bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular disruption of DNA polymerase β for platinum sensitisation and synthetic lethality in epithelial ovarian cancers
Authors: Ali Reem , Alblihy Adel , Miligy Islam M. , Alabdullah Muslim L. , Alsaleem Mansour , Toss Michael S. , Algethami Mashael , Abdel-Fatah Tarek , Moseley Paul , Chan Stephen , Mongan Nigel P. , Narayan Satya , Rakha Emad A. , Madhusudan Srinivasan
Published: March 2021

Targeting PARP1 [Poly(ADP-Ribose) Polymerase 1] for synthetic lethality is a new strategy for BRCA germ-line mutated or platinum sensitive ovarian cancers. However, not all patients respond due to intrinsic or acquired resistance to PARP1 inhibitor. Development of alternative synthetic lethality approaches is a high priority. DNA polymerase β (Polβ), a critical player in base excision repair (BER), interacts with PARP1 during DNA repair. Here we show that polβ deficiency is a predictor of platinum sensitivity in human ovarian tumours. Polβ depletion not only increased platinum sensitivity but also reduced invasion, migration and impaired EMT (epithelial to mesenchymal transition) of ovarian cancer cells. Polβ small molecular inhibitors (Pamoic acid and NSC666719) were selectively toxic to BRCA2 deficient cells and associated with double-strand breaks (DSB) accumulation, cell cycle arrest and increased apoptosis. Interestingly, PARG [Poly(ADP-Ribose) Glycohydrolase] inhibitor (PDD00017273) [but not PARP1 inhibitor (Olaparib)] was synthetically lethal in polβ deficient cells. Selective toxicity to PDD00017273 was associated with poly (ADP-ribose) accumulation, reduced nicotinamide adenine dinucleotide (NAD+) level, DSB accumulation, cell cycle arrest and increased apoptosis. In human tumours, polβ-PARG co-expression adversely impacted survival in patients. Our data provide evidence that polβ targeting is a novel strategy and warrants further pharmaceutical development in epithelial ovarian cancers.
Phase 1 trial of ADI-PEG20 plus cisplatin in patients with pretreated metastatic melanoma or other advanced solid malignancies
Authors: Yao Shuyang , Janku Filip , Subbiah Vivek , Stewart John , Patel Sapna Pradyuman , Kaseb Ahmed , Westin Shannon Neville , Naing Aung , Tsimberidou Apostolia Maria , Hong David , Piha-Paul Sarina Anne , Shi Nai , Johnston Amanda , Bomalaski John , Fu Siqing
Published: March 2021

Background

Arginine depletion interferes with pyrimidine metabolism and DNA damage-repair pathways, and pairing arginine deiminase pegylated with 20,000-molecular-weight polyethylene glycol (ADI-PEG20) with platinum enhances cytotoxicity in vitro and in vivo in arginine auxotrophs.

Methods

This single-centre, Phase 1 trial was conducted using a 3 + 3 dose escalation designed to assess safety, tolerability and determine the recommended Phase 2 dose (RP2D) of ADI-PEG20.

Results

We enrolled 99 patients with metastatic argininosuccinate synthetase 1 (ASS1) deficient malignancies. We observed no dose-limiting toxic effects or treatment-related mortality. Three percent of patients discontinued treatment because of toxicity. After treatment, 5% (5/99) of patients had partial responses, and 41% had stable disease. The median progression-free and overall survival durations were 3.62 and 8.06 months, respectively. Substantial arginine depletion and citrulline escalation persisted in most patients through weeks 24 and 8, respectively. Tumour responses were associated with anti-ADI-PEG20 antibody levels at weeks 8 and 16 (p = 0.031 and p = 0.0357, respectively).

Conclusion

Concurrently administered ADI-PEG20 and cisplatin had an acceptable safety profile and had shown antitumour activity against metastatic ASS1-deficient solid tumours. Further evaluation of this treatment combination is warranted.
Feasibility and beneficial effects of an early goal directed therapy after cardiac arrest: evaluation by conductance method
Authors: Broch Ole , Hummitzsch Lars , Renner Jochen , Meybohm Patrick , Albrecht Martin , Rosenthal Peter , Rosenthal Ann-Christine , Steinfath Markus , Bein Berthold , Gruenewald Matthias
Published: March 2021

