bluuebunny/crossref_metadata_2025 huggingface dataset:
9. Misrepresentation
Authors: Devenney James , Shaw-Mellors Adam
Published: September 2024

Each Concentrate revision guide is packed with essential information, key cases, revision tips, exam Q&As, and more. Concentrates show you what to expect in a law exam, what examiners are looking for, and how to achieve extra marks. This chapter discusses the identification of actionable misrepresentations which affect the fairness of the process by which a contract was entered into, and render that contract voidable for misrepresentation (liable to be set aside and the parties restored to their pre-contractual positions). It identifies three types of misrepresentation depending on the state of mind of the misrepresentor: fraudulent, negligent, or innocent. It distinguishes between remedies available for the different types of pre-contractual statements, specifically rescission and damages for the different types of misrepresentations, and briefly explains the distinction between commercial contracts and the remedies available to consumers under the Consumer Protection from Unfair Trading Regulations 2008.
Article 101(1)
Authors: Whish Richard , Bailey David
Published: September 2024

This chapter discusses Article 101(1) of the Treaty of Functioning of the European Union (TFEU), which prohibits agreements, decisions by associations of undertakings, and concerted practices that restrict competition. It begins by explaining the meaning of ‘undertakings’ and ‘associations of undertakings’. It then considers what is meant by the terms ‘agreements’, ‘decisions’ and ‘concerted practices’, as well as what is meant by the phrase ‘have as their object or effect the prevention, restriction, and distortion of competition’. The chapter then deals with the de minimis doctrine, before explaining the requirement of an effect on trade between Member States. The chapter concludes with a checklist of agreements that, for a variety of reasons, normally fall outside Article 101(1).
Articles 101 and 102: public enforcement by the European Commission and national competition authorities under Regulation 1/2003
Authors: Whish Richard , Bailey David
Published: September 2024

This chapter explains the public enforcement of Articles 101 and 102 by European Commission and the national competition authorities under Regulation 1/2003. It begins by describing the Commission’s powers of investigation and enforcement, including its power to accept commitments, its leniency programme, the cartel settlement procedure and its power to impose financial penalties. It then discusses the operation of Regulation 1/2003 in practice, with particular reference to the European Competition Network (‘the ECN’) that brings together the Commission and the national competition authorities of the Member States (‘the NCAs’) and the ECN+ Directive that strengthens the powers of the NCAs. The chapter concludes by providing a brief account of judicial review of the Commission’s decisions.
Competition Act 1998 and the cartel offence: public enforcement and procedure
Authors: Whish Richard , Bailey David
Published: September 2024

This chapter describes the system of public enforcement under the Competition Act 1998. It begins with a consideration of the way in which inquiries and investigations are carried out under the Competition Act. After a section on complaints, the chapter examines the extent to which it may be possible to receive guidance from the CMA on the application of the Act. Section 5 describes the enforcement of the Competition Act. Section 6 deals with the criminal law cartel offence and section 7 with company director disqualification, a tool that the CMA has used several times in recent years. Section 8 deals with the sectoral regulators’ concurrent powers, with the CMA, to apply the Chapter I and Chapter II prohibitions in the Competition Act in the sectors for which they are responsible. Section 9 describes the system of appeals under the Competition Act. The chapter incorporates the amendments to the Competition Act made by the Digital Markets, Competition and Consumers Act 2024.
Vertical agreements
Authors: Whish Richard , Bailey David
Published: September 2024

This chapter considers how vertical agreements are dealt with by EU and UK competition law. It begins with a discussion of distribution chains in the modern economy, looking at the various ways in which producers market their goods or services to consumers; these have been enormously enhanced by the emergence of e-commerce and the digital economy. Producers may choose to carry on their own distribution function: ‘vertical integration’ is briefly discussed in section 3. Another route to customers is via commercial agency: the competition law considerations of agency are considered in section 4, which also briefly considers vertical sub-contracting relationships. Sections 5 to 9 deal with the application of Article 101 to vertical agreements. Section 5 considers vertical agreements from a policy perspective. Section 6 explains the application of Article 101 to different types of vertical agreement in the light of the case-law of the EU Courts and the Commission’s guidelines on the application of Article 101 to vertical agreements. Section 7 discusses the block exemption for vertical agreements, Regulation 2022/720. Section 8 deals with the individual application of Article 101(3) to vertical agreements. This will be followed by a short section on Regulation 461/2010 on motor vehicle distribution.
Mergers (3): UK
Authors: Whish Richard , Bailey David
Published: September 2024

