bluuebunny/crossref_metadata_2025_split huggingface dataset:
Competition policy and economics
Authors: Whish Richard , Bailey David 
Published: September 2021

Abstract
This chapter provides an overview of competition law and its economic context. Section 2 describes the practices that competition laws attempt to control in order to protect the competition process. Section 3 examines the theory of competition and gives an introductory account of why the effective enforcement of competition law is thought to be beneficial. Section 4 considers the goals of competition law. Section 5 introduces two key economic concepts, market definition and market power, that are important to a better understanding of competition policy. The chapter concludes with a table of market share figures that are significant in the application of EU and UK competition law, while reminding the reader that market shares are only ever a proxy for market power and can never be determinative of market power in themselves.
Overview of EU and UK competition law
Authors: Whish Richard , Bailey David 
Published: September 2021

Abstract
This chapter provides a brief overview of EU and UK competition law and the institutions involved in formulating, interpreting and applying competition law in those jurisdictions. It also explains the relationship between EU competition law and the domestic competition laws of the Member States, in particular in the light of Article 3 of Regulation 1/2003. The rules of the European Economic Area are briefly referred to, and the trend on the part of Member States to adopt domestic competition rules modelled on those in the EU is also noted. Three diagrams at the end of the chapter explain the institutional structure of EU and UK competition law.
Article 102
Authors: Whish Richard , Bailey David 
Published: September 2021

Abstract
This chapter discusses the main features of Article 102 of the Treaty of Functioning of the European Union (TFEU), which is concerned with the abusive conduct of dominant firms. It begins by discussing the meaning of ‘undertaking’ and ‘effect on trade between Member States’ in the context of Article 102. It then considers what is meant by a dominant position and looks at the requirement that any dominant position must be held in a substantial part of the internal market. Thereafter it discusses some general considerations relevant to the concept of abuse of dominance, followed by an explanation of what is meant by ‘exploitative’, ‘exclusionary’ and ‘single market’ abuses. It then discusses possible defences to allegations of abuse, and concludes by considering the consequences of infringing Article 102.
The international dimension of competition law
Authors: Whish Richard , Bailey David 
Published: September 2021

Abstract
This chapter explores the international dimension of competition law from two perspectives. It begins by describing the growth of international institutions involved in the development of competition law and policy, with particular reference to the International Competition Network (the ‘ICN’), the Organisation for Economic Cooperation and Development (the ‘OECD’) and the United Nations Conference on Trade and Development (‘UNCTAD’). It then looks at a more technical issue, which is the extent to which a sovereign state (or the European Union) can apply its competition law extraterritorially to conduct beyond its borders that has a harmful effect within it: this will briefly be considered from a theoretical perspective, after which the positions in the US, EU and UK will be examined in turn. The chapter concludes by briefly examining the extent to which a state may wish to block the application of a foreign competition law to its businesses.
Mergers (3): UK
Authors: Whish Richard , Bailey David 
Published: September 2021

Abstract
This chapter discusses UK law on the control of mergers. The chapter is organized as follows. 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. The subsequent sections discuss various supplementary matters, such as powers of investigation and enforcement. The chapter concludes with a discussion of how the merger control provisions work in practice and a brief account of the provisions on public interest cases, other special cases and mergers in the water industry. The withdrawal by the UK from the EU means that many mergers that were subject to a ‘one-stop shop’ under EU law are now subject to investigation in the UK as well.
Particular sectors
Authors: Whish Richard , Bailey David 
Published: September 2021

