bluuebunny/crossref_metadata_2025 huggingface dataset:
Refining Estimation of the Instantaneous Reproduction Number During Early Pandemic Stages: Addressing Case-Reporting Variability and Serial Interval Uncertainty
Authors: Hettinger Gary , Rubin David , Huang Jing
Published: September 2024

During infectious disease outbreaks, estimates for the instantaneous reproduction number, R(t), are essential for understanding transmission dynamics. This study develops and analyzes new methodology to improve estimation of R(t) when observed case counts are subject to reporting patterns and available serial interval estimates are subject to uncertainty and non-representativeness.

Specifically, we developed a Bayesian time-since-infection model with layers to adjust for reporting measurement error, integrate multiple candidate serial interval estimates, and estimate transmission with an autoregressive time-series model incorporating factors relevant to transmission. Additionally, we provide practical tools to identify reporting patterns and determine when to smooth case counts for more usable R(t) estimates. We evaluated model performance relative to widely adopted methodology by simulating outbreak data, finding improved R(t) estimation with the proposed methodology. We also used 2020 COVID-19 data to analyze transmission trends and predictors, identifying strong day-of-week and social distancing effects that subsequently reduced estimate volatility.

In addition to new approaches for addressing serial interval uncertainty and incorporating transmission predictor information, this study provides an alternative approach for addressing case-reporting patterns without delaying detection or smoothing over relevant transmission signals. These tools and findings may be used or built upon for current and future outbreaks.
Prediction of antibiotic resistance mechanisms using a protein language model
Authors: Yagimoto Kanami , Hosoda Shion , Sato Miwa , Hamada Michiaki
Published: September 2024

Motivation

Antibiotic resistance has emerged as a major global health threat, with an increasing number of bacterial infections becoming difficult to treat. Predicting the underlying resistance mechanisms of antibiotic resistance genes (ARGs) is crucial for understanding and combating this problem. However, existing methods struggle to accurately predict resistance mechanisms for ARGs with low similarity to known sequences and lack sufficient interpretability of the prediction models.

Results

In this study, we present a novel approach for predicting ARG resistance mechanisms using ProteinBERT, a protein language model (pLM) based on deep learning. Our method outperforms state-of-the-art techniques on diverse ARG datasets, including those with low homology to the training data, highlighting its potential for predicting the resistance mechanisms of unknown ARGs. Attention analysis of the model reveals that it considers biologically relevant features, such as conserved amino acid residues and antibiotic target binding sites, when making predictions. These findings provide valuable insights into the molecular basis of antibiotic resistance and demonstrate the interpretability of pLMs, offering a new perspective on their application in bioinformatics.

Availability and implementation

The source code is available for free at https://github.com/hmdlab/ARG-BERT. The output results of the model are published at https://waseda.box.com/v/ARG-BERT-suppl.
Pooling controls from nested case–control studies with the proportional risks model
Authors: Chang Yen , Ivanova Anastasia , Albanes Demetrius , Fine Jason P , Shin Yei Eun
Published: September 2024

The standard approach to regression modeling for cause-specific hazards with prospective competing risks data specifies separate models for each failure type. An alternative proposed by Lunn and McNeil (1995) assumes the cause-specific hazards are proportional across causes. This may be more efficient than the standard approach, and allows the comparison of covariate effects across causes. In this paper, we extend Lunn and McNeil (1995) to nested case–control studies, accommodating scenarios with additional matching and non-proportionality. We also consider the case where data for different causes are obtained from different studies conducted in the same cohort. It is demonstrated that while only modest gains in efficiency are possible in full cohort analyses, substantial gains may be attained in nested case–control analyses for failure types that are relatively rare. Extensive simulation studies are conducted and real data analyses are provided using the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) study.
The influence of temperature and genomic variation on intracranial EEG measures in people with epilepsy
Authors: McNicholas Olivia C , Jiménez-Jiménez Diego , Oliveira Joana F A , Ferguson Lauren , Bellampalli Ravishankara , McLaughlin Charlotte , Chowdhury Fahmida Amin , Martins Custodio Helena , Moloney Patrick , Mavrogianni Anna , Diehl Beate , Sisodiya Sanjay M
Published: September 2024

