bluuebunny/crossref_metadata_2025 huggingface dataset:
Computational support, not primacy, distinguishes compensatory memory reorganization in epilepsy
Authors: Tracy Joseph I , Chaudhary Kapil , Modi Shilpi , Crow Andrew , Kumar Ashith , Weinstein David , Sperling Michael R
Published: March 2021

Temporal lobe epilepsy is associated with impairment in episodic memory. A substantial subgroup, however, is able to maintain adequate memory despite temporal lobe pathology. Missing from prior work in cognitive reorganization is a direct comparison of temporal lobe epilepsy patients with intact status with those who are memory impaired. Little is known about the regional activations, functional connectivities and/or network reconfigurations that implement changes in primary computations or support functions that drive adaptive plasticity and compensated memory. We utilized task functional MRI on 54 unilateral temporal lobe epilepsy patients and 24 matched healthy controls during the performance of a paired-associate memory task to address three questions: (i) which regions implement paired-associate memory in temporal lobe epilepsy, and do they vary as a function of good versus poor performance, (ii) is there unique functional connectivity present during memory encoding that accounts for intact status by preservation of primary memory computations or the supportive computations that allow for intact memory responses and (iii) what features during memory encoding are most distinctive: is it the magnitude and location of regional activations, or the presence of enhanced functional connections to key structures such as the hippocampus? The study revealed non-dominant hemisphere regions (right posterior temporal regions) involving both increased regional activity and increased modulatory communication with the hippocampi as most important to intact memory in left temporal lobe epilepsy compared to impaired status. The profile involved areas that are neither contralateral homologues to left hemisphere memory areas, nor regions traditionally considered computationally primary for episodic memory. None of these areas of increased activation or functional connectivity were associated with advantaged memory in healthy controls. Our emphasis on different performance levels yielded insight into two forms of cognitive reorganization: computational primacy, where left temporal lobe epilepsy showed little change relative to healthy controls, and computational support where intact left temporal lobe epilepsy patients showed adaptive abnormalities. The analyses isolated the unique regional activations and mediating functional connectivity that implements truly compensatory reorganization in left temporal lobe epilepsy. The results provided a new perspective on memory deficits by making clear that they arise not just from the knockout of a functional hub, but from the failure to instantiate a complex set of reorganization responses. Such responses provided the computational support to ensure successful memory. We demonstrated that by keeping track of performance levels, we can increase understanding of adaptive brain responses and neuroplasticity in epilepsy.
T1-Weighted/T2-Weighted Ratio Mapping at 5 Months Captures Individual Differences in Behavioral Development and Differentiates Infants at Familial Risk for Autism from Controls
Authors: Darki Fahimeh , Nyström Pär , McAlonan Grainne , Bölte Sven , Falck-Ytter Terje
Published: March 2021

Identifying structural measures that capture early brain development and are sensitive to individual differences in behavior is a priority in developmental neuroscience, with potential implications for our understanding of both typical and atypical populations. T1-weighted/T2-weighted (T1w/T2w) ratio mapping, which previously has been linked to myelination, represents an interesting candidate measure in this respect, as an accessible measure from standard magnetic resonance imaging (MRI) sequences. Yet, its value as an early infancy measure remains largely unexplored. Here, we compared T1w/T2w ratio in 5-month-old infants at familial risk (n = 27) for autism spectrum disorder (ASD) to those without elevated autism risk (n = 16). We found lower T1w/T2w ratio in infants at high risk for ASD within widely distributed regions, spanning both white and gray matter. In regions differing between groups, higher T1w/T2w ratio was robustly associated with higher age at scan (range: ~ 4–6.5 months), implying sensitivity to maturation at short developmental timescales. Further, higher T1w/T2w ratio within these regions was associated with higher scores on measures of concurrent developmental level. These findings suggest that T1w/T2w ratio is a developmentally sensitive measure that should be explored further in future studies of both typical and atypical infant populations.
The Integral Chow Ring of the Stack of 1-Pointed Hyperelliptic Curves
Authors: Pernice Michele
Published: March 2021

In this paper we give a complete description of the integral Chow ring of the stack $\mathscr{H}_{g,1}$ of 1-pointed hyperelliptic curves, lifting relations and generators from the Chow ring of $\mathscr{H}_g$. We also give a geometric interpretation for the generators.
Finding commonalities in rare diseases through the undiagnosed diseases network
Authors: Yates Josephine , Gutiérrez-Sacristán Alba , Jouhet Vianney , LeBlanc Kimberly , Esteves Cecilia ,   Undiagnosed Diseases Network, DeSain Thomas N , Benik Nick , Stedman Jason , Palmer Nathan , Mellon Guillaume , Kohane Isaac , Avillach Paul
Published: March 2021

Objective

When studying any specific rare disease, heterogeneity and scarcity of affected individuals has historically hindered investigators from discerning on what to focus to understand and diagnose a disease. New nongenomic methodologies must be developed that identify similarities in seemingly dissimilar conditions.