This chapter discusses UK law on the control of mergers. UK law on the control of mergers is contained in Part 3 of the Enterprise Act 2002, which was amended by the Enterprise and Regulatory Reform Act 2013 and by the Digital Markets, Competition and Consumers Act 2024. Section 2 provides an overview of the domestic system of merger control. Section 3 explains the procedure of the Competition and Markets Authority (CMA) when determining whether a merger should be referred for an in-depth ‘Phase 2’ investigation and when deciding to accept ‘undertakings in lieu’ of a reference. Section 4 describes how Phase 2 investigations are conducted and Section 5 discusses the ‘substantially lessening competition’ (‘SLC’) test. Section 6 explains the enforcement powers in the Enterprise Act 2002, including the remedies that the CMA can impose in merger cases. Various supplementary matters are dealt with in section 7. Section 8 considers how the merger control provisions work in practice and contains a table of the Phase 2 decisions under the Enterprise Act to have been published on the website of the CMA since the tenth edition of this book. Section 9 explains the provisions for certain mergers in digital markets introduced by the DMCCA. Section 10 briefly describes the provisions on public interest cases, other special cases and mergers in the water industry. Section 11 concludes by explaining the provisions of the National Security and Investment Act 2021, which confers on the Secretary of State powers to scrutinise and intervene in certain acquisitions of control on national security grounds.
5. Instruments and the Hierarchy of Norms
Authors: Craig Paul , de Búrca Gráinne
Published: September 2024

All books in this flagship series contain carefully selected substantial extracts from key cases, legislation, and academic debate, providing students with a stand-alone resource. This chapter examines two related issues: the EU’s legal and non-legal instruments; and the hierarchy of norms. The EU has a number of legal and non-legal instruments that are used to attain Union objectives. The principal legal instruments are regulations, directives, and decisions. The hierarchy of norms refers to the idea that in a legal system there will be a vertical ordering of legal acts, with those in the lower rungs of the hierarchy being subject to legal acts of a higher status. There are currently five principal tiers to the hierarchy of norms in EU law, which are, in descending order: the constituent Treaties and Charter of Rights; general principles of law; legislative acts; delegated acts; and implementing acts. The chapter discusses the meaning of these different tiers. The UK version contains a further section analysing issues concerning the hierarchy of norms in relation to the UK post-Brexit.
19. Free Movement of Goods: Duties, Charges, and Taxes
Authors: Craig Paul , de Búrca Gráinne
Published: September 2024

All books in this flagship series contain carefully selected substantial extracts from key cases, legislation, and academic debate, providing students with a stand-alone resource. This chapter deals with Member State action that creates barriers to trade. The most obvious form of protectionism occurs through customs duties or charges that have an equivalent effect, with the object of rendering foreign goods more expensive than their domestic counterparts. This is addressed by Articles 28–30 of the Treaty on the Functioning of the European Union (TFEU). A state may also attempt to benefit domestic goods by taxes that discriminate against imports, which is covered by Articles 110–113 TFEU. These issues are considered within the chapter. The UK version contains a further section analysing the way in which issues of customs duties and taxation are likely to be resolved in future trade relations between the EU and the UK.
28. Competition Law: Article 101
Authors: Craig Paul , de Búrca Gráinne
Published: September 2024

All books in this flagship series contain carefully selected substantial extracts from key cases, legislation, and academic debate, providing students with a stand-alone resource. EU competition law covers anti-competitive agreements between firms, abuse of a dominant position, and mergers. Article 101 TFEU is the principal vehicle for the control of anti-competitive agreements. This chapter examines its key features. These include: the meaning given to the terms agreement and concerted practice; the relationship between Article 101(1) and (3); the extent to which economic analysis does and should take place within Article 101(1); and the interpretation accorded to Article 101(3), including whether non-economic factors can be considered. The discussion then shifts to more detailed examination of vertical agreements, followed by an outline of the reform of the enforcement regime for Articles 101 and 102. The UK version contains a further section analysing issues concerning EU competition law and the UK post-Brexit.
EU Law
Authors: Craig Paul , de Búrca Gráinne
Published: September 2024

All books in this flagship series contain carefully selected substantial extracts from key cases, legislation, and academic debate, providing students with a stand-alone resource. The eighth edition of EU Law: Text, Cases, and Materials provides clear analysis of all aspects of European law in the post Lisbon era. This edition looks in detail at the way in which the provisions of the Lisbon Treaty have worked since the Treaty became operational, especially innovations such as the hierarchy of norms, the different types of competence, and the legally binding Charter of Rights. The coming into effect of the new Treaty was overshadowed by the financial crisis, which has occupied a considerable part of the EU’s time since 2009. The EU has also had to cope with the refugee crisis, the pandemic crisis, the rule of law crisis, and the Brexit crisis. There has nonetheless been considerable legislative activity in other areas, and the EU Courts have given important decisions across the spectrum of EU law. The eighth edition has incorporated the changes in all these areas. The book covers all topics relating to the institutional and constitutional dimensions of the EU. In relation to EU substantive law, there is detailed treatment of the four freedoms, the single market, competition, equal treatment, citizenship, state aid, and the area of freedom, security, and justice. Brexit is the rationale for the decision to have a separate UK version of the book. There is no difference in the chapters between the two versions, insofar as the explication of the EU law is concerned. The difference resides in the fact that in the UK version there is an extra short section at the end of each chapter explaining how, for example, direct effect, primacy, or free movement are relevant in post-Brexit UK. Law students in the UK need to know this, law students in the EU and elsewhere do not.
14. Preliminary Rulings
Authors: Craig Paul , de Búrca Gráinne
Published: September 2024

