bluuebunny/crossref_metadata_2025 huggingface dataset:
Incorporation of quantitative MRI in a model to predict temporal lobe epilepsy surgery outcome
Authors: Morita-Sherman Marcia , Li Manshi , Joseph Boney , Yasuda Clarissa , Vegh Deborah , De Campos Brunno Machado , Alvim Marina K M , Louis Shreya , Bingaman William , Najm Imad , Jones Stephen , Wang Xiaofeng , Blümcke Ingmar , Brinkmann Benjamin H , Worrell Gregory , Cendes Fernando , Jehi Lara
Published: July 2021

Quantitative volumetric brain MRI measurement is important in research applications, but translating it into patient care is challenging. We explore the incorporation of clinical automated quantitative MRI measurements in statistical models predicting outcomes of surgery for temporal lobe epilepsy. Four hundred and thirty-five patients with drug-resistant epilepsy who underwent temporal lobe surgery at Cleveland Clinic, Mayo Clinic and University of Campinas were studied. We obtained volumetric measurements from the pre-operative T1-weighted MRI using NeuroQuant, a Food and Drug Administration approved software package. We created sets of statistical models to predict the probability of complete seizure-freedom or an Engel score of I at the last follow-up. The cohort was randomly split into training and testing sets, with a ratio of 7:3. Model discrimination was assessed using the concordance statistic (C-statistic). We compared four sets of models and selected the one with the highest concordance index. Volumetric differences in pre-surgical MRI located predominantly in the frontocentral and temporal regions were associated with poorer outcomes. The addition of volumetric measurements to the model with clinical variables alone increased the model’s C-statistic from 0.58 to 0.70 (right-sided surgery) and from 0.61 to 0.66 (left-sided surgery) for complete seizure freedom and from 0.62 to 0.67 (right-sided surgery) and from 0.68 to 0.73 (left-sided surgery) for an Engel I outcome score. 57% of patients with extra-temporal abnormalities were seizure-free at last follow-up, compared to 68% of those with no such abnormalities (P-value = 0.02). Adding quantitative MRI data increases the performance of a model developed to predict post-operative seizure outcomes. The distribution of the regions of interest included in the final model supports the notion that focal epilepsies are network disorders and that subtle cortical volume loss outside the surgical site influences seizure outcome.
Flush+Reload Attacks on SEED
Authors: Seddigh Milad , Soleimany Hadi
Published: July 2021

Flush+Reload is a powerful access-driven cache attack in which the attacker leverages a security weakness in the X86 processor architecture to extract the private data of the victim. This attack can be mounted in a cross-core setting, where the memory deduplication is enabled and several users are sharing the same physical machine. In this paper, for the first time, we demonstrate that SEED implementation of OpenSSL 1.1.0 running inside the victim VM is vulnerable against the Flush+Reload attacks and the attacker can recover the keys of this encryption. SEED is a standard encryption algorithm that was developed by the Korea Information Security Agency (KISA) and has been used for confidential services in the Republic of Korea. Our work demonstrates that the attacker can retrieve the secret keys of SEED in 3 min in the native setup and 4 min in the cross-VM setup by performing the Flush+Reload technique. Our experimental results show that common implementation of this standard cipher is vulnerable to Flush+Reload attack in both native and cross-VM settings. To the best of our knowledge, this paper presents the first cache-based attack on a SEED block cipher.
Insomnia symptoms and incident heart failure: a population-based cohort study
Authors: Mahmood Asos , Ray Meredith , Dobalian Aram , Ward Kenneth D , Ahn SangNam
Published: July 2021

Aims

Heart failure (HF) is an ongoing epidemic and a serious clinical and public health issue. Currently, little is known about prospective associations between insomnia symptoms and HF incidence. We investigated the longitudinal associations between time-varying insomnia symptoms (difficulty initiating sleep, difficulty maintaining sleep, early-morning awakening, non-restorative sleep) and incident HF.

Methods and results

Data were obtained from the Health and Retirement Study in the US for a population-representative sample of 12,761 middle-aged and older adults (age ≥ 50 years; mean [SD] age, 66.7 [9.4] years; 57.7% females) who were free from HF at baseline in 2002. Respondents were followed for 16 years for incident HF. We employed marginal structural discrete-time survival analyses to adjust for potential time-varying biological, psycho-cognitive, and behavioral factors and to account for bias due to differential loss to follow-up. At baseline, 38.4% of the respondents reported experiencing at least one insomnia symptom. During the 16-year follow-up, 1,730 respondents developed incident HF. Respondents experiencing one (hazard ratio [HR]=1.22; 95% CI: 1.08–1.38), two (HR=1.45; 95% CI: 1.21–1.72), three (HR=1.66; 95% CI: 1.37–2.02), or four (HR=1.80; 95% CI: 1.25–2.59) insomnia symptoms had a higher hazard of incident HF than asymptomatic respondents. Respondents that had trouble initiating sleep (HR=1.17; 95%CI: 1.01–1.36), maintaining sleep (HR=1.14; 95% CI: 1.01–1.28), early-morning awakening (HR=1.20; 95% CI: 1.02–1.43), or non-restorative sleep (HR=1.25; 95% CI: 1.06–1.46) had a higher hazard of incident HF than asymptomatic respondents.