Although beneficial effects of an early goal directed therapy (EGDT) after cardiac arrest and successful return of spontaneous circulation (ROSC) have been described, clinical implementation in this period seems rather difficult. The aim of the present study was to investigate the feasibility and the impact of EGDT on myocardial damage and function after cardiac resuscitation. A translational pig model which has been carefully adapted to the clinical setting was employed. After 8 min of cardiac arrest and successful ROSC, pigs were randomized to receive either EGDT (EGDT group) or therapy by random computer-controlled hemodynamic thresholds (noEGDT group). Therapeutic algorithms included blood gas analysis, conductance catheter method, thermodilution cardiac output and transesophageal echocardiography. Twenty-one animals achieved successful ROSC of which 13 pigs survived the whole experimental period and could be included into final analysis. cTnT and LDH concentrations were lower in the EGDT group without reaching statistical significance. Comparison of lactate concentrations between 1 and 8 h after ROSC exhibited a decrease to nearly baseline levels within the EGDT group (1 h vs 8 h: 7.9 vs. 1.7 mmol/l, P < 0.01), while in the noEGDT group lactate concentrations did not significantly decrease. The EGDT group revealed a higher initial need for fluids (P < 0.05) and less epinephrine administration (P < 0.05) post ROSC. Conductance method determined significant higher values for preload recruitable stroke work, ejection fraction and maximum rate of pressure change in the ventricle for the EGDT group. EGDT after cardiac arrest is associated with a significant decrease of lactate levels to nearly baseline and is able to improve systolic myocardial function. Although the results of our study suggest that implementation of an EGDT algorithm for post cardiac arrest care seems feasible, the impact and implementation of EGDT algorithms after cardiac arrest need to be further investigated.
Enhancement of mechanical and corrosion resistance properties of electrodeposited Ni–P–TiC composite coatings
Authors: Fayyaz Osama , Khan Adnan , Shakoor R. A. , Hasan Anwarul , Yusuf Moinuddin M. , Montemor M. F. , Rasul Shahid , Khan Kashif , Faruque M. R. I. , Okonkwo Paul C.
Published: March 2021

In the present study, the effect of concentration of titanium carbide (TiC) particles on the structural, mechanical, and electrochemical properties of Ni–P composite coatings was investigated. Various amounts of TiC particles (0, 0.5, 1.0, 1.5, and 2.0 g L−1) were co-electrodeposited in the Ni–P matrix under optimized conditions and then characterized by employing various techniques. The structural analysis of prepared coatings indicates uniform, compact, and nodular structured coatings without any noticeable defects. Vickers microhardness and nanoindentation results demonstrate the increase in the hardness with an increasing amount of TiC particles attaining its terminal value (593HV100) at the concentration of 1.5 g L−1. Further increase in the concentration of TiC particles results in a decrease in hardness, which can be ascribed to their accumulation in the Ni–P matrix. The electrochemical results indicate the improvement in corrosion protection efficiency of coatings with an increasing amount of TiC particles reaching to ~ 92% at 2.0 g L−1, which can be ascribed to a reduction in the active area of the Ni–P matrix by the presence of inactive ceramic particles. The favorable structural, mechanical, and corrosion protection characteristics of Ni–P–TiC composite coatings suggest their potential applications in many industrial applications.
Albumin platelet product as a novel score for liver fibrosis stage and prognosis
Authors: Fujita Koji , Yamasaki Kazumi , Morishita Asahiro , Shi Tingting , Tani Joji , Nishiyama Noriko , Kobara Hideki , Himoto Takashi , Yatsuhashi Hiroshi , Masaki Tsutomu
Published: March 2021

Fibrosis-4 index, a conventional biomarker for liver fibrosis stage, is confounded by age and hepatitis activity grade. The current retrospective multicenter study aimed to formulate the novel indices of liver fibrosis by mathematically combining items of peripheral blood examination and to evaluate ability of prognosis prediction. After a novel index was established in a training cohort, the index was tested in a validation cohort. Briefly, a total of 426 patients were enrolled in a training cohort. Albumin and platelet most strongly correlated to fibrosis stage among blood examination. Albumin platelet product (APP) = Albumin × platelet/1000 could differentiate the four stages of liver fibrosis (p < 0.05). APP indicated fibrosis stage independent from hepatitis activity grade. A cut-off value = 4.349 diagnosed cirrhosis with area under ROC more than 0.8. Multivariate analysis revealed that smaller APP independently contributed to HCC prevalence and overall mortality. The results were validated in another 707 patients with HCV infection. In conclusion, APP was not confounded by age or hepatitis activity grade contrary to Fibrosis-4 index. APP is as simple as physicians can calculate it by pen calculation. The product serves physicians in managing patients with chronic liver disease.
A new Zn(ii) MOF assembled from metal–organic cubes (MOCs) as a highly efficient adsorbent for cationic dyes
Authors: Siddique Armeen , I. Mantasha , Rawat Poonam , Singh Ram Niwas , Shahid M. , Trivedi Sweta , Gautam Anshu , Zeeshan Mohd
Published: March 2021

A new MOC [Zn3(Tz)2(tpa)2(DMSO)4] was synthesized. The cluster representation reveals an interwoven pcu 6/4/c1 sqc1 topological type. The MOC exhibits excellent water stability, recyclability, adsorption and separation abilities toward selected dyes.
Spectral tuning of chlorophylls in proteins – electrostatics vs. ring deformation
Authors: Lahav Yigal , Noy Dror , Schapiro Igor
Published: March 2021

Electrostatic interactions with the protein control the spectral tuning of chlorophyll.
Significant role of thorny surface morphology of polyaniline on adsorption of triiodide ions towards counter electrode in dye-sensitized solar cells
Authors: Reza Muhammad , Utami Annisa Nurul , Amalina Auliya Nur , Benu Didi Prasetyo , Fatya Alvian Ikhsanul , Agusta Mohammad Kemal , Yuliarto Brian , Kaneti Yusuf Valentino , Ide Yusuke , Yamauchi Yusuke , Suendo Veinardi
Published: March 2021

