlight the fundamental limits of cognitive space as a representational format for complex cognition.
High-resolution line-scan Brillouin microscopy for live-imaging of mechanical properties during embryo development
Authors: Bevilacqua Carlo , Gomez Juan Manuel , Fiuza Ulla-Maj , Chan Chii Jou , Wang Ling , Hambura Sebastian , Eguren Manuel , Ellenberg Jan , Diz-Muñoz Alba , Leptin Maria , Prevedel Robert
Published: May 2022

Brillouin microscopy (BM) can be used to assess the mechanical properties of biological samples in a 3D, all-optical, and hence non-contact fashion, but its weak signals require long imaging times and illumination dosages harmful to living organisms. Here, we present a line-scanning Brillouin microscope optimized for fast and high-resolution live-imaging of dynamic biological processes with low photo-toxicity. In combination with fluorescence light-sheet imaging, we demonstrate the capabilities of our microscope to visualize the mechanical properties of cells and tissues over space and time in living model organisms such as fruit flies, ascidians, and mouse embryos.
Calcium determines Lactiplantibacillus plantarum intraspecies competitive fitness
Authors: Yu Annabelle O. , Wei Lei , Marco Maria L.
Published: May 2022

The importance of individual nutrients for microbial strain robustness and coexistence in habitats containing different members of the same species is not well understood. To address this for Lactiplantibacillus plantarum in food fermentations, we performed comparative genomics and examined the nutritive requirements and competitive fitness for L. plantarum strains B1.1 and B1.3 isolated from a single sample of teff injera fermentation batter. Compared to B1.1 and other L. plantarum strains, B1.3 has a smaller genome, limited biosynthetic capacities, and large mobilome. Despite these differences, B1.3 was equally competitive with B1.1 in a suspension of teff flour. In commercially-sourced, nutrient-replete MRS (cMRS) medium, strain B1.3 reached three-fold higher numbers than B1.1 within two days of passage. Because B1.3 growth and competitive fitness was poor in mMRS, a modified MRS lacking beef extract, we used mMRS to identify nutrients needed for robust B1.3 growth. No improvement was observed when mMRS was supplemented with nucleotides, amino acids, vitamins, or monovalent metals. Remarkably, the addition of divalent metal salts increased the growth rate and cell yields of B1.3 in mMRS. Metal requirements were confirmed by Inductively Coupled Plasma Mass Spectrometry, showing that total B1.3 intracellular metal concentrations were significantly (up to 2.7-fold) reduced compared to B1.1. Supplemental CaCl2 conferred the greatest effect, resulting in equal growth between B1.1 and B1.3 over successive five passages in mMRS. Moreover, calcium supplementation reversed a B1.3 strain-specific stationary phase, flocculation phenotype. These findings show how L. plantarum calcium requirements affect competitive fitness at the strain level.

Importance

Ecological theory states that the struggle for existence is stronger between closely related species. Contrary to this assertion, fermented foods frequently sustain conspecific individuals, despite their high levels of phylogenetic relatedness. Therefore, we investigated two isolates of Lactiplantibacillus plantarum B1.1 and B1.3 randomly selected from a single batch of teff injera batter. These strains spanned the known genomic and phenotypic range of the L. plantarum species, and in nutrient-replete, laboratory culture medium, strain B1.3 exhibited poor growth and was outcompeted by the more robust strain B1.1. Despite those differences, B1.1 and B1.3 were equally competitive in teff flour. This result shows how these bacteria have adapted for co-existence in that environment. The capacity for the single macronutrient calcium to restore B1.3 competitive fitness in laboratory culture medium suggests that L. plantarum intraspecies diversity found in food systems is fine-tuned to nutrient requirements at the strain level.
A 3-Dimensional bioprinted human gut-liver axis model for studying Alcoholic Liver Disease
Authors: Meher Kranti , Rottela Madhuri , Saranya K , Iyer Subramanian , Kadiyala Gopi , Vangala Subhramanyam , Chandran Satish , Saxena Uday
Published: May 2022

Gut-liver axis is the interaction between the gut, its microbiome and the liver. The crosstalk and interaction between these organs plays an important role in their individual health and disease. Alcoholic liver disease (ALD) is a case in point where dysfunction of intestine actively promotes liver damage by alcohol. A flashpoint in ALD is the breach of intestinal integrity caused by gut bacteria Enterococcus faecalis (E.Faecalis). More specifically, Cytolysin, a toxin secreted by this bacteria may have a central role in the genesis of ALD. 3-D bioprinted human simulations of the gut-liver axis may help better understand the genesis of ALD.