Abstract
This chapter deals with four issues. First it will briefly examine three sectors of the economy that are wholly or partly excluded from EU competition law, namely nuclear energy, military equipment and agriculture; the special regime that once existed for coal and steel products under the former European Coal and Steel Community (‘the ECSC’) Treaty is also mentioned in passing. Secondly, it will explain the application of the EU competition rules apply to the transport sector. Thirdly, the chapter will consider the specific circumstances of four so-called ‘regulated industries’, electronic communications, post, energy and water, where a combination of legislation, regulation and competition law seek to promote competition. Last, but by no means least, the current debate concerning digital platforms is discussed where it is likely that ex ante regulatory rules will be introduced, both in the EU and the UK, to address concerns about anti-competitive conduct and a tendency towards the monopolisation of markets.
Homologous Recombination Deficiency Alterations in Colorectal Cancer: Clinical, Molecular, and Prognostic Implications
Authors: Moretto Roberto , Elliott Andrew , Zhang Jian , Arai Hiroyuki , Germani Marco Maria , Conca Veronica , Xiu Joanne , Stafford Phillip , Oberley Matthew , Abraham Jim , Spetzler David , Rossini Daniele , Antoniotti Carlotta , Marshall John , Shields Anthony , Lopes Gilberto , Lonardi Sara , Pietrantonio Filippo , Tomasello Gianluca , Passardi Alessandro , Tamburini Emiliano , Santini Daniele , Aprile Giuseppe , Masi Gianluca , Falcone Alfredo , Lenz Heinz-Josef , Korn Michael , Cremolini Chiara 
Published: September 2021

Abstract

Background
Tumors with homologous recombination deficiency (HRD) show high sensitivity to platinum salts and poly(ADP-ribose) polymerase–inhibitors in several malignancies. In colorectal cancer (CRC), the role of HRD alterations is mostly unknown.

Methods
Next-generation sequencing, whole transcriptome sequencing, and whole exome sequencing were conducted using CRC samples submitted to a commercial Clinical Laboratory Improvement Amendments certified laboratory. Tumors with pathogenic and/or presumed pathogenic mutations in 33 genes involved in the homologous recombination pathway were considered HRD, the others were homologous recombination proficient (HRP). Furthermore, tumor samples from patients enrolled in the phase III TRIBE2 study comparing upfront FOLFOXIRI+bevacizumab vs FOLFOX+bevacizumab were analyzed with next-generation sequencing. The analyses were separately conducted in microsatellite stable or proficient mismatch repair (MSS/pMMR) and microsatellite instable-high or deficient mismatch repair (MSI-H/dMMR) groups. All statistical tests were 2-sided.

Results
Of 9321 CRC tumors, 1270 (13.6%) and 8051 (86.4%) were HRD and HRP, respectively. HRD tumors were more frequent among MSI-H/dMMR than MSS/pMMR tumors (73.4% vs 9.5%; P  &lt; .001; q &lt; 0.001). In MSS/pMMR group, HRD tumors were more frequently tumor mutational burden high (8.1% vs 2.2%; P  &lt; .001; q &lt; 0.001) and PD-L1 positive (5.0% vs 2.4%; P  &lt; .001; q = 0.001), enriched in all immune cell and fibroblast populations and genomic loss of heterozygosity-high (16.2% vs 9.5%; P = .03). In the TRIBE2 study, patients with MSS/pMMR and HRD tumors (10.7%) showed longer overall survival compared with MSS/pMMR and HRP tumors (40.2 vs 23.8 months; hazard ratio [HR] = 0.66, 95% confidence interval [CI] = 0.45 to 0.98; P = .04). Consistent results were reported in the multivariable model (HR = 0.67, 95% CI = 0.45 to 1.02; P = .07). No interaction effect was evident between homologous recombination groups and treatment arm.

Conclusions
HRD tumors are a distinctive subgroup of MSS/pMMR CRCs with specific molecular and prognostic characteristics. The potential efficacy of agents targeting the homologous recombination system and immune checkpoint inhibitors in this subgroup is worthy of clinical investigation.
pH modulates interaction of 14-3-3 proteins with pollen plasma membrane H+ ATPases independently from phosphorylation
Authors: Pertl-Obermeyer Heidi , Gimeno Ana , Kuchler Verena , Servili Evrim , Huang Shuai , Fang Han , Lang Veronika , Sydow Katharina , Pöckl Magdalena , Schulze Waltraud X , Obermeyer Gerhard 
Published: September 2021