All books in this flagship series contain carefully selected substantial extracts from key cases, legislation, and academic debate, providing students with a stand-alone resource. This chapter focuses on Article 267 of the Treaty on the Functioning of the European Union, which contains the preliminary ruling procedure. Article 267 has been of seminal importance for the development of EU law. It is through preliminary rulings that the European Court of Justice (ECJ) has developed concepts such as direct effect and supremacy. Individuals assert in national courts that the Member State has broken a Union provision, which gives them rights that they can enforce in their national courts. The national court seeks a ruling from the ECJ whether the particular EU provision has direct effect, and the ECJ is thereby able to develop the concept. Article 267 has been the mechanism through which national courts and the ECJ have engaged in a discourse on the appropriate reach of EU law when it has come into conflict with national legal norms. The UK version contains a further section analysing the extent to which the preliminary reference system is relevant in relation to the UK post-Brexit.
15. Review of Legality: Access
Authors: Craig Paul , de Búrca Gráinne
Published: September 2024

All books in this flagship series contain carefully selected substantial extracts from key cases, legislation, and academic debate, providing students with a stand-alone resource. The EU develops policy through regulations, directives, and decisions. Any developed legal system must have a mechanism for testing the legality of such measures. This chapter focuses on access to justice and review of legality by the EU Courts. There are a number of ways in which EU norms can be challenged, but the principal Treaty provision is Article 263 of the Treaty on the Functioning of the European Union (ex Article 230 EC). Five conditions must be satisfied before an act can successfully be challenged: (i) the relevant body must be amenable to judicial review; (ii) the act has to be of a kind that is open to challenge; (iii) the institution or person making the challenge must have standing to do so; (iv) there must be illegality of a type mentioned in Article 263(2); and (v) the challenge must be brought within the time limit indicated in Article 263(6). The UK version contains a further section analysing the relevance of legal challenge to EU norms in relation to the UK post-Brexit.
16. Review of Legality: Grounds of Review
Authors: Craig Paul , de Búrca Gráinne
Published: September 2024

All books in this flagship series contain carefully selected substantial extracts from key cases, legislation, and academic debate, providing students with a stand-alone resource. This chapter discusses the grounds for judicial review of a Union act. Article 263 of the Treaty on the Functioning of the European Union (TFEU) specifies four grounds for review: lack of competence; infringement of an essential procedural requirement; infringement of the Treaty or any rule of law relating to its application; and misuse of power. Judicial review, whether direct through Article 263 or indirect through Article 267, is designed to ensure that decision-making is legally accountable. The UK version contains a further section analysing the relevance of these grounds of review in the UK post-Brexit.
21. Free Movement of Capital
Authors: Craig Paul , de Búrca Gráinne
Published: September 2024

All books in this flagship series contain carefully selected substantial extracts from key cases, legislation, and academic debate, providing students with a stand-alone resource. This chapter focuses on the free movement of capital. It first considers the movement of capital, one of the four freedoms enshrined in the original Rome Treaty. This is followed by discussion of the broader policy issues that impact on this area of the law. There is the relation between free movement of capital and national sovereignty over direct taxation; between free movement of capital, economic and monetary union, and capital markets union; and between free movement of capital and foreign investment that can impact on security and public order. The UK version contains a further section analysing issues concerning free movement of capital between the EU and the UK post-Brexit.
30. Competition Law: Mergers
Authors: Craig Paul , de Búrca Gráinne
Published: September 2024

All books in this flagship series contain carefully selected substantial extracts from key cases, legislation, and academic debate, providing students with a stand-alone resource. This chapter discusses EU law on mergers, first examining the policy reasons underlying merger control. It then considers the jurisdictional, procedural, and substantive aspects to EU merger policy. Jurisdictional issues cover the types of concentration that are subject to the Merger Regulation and the inter-relationship between merger control at EU and national levels. Procedural issues cover matters such as the way in which notice of a proposed merger must be given and the investigative powers possessed by the Commission. Substantive issues of merger policy include matters such as the test for determining whether a merger or concentration should be allowed and the extent to which efficiencies produced by the concentration should be taken into account. The UK version contains a further section analysing issues concerning EU competition law and the UK post-Brexit.
7. Principal and agent
Authors: Beheshti Reza , Saintier Séverine , Thomas Sean
Published: September 2024

This chapter highlights the relationship between principal and agent. It explains that the consent of the principal gives the agent their authority. Principals and agents have certain rights against each other which spring from their agency relationship, most of which may be contractual. The Commercial Agents (Council Directive) Regulations 1993 created rights and obligations for the parties involved in the commercial agency agreement. The chapter then looks at the rights and duties of the agent under general common law. It explains that the withdrawal of consent by either party effectively terminates their relationship and the agent's actual authority to bind the principal.
22. Real security
Authors: Beheshti Reza , Saintier Séverine , Thomas Sean
Published: September 2024