Heatwaves have serious impacts on human health and constitute a key health concern from anthropogenic climate change. People have different individual tolerance for heatwaves or unaccustomed temperatures. Those with epilepsy may be particularly affected by temperature as the electroclinical hallmarks of brain excitability in epilepsy (inter-ictal epileptiform discharges and seizures) are influenced by a range of physiological and non-physiological conditions. Heatwaves are becoming more common and may affect brain excitability. Leveraging spontaneous heatwaves during periods of intracranial EEG recording in participants with epilepsy in a non–air-conditioned telemetry unit at the National Hospital for Neurology and Neurosurgery in London from May to August 2015–22, we examined the impact of heatwaves on brain excitability. In London, a heatwave is defined as three or more consecutive days with daily maximum temperatures ≥28°C. For each participant, we counted inter-ictal epileptiform discharges using four 10-min segments within, and outside of, heatwaves during periods of intracranial EEG recording. Additionally, we counted all clinical and subclinical seizures within, and outside of, heatwaves. We searched for causal rare genetic variants and calculated the epilepsy PRS. Nine participants were included in the study (six men, three women), median age 30 years (range 24–39). During heatwaves, there was a significant increase in the number of inter-ictal epileptiform discharges in three participants. Five participants had more seizures during the heatwave period, and as a group, there were significantly more seizures during the heatwaves. Genetic data, available for eight participants, showed none had known rare, genetically-determined epilepsies, whilst all had high polygenic risk scores for epilepsy. For some people with epilepsy, and not just those with known, rare, temperature-sensitive epilepsies, there is an association between heatwaves and increased brain excitability. These preliminary data require further validation and exploration, as they raise concerns about the impact of heatwaves directly on brain health.
Cerebral white matter damage in patients with end-stage kidney disease associates with cognitive impairment
Authors: Hou Yi-Chou , Tsai Chih-Chien , Chen Ruei-Ming , Liu Yi-Chien , Lu Kuo-Cheng , Chen Yao-Liang , Shen Ting-Wen , Wang Jiun-Jie
Published: September 2024

Background

Damage to brain white matter often occurs in individuals with chronic kidney disease, which might be related to their cognitive decline. This study aims to investigate tract-specific white matter damage in patients with end-stage kidney disease by using fixel-based analysis.

Methods

Images of 31 end-stage kidney disease patients and 16 normal controls (aged: 61.1 ± 10.4 years; 11 men) were acquired from a 1.5T magnetic resonance scanner. The patients were subsequently divided into with normal cognition (N = 17, aged: 66.9 ± 7.2 years; 10 men) and cognitive impairment (N = 14, aged: 72.4 ± 9.4 years; 7 men). Cognitive assessment, and neurologic, hematologic and biochemical samples were collected. Fixel-based analysis was used to examine the tract-specific damage within white matter. Differences between groups were evaluated through connectivity-based fixel enhancement and non-parametric permutation testing. Correlation with biomarkers was conducted through general linear model. Significance was determined with family-wise error-corrected P-value <.05.

Results

Reduced fixel-based metrics were observed in specific tract located the cerebral peduncle, internal capsule, corpus callosum, fornix and superior corona radiata in patients when compared with normal controls, indicating a reduction in fiber content. The fibers crossing the corpus callosum and the fornix/stria terminalis are particularly vulnerable sites, which can be associated with the decrease in both Mini-Mental State Examination (R2 ranged between 0.420 and 0.556) and Montreal Cognitive Assessment (R2 ranged between 0.425 and 0.509), as well as the plasma concentration of calcium (R2 ranged between 0.207 and 0.322). The plasma concentration of indoxyl sulfate was associated with the descending tracts from right posterior limb of internal capsule to cerebral peduncle (R2 ranged between 0.262 and 0.335).

Conclusions

Tract-specific white matter damage can be noticed in the patients with end-stage kidney disease, and could be associated with their cognitive decline.
Pulsed field ablation as a feasible option for the treatment of epicardial left ventricular summit premature complex foci near the coronary arteries: a case report
Authors: Spenkelink Dylan , van Wessel Harry , van Driel Vincent J , Ramanna Hemanth , van der Heijden Jeroen F
Published: September 2024

Background

Radiofrequency catheter ablation in the left ventricular summit region is a challenging procedure due to proximity to the coronary arteries. Pulsed field ablation, a novel non-thermal ablation modality, does not cause damage to coronary arteries and may be used in the left ventricular summit region.

Case summary

We describe a 45-year-old symptomatic patient with epicardial left ventricular summit premature ventricular complexes. Successful ablation of the focus was achieved by pulsed field ablation via a subxiphoid epicardial approach. Radiofrequency ablation would most likely have been ineffective due to the epicardial fat layer and potentially unsafe due to the proximity to the coronary arteries. Six months after ablation, the patient was asymptomatic and without ventricular ectopy.