Abstract
Pollen grains transport the sperm cells through the style tissue via a fast-growing pollen tube to the ovaries where fertilization takes place. Pollen tube growth requires a precisely regulated network of cellular as well as molecular events including the activity of the plasma membrane H+ ATPase, which is known to be regulated by reversible protein phosphorylation and subsequent binding of 14-3-3 isoforms. Immunodetection of the phosphorylated penultimate threonine residue of the pollen plasma membrane H+ ATPase (LilHA1) of Lilium longiflorum pollen revealed a sudden increase in phosphorylation with the start of pollen tube growth. In addition to phosphorylation, pH modulated the binding of 14-3-3 isoforms to the regulatory domain of the H+ ATPase, whereas metabolic components had only small effects on 14-3-3 binding, as tested with in vitro assays using recombinant 14-3-3 isoforms and phosphomimicking substitutions of the threonine residue. Consequently, local H+ influxes and effluxes as well as pH gradients in the pollen tube tip are generated by localized regulation of the H+ ATPase activity rather than by heterogeneous localized distribution in the plasma membrane.
Just-in-Time Training for the Use of ICU Nurse Extenders During COVID-19 Pandemic Response
Authors: Duffy Julie R , Vergara Mario A 
Published: September 2021

ABSTRACT
Landstuhl Regional Medical Center’s response to the coronavirus disease 2019 pandemic included a plan to provide just-in-time training for nursing staff and paraprofessionals from throughout the organization in the event that it became overwhelmed with more critically ill patients than the facility was staffed to manage. Training conducted was a combination of online learning from the Society of Critical Care Medicine and the Association of Critical Care Nurses as well as a 2-hour block of hands-on skills. The three competencies for floating staff from Wright’s Method for Competency Assessment were utilized in the training process, allowing trainees to (1) learn to fly, (2) market themselves in a positive way, and (3) understand crisis management options. Quick implementation of the plan led to over 125 nurses and paraprofessionals receiving the education and training in preparation for the pandemic response. The article further discusses training topics covered and the competency expectations for non-critical care nurses trained.
A New World Monkey Resembles Human in Bitter Taste Receptor Evolution and Function via a Single Parallel Amino Acid Substitution
Authors: Yang Hui , Yang Songlin , Fan Fei , Li Yun , Dai Shaoxing , Zhou Xin , Steiner Cynthia C , Coppedge Bretton , Roos Christian , Cai Xianghai , Irwin David M , Shi Peng 
Published: September 2021

AbstractBitter taste receptors serve as a vital component in the defense system against toxin intake by animals, and the family of genes encoding these receptors has been demonstrated, usually by family size variance, to correlate with dietary preference. However, few systematic studies of specific Tas2R to unveil their functional evolution have been conducted. Here, we surveyed Tas2R16 across all major clades of primates and reported a rare case of a convergent change to increase sensitivity to β-glucopyranosides in human and a New World monkey, the white-faced saki. Combining analyses at multiple levels, we demonstrate that a parallel amino acid substitution (K172N) shared by these two species is responsible for this functional convergence of Tas2R16. Considering the specialized feeding preference of the white-faced saki, the K172N change likely played an important adaptive role in its early evolution to avoid potentially toxic cyanogenic glycosides, as suggested for the human TAS2R16 gene.
A Probabilistic Model for Indel Evolution: Differentiating Insertions from Deletions
Authors: Loewenthal Gil , Rapoport Dana , Avram Oren , Moshe Asher , Wygoda Elya , Itzkovitch Alon , Israeli Omer , Azouri Dana , Cartwright Reed A , Mayrose Itay , Pupko Tal 
Published: September 2021

AbstractInsertions and deletions (indels) are common molecular evolutionary events. However, probabilistic models for indel evolution are under-developed due to their computational complexity. Here, we introduce several improvements to indel modeling: 1) While previous models for indel evolution assumed that the rates and length distributions of insertions and deletions are equal, here we propose a richer model that explicitly distinguishes between the two; 2) we introduce numerous summary statistics that allow approximate Bayesian computation-based parameter estimation; 3) we develop a method to correct for biases introduced by alignment programs, when inferring indel parameters from empirical data sets; and 4) using a model-selection scheme, we test whether the richer model better fits biological data compared with the simpler model. Our analyses suggest that both our inference scheme and the model-selection procedure achieve high accuracy on simulated data. We further demonstrate that our proposed richer model better fits a large number of empirical data sets and that, for the majority of these data sets, the deletion rate is higher than the insertion rate.
Towards spruce-type photosystem II: consequences of the loss of light-harvesting proteins LHCB3 and LHCB6 in Arabidopsis
Authors: Ilíková Iva , Ilík Petr , Opatíková Monika , Arshad Rameez , Nosek Lukáš , Karlický Václav , Kučerová Zuzana , Roudnický Pavel , Pospíšil Pavel , Lazár Dušan , Bartoš Jan , Kouřil Roman 
Published: September 2021