Revealing the adsorption behavior of polyaniline with thorny surface morphology towards triiodide ions and its impact on the dye-sensitized solar cell performance.
Overcoming the phase separation within high-entropy metal carbide by poly(ionic liquid)s
Authors: Leng Yan , Zhang Zihao , Chen Hao , Du Shengyu , Liu Jixing , Nie Shiyang , Dong Yuming , Zhang Pengfei , Dai Sheng
Published: March 2021

High-entropy metal carbide nanoparticles (Mo0.2W0.2V0.2Cr0.2Nb0.2C) have been synthesized by a Br-based poly(ionic liquid)-assisted assembly strategy, and exhibited unexpected activity and stability for the dehydrogenation of ethylbenzene with CO2.
Dual‐mode dual‐band bandpass filter design utilising cylindrical TM‐mode cavities
Authors: Bartlett Chad , Höft Michael
Published: March 2021

This letter presents the design of a novel dual‐mode dual‐band bandpass filter that utilises the TM210 and TM020 modes of cylindrical cavity resonators for millimetre‐wave operation when fed with standard WR‐10 waveguide ports. In this manner, the two selected modes of the cylindrical cavity resonators are demonstrated as a single propagation path for fixed dual‐passband responses without the need of cavity perturbations or tuning screws. The passbands are designated for centre frequencies at approximately 102.8 and 110.9 GHz and exhibit a four‐pole Chebyshev characteristic in each of the passbands, which are separated by a transmission zero location. Simulated and measured results of the prototype are presented to verify the design.
Forgery localization in images based on joint statistics of image blocks with neighbouring blocks
Authors: Singhal Divya , Gupta Abhinav
Published: March 2021

Flawless image forensic analysis necessitates precise identification of tampering regions in digital images along with the determination of state of an image (original or forged). Most of the efforts towards localization of forgeries involve localization of information‐changing forgeries with less focus towards localization of information‐preserving forgeries. This paper proposes a new information‐preserving forgery localization method to localize 10 different tampering types exploiting the fact that joint statistics of locally forged regions and neighbouring original regions is disturbed. The proposed 18‐dimensional detector is trained using ensemble classifier for fine‐grain identification of forged regions in post‐JPEG compressed images and results are compared with two recent state‐of‐the‐art detectors. The results demonstrate the effectiveness of the proposed detector with significant performance gain over existing detectors, particularly for localization in images that are compressed with low quality factors of compression.
Enhancement of antibiotic production by co-cultivation of two antibiotic producing marine Vibrionaceae strains
Authors: Buijs Yannick , Zhang Sheng-Da , Jørgensen Karen Marie , Isbrandt Thomas , Larsen Thomas Ostenfeld , Gram Lone
Published: March 2021

Deciphering the cues that stimulate microorganisms to produce their full secondary metabolic potential promises to speed up the discovery of novel drugs. Ecology-relevant conditions, including carbon-source(s) and microbial interactions, are important effectors of secondary metabolite production. Vice versa secondary metabolites are important mediators in microbial interactions, although their exact natural functions are not always completely understood. In this study, we investigated the effects of microbial interactions and in-culture produced antibiotics on the production of secondary metabolites by Vibrio coralliilyticus and Photobacterium galatheae, two co-occurring marine Vibrionaceae. In co-culture, production of andrimid by V. coralliilyticus and holomycin by P. galatheae, were, compared to monocultures, increased 4.3 and 2.7 fold, respectively. Co-cultures with the antibiotic deficient mutant strains (andrimid− and holomycin−) did not reveal a significant role for the competitor's antibiotic as stimulator of own secondary metabolite production. Furthermore, we observed that V. coralliilyticus detoxifies holomycin by sulphur-methylation. Results presented here indicate that ecological competition in Vibrionaceae is mediated by, and a cue for, antibiotic secondary metabolite production.
“It’s the political economy . . .!” A moment of truth for the eurozone and the EU
Authors: Dani Marco , Chiti Edoardo , Mendes Joana , Menéndez Agustín José , Schepel Harm , Wilkinson Michael A
Published: March 2021

The article discusses the Weiss dispute from a political economy perspective. It first sets this litigation in its wider context, namely the protracted transformation of the Economic and Monetary Union (EMU) over the last decade, a decade which has revealed the structural flaws in its design. It then briefly sketches the changing role of central banking, from a fixation on fighting inflation to a more recent focus on combating deflation. This helps to explain the problematic character of the Weiss rulings and the commentaries they have provoked, illustrating a general failure to consider the limits of law, the result of clinging to different parts of the EMU wreckage, on the assumption that the current constitutional framework remains viable. Finally, the article emphasizes the transformative potential of the Weiss saga. The judicial conflict lays bare the unsustainability of the present arrangements, and reveals the necessity of a choice between genuinely federal integration and coordinated dismantling of EMU.
General Theory on Compatibility of State Aid
Authors: Kreuschitz Viktor , Nehl Hanns Peter
Published: March 2021