Conclusion

Insomnia symptoms, both cumulatively and individually, are associated with incident HF. Public health awareness and screening for insomnia symptoms in at-risk populations should be encouraged to reduce HF incidence.
Functional Dissection of Yeast Hir1p, a WD Repeat–Containing Transcriptional Corepressor
Authors: DeSilva Heshani , Lee Kenneth , Osley Mary Ann
Published: July 2021

The HIR1 gene product is required to repress transcription of three of the four histone gene loci in Saccharomyces cerevisiae, and like its counterpart, the HIR2 protein, it functions as a transcriptional corepressor. Although Hir1p and Hir2p are physically associated in yeast, Hir1p is able to function independently of Hir2p when it is artificially recruited to the histone HTA1 promoter. A deletion analysis of HIR1 has revealed two separate repression domains: one in its N terminus, where seven copies of the β-transducin or WD40 motif reside, and the second in the remaining C-terminal amino acids. Overexpression of the WD repeats in a hir1Δ strain complemented its Hir− phenotype, while overexpression of the C terminus in a wild-type strain caused both Hir− and Spt− phenotypes. The Hir1p C terminus physically interacted in vivo with Hir2p, and both Hir1p repression domains interacted with full-length Hir1p. It was additionally found that the Hir1p WD repeats functionally interacted with the SPT4, SPT5, and SPT6 gene products, suggesting that these repeats may direct Hir1p to different protein complexes.
EMS-Induced Polygenic Mutation Rates for Nine Quantitative Characters in Drosophila melanogaster
Authors: Keightley Peter D , Ohnishi Ohmi
Published: July 2021

Polygenic mutations were induced by treating Drosophila melanogaster adult males with 2.5 mm EMS. The treated second chromosomes, along with untreated controls, were then made homozygous, and five life history, two behavioral, and two morphological traits were measured. EMS mutagenesis led to reduced performance for life history traits. Changes in means and increments in genetic variance were relatively much higher for life history than for morphological traits, implying large differences in mutational target size. Maximum likelihood was used to estimate mutation rates and parameters of distributions of mutation effects, but parameters were strongly confounded with one another. Several traits showed evidence of leptokurtic distributions of effects and mean effects smaller than a few percent of trait means. Distributions of effects for all traits were strongly asymmetrical, and most mutations were deleterious. Correlations between life history mutation effects were positive. Mutation parameters for one generation of spontaneous mutation were predicted by scaling parameter estimates from the EMS experiment, extrapolated to the whole genome. Predicted mutational coefficients of variation were in good agreement with published estimates. Predicted changes in means were up to 0.14% or 0.6% for life history traits, depending on the model of scaling assumed.
Evidence for Genetic Hitchhiking Effect Associated With Insecticide Resistance in Aedes aegypti
Authors: Yan Guiyun , Chadee Dave D , Severson David W
Published: July 2021

Information on genetic variation within and between populations is critical for understanding the evolutionary history of mosquito populations and disease epidemiology. Previous studies with Drosophila suggest that genetic variation of selectively neutral loci in a large fraction of genome may be constrained by fixation of advantageous mutations associated with hitchhiking effect. This study examined restriction fragment length polymorphisms of four natural Aedes aegypti mosquito populations from Trinidad and Tobago, at 16 loci. These populations have been subjected to organophosphate (OP) insecticide treatments for more than two decades, while dichlor-diphenyltrichlor (DDT) was the insecticide of choice prior to this period. We predicted that genes closely linked to the OP target loci would exhibit reduced genetic variation as a result of the hitchhiking effect associated with intensive OP insecticide selection. We also predicted that genetic variability of the genes conferring resistance to DDT and loci near the target site would be similar to other unlinked loci. As predicted, reduced genetic variation was found for loci in the general chromosomal region of a putative OP target site, and these loci generally exhibited larger FST values than other random loci. In contrast, the gene conferring resistance to DDT and its linked loci show polymorphisms and genetic differentiation similar to other random loci. The reduced genetic variability and apparent gene deletion in some regions of chromosome 1 likely reflect the hitchhiking effect associated with OP insecticide selection.
Genetic Analysis of Punt, a Type II Dpp Receptor That Functions Throughout the Drosophila melanogaster Life Cycle
Authors: Simin Karl , Bates Emily A , Horner Michael A , Letsou Anthea
Published: July 2021

TGF-β- (transforming growth factor-β-) mediated signal transduction affects growth and patterning in a variety of organisms. Here we report a genetic characterization of the Drosophila punt gene that encodes a type II serine/threonine kinase TGF-β/Dpp (Decapentaplegic) receptor. Although the punt gene was originally identified based on its requirement for embryonic dorsal closure, we have documented multiple periods of punt activity throughout the Drosophila life cycle. We demonstrate that potentially related embryonic punt phenotypes, defects in dorsoventral patterning and dorsal closure, correspond to distinct maternal and zygotic requirements for punt. In addition, we document postembryonic requirements for punt activity. The tight correspondence between both embryonic and postembryonic loss-of-function punt and dpp phenotypes implicates a role for Punt in mediating virtually all Dpp signaling events in Drosophila. Finally, our comparison of punt homoallelic and heteroallelic phenotypes provides direct evidence for interallelic complementation. Taken together, these results suggest that the Punt protein functions as a dimer or higher order multimer throughout the Drosophila life cycle.
Meta-Analysis of Linkage Data under Worst-Case Conditions: A Demonstration Using the Human OB Region
Authors: Allison David B , Heo Moonseong
Published: July 2021