Materials and Methods

This observational study analyzes 1042 patients from the Undiagnosed Diseases Network (2015-2019), a multicenter, nationwide research study using phenotypic data annotated by specialized staff using Human Phenotype Ontology terms. We used Louvain community detection to cluster patients linked by Jaccard pairwise similarity and 2 support vector classifier to assign new cases. We further validated the clusters’ most representative comorbidities using a national claims database (67 million patients).

Results

Patients were divided into 2 groups: those with symptom onset before 18 years of age (n = 810) and at 18 years of age or older (n = 232) (average symptom onset age: 10 [interquartile range, 0-14] years). For 810 pediatric patients, we identified 4 statistically significant clusters. Two clusters were characterized by growth disorders, and developmental delay enriched for hypotonia presented a higher likelihood of diagnosis. Support vector classifier showed 0.89 balanced accuracy (0.83 for Human Phenotype Ontology terms only) on test data.

Discussions

To set the framework for future discovery, we chose as our endpoint the successful grouping of patients by phenotypic similarity and provide a classification tool to assign new patients to those clusters.

Conclusion

This study shows that despite the scarcity and heterogeneity of patients, we can still find commonalities that can potentially be harnessed to uncover new insights and targets for therapy.
Comparison and interpretability of machine learning models to predict severity of chest injury
Authors: Kulshrestha Sujay , Dligach Dmitriy , Joyce Cara , Gonzalez Richard , O’Rourke Ann P , Glazer Joshua M , Stey Anne , Kruser Jacqueline M , Churpek Matthew M , Afshar Majid
Published: March 2021

Objective

Trauma quality improvement programs and registries improve care and outcomes for injured patients. Designated trauma centers calculate injury scores using dedicated trauma registrars; however, many injuries arrive at nontrauma centers, leaving a substantial amount of data uncaptured. We propose automated methods to identify severe chest injury using machine learning (ML) and natural language processing (NLP) methods from the electronic health record (EHR) for quality reporting.

Materials and Methods

A level I trauma center was queried for patients presenting after injury between 2014 and 2018. Prediction modeling was performed to classify severe chest injury using a reference dataset labeled by certified registrars. Clinical documents from trauma encounters were processed into concept unique identifiers for inputs to ML models: logistic regression with elastic net (EN) regularization, extreme gradient boosted (XGB) machines, and convolutional neural networks (CNN). The optimal model was identified by examining predictive and face validity metrics using global explanations.

Results

Of 8952 encounters, 542 (6.1%) had a severe chest injury. CNN and EN had the highest discrimination, with an area under the receiver operating characteristic curve of 0.93 and calibration slopes between 0.88 and 0.97. CNN had better performance across risk thresholds with fewer discordant cases. Examination of global explanations demonstrated the CNN model had better face validity, with top features including “contusion of lung” and “hemopneumothorax.”

Discussion

The CNN model featured optimal discrimination, calibration, and clinically relevant features selected.

Conclusion

NLP and ML methods to populate trauma registries for quality analyses are feasible.
Weapons of War, Tools of Justice
Authors: Freeman Lindsay
Published: March 2021

Just as the internal combustion engine revolutionized warfare in the early twentieth century, artificial intelligence is shaping warfare in the Digital Age. Fuelled by data rather than gasoline, artificial intelligence (AI) derivative technologies are driven by innovation in both the military and civilian sectors. Today’s defence scientists and engineers, like their predecessors, develop physical equipment and weapons, but instead of simply making them more powerful and lethal, they are also making them more intelligent and connected. As AI is increasingly integrated into military tools, the digital footprints of modern battlefields will grow exponentially, generating new sources and types of data that will fundamentally alter war crimes investigations. This article examines emerging military applications of AI in order to identify what opportunities and challenges these tools might offer international criminal investigators. Will more sensors and smart devices on the battlefield benefit or burden the investigation of war crimes? Moreover, will intelligent machines add to the fog of war or help us see through it?
The Notion of Undertaking
Authors: Kreuschitz Viktor , Nehl Hanns Peter
Published: March 2021

This chapter focuses on the notion of undertaking. The concept of undertaking is based on that of economic activity. Essentially this regards an activity that is subject to market-based competition, or that is at least potentially capable of being provided in competition. There is no single set of criteria to determine this. Instead, a range of different criteria has emerged to determine whether economic activity is involved in particular sectors such as the exercise of public authority of the provision of social security, education, or healthcare. Often a number of such factors have to be weighed. Increasingly there are different activities such as building and exploiting airport facilities, which are economically linked, regarded jointly as economic activities which come within the field of State aid rules.
Distortion of Competition and Effect on Trade between EU Member States
Authors: Kreuschitz Viktor , Nehl Hanns Peter
Published: March 2021

This chapter discusses the distortion of competition and the effect on inter-Member State trade conditions. Article 107(1) TFEU provides that State aid is prohibited if two complementary conditions are fulfilled, namely if the State measure in issue distorts or threatens to distort competition and affects trade between Member States. The common trend within the EU Courts' case law is that no actual assessment of these criteria is required. In order to establish that competition is distorted and trade between Member States affected, it is not necessary to define the market or to carry out a thorough investigation as regards the impact that the contested measure might have upon the economic operators involved. All that matters is whether an advantage is granted to a market operator, at the detriment of another which will, as a matter of fact, encroach upon the good functioning of competition and trade between Member States.
WTO Subsidy Laws: The International Regulation of State Aid
Authors: Kreuschitz Viktor , Nehl Hanns Peter
Published: March 2021