Discussion

For the first time, epicardial pulsed field ablation was successfully used for ablation of left ventricular summit extrasystole, where radiofrequency ablation could not be used because of the proximity of the coronary arteries. We conclude that pulsed field ablation might be a feasible option for this indication.
Successful catheter ablation in an octogenarian with persistent atrial fibrillation complicated by cor triatriatum sinister: a case report
Authors: Okuyama Yusuke , Tamura Atsushi , Ueda Kohei , Matsuoka Shunzo , Nakagawa Yoshihisa
Published: September 2024

Background

Cor triatriatum sinister (CTS) is a rare congenital heart defect sometimes complicated with atrial fibrillation (AF). Catheter ablation (CA) relieves the AF-associated symptoms, but CA for AF with CTS has been reported rarely. Because CTS can be associated with other congenital heart disease, detailed preoperative assessment is important.

Case summary

An 80-year-old man was referred to our institution for shortness of breath that had persisted for 2 months when he was first diagnosed with AF. Transthoracic echocardiography revealed an enlarged left atrium (LA) divided into two chambers by a membrane. Transoesophageal echocardiography showed the membrane extending from the fossa ovalis (FO) to the Coumadin ridge, with the accessory (dorsal) chamber (AC) in closer proximity to the FO. Computed tomography showed that all pulmonary veins (PVs) flowed into the AC, with no PV anomalies. No other heart anomaly was identified, with no thrombus in the LA. With these findings, PV isolation (PVI) with CA was considered safe. Transseptal puncture was performed with intracardiac echocardiography for precise catheterization of the AC. Pulmonary vein isolation was performed successfully. The patient was discharged 4 days after the procedure, without any complications. His symptoms improved post-procedure, and sinus rhythm was maintained without antiarrhythmic drug therapy during the 18-month follow-up.

Discussion

Cor triatriatum sinister is a rare anomaly that accounts for 0.1% of all congenital heart diseases. Cor triatriatum sinister sometimes complicated with symptomatic AF. Detailed preoperative anatomical assessment with multiple imaging modalities helped us achieve safe and effective CA for a patient with AF and CTS, even in an octogenarian.
Multistep procedure for estimating non-linear soil response in low seismicity areas—a case study of Lucerne, Switzerland
Authors: Janusz Paulina , Bergamo Paolo , Bonilla Luis Fabian , Panzera Francesco , Roten Daniel , Loviknes Karina , Fäh Donat
Published: September 2024

The impact of non-linear soil behaviour on seismic hazard in low-to-moderate seismicity areas is often neglected; however, it may become relevant for long return periods. In this study, we used fully non-linear 1-D simulations to estimate the site-specific non-linear soil response in the low seismicity area, using the city of Lucerne in Switzerland as an example. The constitutive model considers the development of pore pressure excess and requires calibration of complex soil models, including the soil dilatancy parameters. In the absence of laboratory measurements, we mainly used the cone penetration test data to estimate the model variables and perform inversion for the dilatancy parameters. Our findings, using Swiss building code-compatible input ground motions, suggest a high probability of strong non-linear behaviour and the possibility of liquefaction at high ground motion levels in the case study area. While the non-linearity observations from strong-motion recordings are not available in Lucerne, the comparison with empirical data from other sites and other methods shows similarity with our predictions. Moreover, we show that the site response modelled is largely influenced by the strong pore pressure effects produced in thin sandy water-saturated layers. In addition, we demonstrate that the variability of the results due to the input motion and the soil parameters is significant, but within reasonable bounds.
Seismic traveltime tomography based on ensemble Kalman inversion
Authors: Li Yunduo , Zhang Yijie , Zhu Xueyu , Gao Jinghuai
Published: September 2024

In this paper, we present a new seismic traveltime tomography approach that combines ensemble Kalman inversion (EKI) with neural networks (NNs) to facilitate the inference of complex underground velocity fields. Our methodology tackles the challenges of high-dimensional velocity models through an efficient NN parametrization, enabling efficient training on coarse grids and accurate output on finer grids. This unique strategy, combined with a reduced-resolution forward solver, significantly enhances computational efficiency. Leveraging the robust capabilities of EKI, our method not only achieves rapid computations but also delivers informative uncertainty quantification for the estimated results. Through extensive numerical experiments, we demonstrate the exceptional accuracy and uncertainty quantification capabilities of our EKI-NNs approach. Even in the face of challenging geological scenarios, our method consistently generates valuable initial models for full wave inversion (FWI).
Return on investments in social determinants of health interventions: what is the evidence?
Authors: Nikpay Sayeh , Zhang Zhanji , Karaca-Mandic Pinar
Published: September 2024