To date, few methods have been developed explicitly for meta-analysis of linkage analyses. Moreover, the methods that have been developed or suggested generally depend on certain ideal situations and have not been widely applied. In this article, we apply standard statistical theory and meta-analytic techniques in novel ways to five published papers discussing the evidence of linkage of body mass index (BMI) to the region of the human genome containing the OB gene. These methods are “inference based,” meaning that they allow one to make statements about the statistical significance of the entire body of evidence. As currently developed, they do not allow specific statements to be made about the amount of variance explained by any putative locus or allow precise confidence intervals to be placed around the putative location of a linked locus. By applying these techniques to the literature on linkage in the human OB gene region, we are able to show that the evidence for linkage somewhere in the region is extremely strong (P = 1.5 × 10−5).
Genetic Conflicts, Multiple Paternity and the Evolution of Genomic Imprinting
Authors: Spencer Hamish G , Feldman Marcus W , Clark Andrew G
Published: July 2021

We present nine diallelic models of genetic conflict in which one allele is imprintable and the other is not to examine how genomic imprinting may have evolved. Imprinting is presumed to be either maternal (i.e., the maternally derived gene is inactivated) or paternal. Females are assumed to be either completely monogamous or always bigamous, so that we may see any effect of multiple paternity. In contrast to previous verbal and quantitative genetic models, we find that genetic conflicts need not lead to paternal imprinting of growth inhibitors and maternal imprinting of growth enhancers. Indeed, in some of our models—those with strict monogamy—the dynamics of maternal and paternal imprinting are identical. Multiple paternity is not necessary for the evolution of imprinting, and in our models of maternal imprinting, multiple paternity has no effect at all. Nevertheless, multiple paternity favors the evolution of paternal imprinting of growth inhibitors and hinders that of growth enhancers. Hence, any degree of multiple paternity means that growth inhibitors are more likely to be paternally imprinted, and growth enhancers maternally so. In all of our models, stable polymorphism of imprinting status is possible and mean fitness can decrease over time. Neither of these behaviors have been predicted by previous models.
Text and Data Mining Exception in South America: A Way to Foster AI Development in the Region
Authors: Jackson Bertón Matías
Published: July 2021

In 2015, authors wondered if Europe was falling behind in the artificial intelligence (AI) race because of the lack of a text and data mining (TDM) exception. What can then be said for South America? Copyright regimes and their interaction with the development of digital technologies on this continent have been overlooked by authors. This paper intends to start filling this gap by mapping the current state of copyright exceptions that serve computational analysis in South America. After reviewing the copyright regimes of the five largest economies of the region (i.e. Argentina, Brazil, Chile, Colombia and Peru), I concluded that they are not prepared for digital research techniques such as text and data mining. Researchers in these countries are at a competitive disadvantage, as rigid and outdated copyright regimes act as a constraint against keeping pace with the latest developments in subsequent years. If policymakers want to develop their nations’ AI capabilities, as many governments and international organizations claim they do, they will need to look for a more flexible and enabling approach to copyright.
2. Financial services
Authors: Firth Clare , Seymour Jennifer , Crompton Lucy , Fox Helen , Seabridge Frances , Seymour Jennifer , Smart Elizabeth
Published: July 2021

This chapter first introduces the regulation of financial services. It puts the Financial Services and Markets Act 2000 (FSMA 2000) into context and explains the need for authorisation under the Act. It considers what is covered by the general prohibition as well as the meanings of ‘regulated activity’ and ‘specified investment’. The chapter then discusses the position of solicitors, specifically those who are regulated by the Law Society, a designated professional body. The FSMA 2000 has been amended by the Financial Services Act 2012. This introduced changes to the regulation of financial services, including the renaming of the Financial Services Authority as the Financial Conduct Authority.
8. Corporation tax
Authors: Firth Clare , Seymour Jennifer , Crompton Lucy , Fox Helen , Seabridge Frances , Seymour Jennifer , Smart Elizabeth
Published: July 2021

All companies incorporated in the UK which actively carry on business are liable to pay corporation tax (CT) on their taxable profits. This chapter considers the charge to CT with particular focus on calculating chargeable income profits and allowable deductions; the treatment of company capital gains and capital losses; trading loss relief; capital allowances; and close companies.
10. Taxation of sole proprietors and partnerships
Authors: Firth Clare , Seymour Jennifer , Crompton Lucy , Fox Helen , Seabridge Frances , Seymour Jennifer , Smart Elizabeth
Published: July 2021