This chapter provides an overview of the notion of real security. It looks at the true real security devices recognised by law, which are lien, pledge, charge, and mortgage, before clarifying that the commercial effects of both true security interests and quasi-security interests are the same. Additionally, true security interests are consensual, which ensures that no security interest can be created without the consent of the creditor and debtor. The chapter then looks into the classification of security interests and the forms of possessory security and non-possessory security. It then presents the cases concerned with quasi-security and the retention of title clauses.
24. Money and the transfer of obligations
Authors: Beheshti Reza , Saintier Séverine , Thomas Sean
Published: September 2024

This chapter presents the nature of money and the financing role played by transfers of different types of obligation. It considers the idea of money, which is central to a developed capitalist economy, thus becoming a universal means of exchange. Meanwhile, the conflicting needs of the parties can only be accommodated by the supplier transferring to a third party the right to receive payment from the customer, in return for an immediate cash payment. The chapter then enumerates the practice of assignment and negotiation as mechanisms of transferring obligations. It also discusses the classification of property, cryptocurrencies, and other digital assets.
The Influence of Pulmonary Arterial Hypertension In Pregnancy: A Review
Authors: Renaud Jodie , Foroshani Saam , Frishman William H. , Aronow Wilbert S.
Published: September 2024

Pulmonary arterial hypertension (PAH) is a severe condition characterized by increased pulmonary vascular resistance and right ventricular failure. This review examines the intersection of PAH and pregnancy, highlighting the significant physiological, hemodynamic, and hormonal changes that exacerbate PAH during gestation. Pregnancy is contraindicated in PAH patients due to high maternal and fetal morbidity and mortality rates. However, some patients choose to continue their pregnancies, necessitating a comprehensive understanding of the implications and management strategies. Effective management of PAH in pregnant patients involves individualized treatment plans. Prepartum management focuses on optimizing therapy and monitoring hemodynamic status. Prostacyclin analogs and phosphodiesterase inhibitors are commonly used, though their safety profiles require further investigation. Intrapartum management prioritizes preventing right ventricular failure, utilizing therapies such as intravenous epoprostenol, inhaled iloprost, and inhaled nitric oxide. Managing PAH in pregnancy requires careful planning, continuous monitoring, and tailored therapeutic strategies to navigate the complex interplay of physiological changes and mitigate risks. Future research should focus on elucidating the pathophysiology of PAH during pregnancy and developing safer, more effective treatments to improve maternal and fetal outcomes.
Vasopressor-Inotropic Score: Review of Literature
Authors: Flores Jackeline , Nugent Kenneth
Published: September 2024

Patients undergoing cardiac surgery often receive vasopressor and inotropic medications during the surgical procedure and during intensive care unit (ICU) management following surgery. Patients with cardiogenic shock, septic shock, and other clinical disorders associated with shock also receive vasopressor medications during their ICU care. The level of support and the duration of support are likely associated with outcomes, including mortality and new organ dysfunction, such as acute kidney injury. The vasopressor-inotropic score provides a simple method to determine the level of support during the care of these patients; this score includes the infusion rates of norepinephrine, epinephrine, dopamine, dobutamine, and other inotropic medications. It has been studied in patients undergoing cardiac surgery, coronary artery bypass grafting, cardiac transplantation, left ventricular assist device implantation, septic shock, and traumatic brain injury. Higher scores are associated with poor outcomes and complications during ICU care. The studies analyzed in this review demonstrate the utility of the vasopressor-inotropic score in a variety of clinical disorders associated with shock. Electronic medical record systems should develop algorithms to calculate this score and provide continuous up-to-date measurements. This could help clinicians identify patients at risk for mortality and important complications, such as acute kidney injury.
Beyond the Gut: Exploring Cardiovascular Implications of Celiac Disease
Authors: Verma Sakshi , Kumari Verkha , Yangzom De-Kee , Anamika FNU , Aggarwal Kanishk , Singh Bhupinder , Jain Rohit
Published: September 2024

Celiac disease (CD) is an autoimmune disorder that presents with gastrointestinal symptoms including diarrhea, weight loss, and abdominal bloating due to the inflammation in the small intestine. It has been associated with various extraintestinal manifestations, including mucocutaneous findings such as dermatitis herpetiformis, anemia, dental enamel defects, osteoporosis, and arthritis. Studies have revealed an increasing association between CD and cardiovascular diseases (CVDs), including atherosclerosis, cardiomyopathy, and arrhythmia. Chronic inflammation, nutritional deficiencies from malabsorption, endothelial dysfunction, thrombophilic autoantibodies, thrombocytosis, and protein C and S deficiency have been proposed as the probable mechanisms for the association between the 2 conditions. This article aims to provide a review of the pathophysiological mechanism of celiac disease causing various CVDs and to compare and contrast the existing studies suggesting both favorable and unfavorable CVD outcomes in patients with CD.
Cardiac Complications of Multiple Myeloma Treatments
Authors: Khurshid Aatif , Frishman William H. , Aronow Wilbert S.
Published: September 2024