There has been an increasing recognition of the importance and the value of addressing social determinants of health (SDOH) to improve population health outcomes, manage health care costs, and reduce health inequities. Despite the strong interest in investing in SDOH initiatives by various stakeholders, the literature on the return from such investments is scarce. The differences in study populations and methodologies, and the lack of data on SDOH intervention outcomes and/or costs, make it challenging to quantify and generalize outcomes for decision-making. We reviewed the literature on SDOH interventions focused on food and housing insecurity, and developed a methodology for estimating a key outcome: the return on investment (ROI), defined as the net returns from an intervention divided by its costs. The ROI estimates we report can be used by stakeholders to prioritize among alternative SDOH interventions for fundraising, investing, and implementing purposes. The average ROI for food-insecurity programs was 85% (ranging from 1% to 287%; except for 1 study‘s ROI, −31%) and for housing-insecurity programs was 50% (ranging from 5% to 224%; except for 1 ROI, −38%). In addition, these estimates can serve as key inputs for designing and employing innovative financing and policy solutions to increase the use of these interventions.
17. Contaminated land
Authors: Bell Stuart , McGillivray Donald , Pedersen Ole W. , Lees Emma , Stokes Elen
Published: September 2024

This chapter focuses on the regime for regulating contaminated land in England and Wales with a focus on historical pollution. The chapter discusses key definitions such as ‘contamination’, who has responsibility for cleaning up contamination, and considers whether it is at all justified to impose responsibility retroactively for pollution which may have occurred lawfully many years ago.
28. International Refugee and Migration Law
Authors: Gilbert Geoff , Bentajou Anna Magdalena
Published: September 2024

This chapter explores the definition of refugee status in international law, its scope and limitations and consequent protection gaps for those forcibly displaced, including internally displaced persons (IDPs), who have crossed no international border. There is no equivalent definition for migrants, but like refugees, asylum-seekers, and IDPs, international human rights law provides a framework for their protection. The chapter explains the difference between refugee status and asylum, focusing on non-refoulement in international law. It discusses the rights that are guaranteed during displacement, particularly those pertaining to detention and humanitarian relief. Given that refugee status is intended to be temporary, the final section looks at cessation and durable solutions, either following voluntary return, through local integration, or resettlement in some third State.
21. Policing—Powers, Accountability, and Governance
Authors: Elliott Mark , Thomas Robert
Published: September 2024

This chapter is concerned with three key constitutional issues relating to policing—the roles, functions, and powers of which are multifarious and complex meaning that, inevitably, so are public law’s responses. First, the chapter considers the extent and limits of the powers of the police—and, correlatively, the relevant rights of individuals. Second, the chapter examines the arrangements for overseeing the police and holding them to account. Third, the chapter addresses police governance, including the introduction of Police and Crime Commissioners and the balance between political direction and police independence.
10. The International Protection Of Substantive Rights (II)
Authors: Cançado Trindade Antônio Augusto , González-Salzberg Damián A.
Published: September 2024

This chapter continues the discussion of the international protection of substantive rights commenced in Chapter 9. It focuses on rights held by individuals as members of specific social collectives and well as on a fundamental right that belongs to a collective or people rather than to their members individually. The chapter starts with a discussion of the prohibition of discrimination, which is both a fundamental right and a general guarantee applicable to respecting and protecting all rights. Then, it delves into the discussion of rights held by individuals belonging to two social groups, covering the topics of women’s and children’s rights. The chapter concludes by exploring the right to self-determination of peoples, a paradigmatic example of a right whose right-holder is a collective of individuals, as well as the rights of indigenous peoples.
1. The Nature of the International Legal System
Authors: Dixon Martin , McCorquodale Robert , Williams Sarah
Published: September 2024

International law is a description of an entire legal system: the international legal system. It is an international legal system by which legal rules are created in order to structure and organise societies and relationships. It acknowledges the influence of political, economic, social and cultural processes upon the development of legal rules. This chapter discusses the relevance of international law; the international community and international law; theories of international law; and the practice of international law.
4. Crimes of negligence
Authors: Ormerod David , Laird Karl , Gibson Matthew
Published: September 2024

Negligence refers to conduct that does not conform to what would be expected of a reasonable person. Along with intention and recklessness, negligence involves a failure to comply with an objective standard of conduct; that is, all of them are forms of fault. To prove negligence, the prosecution are not required to show that the accused failed to foresee a relevant risk; they only have to establish that D’s conduct failed to comply with a reasonable standard. A person is negligent if unable to comply with an objective standard of behaviour set by the law. This chapter deals with crimes of negligence and negligence as mens rea, negligence as the basis of liability, degrees of negligence, negligence as a form of culpable fault, and negligence and capacity.
22. Fraud
Authors: Ormerod David , Laird Karl , Gibson Matthew
Published: September 2024