This chapter presents a general theory on the compatibility of State aid, considering the relation between general and sectoral regulation and State aid control. State aid control is one of the most important powers of the Commission. The origins of the prohibition of subsidies can be found in Chapter IV, Section C of the Havana Charter for an International Trade Organization of 1947. Due to the lack of ratification by the US Congress, that Charter was abandoned in 1950 and never entered into force. However, the Treaty on European Coal and Steel Community (ECSC) drew a lot of inspiration from the Havana Charter, and established, amongst others, a general prohibition on subsidies or State assistance (Article 4 ECSC). The Spaak report proposed to extend that prohibition to all sectors of the economy. At the same time, it foresaw the possibility to exceptionally authorize State aid, and proposed to confer the power of authorization to the Commission.
Direct Actions and Judicial Review before the Union Courts
Authors: Kreuschitz Viktor , Nehl Hanns Peter
Published: March 2021

This chapter addresses access to justice in the context of centralized enforcement of EU State aid law and judicial review before the Union courts. The subject matter of litigation is State aid measures adopted in particular by the European Commission as the main supervisory body in this field pursuant to Article 108 TFEU. The term ‘access to justice’ is meant to comprise both the various conditions of standing for bringing direct actions against such measures before the General Court (GC), which essentially comprise actions for annulment (Article 263 TFEU), actions for failure to act (Article 265 TFEU), and actions for damages (Article 268 in combination with Article 340(2) TFEU). The chapter also looks at the nature and the types of acts that are possibly subject to judicial review before the GC.
Anti-subsidy Law and Practice of the European Union
Authors: Kreuschitz Viktor , Nehl Hanns Peter
Published: March 2021

This concluding chapter explores EU's anti-subsidy instruments, which are designed to address subsidization by other WTO members. After a hesitant start, the EU since 1995 has progressively used the AS instrument to act against subsidization by third-country governments. While initially focusing on relatively clear-cut export subsidies, over time the EU has more and more also countervailed domestic subsidy programmes. This is clearest in the AS cases initiated against China during the past five years, where the majority of the countervailed programmes have consisted of domestic subsidies. In this context, it is important to note that the findings of specificity reached by the EU in cases concerning China are largely based on the use of facts available, resulting from the imposition of very high burdens of proof on the Chinese government that domestic subsidies in fact are not specific.
Cyprus
Authors: Ioannidou Maria
Published: March 2021

This chapter examines how the Antitrust Damages Directive has been transposed in Cyprus. It begins with a discussion of the transposition procedure, focusing on the Cypriot competition regime as well as the state of private enforcement in Cyprus. In particular, it provides an overview of the law currently in force against anticompetitive agreements and abuse of dominant position, the Protection of Competition Law of 2008 (13(I)/2008), as amended in 2014 (Law 41(I)/2014) (Cypriot Competition Act), and the provisions relevant to private competition law enforcement. The chapter then considers the history and the different steps of the transposition process before describing the scope of the transposition measure. It also analyses the different provisions of the Cypriot Damages Act and issues that arose during the transposition, such as parent company liability, the binding force of decisions of competition authorities of other Member States, and presumption and quantification of damage caused by cartels or other antitrust infringements.
Lithuania
Authors: Malinauskaite Jurgita
Published: March 2021

This chapter discusses the transposition of the Antitrust Damages Directive in Lithuania. It first provides background on the transposition procedure, focusing on the copying method (also known as literal transposition) adopted by the government, the consultation process for the implementation of the Directive, and assessment of the Directive’s impact on the Lithuanian legal system. It then considers the substantive and temporal scope of Lithuania’s revised competition law before concluding with an analysis of specific issues that arose during the transposition, including those relating to the claimants’ right to full compensation, access to evidence and disclosure of evidence, the effect of national decisions and limitation periods for filing civil damages claims, joint and several liability, the passing-on of overcharges, the quantification of harm, and consensual dispute resolution.
The Netherlands
Authors: Kortmann Jeroen , Mineur Simon
Published: March 2021

This chapter focuses on the transposition of the Antitrust Damages Directive in the Netherlands. It first provides a general overview of the transposition procedure, taking into account the Dutch private enforcement context. In particular, it examines how the Directive was transposed into Dutch law, beginning with the Proposal of Law and culminating in the ‘Implementation Act’ that entered into force on 10 February 2017. The chapter goes on to discuss the structural choices made by the Dutch legislature in implementing the Directive's provisions, paying special attention to the scope of the Dutch transposition of the Directive, before analysing specific issues that arose during the transposition, including those relating to the ‘no exemption’ provision for Dutch farmers, limitation periods, effects of National Competition Authorities' final infringement decisions, disclosure and protection of documents, evidentiary presumptions on damage and passing-on, joint and several liability, liability of parent companies, and collective redress.
Spain
Authors: Marcos Francisco
Published: March 2021