Abstract
The largest stable photosystem II (PSII) supercomplex in land plants (C2S2M2) consists of a core complex dimer (C2), two strongly (S2) and two moderately (M2) bound light-harvesting protein (LHCB) trimers attached to C2 via monomeric antenna proteins LHCB4–6. Recently, we have shown that LHCB3 and LHCB6, presumably essential for land plants, are missing in Norway spruce (Picea abies), which results in a unique structure of its C2S2M2 supercomplex. Here, we performed structure–function characterization of PSII supercomplexes in Arabidopsis (Arabidopsis thaliana) mutants lhcb3, lhcb6, and lhcb3 lhcb6 to examine the possibility of the formation of the “spruce-type” PSII supercomplex in angiosperms. Unlike in spruce, in Arabidopsis both LHCB3 and LHCB6 are necessary for stable binding of the M trimer to PSII core. The “spruce-type” PSII supercomplex was observed with low abundance only in the lhcb3 plants and its formation did not require the presence of LHCB4.3, the only LHCB4-type protein in spruce. Electron microscopy analysis of grana membranes revealed that the majority of PSII in lhcb6 and namely in lhcb3 lhcb6 mutants were arranged into C2S2 semi-crystalline arrays, some of which appeared to structurally restrict plastoquinone diffusion. Mutants without LHCB6 were characterized by fast induction of non-photochemical quenching and, on the contrary to the previous lhcb6 study, by only transient slowdown of electron transport between PSII and PSI. We hypothesize that these functional changes, associated with the arrangement of PSII into C2S2 arrays in thylakoids, may be important for the photoprotection of both PSI and PSII upon abrupt high-light exposure.
Phylogenetic Signal and Bias in Paleontology
Authors: Asher Robert J , Smith Martin R 
Published: September 2021

AbstractAn unprecedented amount of evidence now illuminates the phylogeny of living mammals and birds on the Tree of Life. We use this tree to measure the phylogenetic value of data typically used in paleontology (bones and teeth) from six data sets derived from five published studies. We ask three interrelated questions: 1) Can these data adequately reconstruct known parts of the Tree of Life? 2) Is accuracy generally similar for studies using morphology, or do some morphological data sets perform better than others? 3) Does the loss of non-fossilizable data cause taxa to occur in misleadingly basal positions? Adding morphology to DNA data sets usually increases congruence of resulting topologies to the well-corroborated tree, but this varies among morphological data sets. Extant taxa with a high proportion of missing morphological characters can greatly reduce phylogenetic resolution when analyzed together with fossils. Attempts to ameliorate this by deleting extant taxa missing morphology are prone to decreased accuracy due to long-branch artifacts. We find no evidence that fossilization causes extinct taxa to incorrectly appear at or near topologically basal branches. Morphology comprises the evidence held in common by living taxa and fossils, and phylogenetic analysis of fossils greatly benefits from inclusion of molecular and morphological data sampled for living taxa, whatever methods are used for phylogeny estimation. [Concatenation; fossilization; morphology; parsimony; systematics; taphonomy; total-evidence.]
Using Accreditation to Transform Diversity, Equity, and Inclusion Efforts Into Diversity, Equity, and Inclusion Systems
Authors: Nora Lois Margaret 
Published: September 2021