This chapter considers the offences under the Fraud Act 2006 and the important body of case law that now exists interpreting the 2006 Act. It discusses the common elements of the offence of fraud; namely, dishonesty (including the impact of Ivey and Barton and Booth), with intent to gain or cause loss or to expose to a risk of loss, and remoteness of intention. The fraud offences are each examined in turn: fraud by false representation, fraud by failing to disclose information, fraud by abuse of position, possession of articles for fraud, and making or supplying articles for use in frauds. The chapter provides extensive discussion of the desirability of having a general fraud offence and examines the difficulties encountered in relying so much upon the concept of dishonesty.
26. Lenders’ Rights and Remedies
Authors: McFarlane Ben , Hopkins Nicholas , Nield Sarah
Published: September 2024

All books in this flagship series contain carefully selected substantial extracts from key cases, legislation, and academic debate, providing able students with a stand-alone resource. This chapter concentrates on the rights and powers conferred upon the lender to enforce its security over land. A lender’s rights and remedies arise from the nature of its security, the powers implied by the Law of Property Act 1925, and any express powers. The lender’s right to take possession originated at common law, but is now conferred by s 87(1) of the 1925 Act. The lender’s power of sale and to appoint a receiver are implied by s 101(1)(i) and (iii) of the 1925 Act, respectively, and can only be exercised if the borrower has defaulted. The duties that a lender or receiver owes when selling the mortgaged property are explained, as well as the position of a purchaser from a lender or receiver where there has been a breach of duty.
6. The law and institutions of the European Union (EU)
Authors: Rutherford Helen , Kotecha Birju , Macfarlane Angela
Published: September 2024

After the ‘Brexit’ referendum, the UK left the European Union (EU) at the end of January 2020. Whilst the UK is now no longer a Member State of the EU, the UK’s membership had a significant and, some might argue, lasting influence on the English legal system, and awareness of EU law is still going to be valuable. This chapter looks at the (historical) impact of EU membership on the English legal system including its effect on law-making institutions such as Parliament. The chapter offers very useful background reading on how EU law is made, interpreted, and applied in Member States. The EU is administered by several supranational institutions including the European Council, the Council of the European Union, the European Commission, the European Parliament, and the Court of Justice of the European Union (CJEU). The main sources of EU law are: primary legislation, i.e. the treaties; secondary legislation, including regulations and directives; and the case law of the CJEU. The chapter explains the role of these bodies and the various sources of EU law, including whether EU law is said to have direct effect, i.e. be enforceable by individuals before national courts, or indirect effect, where national courts are obliged to interpret national legislation and case law, so far as possible to conform with a relevant directive. The chapter finally turns to examine the consequences of the UK’s withdrawal, including the role of important legislation such as the EU Withdrawal Act 2018, and the Retained EU Law (Revocation and Reform) Act 2023.
1. Criminal law in context
Authors: Allen Michael J. , Edwards Ian
Published: September 2024

Course-focused and comprehensive, the Textbook on series provides an accessible overview of the key areas on the law curriculum. This introductory chapter answers the following questions: What is a crime? What purpose or function does the criminal law serve? What reasons are there for the criminalisation of some types of conduct? What are the purposes of punishment? What are the political and social contexts in which criminal law operates? The chapter provides an overview of key aspects of the criminal process, including mode of trial, the decision to prosecute, the burden and standard of proof, the functions of judge and jury, and sentencing. It also considers the impact of the European Convention on Human Rights on English law. A Law in Context feature examines the use of the criminal law during the COVID-19 pandemic.
2. Actus reus
Authors: Allen Michael J. , Edwards Ian
Published: September 2024

Course-focused and comprehensive, the Textbook on series provides an accessible overview of the key areas on the law curriculum. This chapter explains the concept of actus reus. It discusses the elements of crime, defining an actus reus, proving an actus reus, that conduct must be voluntary, state of affairs offences, omissions liability (situations in which a person will be liable for failing to act), causation (including the principles of factual and legal causation), and coincidence in time of actus reus and mens rea. A Law in Context feature analyses critically English law’s approach to liability for causing another person’s suicide.
1. Introduction
Authors: Keane Adrian , McKeown Paul
Published: September 2024