This chapter examines the transposition of the Antitrust Damages Directive in Spain. It begins with a general overview of the transposition process, focusing on the Transposition Decree that inserts new articles in the Defence Competition Act of 2007 and in the Civil Procedure Act. It then describes the material, territorial, and temporal scope of the Transposition Decree before analysing the main issues concerning antitrust damages claims affected by the Transposition Decree or that may be relevant in future actions for damages, such as those relating to the jurisdiction of competent courts to decide damages claims based on infringements of competition law, the right to full compensation, joint and several/parental liability, passing-on of the harm and claims by indirect purchasers/suppliers, the limitation period for bringing damages claims, the use of alternative dispute resolution procedures, measures to facilitate claims, and collective claims and consumer redress.
United Kingdom
Authors: Rodger Barry
Published: March 2021

This chapter focuses on the transposition of the Antitrust Damages Directive in the United Kingdom. It first provides a general background on the transposition process, with emphasis on developments in relation to private litigation involving both UK and EU competition law in the UK courts. It then considers the substantive and temporal scope of the UK transposition measure before analysing some of the specific issues concerning implementation of the Directive, such as those relating to limitation periods, binding force of competition authority decisions, disclosure and protection of certain documents/admissability of evidence, presumption of harm and quantification of damages, passing-on defence and indirect purchasers, joint and several liability, parent company liability, consensual dispute resolution, collective redress, litigation costs and funding, and specialised court structure.
Applicable Law
Authors: Brealey Mark , George Kyla
Published: March 2021

This chapter discusses the principles that govern the applicable law for cases involving a breach of the competition rules. It begins with an overview of the relevant legal framework applicable to restrictive conduct since 1996, with emphasis on Regulation (EC) 864/2007 on the law applicable to non-contractual obligations from 11 January 2009 to date (Rome II), the Private International (Miscellaneous Provisions) Act 1995 (from 1 May 1996 to 10 January 2009), and English common law principles (prior to 1 May 1996). It also considers the temporal, material, and geographical scope of Rome II, along with its special rules for determining the applicable law to ‘acts restricting free competition’, the affected market, non-compensatory remedies, and unfair competition. The chapter concludes with an analysis of the relevant principles of Rome I that govern the applicable law to contractual obligations.
Disclosure
Authors: Brealey Mark , George Kyla
Published: March 2021

This chapter focuses on disclosure in the High Court and the Competition Appeal Tribunal (CAT) with respect to claims for damages for breach of the competition rules. It first considers the legal framework for disclosure in the High Court, how to make an application when seeking disclosure or inspection of evidence relating to a competition claim, and the specific nature of the application. It then discusses pre-action disclosure, early disclosure, disclosure at first case management conference, specific disclosure, disclosure from non-parties, and disclosure in judicial review. After describing the CAT rules for disclosure in appeals and judicial review proceedings and disclosure in damages claims, the chapter analyses issues relating to disclosure and inspection of confidential information. It also explains the basic principles underlying disclosure and privilege, before concluding with an overview of how requests for information are made under the Freedom of Information Act 2000.
Burden and Standard of Proof
Authors: Brealey Mark , George Kyla
Published: March 2021

This chapter examines issues of burden and standard of proof that arise in competition proceedings. It first provides an overview of relevant terminology such as burden, legal burden, evidential burden, and standard of proof before discussing the burden of proof, presumption, and standard of proof with regard to civil claims and criminal cases. It also considers the burden of proof, standard of proof, and presumption of innocence in appeals made to the Competition Appeal Tribunal (CAT) against infringement decisions. In particular, it explains the criminal nature of the appeal proceedings and shows that the legal burden of proving the infringement remains on the Competition and Markets Authority (CMA). The CAT decisions in Napp Pharmaceutical Holdings v DGFT, Claymore Dairies v OFT, and Flynn Pharma Ltd & Pfizer CMA with respect to standard of proof and presumption of innocence are cited.
Expert Evidence
Authors: Brealey Mark , George Kyla
Published: March 2021

This chapter examines the use of expert evidence, and more specifically the role of economic experts and economic analysis, in competition-related litigation. It first provides an overview of the duties and responsibilities of experts, focusing on how expert evidence differs from factual evidence, issues addressed by expert evidence, the rules that apply to the production of expert evidence in the High Court and in the Competition Appeal Tribunal (CAT), and conflict of interest involving experts. The chapter then presents a practical guide to the use of experts in the course of competition litigation, covering the requirements of the relevant CAT Rules and Civil Procedure Rules 1998 (CPR), from instructing an expert to the submission of the formal written report, discussions between experts and joint statements after service of reports, and hearing of expert evidence at trial. Statutory provisions regarding concurrent expert evidence or ‘hot tubbing’ are also considered.
Damages
Authors: Brealey Mark , George Kyla
Published: March 2021