The Liaison Committee on Medical Education accreditation process is an important component of professional regulation and is used by medical schools to strengthen their medical education programs. Accreditation-related consultations with schools often include a review of relevant documents, stakeholder interviews, and mock site visits. A review by the author of this commentary of these consultations at 17 schools showed variability in how information regarding diversity, equity, and inclusion (DEI) was incorporated and discussed in accreditation-related materials and interviews.
At all schools, DEI information emerged in materials related to the accreditation standards that specifically inquire into DEI. However, at some schools, DEI emerged more broadly across a variety of standards. These differences suggest that considering the totality of the Liaison Committee on Medical Education standards and elements may be a useful tool for enabling schools to analyze and describe their DEI efforts, consider additional ways to engage in continuous quality improvement related to DEI, and achieve institutional DEI goals.
In addition, a small number of the reviewed schools appeared to have had particular success in meeting institutional DEI goals. An appreciative inquiry-informed review suggested that these exemplar schools had both area-specific and cross-functional systems focused on achieving DEI goals. In addition, senior leadership demonstrated a commitment to DEI, DEI champions were empowered, and leaders displayed legislative-style and systems leadership skills. Schools that nurture these characteristics may be better positioned to advance DEI. Scholarly evaluation of these observations is necessary.
Methamphetamines and Acetabular Reoperation Rates: Poor Outcomes From the Front Lines
Authors: Zusman Natalie L. , Woelber Erik , McKibben Natasha S. , Gallacher David M. , Thompson Austin R. , Friess Darin M. , Working Zachary M. 
Published: September 2021

Objectives:
To compare acetabular fracture reoperation rates within 1 year of surgery in methamphetamine (“meth”) abusers and abstainers.

Design:
Retrospective database analysis.

Setting:
Level 1 academic trauma facility, 2008–2018.

Patients/Participants:
Three hundred seventy-one patients who underwent unilateral traumatic acetabular open reduction internal fixation during the study period, 36 of whom abused methamphetamines through self-report or toxicology. One hundred four were excluded for indeterminate abuse histories.

Intervention:
Open reduction internal fixation.

Main Outcome Measurements:
Reoperation resulting from major surgical complications, including hematoma, seroma, deep wound infection, failure of fixation, or arthrosis with conversion to arthroplasty.

Results:
More than 10% of our cohort used meth, representing patients who were a mean 8 years younger and sustained a higher rate of high-energy mechanisms than sober peers. Meth abusers had a greater than 2-fold reoperation rate at 90 days and 1 year compared with abstainers (17% vs. 7% and 25% vs. 11%, respectively). The adjusted odds ratio of 1-year reoperation in meth users was 3.2 (confidence interval 1.2–8.5, P = 0.03). The adjusted 1-year survival of native hip after acetabular fractures in meth users approaches 55%.

Conclusions:
Methamphetamine use is a nonmodifiable factor associated with a 3-fold increase in adjusted odds for 1-year reoperation after surgical fixation of acetabular fractures.

Level of Evidence:
Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.
Assessing Readiness for Telehealth in Rural Communities
Authors: Bowen Annie 
Published: September 2021

ABSTRACT:
As rural communities often lack access to quality, affordable healthcare, telehealth has the potential to reduce healthcare gaps for rural residents. Qualitative research with interpretive phenomenology through use of the Health Promotion Model and Appreciative Inquiry was used to create and pilot a telehealth survey about residents' readiness in using telehealth. The survey of three rural counties in southern Ohio identified three themes: a knowledge gap related to telehealth; infrastructure; and a desire for easier access to healthcare. Telehealth can be considered a viable, cost-effective alternative for rural populations.
Combined DNA repair defects in testicular metastasis from prostate cancer sensitize to immune checkpoint blockade
Authors: Vlachostergios Panagiotis J. 
Published: September 2021

Abstract
Testicular metastasis in prostate cancer is uncommon and may be a culprit of widespread disease which portends a worse prognosis. Little is known about the molecular biology of metastases to the testicles and whether there is any role for targeted therapeutics. Here we report a case of prostate cancer recurring with testicular and lung metastases. Targeted sequencing of the patient's left testicular tumor after orchiectomy disclosed inactivating mutations in the CDK12 and ARID1A genes, and MSH2 and MSH6 loss resulting in high microsatellite instability and high tumor mutational burden. The patient experienced a complete radiographic and prostate-specific antigen response at 12 weeks of PD-1 immune checkpoint blockade with pembrolizumab and continues uneventfully on treatment. Molecular characterization of this rare phenotypic subtype of prostate cancer in larger studies may help deliver precision therapies with the potential to improve outcomes.