Multiple myeloma (MM) arises in plasma cells, a type of white blood cell. The cancerous plasma cells produce monoclonal immunoglobulins in the bone marrow. The extent of proliferation in the malignant state can manifest in many complications including osteopenia, osteolytic lesions, pathologic fractures, hypercalcemia, anemia, and kidney dysfunction. As is the case with the treatment of other malignancies, the research relating to the management of MM is dynamic and evolving. In this review, we aim to succinctly summarize and categorize the major treatment options of MM, including both new treatments and also older treatments that are now less frequently utilized, with a specific focus on the cardiotoxicity of these agents.
Ectopic Nasal Septum Neuroglial Tissue: A Case Review
Authors: Sayegh Odai , Jumei’an Ala’ , Ababneh Hamza , Azaizeh Alhareth , Alnaser Mutaz , Aljader Mutaz , Ellati Riyad , Al Bdour Mohammad
Published: September 2024

Ectopic neuroglial tissue, or heterotopic brain tissue, presents a rare congenital condition characterized by the presence of benign neuroglial cells outside the central nervous system. Diagnosing neuroglial heterotopia solely based on clinical examination and radiological tests can be challenging, necessitating confirmation through histopathologic examination. These lesions may mimic other conditions such as dermoid cysts, pilar cysts, or lipomas. Here, we report a case of a 19-month-old boy with a mass lesion on the dorsum of the nose since birth. The lesion was initially suspected to be a congenital dermoid cyst, and the patient underwent surgical excision under general anesthesia. However, histopathological examination revealed it as an isolated nasal septum neuroglial heterotopia.
Hump Rasping Using Powered Instruments: A Retrospective Review
Authors: Aldosari Badi F. , Alhajress Rafeef I. , Bogari Ahmad O.
Published: September 2024

Background:

Nasal hump reduction, a common procedure in rhinoplasty, aims to create a harmonious nasal appearance with smooth dorsal lines. An alternative to traditional osteotomes is the carbide-tip nasal rasp, effective in eliminating modest contour deformities. However, the broad movements and physical forces of manual rasping can significantly weaken the osseocartilaginous vault. Power-assisted instruments have been used to reduce soft tissue trauma. Although long-term clinical outcomes of power-assisted instrumentation are pending, initial reports have been positive.

Methods:

This retrospective chart review encompassed 220 consecutive rhinoplasty cases conducted by the senior author, all involving women aged 19–37 years. Excluding 80 cases that did not involve bone reduction, the analysis concentrated on 140 patients who underwent bone reduction procedures. The success of nasal hump reduction was evaluated based on the joint satisfaction of both the patient and the surgeon with the surgical improvement.

Results:

The open rhinoplasty approach was predominantly used for surgical exposure to minimize inadvertent rasping of the nasal cartilage. Among the 140 patients undergoing power-assisted bone removal, all but five achieved an initially satisfactory refinement of the bony nasal contour. Notably, no serious complications were observed throughout the study. Unfortunately, one patient did not comply with the monthly steroid injections, leading to the necessity of revision surgery for the removal of regenerated bone.

Conclusion:

The integration of power-assisted instrumentation in rhinoplasty procedures represents a promising advancement, addressing challenges associated with traditional methods.
Three-Dimensional Microarchitecture of Lamina Cribrosa Pores in High and Normal Tension Glaucoma Using Optical Coherence Tomography
Authors: Bastelica Paul , Labbé Antoine , Hamard Pascale , Rossant Florence , Urien Hélène , Sublime Jérémie , Claudel Hélène , Ding Nan , Paques Michel , Baudouin Christophe
Published: September 2024

Précis:

The lamina cribrosa (LC) pores of patients with high-tension glaucoma (HTG) appear to take a more tortuous pathway than the LC pores of patients with non-glaucomatous (NG).

Objective:

To compare the LC pore microarchitecture in patients with HTG, normal tension glaucoma (NTG), and NG, by reconstructions of the LC made from tomographic images.

Patients and Methods:

Spectral domain-optical coherence tomography images of 52 eyes (18 NG, 18 HTG, and 16 NTG) of 29 patients were analyzed. Pores were traced using segmentation software. Pore length, tortuosity, and verticality were the 3 quantitative parameters compared among the 3 groups. Correlation analyses were performed to determine the effects of covariates on the 3 quantitative parameters.

Results:

Pore tortuosity in HTG (1.419 ± 0.093) was significantly higher (P = 0.011) than in NG (1.347 ± 0,034) but did not differ from that of NTG eyes (P = 0.251). In addition, NTG had significantly shorter pores (P = 0.005) than NG. No difference in pore tortuosity or verticality was found between NG and NTG (P = 0.587 and P = 0.120, respectively). Pore verticality and length in HTG eyes did not significantly differ from that of NG eyes (P = 0.049 and P = 0.033, respectively) and NTG eyes (P = 0.827 and P = 0.968, respectively). All of the quantitative parameters measured were not correlated with age but were associated with glaucoma severity (Visual Field Index, mean deviation, retinal nerve fiber layer, and ganglion cell complex), except for pore verticality, which was not correlated with retinal nerve fiber layer.