Evidence is information by which facts tend to be proved, and the law of evidence is that body of law and discretion regulating the means by which facts may be proved in both courts of law and tribunals and arbitrations in which the strict rules of evidence apply. This introductory chapter discusses truth and the fact-finding process and explains how getting to the truth in court is hampered by practical constraints, the adversarial system, the rules of evidence themselves, and the fact that litigation is a human endeavour that necessarily provides scope for differences of opinion, error, deceit, and lies. The chapter also contains a brief history of the development of the law to date.
7. Examination-in-chief
Authors: Keane Adrian , McKeown Paul
Published: September 2024

The questioning of witnesses, which generally falls into three stages, known as examination-in-chief, cross-examination, and re-examination, is central to the English adversary system of justice. This chapter focuses on the first stage, examination-in-chief. In this stage the party calling a witness, or counsel on his behalf, will seek to elicit evidence that supports his version of the facts in issue. The discussions cover young and vulnerable witnesses; the rule against leading questions and the exceptions to the rule; refreshing the memory in court and out of court; the rule against previous consistent or self-serving statements and the common law exceptions to the rule (complaints in sexual cases, statements admissible to rebut allegations of recent fabrication, statements made on accusation, previous identification, statements admissible as part of the res gestae and statements in documents used to refresh the memory and received in evidence); and unfavourable and hostile witnesses.
10. Visual and voice identification
Authors: Keane Adrian , McKeown Paul
Published: September 2024

This chapter considers the risk of mistaken identification, and the law and procedure relating to evidence of visual and voice identification. In respect of evidence of visual identification, the chapter addresses: the Turnbull guidelines, including when a judge should stop a case and the direction to be given to the jury; visual recognition, including recognition by the jury themselves from a film, photograph, or other image; evidence of analysis of films, photographs, or other images; pre-trial procedure, including procedure relating to recognition by a witness from viewing films, photographs, either formally or informally; and admissibility where there have been breaches of pre-trial procedure. In respect of evidence of voice identification, the chapter addresses: pre-trial procedure; voice comparison by the jury with the assistance of experts or lay listeners; and the warning to be given to the jury (essentially an adaption of the Turnbull warning, but with particular focus on the factors which might affect the reliability of voice identification).
Contract Law Concentrate
Authors: Shaw-Mellors Adam , Devenney James
Published: September 2024

Each Concentrate revision guide is packed with essential information, key cases, revision tips, exam Q&As, and more. Concentrates show you what to expect in a law exam, what examiners are looking for, and how to achieve extra marks. Contract Law Concentrate contains a wealth of information on the field of contract law to aid with revision and understanding the elements of the contract law syllabus. It looks specifically at the components of agreement, enforceability criteria comprising intention to create legal relations, consideration, and the doctrine of promissory estoppel. It also focuses on some problems associated with reaching agreement, such as whether the terms are sufficiently certain, and mistakes which prevent agreement. The doctrine of privity determines who has the ability to enforce the contract and whether a third party can take the intended benefit of a contract. Contract Law Concentrate focuses on the terms (or promises) of the contract and breach of contract when those promises are broken. It also examines exemption clauses and unfair contract terms. Next it looks at remedies for the breach of contract. It then turns to contractual impossibility and risk where the default rules of common mistake (initial impossibility) and frustration (subsequent impossibility) will determine the parties’ positions in the absence of party allocation. Finally, it outlines contractual remedies for actionable misrepresentations and looks briefly at the common law doctrine of duress and the equitable doctrine of undue influence.
1. Agreement
Authors: Devenney James , Shaw-Mellors Adam
Published: September 2024

Each Concentrate revision guide is packed with essential information, key cases, revision tips, exam Q&As, and more. Concentrates show you what to expect in a law exam, what examiners are looking for, and how to achieve extra marks. This chapter discusses the components of agreement; an essential ingredient of a contract. Traditionally, an agreement is comprised of an offer and a corresponding acceptance. There are two types of agreement: bilateral and unilateral. Bilateral agreements are by far the most common in practice and consist of a promise in exchange for a promise. Unilateral agreements consist of a promise in exchange for an act. This chapter analyses the agreement process in terms of offer, acceptance, and revocation of offers in bilateral and unilateral scenarios in order to provide structures and scenarios for future use. It also explains the two-contract analysis which is used to impose pre-contractual liability in English law.
2. Agreement problems
Authors: Devenney James , Shaw-Mellors Adam
Published: September 2024

Each Concentrate revision guide is packed with essential information, key cases, revision tips, exam Q&As, and more. Concentrates show you what to expect in a law exam, what examiners are looking for, and how to achieve extra marks. This chapter focuses on issues which may prevent the parties from reaching agreement. Agreement problems generally affect the agreement by rendering it void. It is necessary, however, to distinguish a void contract from one which is merely voidable. If an apparent agreement is too uncertain in its terms (e.g. because it is vague or essential terms are missing), the courts will not enforce it because they will not construct a binding contract for the parties. An apparent agreement may be void where the parties entered into the agreement under a ‘fundamental’ mistake which the law recognizes as preventing the parties from ever reaching agreement.
13. The buyer’s remedies
Authors: Beheshti Reza , Saintier Séverine , Thomas Sean
Published: September 2024