This chapter examines the processes used to quantify damages in competition cases. It begins with a discussion of compensatory damages and the various ways that they are assessed by the courts. Compensatory damages are designed to restore the claimant to the position the claimant would have been in had the restrictive conduct not occurred. Hence, the assessment necessarily involves a hypothetical scenario known as a counterfactual. Other factors to consider in calculating damages include proof of loss and collateral benefits. The chapter proceeds by analysing the remoteness of damage, focusing on the burden of proving causation, the scope of the defendant’s liability, and contingencies. It also explains how damages may be reduced because of a failure to mitigate or through contributory negligence, before concluding with an overview of the issue of pass-on, the principle of joint and several liability for the damage, and contribution proceedings.
Criminal Proceedings
Authors: Brealey Mark , George Kyla
Published: March 2021

This chapter examines the criminal aspect of competition law, with particular emphasis on the cartel offence created by Section 188 of the Enterprise Act 2002. It first provides an overview of the common law governing cartel offences, the criminal nature of breaches of the competition rules, and relevant provisions of Section 188 Enterprise Act with respect to cartel offences. It then considers the four types of arrangements deemed to be an offence, namely, price-fixing, limiting production or supply, market sharing, and bid-rigging. It also discusses exclusions and defences based on the amendment to the cartel offence introduced on or after 1 April 2014 by the Enterprise and Regulatory Act 2013 (ERRA 13). Finally, it decribes the criminal prosecution of the cartel offence and the sentences relating to the cartel offence.
Alternative Dispute Resolution
Authors: Brealey Mark , George Kyla
Published: March 2021

This chapter examines the use of alternative dispute resolution (ADR) for resolving competition-related disputes. It first provides an overview of the benefits of mediation as a means of resolving competition disputes and how ADR is encouraged in competition litigation. It then considers the relevant ADR provisions in the Civil Procedure Rules 1998 (CPR) and in the Competition Appeal Tribunal (CAT) Rules, before discussing cross-border mediations and how disputes are mediated and regulated. It also offers practical guidance on when to mediate, choosing a mediator, the typical stages of a mediation process, the role of a mediation agreement, and the implications of mediation confidentiality. Finally, it explains the specific provisions relating to voluntary redress schemes, a form of ADR.
International Disaster Law
Authors: Pronto Arnold N.
Published: March 2021

This chapter details how disasters, whether widespread or localized, pose a major threat to human security, as their effects place significant strain on human support systems. What is more, disasters invariably have a disproportionately harmful impact on the particularly vulnerable, who typically subsist at the margins of society, usually in harm’s way. For many States, the impact of specific disasters can be measured in terms of setbacks to human development. The imperative to provide aid and assistance following the onset of disasters is increasingly viewed as a key interest of the international community. The United Nations devotes significant resources to the coordination of efforts at the international level aimed at facilitating cooperation in the provision of humanitarian assistance. The organization has also become the central locus for contemplation at the global level on best practices in disaster risk reduction. The chapter then describes the outlines of an emerging international disaster law, motivated in large part by a growing awareness of the role law can play in efforts to reduce vulnerability to, and mitigate the impact of, disasters. Such sentiments are, in turn, driven by an appreciation of the potential deleterious consequences for global security arising from the widespread dislocation brought about by major disasters.
The Formation of the Reinsurance Contract
Authors: Edelman Colin , Burns Andrew
Published: March 2021

This chapter discusses the formation of the reinsurance contract. A reinsurance contract is formed according to normal contractual principles. There needs to be an offer and an acceptance of that offer to form an agreement, with consideration for the bargain and an intention by the parties to create legal relations between them. The relationship between reinsurer and reinsured may be one of utmost good faith when concluding the contract, but the essential requirements for the formation of a contract are the same. The final offer and acceptance are the mechanisms for the formation of a reinsurance contract. A broker is normally (at least for most purposes) the agent of the reinsured for the purposes of the placement of the reinsurance. Ultimately, it is always important to look at the reality of the legal relationships and not rely on the superficial appearance of who is making an offer to whom. The chapter then looks at the Market Reform Contract (MRC) slip.
Applicable Law and Jurisdiction
Authors: Edelman Colin , Burns Andrew
Published: March 2021

This chapter explores the law applicable to reinsurance. Section 2(1) of the Contracts (Applicable Law) Act 1990 provides for the incorporation of the 1980 Rome Convention on the law applicable to contractual obligations into the law of the United Kingdom. Article 1(4) of the Convention expressly provides that reinsurance contracts, unlike contracts of insurance, are subject to the rules of the Convention. However, the Convention does not have retrospective effect and therefore only applies to contracts entered into after April of 1991 when the Convention came into force. For a contract concluded before that date, the determination of its proper law depended and still depends on common law principles. At common law, the starting point is to investigate whether the parties have expressly selected a body of law at the time of contracting or whether such selection can be implied from the express terms of the contract. If the court is unable to ascertain the governing law from the contract it will then look to determine with which system of law the contract has the closest connection.
Health-Related Quality of Life After Polytrauma: A Systematic Review
Authors: Silverstein Lily A. , Higgins Jacob T. , Henderson Stephanie
Published: March 2021

Background:

Following hospital discharge after traumatic injuries, many patients' rehabilitation is inhibited by poor health-related quality of life (HRQoL).