Conclusion:

The LC pores of patients with HTG appear to be more tortuous than the pores of patients with NG, and the pores of patients with NTG are shorter than those of patients with NG. Changes in pore parameters appear to be associated with the severity of glaucomatous optic neuropathy.
Orbital Myeloma and Plasmacytoma: An Australian Study
Authors: Xiong Jessica , Tong Jessica Y. , Hyer Jonathan , O’Donnell Brett , Selva Dinesh , Hardy Thomas , McNab Alan , Sullivan Timothy J. , Taylor Simon , Figueira Edwin , Allende Alexandra , Tumuluri Krishna
Published: September 2024

Purpose:

The purpose of this study was to provide Australian data on the clinical and radiological features and outcomes in patients with orbital plasmacytomas.

Methods:

Multicentre retrospective review of orbital plasmacytoma and orbital involvement in multiple myeloma (MM) from 2005 to 2022 in Australia.

Results:

Twenty-one participants were identified. The median age was 62 years (range 34–88 years), and 11 (52%) were females. Eighteen (84%) had a known diagnosis of MM prior to their orbital presentation, with all patients eventually being diagnosed with systemic MM. Thirteen (72%) were receiving active treatment for systemic myeloma on presentation, while 3 (17%) were in remission. All but 1 had unilateral orbital involvement (n = 20, 95%). Common presenting symptoms and signs were decreased visual acuity (n = 13, 62%), proptosis (n = 11, 52%), limited motility (n = 15, 71%), and optic neuropathy (n = 5, 24%). Radiologically, 15 (71%) involved the superotemporal orbit, 7 (33%) inferotemporal orbit, and 16 (76%) involved ≥1 extraocular muscle. Sixteen (76%) were biopsied and confirmed orbital plasmacytoma on histopathology. Treatment modalities included intravenous and oral steroids (n = 7, 33%), chemotherapy (n = 9, 43%), radiotherapy (n = 13, 62%), stem cell transplant (n = 3, 14%), and surgical debulking and decompression (n = 3, 14%). Mortality was high, with 15 (71%) having MM-related mortality.

Conclusions:

This is the largest cohort of Australian data on orbital plasmacytomas. Most patients have a diagnosis of systemic MM at presentation. It is crucial to recognize and treat these patients early due to a poor systemic prognosis.
Synchronous Bilateral Ovarian Carcinomas With Right Mesonephric-like Adenocarcinoma and Left High-grade Serous Carcinoma: A Case Report and Review of the Literature
Authors: Maharjan Daisy , Collins Katrina , Hou Tieying , Umphress Brandon , Robertson Sharon E. , Segura Sheila
Published: September 2024

Mesonephric-like adenocarcinomas (MLAs) are rare neoplasms of the uterus corpus and ovary, while high-grade serous carcinoma (HGSC) is the most common and lethal epithelial ovarian malignancy. We report a case of a 56-yr-old woman who presented with bilateral solid and cystic ovarian masses. She underwent a total abdominal hysterectomy with bilateral salpingo-oophorectomy, lymphadenectomy, omentectomy, and peritoneal biopsies. Histopathologic examination of the bilateral ovarian masses revealed 1 ovary with MLA, and the other ovary showed HGSC in association with serous tubal intraepithelial carcinoma. The morphology, immunophenotypes, and molecular profiling of the HGSC and the MLA were distinct and as expected for the different tumor types: HGSC was diffusely positive for WT-1, estrogen receptor, and p53 (mutant pattern), while negative for GATA-3 and TTF-1; MLA was positive for GATA-3 and TTF-1, while negative for WT1, estrogen receptor, and p53 (wild-type pattern); both tumors were diffusely positive for PAX-8. The HGSC revealed a TP53 c.659A>G (p.Y220C) mutation, and the MLA revealed a KRAS c.34G>T (p. G12C) mutation and a PIK3CA c.1034A>T (p.N345I) mutation. To the best of our knowledge, this is the first reported case of synchronous bilateral ovarian carcinomas with MLA and contralateral ovarian HGSC.
Examining uncertainty in journal peer reviewers’ recommendations: a cross-sectional study
Authors: Barnett Adrian , Allen Liz , Aldcroft Adrian , Lash Timothy L. , McCreanor Victoria
Published: September 2024

The peer review process is used throughout science but has often been criticized for being inconsistent, with decisions dependent on the peers who did the reviewing. Much of the decision inconsistency arises from the differences between reviewers in terms of their expertise, training and experience. Another source of uncertainty is within reviewers as they must make a single recommendation (e.g. ‘Accept’), when they may have wavered between two (e.g. ‘Accept’ or ‘Reject’). We estimated the size of within-reviewer uncertainty using post-review surveys at three journals. We asked reviewers to think outside the recommendation they gave (e.g. ‘Accept’) and assign percentages to all other recommendations (e.g. ‘Major revision’). Reviewers who were certain could assign 100% to one recommendation. Twenty-three per cent of reviewers reported no uncertainty (95% confidence interval 19–27%). Women were associated with more uncertainty at one journal, and protocol papers were associated with more uncertainty at one journal. Reviewers commonly experience some uncertainty when peer-reviewing journal articles. This uncertainty is part of the variability in peer reviewers’ recommendation.
Comparative venom analysis between melanistic and normally coloured phenotypes of the common adder (
Vipera berus
)
Authors: Schulte Lennart , Uhrig Lilien , Eichberg Johanna , Schwartze Michael , Auth Ingve , Schulz Miriam , Lindner Thomas , Hien Paul , Hardes Kornelia , Vilcinskas Andreas , Lüddecke Tim
Published: September 2024