This chapter focuses on the concepts of subsidy control under World Trade Organization (WTO), prohibiting certain types of subsidies that might have a harmful effect on economic activity in other WTO members. A major innovation of the Agreement on Subsidies and Countervailing Measures (SCM Agreement) was the classification of subsidies into three categories, often referred to as ‘red light’, ‘yellow light’, and ‘green light’. ‘Red light’ subsidies are prohibited per se, with no need to actually prove any adverse effect. The ‘yellow light’ or ‘actionable subsidies’ are not prohibited, but may be challenged only if they cause ‘adverse effects’. Under the ‘green light’ category, certain selected types of subsidies were non-actionable even if they were specific and caused one of the harms listed in Articles 5 and 6 of the SCM Agreement.
Damages Actions in the Enforcement of EU Competition Law
Authors: Rodger Barry , Ferro Miguel Sousa , Marcos Francisco
Published: March 2021

This chapter sets the context for the EU’s Antitrust Damages Directive of 2014 in order to understand its significance and potential impact. It first provides a historical background to EU competition law before discussing its public enforcement, focusing on the traditional role of the European Commission in enforcing the EU competition law rules. It then considers developments in EU law private enforcement, citing the role of the Court of Justice of the European Union (CJEU) and European Commission in seeking to promote and facilitate private enforcement, particularly damages actions. It also examines the experience of damages actions in the EU, the issue of collective redress, the US antitrust private enforcement context and experience, and EU private international law rules and their significance for raising damages actions across the Member States’ courts. The chapter concludes with an assessment of the development of competition law damages actions under EU law.
Germany
Authors: Kersting Christian
Published: March 2021

This chapter focuses on the transposition of the Antitrust Damages Directive in Germany. It first provides an overview of the transposition procedure, focusing on the role of the Federal Ministry for Economic Affairs and Energy in drafting the legislation to transpose directive 2014/104/EU into German law. It then considers the scope of the German regime regarding cartel damages and how it was incorporated into the German Act against Restraints of Competition (Gesetz gegen Wettbewerbsbeschränkungen, GWB) for exclusive application to competition law infringements. It also examines specific issues that arose during the transposition, including those relating to the directive’s definitions, the binding force of decisions of other Member States, parent company liability for fines, group liability for damages, the presumption and quantification of damages, joint and several liability and recovery of contribution from co-infringers, the liability of immunity recipients, the liability of small and medium-sized enterprises, disclosure of evidence, and settlements.
Greece
Authors: Ioannidou Maria
Published: March 2021

This chapter focuses on the transposition of the Antitrust Damages Directive in Greece. It begins with a discussion of the transposition procedure, focusing on the Greek private competition law enforcement landscape. In particular, it considers the country’s Damages Act transposing the Damages Directive in the Greek legal order, adopted by Parliament (plenary session) on 14 March 2018, and the level of private competition litigation in Greece. The factors that partly explain the delay in the transposition of the Damages Directive by the Greek legislature are also examined. The chapter goes on to describe the substantive and temporal scope of the Damages Act as well as specific issues that arose during the transposition, including those relating to limitation periods, the binding force of decisions of other Member States, joint and several liability, parent company liability, presumption and quantification of damages by cartels, access to evidence, collective redress, and consensual dispute resolution.
Parties and Group Litigation
Authors: Brealey Mark , George Kyla
Published: March 2021

This chapter discusses the special considerations that apply to identifying the relevant parties in competition litigation as well as the way that claimants may group together to commence collective proceedings. It first explains private actions in the High Court, with emphasis on the nature of claimant and defendant. It considers the category of claimant under Articles 101 and 102 of the Treaty on the Functioning of the European Union (TFEU) and under the Competition Act 1998, along with the concept of ‘undertaking’, parent companies, subsidiary companies, and sister companies in relation to the defendants. The chapter also examines representative actions in the High Court during group litigation, collective proceedings in the Competition Appeal Tribunal (CAT), and settlement of collective proceedings. Different types of collective settlement are highlighted.
Interim Remedies
Authors: Brealey Mark , George Kyla
Published: March 2021

This chapter considers interim remedies that are available in the High Court and the Competition Appeal Tribunal (CAT), with a focus on interim injunctions, interim payments, security for costs, and stay of proceedings. It begins with a discussion of the High Court’s jurisdiction to grant interim or interlocutory injunctions, from interim injunctions in general to mandatory injunctions, quia timet injunctions, freezing injunctions, search orders, anti-suit injunctions, and interim injunctions in aid of foreign proceedings. It also describes the practice and procedure to be followed on an application for an interim injunction, before analysing interim payments, security for costs, and stay of proceedings in greater detail. Finally, it examines interim remedies in the CAT, taking into account a range of issues relating to interim orders in appeals, interim injunctions in private actions, interim payment, security for costs, and stay of proceedings.
Factual Evidence
Authors: Brealey Mark , George Kyla
Published: March 2021