This chapter presents the remedies for buyers if a seller breaches their obligations under the contract. Some breaches allow the buyer to reject the goods and terminate the contract. The buyer's basic remedies under the Act are the right to reject the goods, terminate the contract, and claim damages. The Consumer Rights Act 2015 (CRA 2015) provides a distinctive legal regime for consumer sale, which includes four remedies to the consumer where goods are not in conformity with the contract. The chapter then enumerates the rights under CRA 2015: the right to reject goods, the right to cure encompassing the repair or replacement of the goods, reduction of the price payable, and a final right to reject.
21. Credit and security
Authors: Beheshti Reza , Saintier Séverine , Thomas Sean
Published: September 2024

This chapter discusses the interplay between credit and security. In a commercial context, credit refers to a person's financial status or reputation for solvency or a sum of money owed from the bank's records. Additionally, credit facilities play a key role in financing the acquisition of goods and services or supporting general business activity. Credit is supplied whenever the payment of a debt is contractually deferred through either loan credit and sales credit or fixed sum and revolving credit. The chapter then provides an overview of the variety of arrangements developed to fulfil the creditor's desire for either real or personal security.
23. Personal security
Authors: Beheshti Reza , Saintier Séverine , Thomas Sean
Published: September 2024

This chapter examines the extent of personal security. Personal security is provided by means of contracts of suretyship, wherein the surety undertakes to be answerable for the contractual performance of another. Moreover, contracts of suretyship may be used to secure the performance of any kind of contractual undertaking, but they are most commonly used to secure payment of debts. The chapter cites that a contract of suretyship may be either a guarantee or an indemnity, but neither of them is used consistently. It also introduces letters of comfort as a means of reassuring a potential creditor about repaying the debt.
Converging functional phenotyping with systems mapping to illuminate the genotype–phenotype associations
Authors: Sun Ting , Shi Zheng , Jiang Rujia , Moshelion Menachem , Xu Pei
Published: September 2024

Illuminating the phenotype–genotype black box under complex traits is an ambitious goal for researchers. The generation of temporally or spatially phenotypic data today has far outpaced its interpretation, due to their highly dynamic nature depending on the environment and developmental stages. Here, we propose an integrated enviro-pheno-geno functional approach to pinpoint the major challenges of decomposing physiological traits. The strategy first features high-throughput functional physiological phenotyping (FPP) to efficiently acquire phenotypic and environmental data. It then features functional mapping (FM) and the extended systems mapping (SM) to tackle trait dynamics. FM, by modeling traits as continuous functions, can increase the power and efficiency in dissecting the spatiotemporal effects of QTLs. SM could enable reconstruction of a genotype–phenotype map from developmental pathways. We present a recent case study that combines FPP and SM to dissect complex physiological traits. This integrated approach will be an important engine to drive the translation of phenomic big data into genetic gain.
Economic Analyses for Disease Surveillance Planning and Advocacy
Authors: Hampton Lee M
Published: September 2024

Public health disease surveillance can guide a range of decisions related to the protection of populations. Economic analysis can be used to assess how surveillance for specific diseases can substitute for or complement other public health interventions and how to structure surveillance most efficiently. Assessing the value and costs of different disease surveillance options as part of broader disease prevention and control efforts is important for both using available resources efficiently to protect populations and communicating the need for additional resources as appropriate.
SARS-CoV-2 Variants May Affect Saliva RT-PCR Assay Sensitivity
Authors: Chwa Jason S , Shin Yunho , Lee Yesun , Fabrizio Thomas , Congrave-Wilson Zion , Cheng Wesley A , Jumarang Jaycee , Kim Minjun , Webby Richard , Bender Jeffrey M , Pannaraj Pia S
Published: September 2024

Background

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants demonstrate predilection for different regions of the respiratory tract. While saliva-based reverse transcription-polymerase chain reaction (RT-PCR) testing is a convenient, cost-effective alternative to nasopharyngeal swabs (NPS), few studies to date have investigated whether saliva sensitivity differs across variants of concern.