Snake venom is an ecologically relevant functional trait directly linked with a snake’s fitness and survival, facilitating predation and defence. Snake venom variation occurs at all taxonomic levels, but the study at the intraspecific level is still in its early stages. The common adder (
Vipera berus
) exhibits considerable variation in colour phenotypes across its distribution range. Melanistic (fully black) individuals are the subject of myths and fairytales, and in German folklore such ‘hell adders’ are considered more toxic than their normally coloured conspecifics despite any formal investigation. Here, we provide the first comparative analysis of venoms from melanistic and normally coloured common adders. Specifically, we compared the venom profiles by sodium dodecylsulfate polyacrylamide gel electrophoresis and reversed-phase high-performance liquid chromatography and tested the venoms’ protease, phospholipase A
2
and cytotoxic activities. Phospholipase A
2
activity was similar in both phenotypes, whereas general protease activity was higher in the melanistic venom, which was also more cytotoxic at two concentrations (6.25 and 12.5 µg ml
−1
). These minor differences between the venoms of melanistic and normally coloured adders are unlikely to be of clinical relevance in the context of human envenomation. In light of our results, the claim that melanistic adders produce more toxic venom than their normally coloured conspecifics appears rooted entirely in folklore.
16S rRNA phylogeny and clustering is not a reliable proxy for genome-based taxonomy in Streptomyces
Authors: Kiepas Angelika B. , Hoskisson Paul A. , Pritchard Leighton
Published: September 2024

Streptomyces is among the most extensively studied genera of bacteria but its complex taxonomy remains contested and is suspected to contain significant species-level misclassification. Resolving the classification of Streptomyces would benefit many areas of applied microbiology that rely on an accurate ground truth for grouping of related organisms, including comparative genomics-based searches for novel antimicrobials. We survey taxonomic conflicts between 16S rRNA and whole genome-based Streptomyces classifications using 2276 publicly available Streptomyces genome assemblies and 48 981 publicly available full-length 16S rRNA Streptomyces sequences from silva, Greengenes, Ribosomal Database Project (RDP), and NCBI (National Centre for Biotechnology Information) databases. We construct a full-length 16S gene tree for 14 239 distinct Streptomyces sequences that resolves three major lineages of Streptomyces, but whose topology is not consistent with existing taxonomic assignments. We use these sequence data to delineate 16S and whole genome landscapes for Streptomyces, demonstrating that 16S and whole-genome classifications are frequently in disagreement, and that 16S zero-radius Operational Taxonomic Units (zOTUs) are often inconsistent with Average Nucleotide Identity (ANI)-based taxonomy. Our results strongly imply that 16S rRNA sequence data does not map to taxonomy sufficiently well to delineate Streptomyces species routinely. We propose that alternative marker sequences should be adopted by the community for classification and metabarcoding. Insofar as Streptomyces taxonomy has been determined or supported by 16S sequence data and may in parts be in error, we also propose that reclassification of the genus by alternative approaches may benefit the Streptomyces community.
Impact of elevated IOP on lamina cribrosa oxygenation; A combined experimental-computational study on monkeys
Authors: Lu Yuankai , Hua Yi , Wang Bingrui , Zhong Fuqiang , Theophanous Andrew , Tahir Shaharoz , Lee Po-Yi , Sigal Ian A.
Published: September 2024

Purpose

Our goal is to evaluate how lamina cribrosa (LC) oxygenation is affected by the tissue distortions resulting from elevated IOP.

Design

Experimental study on monkeys

Subjects

Four healthy monkey eyes with OCT scans with IOP of 10 to 50 mmHg, and then with histological sections of LC.

Methods

Since in-vivo LC oxygenation measurement is not yet possible, we used 3D eye-specific numerical models of the LC vasculature which we subjected to experimentally-derived tissue deformations. We reconstructed 3D models of the LC vessel networks of 4 healthy monkey eyes from histological sections. We also obtained in-vivo IOP-induced tissue deformations from a healthy monkey using OCT images and digital volume correlation analysis techniques. The extent that LC vessels distort under a given OCT-derived tissue strain remains unknown. We therefore evaluated two biomechanics-based mapping techniques: cross-sectional and isotropic. The hemodynamics and oxygenations of the four vessel networks were simulated for deformations at several IOPs up to 60mmHg. The results were used to determine the effects of IOP on LC oxygen supply, assorting the extent of tissue mild and severe hypoxia.

Main Outcome Measures

IOP-induced deformation, vasculature structure, blood supply, and oxygen supply for LC region

Result

IOP-induced deformations reduced LC oxygenation significantly. More than 20% of LC tissue suffered from mild hypoxia when IOP reached 30 mmHg. Extreme IOP(>50mmHg) led to large severe hypoxia regions (>30%) in the isotropic mapping cases.