This chapter examines the use of factual evidence in cases involving a breach of competition rules. Potential sources of factual evidence range from the evidence of witnesses to statements of case and application notices supported by a statement of truth, contemporaneous documents, affidavits, and the admissions of other parties to the alleged anti-competitive agreement or concerted practice. The chapter first provides an overview of factual evidence used in High Court proceedings, including witness evidence and sources other than witness statements, as well as the formal requirements for witness statements. It then explores issues such as confidentiality, hearsay notices, witness summaries and summons, video links, depositions, and letters of request. It also discusses the use of factual evidence in Competition Appeal Tribunal (CAT) proceedings, focusing on issues such as admissibility and the admission or exclusion of fresh evidence.
Appeals to the Court of Appeal
Authors: Brealey Mark , George Kyla
Published: March 2021

This chapter discusses the legal principles applicable to appeals from the High Court to the Court of Appeal and appeals from the Competition Appeal Tribunal (CAT) to the Court of Appeal, as well as the extent to which fresh evidence may be adduced in the Court of Appeal. It first considers the general rules about appeals from the High Court to the Court of Appeal, along with the statutory basis of the Court of Appeal’s power to hear appeals from the High Court. Other issues such as appellant’s notice, respondent’s statement of objection, appeals against case management decisions, and grounds for appeal are also examined. The chapter proceeds by analysing the procedure and grounds for appeal from the CAT to the Court of Appeal, before concluding with an assessment of the conditions that must be met to justify the reception of fresh evidence or a new trial in the Court of Appeal.
Transnationalization of Security
Authors: Altwicker Tilmann
Published: March 2021

This chapter explains how ‘security’ is in a process of ‘transnationalization’, namely it is becoming a cross-border issue. Thus, in the twenty-first century, the primary examples of sources of ‘insecurity’—such as transnational terrorism, transnational crime, mass migration, cross-border environmental hazards, and problems of energy security—are no longer perceived as ‘domestic affairs’. The ensuing processes of transnationalization are naturally also processes of transnationalization of and by international law. The chapter then analyses three major framings used for the transnationalization of security, namely, ‘war’, ‘crime’, and ‘risk’ and their conceptualization in international law. It discusses the two major challenges faced in the transnationalization of security by international law: the problem of jurisdictional dysfunctionalities under international law and the problem of applying international human rights law to transnational security cases. Finally, the chapter evaluates the contribution of international law to the process of the transnationalization of security.
Armed Conflicts, International Law, and Global Security
Authors: Kellenberger Jakob
Published: March 2021

This chapter addresses the relationship between armed conflicts, international law, and global security. While today protracted non-international armed conflicts are the prevalent type of armed conflict, international armed conflicts seem likely to again become a major threat to global security in the future. This hypothesis is based, amongst other factors, on recent military confrontations involving a number of States in Syria, the Russian involvement in Crimea, US tensions with Iran and North Korea, and broader regional tensions in the South China Sea. The chapter provides an overview of the interrelation between armed conflicts and other threats to global security before looking at armed conflicts currently raging in various geographical regions of the world. It then considers the adequacy and effectiveness of the existing international regulatory framework governing armed conflicts in light of the broader challenges facing the contemporary world order.
Nuclear Non-proliferation and Disarmament under International Law
Authors: Asada Masahiko
Published: March 2021

This chapter traces the history of attempts and achievements in regulating the use of nuclear energy and material, focusing on nuclear non-proliferation and disarmament. Ever since its invention, the nuclear weapon has occupied a special place in the global security order, both militarily and politically, due to its extraordinary destructive power. This picture is further complicated by the fact that nuclear material has both military and civilian uses. Civilian use of nuclear material includes generating electricity through nuclear reactors. Nuclear material also has medical, agricultural, and other peaceful applications, such as its use in the treatment of cancer. The chapter assesses in detail such treaties as the Partial Test Ban Treaty, the Treaty on the Non-Proliferation of Nuclear Weapons, the Comprehensive Nuclear-Test-Ban Treaty, and the Treaty on the Prohibition of Nuclear Weapons. It also looks at the current challenges involving the Democratic People’s Republic of Korea and Iran.
National Security, Surveillance, and Human Rights
Authors: Christakis Théodore , Bouslimani Katia
Published: March 2021

This chapter reflects on the relationship between national security, surveillance, and human rights. The possibility to adopt restrictive measures in case of threats to national security is an essential component of the international legal system and one of those ‘adjustment variables’ that allow international human rights law to accommodate and ascertain its social functions. The abuse of these mechanisms, however, is also a major threat to the legal order, judicial security, and the rule of law. Domestic rulers and security agencies have often used ‘national security’ as a pretext to violate human rights and fundamental freedoms; to monitor political opponents; to conceal embarrassing or illegal behaviour; to bypass investigation by independent and democratic bodies; or to suppress political and social unrest. In a democracy, surveillance must be balanced with public liberties, and especially with privacy. The chapter looks at the case law of the European Court of Human Rights on national surveillance. It presents the three main criteria used by the Court to assess the compatibility of surveillance laws with the European Convention of Human Rights.
Peace Diplomacy and Conflict Prevention
Authors: Trapp Kimberley N. , Urs Priya
Published: March 2021