Here we developed a 3 dimensional bioprinted in vitro model composed of human origin intestinal and liver cells to explore the role of Cytolysin and ethanol in intestinal and liver damage. We find that neither Cytolysin or ethanol are sufficient for cell damage but a combination of the two act in concert to cause maximum breach in intestinal integrity. Secondly we find that enhanced transport of macromolecules thru the intestinal layer is not caused by overt cell toxicity but occurs through potentially paracellular/transcellular pathways. Our model will be used to test repurposed and new drugs/ biologics for treatment of ALD as well as other intestinal inflammatory diseases.
Detection of low numbers of bacterial cells in pharmaceutical drug product using Raman Spectroscopy and PLS-DA multivariate analysis
Authors: Grosso R.A. , Walther A.R. , Brunbech E. , Sørensen A. , Schebye B. , Olsen K.E. , Qu H. , Hedegaard M.A.B. , Arnspang E. C.
Published: May 2022

Sterility testing is a laborious and slow process to detect contaminants present in drug products. Raman spectroscopy is a promising label-free tool to detect microorganisms and thus gaining relevance as future alternative culture-free method for sterility testing in pharmaceutical industry. However, reaching detection limits similar to standard procedures while keeping a high accuracy remains challenging, due to weak bacterial Raman signal. In this work, we show a new non-invasive approach focusing on detect different bacteria in concentrations below 100 CFU/ml within drug product containers using Raman spectroscopy and multivariate data analysis. Even though Raman spectra form drug product with and without bacteria are similar, a partial least squared discriminant analysis (PLS-DA) model shows great performance to distinguish samples with bacteria contaminants in limits below 10 CFU/ml. We use spiked samples with bacteria spores for independent validation achieving a detection accuracy of 99%. Our results indicate a great potential of this rapid, and cost-effective approach to be use in quality control of pharmaceutical industry.
The EGFR-STYK1-FGF1 axis sustains functional drug tolerance to EGFR inhibitors in EGFR-mutant non-small cell lung cancer
Authors: Eggermont Carolien , Giron Philippe , Noeparast Maxim , Vandenplas Hugo , Aza-Blanc Pedro , Gutierrez Gustavo J. , De Grève Jacques
Published: May 2022

Non-small cell lung cancer (NSCLC) patients harboring activating mutations in epidermal growth factor receptor (EGFR) are sensitive to therapy with EGFR tyrosine kinase inhibitors (TKI). Despite remarkable clinical responses using EGFR TKI, surviving drug tolerant cells serve as a reservoir from which drug resistant tumors may emerge. This study addresses the need for improved efficacy of EGFR TKI by identifying targets involved in functional drug tolerance against them. To this aim, a high-throughput siRNA kinome screen was performed using two EGFR TKI-sensitive EGFR-mutant NSCLC cell lines in the presence/absence of the second-generation EGFR TKI afatinib. From the screen, Serine/Threonine/Tyrosine Kinase 1 (STYK1) was identified as a target that when downregulated potentiates the effects of EGFR inhibitionin vitro. We found that chemical inhibition of EGFR combined with the siRNA-mediated knockdown of STYK1 led to a significant decrease in cancer cell viability and anchorage-independent cell growth. Further, we show that STYK1 selectively interacts with mutant EGFR and that the interaction is disrupted upon EGFR inhibition. Finally, we identified fibroblast growth factor 1 (FGF1) as a downstream effector of STYK1 in NSCLC cells. Accordingly, downregulation of STYK1 counteracted the afatinib-induced upregulation of FGF1. Altogether, we unveil STYK1 as a valuable target to repress the pool of surviving drug tolerant cells arising upon EGFR inhibition. Co-targeting of EGFR and STYK1 could lead to a better overall outcome for NSCLC patients.
2,4-Diacetylphloroglucinol Against Candida albicans: Biofilm Formation, Aspartyl Protease Production and Ultrastructure Changes
Authors: Stepanov Artyom A. , Vasilchenko Alexey S.
Published: May 2022

The dimorphic fungus Candida albicans is the one of the most important opportunistic pathogen of human. The use of fungicides against candida encounters sub-inhibitory effects, which are fungal stress response and undesirable for the host. In this work we investigated antifungal action of 2,4-diacetylphloroglucinol against Candida albicans ATCC 10231 with focus on they biofilm forming ability under the treatment.

It was found that 2,4-DAPG reduced ability of candida cells to form biofilm, but complete inhibition or irradiation did not achieve. Moreover, Candida albicans cells in the adherent state have been characterized by reduced susceptibility to 2,4-DAPG comparing to planktonic cells.

Investigation of mechanisms which could be explain the antibiofilm action of 2,4-DAPG has revealed the reduction in cell’s surface hydrophobicity and inhibition of yeast-to-hyphae transition. Biofilms formed under the sub-inhibitory concentrations of 2,4-DAPG were depleted in protein and carbohydrate content. Furthermore, we microscopically visualized the treated biofilms and have revealed numerous cannels localized on hyphae and associated with secretion of aspartyl proteases (Sap).

We assumed what excretion of Sap is triggered by reactive oxygen generated upon affecting of mitochondrion respiration by 2,4-DAPG. Introducing of antioxidant Trolox simultaneously with 2,4-DAPG lead to reducing of Sap production. Thus, production of aspartyl proteases is a one of undesirable side effect of Candida albicans treatment, but using 2,4-DAPG in combination with antioxidants is the solution to overcome it.