Conclusion

Our models predicted that moderately elevated IOP can lead to mild hypoxia in a substantial part of the LC, which, if sustained chronically, may contribute to neural tissue damage. For extreme IOP elevations, severe hypoxia was predicted, which would potentially cause more immediate damage. Our findings suggest that despite the remarkable LC vascular robustness, IOP-induced distortions can potentially contribute to glaucomatous neuropathy.
Mapping the topographic organization of the human zona incerta using diffusion MRI
Authors: Haast Roy AM , Kai Jason , Taha Alaa , Liu Violet , Gilmore Greydon , Guye Maxime , Khan Ali R. , Lau Jonathan C.
Published: September 2024

The zona incerta (ZI) is a deep brain region originally described by Auguste Forel as an “immensely confusing area about which nothing can be said.” Despite the elusive nature of this structure, mounting evidence supports the role of the ZI and surrounding regions across a diverse range of brain functions and as a candidate target for neuromodulatory therapies. Usingin vivodiffusion MRI and data-driven connectivity, we identify a topographic organization between the ZI and neocortex. Specifically, our methods identify a rostral-caudal gradient predominantly connecting the frontopolar and ventral prefrontal cortices with the rostral ZI, and the primary sensorimotor cortices with the caudal ZI. Moreover, we demonstrate how clustering and gradient approaches build complementary evidence including facilitating the mapping of a central region of the ZI, connected with the dorsal prefrontal cortex. These results were shown to be replicable across multiple datasets and at the individual subject level, building evidence for the important role of the ZI in mediating frontal lobe-associated tasks, ranging from motor to cognitive to emotional control. Finally, we consider the impact of this topographic organization on the refinement of neuromodulatory targets. These results pave the way for an increasingly detailed understanding of ZI substructures, and considerations forin vivotargeting of the ZI for neuromodulation.
Dynamic estimation of the attentional field from visual cortical activity
Authors: Bloem Ilona M. , Bakst Leah , McGuire Joseph T. , Ling Sam
Published: September 2024

Navigating around the world, we must adaptively allocate attention to our surroundings based on anticipated future stimuli and events. This allocation of spatial attention boosts visuocortical representations at attended locations and locally enhances perception. Indeed, spatial attention has often been analogized to a “spotlight” shining on the item of relevance. Although the neural underpinnings of the locus of this attentional spotlight have been relatively well studied, less is known about the size of the spotlight: to what extent can the attentional field be broadened and narrowed in accordance with behavioral demands? In this study, we developed a paradigm for dynamically estimating the locus and spread of covert spatial attention, inferred from visuocortical activity using fMRI in humans. We measured BOLD activity in response to an annulus while participants (4 female, 4 male) used covert visual attention to determine whether more numbers or letters were present in a cued region of the annulus. Importantly, the width of the cued area was systematically varied, calling for different sizes of the attentional spotlight. The deployment of attention was associated with an increase in BOLD activity in corresponding retinotopic regions of visual areas V1—V3. By modeling the visuocortical attentional modulation, we could reliably recover the cued location, as well as a broadening of the attentional enhancement with wider attentional cues. This modeling approach offers a useful window into the dynamics of attention and spatial uncertainty.

Significance Statement

This study explores whether spatial attention can dynamically adapt by shifting and broadening the attentional field. While previous research has focused on the modulation of neural responses at attended locations, less is known about how the size of the attentional field is represented within visual cortex. Using fMRI, we developed a novel paradigm to estimate the spatial tuning of the attentional field and demonstrate that we were able to recover both the location as well as the width of the attentional field. Our findings offer new insights into the neural mechanisms underlying the deployment of spatial attention, contributing to a deeper understanding of how spatial attention supports visual perception.
Unravelling the impact of TLR4 and sex on chronic alcohol consumption-induced lipidome dysregulation in extracellular vesicles
Authors: Perpiñá-Clérigues Carla , Mellado Susana , Galiana-Roselló Cristina , García-García Francisco , Pascual María
Published: September 2024

The lipids that form extracellular vesicles (EVs) play critical structural and regulatory roles, and cutting-edge bioinformatics strategies have shown the ability to decipher lipid metabolism and related molecular mechanisms. We previously demonstrated that alcohol abuse induces an inflammatory immune response through Toll-like receptor 4 (TLR4), leading to structural and cognitive dysfunction. This study evaluated how TLR4 and sex as a variable (male/female) impact the lipidome of plasma-resident EVs after chronic alcohol exposure. Using a mouse model of chronic ethanol exposure in wild-type and TLR4-deficient mice, enrichment networks generated by LINEX2highlighted significant ethanol-induced changes in the EV lipid substrate-product of enzyme reactions associated with glycerophospholipid metabolism. We also demonstrated ethanol-induced differences in Lipid Ontology enrichment analysis in EVs, focusing on terms related to lipid bilayer properties. A lipid abundance analysis revealed higher amounts of significant lipid subclasses in all experimental comparisons associated with inflammatory responses and EV biogenesis/secretion. These findings suggest that interrogating EV lipid abundance with a sensitive lipidomic-based strategy can provide deep insight into the molecular mechanisms underlying biological processes associated with sex, alcohol consumption, and TLR4 immune responses and open new avenues for biomarker identification and therapeutic development.