United Nations (UN) Secretary-General Boutros Boutros-Ghali’s ‘Agenda for Peace’ was the first comprehensive UN engagement with conflict prevention and peace following the end of the Cold War. The Secretary-General divided his agenda into preventive diplomacy, peacemaking, and peacekeeping. But given the interconnectedness of global challenges, and the changing face of threats to international peace and security and armed conflict, a comprehensive approach calls for a blurring of the lines between these temporally defined elements of the architecture of peace. In particular disputes, the toolkit deployed in respect of one aspect of maintaining or securing peace may well be relevant or even critical in respect of another. Flexibility and responsiveness to the particular context is essential. While it remains true that international efforts towards peace and security operate on the sequential conflict cycle paradigm suggested by the Secretary-General, stakeholders increasingly seek to ‘bridge the divides that beset this discussion, between security and development, between crisis response and capacity building’ in order to ‘encompass our new conception of violence in a variety of environments’.
The Law of Reinsurance
Authors: Edelman Colin , Burns Andrew
Published: March 2021

This guide to reinsurance law is an easy-to-read specialist reference focusing solely on reinsurance. Every aspect of the core and subsidiary principles of reinsurance law are covered beginning with an investigation of the definition, purpose, and types of reinsurance. Guidance is given on contractual principles and terms in the reinsurance context, obligations, rights and liabilities of the reinsurer, and the choice of law. With usability and practicality in mind, a number of aspects have been further developed in this edition. There is an increased depth of analysis in addressing ‘Follow the Settlements’, incorporation, non-disclosure, misrepresentation, and the role of good faith in reinsurance contracts. The new edition also addresses the consequences of the Insurance Act 2015 and recent cases on reinsurance arbitration—particularly the appointment of arbitrators and their duties. This book is both practical and authoritative, and is successful in isolating the key issues in reinsurance law to provide an easy and reliable reference source. It is a must-have work for all reinsurance practitioners.
Denying Liability
Authors: Edelman Colin , Burns Andrew
Published: March 2021

This chapter focuses on the duty of fair presentation and the duty of utmost good faith. Before any reinsurance contract is concluded, the reinsured has to make a fair presentation of the risk to the reinsurer. A reinsured must disclose every material circumstance which the reinsured knows or ought to know or, at least, circumstances which would put a prudent reinsurer on notice that it needs to make further enquiries. That disclosure must be in a manner which would be reasonably clear and accessible to a prudent underwriter. A failure to give a fair presentation, if established, may entitle the reinsurer to avoid the contract without returning the premium where the reinsured has been deliberate or reckless or with a return of premium if the insurer would not have entered into the contract on any terms had the information provided been accurate and complete or where the parties have contracted out of the regime imposed by the Insurance Act 2015. The genesis of the duty of utmost good faith was a protection for insurers and reinsurers because the proposer knew everything about the risk and the underwriter knew nothing.
The impact of slow stomatal kinetics on photosynthesis and water use efficiency under fluctuating light
Authors: Eyland David , van Wesemael Jelle , Lawson Tracy , Carpentier Sebastien
Published: March 2021

Dynamic light conditions require continuous adjustments of stomatal aperture. The kinetics of stomatal conductance (gs) is hypothesized to be key to plant productivity and water use efficiency (WUE). Using step-changes in light intensity, we studied the diversity of light-induced gs kinetics in relation to stomatal anatomy in five banana genotypes (Musa spp.) and modeled the impact of both diffusional and biochemical limitations on photosynthesis (A). The dominant A limiting factor was the diffusional limitation associated with gs kinetics. All genotypes exhibited a strong limitation of A by gs, indicating a priority for water saving. Moreover, significant genotypic differences in gs kinetics and gs limitations of A were observed. For two contrasting genotypes, the impact of differential gs kinetics was further investigated under realistic diurnally fluctuating light conditions and at the whole-plant level. Genotype-specific stomatal kinetics observed at the leaf level was corroborated at whole-plant level by transpiration dynamics, validating that genotype-specific responses are still maintained despite differences in gs control at different locations in the leaf and across leaves. However, under diurnally fluctuating light conditions the impact of gs speediness on A and intrinsic (iWUE) depended on time of day. During the afternoon there was a setback in kinetics: absolute gs and gs responses to light were damped, strongly limiting A and impacting diurnal iWUE. We conclude the impact of differential gs kinetics depended on target light intensity, magnitude of change, gs prior to the change in light intensity, and particularly time of day.
Using Weather, Lunar Cycles, and Time of Year to Predict Trauma Incidents in an Urban, Level I Pediatric Trauma Center
Authors: Budziszewski Ross , Nanassy Autumn , Lindholm Erika , Grewal Harsh , Prasad Rajeev
Published: March 2021

Background:

Trauma patterns in adults are influenced by weather conditions, lunar phases, and time of year. The extent to which these factors contribute to pediatric trauma is unclear.

Objective:

The present study aimed to review patients from a single Level I pediatric trauma center to determine the influence of weather, the lunar cycle, and time of year on trauma activity.

Methods:

A retrospective review of trauma activations (n = 1,932) was conducted from 2015 to 2017. Injury type and general demographics were collected. Weather data and lunar cycles were derived from historical databases.