Sole traders and partners are liable to pay income tax on their income in accordance with the Income Tax (Trading and Other Income) Act 2005 (ITTOIA). This chapter discusses income tax liability of sole traders and partners; calculating the trading profits; capital gains and capital losses; trading losses; basis of assessment; capital allowances; and changes in a partnership.
11. Taxation of trusts and settlements
Authors: Firth Clare , Seymour Jennifer , Crompton Lucy , Fox Helen , Seabridge Frances , Seymour Jennifer , Smart Elizabeth
Published: July 2021

Settlements may be created by settlors in their lifetime, or by will, or they may arise under the intestacy rules. This chapter considers the tax implications of such settlements from the perspective of both the trustees and the beneficiaries. It considers each of the three main taxes separately: inheritance tax, capital gains tax, and income tax.
11. Prosecuting an Either-Way Offence
Authors: Hannibal Martin , Mountford Lisa
Published: July 2021

Either-way offences include assault occasioning actual bodily harm, theft, and burglary. These offences can be committed with varying degrees of seriousness depending on the aggravating or mitigating features in the particular case. The more aggravating features, the more serious the offence will be regarded. This chapter examines the procedure for deciding where an either-way offence should be tried which includes the plea before venue and allocation procedure; the relative merits of summary trial and trial on indictment; and for those either-way offences that are to be tried in the Crown Court, the next stage of the proceedings.
20. Private Privilege
Authors: Hannibal Martin , Mountford Lisa
Published: July 2021

The term ‘private privilege’ relates to separate privileges that prevent evidence from being disclosed in litigation, or witnesses from being compelled to answer questions at trial. In a criminal case, privilege may be claimed in two situations: legal professional privilege and the privilege against self-incrimination. This chapter discusses legal professional privilege in criminal cases; legal professional privilege and the courts; waiving legal professional privilege; the privilege against self-incrimination; and the privilege against self-incrimination and the European Convention on Human Rights 1950.
3. Costs Information to the Client and Funding Options
Authors: Macgregor Lucilla , Peacey Charlotte , Ridsdale Georgina
Published: July 2021

Legal representatives are obliged to give clients the best information possible about the likely costs of pursuing and ultimately resolving disputes, and to discuss with the client the best way of funding the action. This funding advice is inextricably linked to a legal representative’s professional conduct duties highlighted in the Handbook. This chapter focuses on the information clients need to know about costs in accordance with the Handbook’s Principles and its Chapter 1 on Client Care in the Code, as well as the different types of funding options available that may or may not be offered to a client. The chapter considers important recent changes in the application of costs and funding options in litigation.
5. Alternative Dispute Resolution
Authors: Macgregor Lucilla , Peacey Charlotte , Ridsdale Georgina
Published: July 2021

This chapter deals with the methods by which the Civil Procedure Rules (CPR) encourage parties to settle their disputes at an early stage and, ultimately, without proceeding to trial. It also looks at the methods of dispute resolution that may be available. The chapter includes a detailed look at the most common dispute resolution methods. Further, it covers the different types of alternative dispute resolution (ADR); the integration of ADR into the CPR; the philosophy of ADR; and a detailed look at mediation.
7. Pre-Action Substantive Matters
Authors: Macgregor Lucilla , Peacey Charlotte , Ridsdale Georgina
Published: July 2021

The role of a student or practitioner in the dispute resolution (or litigation) department is to assist in the procedural and theoretical aspects of a client’s case. These latter aspects can include consideration of matters that can determine where an action proceeds and whether it is capable of proceeding. This chapter deals with issues that may be considered either before seeing a client on a new matter, at the first meeting, or, more commonly, after receiving detailed instructions and reflecting on the overall issues in the case. It considers jurisdiction and governing law; the capacity to sue or be sued; limitation; the legal components of an action; and remedies.
13. Interim Applications—General Considerations
Authors: Macgregor Lucilla , Peacey Charlotte , Ridsdale Georgina
Published: July 2021

An interim application is any application made to the court that requires a judicial decision. This is usually in the time between a case being issued and the final trial or determination of the action. This chapter considers the nature of interim applications. It discusses the interim applications made with and without notice, and those made with and without a hearing. It also explains common procedure and time estimates.
20. Assessment of Costs Proceedings
Authors: Macgregor Lucilla , Peacey Charlotte , Ridsdale Georgina
Published: July 2021

This chapter focuses on the practical considerations and procedures involved in assessing costs once the litigation is concluded. The client must understand that, despite receiving a costs order in his favour, agreeing a liability to pay, or being ordered to pay costs, if the amount of costs cannot be agreed between the parties, then further proceedings and costs are incurred before a resolution is secured. The chapter covers detailed assessments of costs. It discusses the procedures for the assessment of costs and costs-only proceedings.
3. An Outline of a Conveyancing Transaction
Authors: Richards Mark
Published: July 2021

This chapter explains the process of conveyancing as a whole through an outline of a typical conveyancing transaction. It describes a transaction in outline; energy performance certificates; the Land Registry Portal; and the Law Society’s Conveyancing Quality Scheme; and the future of conveyancing.
8. Deducing and Investigating Title
Authors: Richards Mark
Published: July 2021

Deducing title is the process by which the seller demonstrates to the buyer that the seller owns the property and can convey it. In a modern conveyancing transaction the parties will deduce and investigate title before contracts are exchanged. This chapter explains the process of deducing title; investigating title; and some special title situations.
10. Exchange of Contracts
Authors: Richards Mark
Published: July 2021