Objective:

The purpose of this review is to identify factors that influence the HRQoL of polytrauma patients after hospital discharge.

Methods:

A systematic literature search was performed in CINAHL and PubMed databases for English-language articles published between January 2015 and January 2020. Articles that dealt with pediatric or narrow adult populations, exclusively considered brain and spinal cord injuries, burn injuries, or isolated fractures were excluded. In total, 22 nonexperimental cohort studies were eligible for inclusion.

Results:

Based on these studies, with minor disagreements explainable by deficient sampling, variables that impacted HRQoL fell into 11 categories: demographics, preinjury HRQoL, preexisting conditions, mental health status, injury type and location, injury severity, course of hospitalization, time after injury, financial and employment status, functional capacity, and pain.

Conclusion:

The finding with the greatest implications was that mental health, positive coping, self-efficacy, and perception of physical state significantly influence HRQoL after injury and, along with other modifiable variables, can be optimized by directed treatment. Additionally, targeted assessments and interventions can be utilized to improve quality of life for patients with nonmodifiable risk factors.
Facilitating Advance Care Planning for Patients With Severe COPD
Authors: Hirakawa Yoshihisa , Aita Kaoruko , Nishikawa Mitsunori , Arai Hidenori , Miura Hisayuki
Published: March 2021

Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity worldwide. Patients with severe COPD often fail to receive adequate palliative care and are subject to undesired hospital transfers and cardiopulmonary resuscitation. Although promoting advance care planning (ACP) in the community can help ensure the optimal delivery of palliative care for patients with COPD, the key challenges to routinely implementing ACP are not known. The aim of this study was to identify the perception of healthcare professionals with regard to ACP for adults living with severe COPD and the challenges to facilitating ACP. A multicenter qualitative study design was used. In-depth semistructured interviews were held involving 38 healthcare professionals from 19 institutions in Japan. Text data were analyzed by content analysis. Five main themes capturing the challenges to routine implementation of ACP were identified: daily decision-making; sense of ethical decision-making; in-depth interviewing skills; collaborative information sharing among team members; and knowledge dissemination regarding ACP. The model demonstrates the complexity inherent in ACP facilitation for community-dwelling adults with severe COPD, with all the elements required for successful ACP implementation. We recommend an approach that recognizes the importance of stakeholder education, particularly educating professionals to develop the knowledge, attitudes, and skills required for ACP facilitation: in-depth interviewing, collaborative information sharing, and ethical analysis, focusing on decision-making concerning everyday life support.
The Journey of a Home Care Nurse Residency Program
Authors: Linscheid Nancy J. , Bell Dennia J.
Published: March 2021

UnityPoint at Home launched a Nurse Residency Program to attract newly licensed registered nurses to begin their career in home healthcare. The program broadened recruitment options by providing new graduates with a dedicated program to ease transition into the workforce, and allowed us to cultivate relationships with regional nursing education programs. Since its inception 3 years ago, the residency program has expanded to several organizational regions and added a hospice track. The 1-year retention rate is 93%, and for those who entered the program 2 or more years ago, the retention rate is 89%. The purpose of this article is to describe the journey of UnityPoint at Home's Nurse Residency Program, from development of the pilot to integration in several organizational regions.
Effects of inflammatory pain on CB1 receptor in the midbrain periaqueductal gray
Authors: Wilson-Poe Adrianne R. , Wiese Beth , Kibaly Cherkaouia , Lueptow Lindsay , Garcia Jeniffer , Anand Preeti , Cahill Catherine , Morón Jose A.
Published: March 2021

Introduction:

The periaqueductal gray (PAG) mediates the antinociceptive properties of analgesics, including opioids and cannabinoids. Administration of either opioids or cannabinoids into the PAG induces antinociception. However, most studies characterizing the antinociceptive properties of cannabinoids in the PAG have been conducted in naive animals. Few studies have reported on the role of CB1 receptors in the PAG during conditions which would prompt the administration of analgesics, namely, during pain states.

Objectives:

To examine inflammatory pain-induced changes in CB1 receptor expression and function in the midbrain periaqueductal gray.

Methods:

In this study, we used the Complete Freund Adjuvant model to characterize CB1 receptor expression and G-protein coupling during persistent inflammatory pain.

Results:

Inflammatory pain induced an upregulation in the expression of synaptic CB1 receptors in the PAG. Despite this pain-induced change in CB1 expression, there was no corresponding upregulation of CB1 mRNA after the induction of inflammatory pain, suggesting a pain-induced recruitment of CB1 receptors to the synaptic sites within PAG neurons or increased coupling efficiency between the receptor and effector systems. Inflammatory pain also enhanced ventrolateral PAG CB1 receptor activity, as there was an increase in CP55,940-stimulated G-protein activation compared with pain-naïve control animals.