Results:

Days with no precipitation increased the total number of injuries of all types compared with those with precipitation (p < .001). Blunt and penetrating injuries were more likely to occur during full moons, whereas burn injuries were significantly higher during new moons (p < .001). Blunt trauma was significantly higher in September than all other months, F(11, 1,921) = 4.25, p < .001, whereas January had a significantly higher number of burns than all other months (p < .001).

Conclusions:

Pediatric trauma trends associated with external factors such as weather, lunar cycles, and time of year can inform hospital staffing decisions in anticipation of likely injuries and help direct injury prevention efforts.
GnRH analogue followed by surgery in treatment of vaginal leiomyoma-a case report
Authors: Liu Yinxia , Wang Xiaoli , He Yuedong
Published: March 2021

Rationale:

Vaginal leiomyoma is a rare type of leiomyoma that occurs on the wall of vagina. Treatment for vaginal leiomyoma is varied and is based on the location and size of the leiomyoma.

Patient concerns:

In this case, a 24-year-old newly married Chinese woman complained of dyspareunia. The physical examination revealed a solid mass on the anterior wall of vagina. It almost filled up the whole vagina cavity.

Diagnosis:

Transvaginal ultrasound showed a tumor on the anterior wall of vagina. Pelvic computed tomography (CT) and magnetic resonance imaging (MRI) also confirmed the tumor on vaginal wall. Fine needle aspiration biopsy confirmed fibrous and smooth muscle tissue in the tumor, and immunohistochemical examination found the estrogen receptor (ER) and progesterone receptor (PR) were positive.

Interventions:

6 courses of gonadotropin-releasing hormone (GnRH) analogue were given before the patient underwent complete surgical resection through vagina.

Outcome:

No postoperative complications occurred, and the patient was discharged from the hospital 3 days after surgery. Follow-up after 3 months revealed negative symptoms of genitourinary system. No sign of recurrence was found.

Conclusion:

In this case, vaginal leiomyoma was diagnosed with help of imagological examinations like ultrasound, CT, and MRI, as well as pathological examination like fine needle aspiration biopsy. Preoperative GnRH analogue treatment can ensure smooth surgical procedure, and reduce blood loss during surgery.
Altererythrobacter muriae sp. nov., isolated from hypersaline Añana Salt Valley spring water, a continental thalassohaline-type solar saltern
Authors: Azpiazu-Muniozguren Maia , Martinez-Ballesteros Ilargi , Gamboa Javier , Seoane Sergio , Alonso Rodrigo , Laorden Lorena , Garaizar Javier , Bikandi Joseba
Published: March 2021

A novel salt-tolerant alpha-proteobacterium, designated SALINAS58T, was isolated from Santa Engracia hypersaline spring water in the Añana Salt Valley, Álava, Spain. The isolate was Gram-negative, aerobic, non-motile, catalase-positive, oxidase-negative, rod-shaped and formed orange colonies on marine agar. Optimal growth was observed at pH 6.0–6.5, at 30 °C and in the presence of 1% (w/v) NaCl. The main cellular fatty acids (>20%) were summed feature 8 (C18 : 1
ω7c and/or C18 : 1
ω6c) and summed feature 3 (C16 : 1
ω7c and/or C16 : 1
ω6c). The major respiratory quinone was ubiquinone Q-10 and the major polar lipids detected were diphosphatidylglycerol, phosphatidylethanolamine, phosphatidilglycerol, four unidentified glycolipids and one unidentified phospholipid. Strain SALINAS58T had the highest 16S rRNA gene sequence similarity to

Altererythrobacter marensis

MSW-14T (96.6%),

Altererythrobacter aquaemixtae

JSSK-8T (96.5%) and

Pontixanthobacter luteolus

SW-109T (96.5%) followed by

Altererythrobacter atlanticus

26DY36T (96.4%). Results of the phylogenetic analysis, based on 16S rRNA gene sequences, and phylogenetic approaches based on whole genome nucleotide differences, showed that strain SALINAS58T could be distinguished from recognized species of the genus

Altererythrobacter

. The genomic DNA G+C content was 61.4 mol%. Digital DNA–DNA hybridization, average nucleotide identity and average aminoacid identity values between the genome of strain SALINAS58T and

A. marensis

MSW-14T were 18.4, 73.1 and 68.1%, respectively. Based on data from this polyphasic characterization, strain SALINAS58T (=CECT 30029T=LMG 31726T) is considered to be classified as representing a novel species in the genus

Altererythrobacter

, for which the name Altererythrobacter muriae sp. nov. is proposed.
HiSpike: A high-throughput cost effective sequencing method for the SARS-CoV-2 spike gene
Authors: Fass Ephraim , Valenci Gal Zizelski , Rubinstein Mor , Freidlin Paul J , Rosencwaig Shira , Kutikov Inna , Werner Robert , Ben-Tovim Nofar , Bucris Efrat , Zuckerman Neta S , Mor Orna , Mendelson Ella , Dveyrin Zeev , Rorman Efrat , Nissan Israel
Published: March 2021