Exchange of contracts is the most critical stage in the conveyancing process as it represents the point at which the parties become legally bound to proceed. This chapter examines pre-exchange matters; the process by which contracts are actually exchanged; and matters that should be attended to immediately after exchange has taken place. It also considers the risk and responsibility for buildings insurance, and the consequences of the buyer occupying the property before completion.
16. Leaseholds
Authors: Richards Mark
Published: July 2021

This chapter first examines some of the more commonly encountered elements or clauses in most leases. Essentially, it sets out what one might expect to see in a lease of either residential or commercial property. The discussions then turn to the Council of Mortgage Lenders’ Handbook for Solicitors and Licensed Conveyancers England and Wales; defective leases; liability on covenants in leases: enforcement; granting new leases; existing leases; and enfranchisement.
19. Landlord and Tenant Act 1954, Part II
Authors: Richards Mark
Published: July 2021

This chapter considers the provisions of the Landlord and Tenant Act 1954, Part II, which provides security of tenure for the majority of business tenants by giving them a statutory right to renew their lease or tenancy. It explains the need for ‘tenancy’; need for ‘occupation’; need for ‘the purposes of a business’; key methods of termination under the Act; section 40 notices; interim rent applications; landlord’s statutory grounds of opposition; tenant’s right to compensation; and the terms of the new tenancy.
3. Liability of partners to outsiders
Authors: Slorach J. Scott , Ellis Jason
Published: July 2021

Partners will incur debts and other obligations in the course of carrying on the partnership’s business. This chapter examines the nature of the partners’ liabilities in these circumstances and the extent to which an individual partner can bind the partnership as a whole. It then considers whether it is possible for individuals who are not partners at the time the debt or obligation was incurred to be liable for that debt or obligation.
5. Termination of and retirement from a partnership
Authors: Slorach J. Scott , Ellis Jason
Published: July 2021

An individual may cease to be a partner on the happening of one of the following events: the dissolution of the partnership; his retirement; or his expulsion from the partnership. If the partnership is dissolved, the partnership will come to an end and its assets and business will be dealt with accordingly. The situation is different on the retirement or expulsion of a partner. Here, the former partners can carry on the business, albeit through the medium of a newly constituted partnership. This chapter considers the legal consequences of the occurrence of these events.
15. Disclosure obligations of companies and company accounts
Authors: Slorach J. Scott , Ellis Jason
Published: July 2021

This chapter considers the information about companies that is publicly available, paying particular attention to the rules with which the company must comply in relation to its accounts. It also provides some guidance on how to interpret the published accounts of a company.
18. The corporation tax system
Authors: Slorach J. Scott , Ellis Jason
Published: July 2021

This chapter deals with the corporation tax system, which determines the tax liability of companies. It discusses the calculation of profits; tax assessment; relief for trade losses; and taxation of close companies.
22. Capital gains tax and inheritance tax on business assets
Authors: Slorach J. Scott , Ellis Jason
Published: July 2021

This chapter examines the capital gains tax (CGT) and inheritance tax (IHT) regimes that apply to individuals in relation to businesses and business assets. Under the provisions of the Taxation of Chargeable Gains Act (TCGA) 1992, CGT is payable when a taxable person makes a disposal of chargeable assets giving rise to a chargeable gain unless an exemption or relief applies. The chapter first discusses the various rules which need to be considered to establish a taxpayer’s CGT liability on any given disposal. It then covers CGT in the business context; disposals of partnership property; disposals of shares; disposals of business assets owned by those involved in the business; the purchase by a company of its own shares; and inheritance tax.
23. Value Added Tax
Authors: Slorach J. Scott , Ellis Jason
Published: July 2021

This chapter discusses value added tax (VAT) in the UK. VAT is charged on supplies of goods and services made in the UK. Where a person makes taxable supplies in excess of a set limit in any one-year period, he must register with HMRC. He must then account to HMRC for VAT on all taxable supplies made. The total amount payable may be reduced by the amount of VAT paid on certain taxable supplies made to him. The liability to pay VAT to HMRC rests on suppliers of goods and services. However, the cost of the tax is actually borne by suppliers’ customers who are charged VAT on the goods and services they purchase. VAT is charged in the UK under the Value Added Tax Act (VATA) 1994.
A Practical Approach to Civil Procedure
Authors: Sime Stuart
Published: July 2021

A Practical Approach to Civil Procedure guides the reader through the procedural requirements employed in the civil courts. The volume provides an overview of the key statutory provisions, rules, practice directions, and case law which govern the various stages of a civil litigation claim. Providing practical guidance, the text charts the progress of a typical civil litigation claim, from funding litigation, the importance of alternative dispute resolution processes, issuing and serving proceedings, case management, and through to trial, enforcement, and appeal. Relevant sample documentation is featured throughout and introduces the forms and documents which will be encountered in practice, while key points summaries featured at the end of chapters highlight the essential points covered. This edition has been revised to incorporate rule changes up to the Civil Procedure (Amendment No 2) Rules 2021 and the 129th Update. Changes incorporated into the new edition include:

Pre-action protocol for small claim road traffic accident cases and the new PD 27B;

procedural aspects of the tariff system for whiplash injuries under the Civil Liability Act 2018;

recent case law on service of claim forms and particulars of claim;

revised rules on costs management;

changes to the rules on statements of truth;

revisions to the chapter on summary judgment, including the cheque rule and the approach taken in summary judgment applications for discretionary remedies;

replacement PD 51U on disclosure of documents in the Business and Property Courts;

case law developments on legal professional privilege and without prejudice privilege;

developments on search orders, and case law on imaging orders;

further guidance on remote hearings;

and debt respite procedures.
3. The Civil Courts
Authors: Sime Stuart
Published: July 2021

This chapter describes the civil courts in England and Wales. It covers the composition and administration of magistrates’s courts, County Court, and the High Court; jurisdiction; High Court Divisions (Queen’s Bench Division (QBD), Chancery Division (ChD), and Family Division), and specialist courts (Business and Property Courts, Technology and Construction Court, Commercial Court, Administrative Court, Companies Court, Patents Court, and Intellectual Property Enterprise Court). For most civil claims the claimant has a free choice between the High Court and the County Court. Common law claims are suitable for the Queen’s Bench Division, whereas equity claims are more suitable for the Chancery Division. The High Court should be used for the more important and complex claims.
4. Overriding Objective and Human Rights
Authors: Sime Stuart
Published: July 2021

This chapter discusses the sources of procedural law, the general principles relevant to civil procedure established by the overriding objective, the European Convention on Human Rights, and some rules on how the courts approach construing the Civil Procedure Rules 1998 (CPR). The CPR and practice directions (PDs) are the procedural rules governing civil proceedings. The most important rule is the ‘overriding objective’ of dealing with claims justly and at proportionate cost. The most important Convention rights in civil litigation are the right to a fair trial, the right to respect for private and family life, and the right to freedom of expression.
8. Part 8 Claims and Petitions
Authors: Sime Stuart
Published: July 2021

This chapter discusses Part 8 claims and petitions, which are forms of originating process. Most types of proceedings which have to be brought by either Part 8 claim form or petition are very narrow and specialized, but some are of great importance. The most important types of proceedings which must be commenced by petition are those for divorce, judicial separation, bankruptcy, and the winding-up of companies.
18. Requests for Further Information
Authors: Sime Stuart
Published: July 2021

A party may sometimes take the view that the statement of case provided by the other side is not as clear as it should be, or fails to set out the other side’s case with the precision that would be expected. In such cases a request may be made for further information about the facts on which the other side’s case is based. This chapter discusses the rules on requests for further information; the response; objecting to requests; orders for responses; requests in freezing injunctions; and collateral use.
23. Interim Applications
Authors: Sime Stuart
Published: July 2021

An order is a formal decision by the court granting a remedy or relief to a party, usually in the stages before the final determination of a case. Interim orders are sometimes made after the substantive hearing of a claim, and sometimes the relief granted at trial includes various types of orders. This chapter discusses pre-action interim remedies; obligation to apply early; applications with and without notice; interim hearings; summary determination of interim costs; and varying or revoking interim orders.
32. Witness Statements, Affidavits, and Depositions
Authors: Sime Stuart
Published: July 2021

This chapter discusses the rules relating to the use of written evidence in civil proceedings. Under the Civil Procedure Rules 1998 (CPR), evidence given in civil trials is given primarily from the witness box, but with witness statements exchanged well before trial standing as the evidence-in-chief of the witnesses. The parties are required to exchange their witnesses’ statements in order to save time and costs at trial, and to enable the parties to evaluate the merits of their dispute with a view to settlement. Written evidence in support of interim applications can be given by a variety of different methods, but the principal means is by way of signed witness statements.
37. Sanctions
Authors: Sime Stuart
Published: July 2021

A court can impose sanctions to ensure that its case management directions and orders are complied with, and to retain control over the conduct of litigation. These range from adverse interim costs orders through to striking out the whole or part of the defaulting party’s statement of case. This chapter discusses sanctions for non-compliance with pre-action protocols, with the Civil Procedure Rules 1998 (CPR), and with directions; application for sanctions; non-compliance with an unless order; striking out; less serious immediate sanctions; extending time and correcting errors; and relief from sanctions and setting aside.
39. Trial
Authors: Sime Stuart
Published: July 2021

This chapter discusses the issues that need to be addressed in the period leading up to a trial. These include contacting witnesses to ensure their availability; obtaining witness summonses where appropriate; briefing trial counsel; agreeing and compiling trial bundles; and counsel preparing speeches, examination-in-chief, and cross-examination of witnesses.
41. Judgments and Orders
Authors: Sime Stuart
Published: July 2021

This chapter discusses the rules on judgments and orders. Although there is likely to be a delay between judgment being pronounced and the judgment being sealed and served, r 40.7(1) of the Civil Procedure Rules 1998 (CPR) provides that judgment in fact takes effect from the day it was given. After a judgment or order has been pronounced by the court, the next step is to have it drawn up. This chapter discusses settlements; orders made at hearings; form of judgments and orders; general rules relating to drawing up orders and judgments; and register of judgments.
42. Interim Injunctions
Authors: Sime Stuart
Published: July 2021