Conclusion:

These findings complement a growing body of evidence which demonstrate pain-induced changes in brain regions that are responsible for both the analgesic and rewarding properties of analgesic pharmacotherapies. Because much of our understanding of the pharmacology of cannabinoids is based on studies which use largely pain-naïve male animals, this work fills in important gaps in the knowledge base by incorporating pain-induced adaptations and cannabinoid pharmacology in females.
ANTERIOR OR POSTERIOR ANKLE FOOT ORTHOSES FOR ANKLE SPASTICITY: WHICH ONE IS BETTER?
Authors: Suputtitada Areerat , Chatkungwanson Watchara , Seehaboot Kittikorn , Chen Carl PC
Published: March 2021

Backgroud

Ankle foot orthoses (AFOs) have been widely used in stroke patients to assist in safe, energy efficient walking. Since they provide mediolateral ankle stability during stance, adequate toes clearance during swing phase and also facilitation of heel strike.

Objective

To compare the efficacy of anterior or posterior plastic ankle foot orthoses (AFOs) for ankle spasticity.

Methods

Crossover design with randomization for the interventions, blinded assessors was used. 20 patients with chronic stroke, Modified Ashworth scale (MAS) of ankle ≤ 2 and Tardieu angle ≥ 20 degrees. The participants were random to treat with anterior or posterior plastic AFOs and then were crossover to treat with the other one. Outcomes measurement was performed by using passive range of motion (PROM), MAS, walking velocity, stretch reflex surface EMG and walking surface EMG of medial gastrocnemius muscle. Patient satisfaction was evaluated at 1 month.

Results

Twenty stroke patients with ankle spasticity were recruited. Mean age was 46.60(38-60) years old.Mean duration. of times since stroke was 9.35 (6-15) months. Comparison between two types of orthoses revealed statistically significant improvement of walking surface EMG of medial gastrocnemius muscles when using anterior plastic AFO more than posterior plastic AFO at p=0.015. Patients satisfaction were statistically significant higher when using anterior plastic AFO more than posterior plastic AFO at p<0.05.

Conclusion

Anterior plastic AFO has more efficacy in reduced dynamic ankle spasticity during walking than posterior plastic AFO proven by comparison the dynamic electromyography changes in dynamic spasticity during walking.
Testing Black-White disparities in biological aging in older adults in the United States: analysis of DNA-methylation and blood-chemistry methods
Authors: Graf GH , Crowe CL , Kothari M , Kwon D , Manly JJ , Turney IC , Valeri L , Belsky DW
Published: March 2021

Biological aging is a proposed mechanism through which social determinants drive health disparities. We conducted proof-of-concept testing of eight DNA-methylation and blood-chemistry quantifications of biological aging as mediators of disparities in healthspan between Black and White participants in the United States Health and Retirement Study (HRS; n=9005). We quantified biological aging from four DNA-methylation “clocks” (Horvath, Hannum, PhenoAge, and GrimAge), a DNA-methylation Pace of Aging (DunedinPoAm), and three blood-chemistry measures (PhenoAge, Klemera-Doubal method Biological Age, and homeostatic dysregulation). We quantified Black-White disparities in healthspan from cross-sectional and longitudinal data on physical-performance tests, self-reported activities of daily living (ADL) limitations and physician-diagnosed chronic diseases, self-rated health, and survival. DNA-methylation and blood-chemistry quantifications of biological aging were moderately correlated (Pearson-r range 0.1-0.4). GrimAge, DunedinPoAm and all three blood-chemistry measures were associated with healthspan characteristics (e.g. mortality effect-size range 1.71-2.32) and showed evidence of more advanced/faster biological aging in Black compared with White participants (Cohen’s d=.4-.5). These measures accounted for 13-95% of Black-White differences in healthspan-related characteristics. Findings that Black Americans are biologically older and aging more rapidly than White Americans of the same chronological age suggest that eliminating disparities in the pace of aging can contribute building to aging health equity.
Redesigning SARS-CoV-2 clinical RT-qPCR assays for wastewater RT-ddPCR
Authors: Gonzalez Raul , Larson Allison , Thompson Hannah , Carter Errin , Cassi Xavier Fernandez
Published: March 2021

COVID-19 wastewater surveillance has gained widespread acceptance to monitor community infection trends. Wastewater samples primarily differ from clinical samples by having low viral concentrations due to dilution, and high levels of PCR inhibitors. Therefore, wastewater samples should be processed by appropriately designed and optimized molecular workflows to accurately quantify targets. Digital PCR has shown to be more sensitive and resilient to environmental matrix inhibition. However, most SARS-CoV-2 assays have been designed for clinical use on RT-qPCR instruments, then adopted to digital PCR platforms. But it is unknown whether clinical RT-qPCR assays are adequate to use on digital PCR platforms. Here we designed an N and E gene multiplex (ddCoV_N and ddCoV_E) specifically for RT-ddPCR and benchmarked them against the nCoV_N2 and E_Sarbeco assays. ddCoV_N and ddCoV_E have equivalent limits of detections and wastewater sample concentrations to NCoV_N2 and E_Sarbeco but showed improved signal-to-noise ratios that eased interpretation and ability to multiplex. From GISAID downloaded unique sequences analyzed, 2.12% and 0.83% present a mismatch or would not be detected by the used primer/probe combination for the ddCoV_N and ddCoV_E, respectively.