The changing nature of the corona virus of the SARS-CoV-2 pandemic poses unprecedented challenges to the world’s health systems. New and virulent emerging spike gene variants, such as the UK 20I/501Y.V1 and South African 20H/501Y.V2, could jeopardize global efforts to produce immunity and reduce mortality. These challenges require effective real-time genomic surveillance solutions that the medical community can quickly adopt. The SARS-CoV-2 spike protein mediates host receptor recognition and entry into the cell and therefore, it is most susceptible to generation of variants with increased transmissibility and pathogenicity. The spike protein is also the primary target of neutralizing antibodies in COVID-19 patients and the most common antigen for induction of effective vaccine immunity. Therefore, tight monitoring of the spike protein gene variants is key to mitigating COVID-19 spread and vaccine escape mutants. Currently, the ARTIC method for SARS-CoV-2 whole genome sequencing is applied worldwide. However, this method commonly requires more than 96 hours (4-5 days) from start to finish and at present high sample sequence demands, sequencing resources are quickly exhausted. In this work, we present HiSpike, a method for high-throughput targeted next generation sequencing (NGS) of the spike gene. This simple three-step method can be completed in less than 30 hours and can sequence 10-fold more samples compared to the conventional ARTIC method and at a fraction of the cost. HiSpike was proven valid, and has identified, at high quality, multiple spike variants from real-time field samples, such as the UK and the South African variants. This method will certainly be effective in discovering future spike mutations. Therefore, running HiSpike for full sequencing of the spike gene of all positive SARS-CoV-2 samples could be considered for near real-time detection of known and emerging spike mutations as they evolve. HiSpike provides affordable sequencing options to help laboratories conserve resources, hence it provides a tool for widespread monitoring, that can support critical knowledge-based decisions.
Subjective sleep quality and objective sleep physiology in migraineurs: a meta-analysis
Authors: Stanyer E.C. , Creeney H. , Nesbitt A.D. , Holland P. R. , Hoffmann J.
Published: March 2021

Objectives

Sleep disturbance is often associated with migraine. However, there is a paucity of research investigating objective and subjective measures of sleep in migraineurs. This meta-analysis aims to determine whether there are differences in subjective sleep quality measured using the Pittsburgh Sleep Quality Index (PSQI) and objective sleep physiology measured using polysomnography between adult and pediatric migraineurs, and healthy controls.

Methods

A systematic search of five databases was conducted to find case-controlled studies which measured polysomnography and/or PSQI in migraineurs. Effect sizes (Hedges’ g) were entered into a random effects model meta-analysis.

Results

32 separate studies were eligible. Overall, adult migraineurs had higher PSQI scores than healthy controls (g = 0.75, p < .001). This effect was larger in chronic than episodic migraineurs (g = 1.03, p < .001, g = 0.63, p < .001 respectively). For polysomnographic studies, adult and pediatric migraineurs displayed a lower percentage of REM sleep (g = −0.22, p = 0.017, g = −0.71, p = 0.025 respectively) than healthy controls. Pediatric migraineurs also displayed less total sleep time (g = −1.37, p = 0.039), more wake (g = 0.52, p < .001) and shorter sleep onset latency (g = −0.37, p < .001) than healthy controls.

Conclusion

Migraineurs have significantly poorer subjective sleep quality, and altered sleep compared to healthy individuals – a finding which is particularly evident in children. This has implications for developing appropriate treatments. Further longitudinal empirical studies are required to enhance our understanding of this relationship.
Molecular pathology and synaptic loss in primary tauopathies: [18F]AV-1451 and [11C]UCB-J PET study
Authors: Holland Negin , Malpetti Maura , Rittman Timothy , Mak Elijah E , Passamonti Luca , Kaalund Sanne S , Hezemans Frank H. , Jones P. Simon , Savulich George , Hong Young T. , Fryer Tim D. , Aigbirhio Franklin I. , O’Brien John T , Rowe James B
Published: March 2021

The relationship betweenin vivosynaptic density and tau burden in primary tauopathies is key to understanding the impact of tauopathy on functional decline and in informing new early therapeutic strategies. In this cross-sectional observational study, we determine thein vivorelationship between synaptic density and molecular pathology, in the primary tauopathies of Progressive Supranuclear Palsy (PSP) and Corticobasal Degeneration (CBD), as a function of disease severity.

Twenty three patients with PSP, and twelve patients with Corticobasal Syndrome (CBS) were recruited from a tertiary referral centre. Nineteen education, sex and gender-matched control participants were recruited from the National Institute for Health Research ‘Join Dementia Research’ platform. Cerebral synaptic density and molecular pathology, in all participants, were estimated using PET imaging with the radioligands [11C]UCB-J and [18F]AV-1451, respectively. Patients with CBS also underwent amyloid PET imaging with [11C]PiB to exclude those with likely Alzheimer’s pathology – we refer to the amyloid negative cohort as having CBD although acknowledge other pathologies exist. Disease severity was assessed with the PSP rating scale; regional non-displaceable binding potentials (BPND) of [11C]UCB-J and [18F]AV-1451 were estimated in regions of interest from the Hammersmith Atlas, excluding those with known off-target binding for [18F]AV-1451. As an exploratory analysis, we also investigated the relationship between molecular pathology in cortical brain regions, and synaptic density in connected subcortical areas.