This chapter discusses the rules on interim injunctions. Interim injunctions are temporary orders made with the purpose of regulating the position between the parties to an action pending trial. Such an order is particularly useful where there is evidence that the respondent’s alleged wrongdoing will cause irreparable damage to the applicant’s interests in the period between issue of process and trial. The chapter covers judges able to grant injunctions; pre-action applications for interim injunctions; applications during proceedings; principles for the granting of interim injunctions; defences and bars to relief that may be raised on an application for an interim injunction; interim injunction orders; and effect of not applying for interim relief.
The growing rural–urban divide in US life expectancy: contribution of cardiovascular disease and other major causes of death
Authors: Abrams Leah R , Myrskylä Mikko , Mehta Neil K
Published: July 2021

Background

The US rural disadvantage in life expectancy (LE) relative to urban areas has grown over time. We measured the contribution of cardiovascular disease (CVD), drug-overdose deaths (DODs) and other major causes of death to LE trends in rural and urban counties and the rural–urban LE gap.

Methods

Counterfactual life tables and cause-of-death decompositions were constructed using data on all US deaths in 1999–2019 (N = 51 998 560) from the Centers for Disease Control and Prevention.

Results

During 1999–2009, rural and urban counties experienced robust LE gains, but urban LE increased by 1.19 years more in women and 0.86 years more in men compared with rural LE. During 2010–2019, rural counties experienced absolute declines in LE (women −0.20, men −0.30 years), whereas urban counties experienced modest increases (women 0.55, men 0.29 years). Counterfactual analysis showed that slowed CVD-mortality declines, particularly in ages 65+ years, were the main reason why rural LE stopped increasing after 2010. However, slow progress in CVD-mortality influenced LE trends more in urban areas. If CVD-mortality had continued to decline at its pre-2010 pace, the rural–urban LE gap would have grown even more post 2010. DODs and other causes of death also contributed to the LE trends and differences in each period, but their impact in comparison to that of CVD was relatively small.

Conclusions

Rural disadvantage in LE continues to grow, but at a slower pace than pre 2010. This slowdown is more attributable to adverse trends in CVD and DOD mortality in urban areas than improvements in rural areas.
A Systematic Review and Meta-analysis of Animal Studies Investigating the Relationship Between Serum Antibody, T Lymphocytes, and Respiratory Syncytial Virus Disease
Authors: McGinley Joseph , Thwaites Ryan , Brebner Will , Greenan-Barrett Lewis , Aerssens Jeroen , Öner Deniz , Bont Louis , Wildenbeest Joanne , Martinón-Torres Federico , Nair Harish , Pollard Andrew J , Openshaw Peter , Drysdale Simon ,   REspiratory Syncytial virus Consortium in EUrope (RESCEU) Investigators, Rosen Brian , Aerssens Jeroen , Gallichan Scott , Leach Amanda , Dormitzer Phil , Kena Swanson , Giaquinto Carlo , van den Berge Maarten , Kølsen Fischer Thea , Meijer Adam , Martinón-Torres Federico , Openshaw Peter , Díaz Carlo , Molero Eva , Pollard Andrew , Bont Louis , Nair Harish , Campbell Harry , Beutels Philippe
Published: July 2021

Background

Respiratory syncytial virus (RSV) infections occur in human populations around the globe, causing disease of variable severity, disproportionately affecting infants and older adults (>65 years of age). Immune responses can be protective but also contribute to disease. Experimental studies in animals enable detailed investigation of immune responses, provide insights into clinical questions, and accelerate the development of passive and active vaccination. We aimed to review the role of antibody and T-cell responses in relation to RSV disease severity in animals.

Methods

Systematic review and meta-analysis of animal studies examining the association between T-cell responses/phenotype or antibody titers and severity of RSV disease. The PubMed, Zoological Record, and Embase databases were screened from January 1980 to May 2018 to identify animal studies of RSV infection that assessed serum antibody titer or T lymphocytes with disease severity as an outcome. Sixty-three studies were included in the final review.

Results

RSV-specific antibody appears to protect from disease in mice, but such an effect was less evident in bovine RSV. Strong T-cell, Th1, Th2, Th17, CD4/CD8 responses, and weak Treg responses accompany severe disease in mice.

Conclusions

Murine studies suggest that measures of T-lymphocyte activity (particularly CD4 and CD8 T cells) may be predictive biomarkers of severity. Further inquiry is merited to validate these results and assess relevance as biomarkers for human disease.
‘It makes life so much easier’—experiences of users of the MicroGuide™ smartphone app for improving antibiotic prescribing behaviour in UK hospitals: an interview study
Authors: Hand Kieran S , Clancy Bridget , Allen Mike , Mayes Amazigom , Patel Yash , Latter Susan M
Published: July 2021

Objectives

To understand the impact on prescribing behaviour of an antimicrobial therapy guidelines smartphone app, in widespread use in hospitals in the UK.

Methods

Twenty-eight doctors and five nurse prescribers from four purposively selected hospitals in the UK participated in behavioural theory-informed semi-structured interviews about their experiences of using the MicroGuide™ smartphone app. Data were analysed using a thematic content analysis.