Across brain regions, there was apositivecorrelation between [11C]UCB-J and [18F]AV-1451 BPND(β=0.4, t=4.7, p<0.0001). However, the direction of this correlation became less positive as a function of disease severity in patients(β = -0.03, T = -4.0, p = 0.002). Between brain regions, cortical [18F]AV-1451 binding wasnegativelycorrelated with synaptic density in subcortical areas (caudate nucleus, putamen, and substantia nigra).

Brain regions with higher synaptic density are associated with a higher [18F]AV-1451 binding in PSP/CBD, but this association diminishes with disease severity. Moreover, higher cortical [18F]AV-1451 binding correlates with lower subcortical synaptic density. Longitudinal imaging is required to confirm the mediation of synaptic loss by molecular pathology. However, the effect of disease severity suggests a biphasic relationship between synaptic density and tauopathy, with synapse rich regions vulnerable to accrual of pathology, followed by a loss of synapses in response to pathology. Given the importance of synaptic function for cognition, our study elucidates the pathophysiology of primary tauopathies and may inform the design of future clinical trials.
Short-stay admissions and lower staffing associated with larger COVID-19 outbreaks in Maryland nursing homes
Authors: Mattingly T. Joseph , Trinkoff Alison , Lydecker Alison D , Kim Justin J. , Yoon Jung Min , Roghmann Mary-Claire
Published: March 2021

Objectives

Identify facility factors associated with a larger COVID-19 outbreak among residents in Maryland nursing homes (NHs).

Design

Observational

Setting and Participants

All Maryland NHs.

Methods

Resident COVID-19 cases were collected for each Maryland NH from January 1, 2020 through July 1, 2020. Cumulative COVID-19 incidence through July 1, 2020 was collected for each county and Baltimore City. Facility characteristics for each Maryland NH were collected from time periods prior to January 1, 2020. NH outbreaks were defined as larger when total resident COVID-19 cases exceeded 10% of licensed beds. Descriptive and multivariable analyses were conducted to assess the strongest predictors for the primary outcome of larger COVID-19 outbreak.

Results

NHs located in counties with high cumulative incidence of COVID-19 were more likely to have larger outbreaks (OR 4.5, 95% CI 2.3-8.7, p<0.01). NHs with at least 100 beds were more likely to have larger outbreaks, especially among facilities with >140 licensed beds (100-140 beds vs <100 beds: OR 1.9, 95% CI 0.9-4.1, p=0.09; >140 beds vs <100 beds: OR 2.9, 95% CI 1.3-6.1, p<0.01). NHs with more short-stay residents (OR 2.2, 95% CI 1.1-4.8, p=0.04) or fewer Certified Nursing Assistant hours daily (OR 2.6, 95% CI 1.3-5.3, p<0.01) also were more likely to have larger outbreaks. Resident race and gender were not significant predictors of larger outbreaks after adjustment for other factors.

Conclusions

Large NHs with lower staffing levels and many short-stay residents in counties with high COVID-19 incidence were at increased risk for COVID-19 outbreaks. Understanding the characteristics of nursing homes associated with larger outbreaks can help us prepare for the next pandemic.

Brief summary

Maryland nursing homes in counties with a high COVID-19 incidence, more licensed beds, a higher proportion of short-stay residents, or lower CNA staffing hours were more likely to have a larger outbreak early in the pandemic.
An IPI based immune prognostic model for diffuse large B-cell lymphoma
Authors: Mu Shidai , Shi Deyao , Ai Lisha , Fan Fengjuan , Peng Fei , Sun Chunyan , Hu Yu
Published: March 2021

Background

International Prognostic Index (IPI) was widely used to better discriminate prognosis of patients with diffuse large B-cell lymphoma (DLBCL). However, there is a significant need to identify novel valuable biomarkers in the context of targeted therapies, such as immune checkpoint blockade (ICB) therapy.

Methods

Gene expression data and clinical information of DLBCL were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets. 371 immune-related hub genes in DLBCL patients with different IPI levels were identified by weighted gene co-expression network analysis (WGCNA), and 8 genes were selected to construct an IPI-based immune prognostic model (IPI-IPM). Afterward, the genetic, somatic mutational and molecular profiles of IPI-IPM subgroups were analyzed, as well as the potential clinical response of ICB in different IPI-IPM subgroups.

Results

The IPI-IPM was constructed based on the expression of CMBL, TLCD3B, SYNDIG1, ESM1, EPHA3, HUNK, PTX3 and IL12A, where high-risk patients had shorter overall survival (OS) than low-risk patients, consistent with the results in the GEO cohorts. The comprehensive results showed that high IPI-IPM risk scores were correlated with immune-related signaling pathways, high KMT2D and CD79B mutation rates, as well as up-regulation of inhibitory immune checkpoints including PD-L1, BTLA and SIGLEC7, indicating more potential response to ICB therapy.

Conclusion

The IPI-IPM has independent prognostic significance for DLBCL patients, which provides an immunological perspective to elucidate the mechanisms on tumor progression, also sheds a light on developing immunotherapy for DLBCL.