Results

Five themes emerged from the interview data: convenience and accessibility; validation of prescribing decisions; trust in app content; promotion of antimicrobial stewardship; and limitations and concerns. Participants appreciated the perceived convenience, accessibility and timesaving attributes of the app, potentially contributing to more prompt treatment of patients with time-critical illness. The interviewees also reported finding it reassuring to use the app to support decision-making and to validate existing knowledge. They trusted the app content authored by local experts and considered it to be evidence-based and up-to-date. This was believed to result in fewer telephone calls to the microbiology department for advice. Participants recognized the value of the app for supporting the goals of antimicrobial stewardship by promoting the responsible and proportionate use of antimicrobials. Finally, a number of limitations of the app were reported, including the risk of de-skilling trainees, cultural problems with using smartphones in clinical environments and software technical problems.

Conclusions

The MicroGuide app was valued as a means of addressing an unmet need for updated, concise, trustworthy specialist information in an accessible format at the bedside to support safe and effective antimicrobial prescribing.
Physical Activity From Adolescence Through Midlife and Associations With Body Mass Index and Endometrial Cancer Risk
Authors: Saint-Maurice Pedro F , Sampson Joshua N , Michels Kara A , Moore Steven C , Loftfield Erikka , McClain Kathleen , Cook Michael B , Trabert Britton , Matthews Charles E
Published: July 2021

Background

Physical activity is associated with lower risk for endometrial cancer, but the extent to which the association is mediated by body mass index (BMI) in midlife is unclear. This study describes the physical activity–endometrial cancer association and whether BMI mediates this relationship.

Methods

Participants were 67 705 women in the National Institutes of Health-AARP Diet and Health Study (50-71 years) who recalled their physical activity patterns starting at age 15-18 years. We identified 5 long-term physical activity patterns between adolescence and cohort entry (ie, inactive, maintained low, maintained high, increasers, decreasers). We used Cox regression to assess the relationship between these patterns and midlife BMI and endometrial cancer, adjusting for covariates. Mediation analysis was used to estimate the proportion of the physical activity–endometrial cancer association that was mediated by midlife BMI.

Results

During an average 12.4 years of follow-up 1468 endometrial cancers occurred. Compared with long-term inactive women, women who maintained high or increased activity levels had a 19% to 26% lower risk for endometrial cancer (maintained high activity: hazard ratio = 0.81, 95% confidence interval [CI] = 0.67 to 0.98; increasers: hazard ratio = 0.74, 95% CI = 0.61 to 0.91). They also had a 50% to 77% lower risk for obesity in midlife (eg, maintained high activity: odds ratio for a BMI of 30-39.9 kg/m2 = 0.50, 95% CI = 0.46 to 0.55; and maintained high activity, odds ratio for a BMI of ≥40 kg/m2 = 0.32, 95% CI = 0.26 to 0.39). BMI was a statistically significant mediator accounting for 55.5% to 62.7% of the physical activity–endometrial cancer associations observed.

Conclusions

Both maintaining physical activity throughout adulthood and adopting activity later in adulthood can play a role in preventing obesity and lowering the risk for endometrial cancer.
Project Forward: A Population-Based Cohort Among Young Adult Survivors of Childhood Cancers
Authors: Milam Joel , Freyer David R , Miller Kimberly A , Tobin Jessica , Wojcik Katherine Y , Ramirez Cynthia N , Ritt-Olson Anamara , Thomas Stefanie M , Baezconde-Garbanati Lourdes , Cousineau Michael , Modjeski Denise , Gupta Sapna , Hamilton Ann S
Published: July 2021

Background

Childhood cancer survivors (CCS) face increased risk of morbidity and are recommended to receive lifelong cancer-related follow-up care. Identifying factors associated with follow-up care can inform efforts to support the long-term health of CCS.

Methods

Eligible CCS (diagnosed between 1996 and 2010) identified through the Los Angeles County Cancer Surveillance Program responded to a self-report survey that assessed demographic, clinical, health-care engagement, and psychosocial risk and protective factors of recent (prior 2 years) cancer-related follow-up care. Weighted multivariable logistic regression was conducted to identify correlates of care. All statistical tests were 2-sided.

Results

The overall response rate was 44.9%, with an analytical sample of n = 1106 (54.2% Hispanic; mean [SD] ages at survey, diagnosis, and years since diagnosis were 26.2 [4.9], 11.6 [5.4], and 14.5 [4.4] years, respectively). Fifty-seven percent reported a recent cancer-related visit, with lower rates reported among older survivors. Having insurance, more late effects, receipt of a written treatment summary, discussing long-term care needs with treating physician, knowledge of the need for long-term care, having a regular source of care, and higher health-care self-efficacy were statistically significantly associated with greater odds of recent follow-up care, whereas older age, Hispanic or Other ethnicity (vs non-Hispanic White), and years since diagnosis were associated with lower odds of recent care (all Ps < .05).

Conclusions

Age and ethnic disparities are observed in receipt of follow-up care among young adult CCS. Potential intervention targets include comprehensive, ongoing patient education; provision of written treatment summaries; and culturally tailored support to ensure equitable access to and the utilization of care.