Methods

SARS-CoV-2 RT-PCR was performed on paired NPS and saliva specimens collected from individuals with acute coronavirus disease 2019 (COVID-19) symptoms or exposure to a COVID-19 household contact. Viral genome sequencing of NPS specimens and Los Angeles County surveillance data were used to determine the variant of infection. Saliva sensitivity was calculated using NPS-positive RT-PCR as the reference standard. Factors contributing to the likelihood of saliva SARS-CoV-2 RT-PCR positivity were evaluated with univariate and multivariable analyses.

Results

Between June 2020 and December 2022, 548 saliva samples paired with SARS-CoV-2 positive NPS samples were tested by RT-PCR. Overall, saliva sensitivity for SARS-CoV-2 detection was 61.7% (95% CI, 57.6%–65.7%). Sensitivity was highest with Delta infection (79.6%) compared to pre-Delta (58.5%) and Omicron (61.5%) (P = 0.003 and 0.01, respectively). Saliva sensitivity was higher in symptomatic individuals across all variants compared to asymptomatic cases [pre-Delta 80.6% vs 48.3% (P < 0.001), Delta 100% vs 72.5% (P = 0.03), Omicron 78.7% vs 51.2% (P < 0.001)]. Infection with Delta, symptoms, and high NPS viral load were independently associated with 2.99-, 3.45-, and 4.0-fold higher odds of SARS-CoV-2 detection by saliva-based RT-PCR (P = 0.004, <0.001, and <0.001), respectively.

Conclusions

As new variants emerge, evaluating saliva-based testing approaches may be crucial to ensure effective virus detection.
Impact of X-linked hypophosphatemic rickets/osteomalacia on health and quality of life: baseline data from the SUNFLOWER longitudinal, observational cohort study
Authors: Namba Noriyuki , Ito Nobuaki , Michigami Toshimi , Kang Hee Gyung , Kubota Takuo , Miyazaki Osamu , Shintani Ayumi , Kabata Daijiro , Nishida Yayoi , Fukumoto Seiji , Ozono Keiichi
Published: September 2024

The SUNFLOWER study was initiated in Japan and South Korea to clarify the course of X-linked hypophosphatemic rickets/osteomalacia (XLH); delineate its physical, mental, and financial burdens; and collect information on treatment. Here, we report cross-sectional data at the time of patient enrollment to better understand the real-world management and complications in patients with XLH and examine the effect of XLH on quality of life (QOL). This is an ongoing, longitudinal, observational cohort study of patients with a diagnosis of XLH. Data from 147 patients (118 in Japan and 29 in South Korea) were evaluated. In total, 77 children (mean age, 9.7 yr; 67.5% female) and 70 adults (mean age, 37.6 yr; 65.7% female) were enrolled. PHEX gene mutations were confirmed in 46/77 (59.7%) children and 37/70 (52.9%) adults. Most patients in both age groups were receiving a combination of phosphate and active vitamin D at baseline. The mean height Z-score was −2.21 among adults (male: −2.34; female: −2.14). The mean Rickets Severity Score in children was 1.62. Whereas children appeared to have low pain levels (mean revised faces pain scale score, 1.3), adults reported mild-to-moderate pain (mean Brief Pain Inventory pain severity, 2.02). Mean QOL in children (assessed using the 10-item short-form health survey for children) was low, with a score below normative level for physical functioning. In adults, results from the Western Ontario and McMaster Universities osteoarthritis index indicated the presence of pain, stiffness, and decreased physical function. The respective mean total days/year of work/school non-attendance due to symptoms/complications and management of XLH were 0.7 and 3.0 among adults, and 6.4 and 6.1 among children. Our findings reconfirmed a relationship between disease and QOL in patients with XLH. We anticipate that these data will be important in enabling clinicians to understand the daily reality of patients with XLH.
QTc prolongation across CDK4/6 inhibitors: a systematic review and meta-analysis of randomized controlled trials
Authors: Murad Bruno , Reis Pedro C A , Deberaldini Marinho Alice , Marin Comini Ana Carolina , Pinheiro Xavier Débora , Mella Soares Pessoa Beatriz , Raheem Farah , Ernst Brenda , Mina Lida A , Batalini Felipe
Published: September 2024

Background

Cyclin-dependent kinases (CDK) 4/6 inhibitors have significantly improved outcomes for patients with ER+/HER2− breast cancer. Nevertheless, they differ from each other in terms of chemical, biological, and pharmacological features, as well as toxicity profiles. We aim to determine whether QTc prolongation is caused by CDK4/6i in general or if it is associated with ribociclib only.

Methods

We systematically searched PubMed, Embase, and Cochrane Library for randomized controlled trials (RCTs) comparing the prevalence of QTc prolongation as an adverse event in HR+ breast cancer patients treated with CDK4/6i vs those without CDK4/6i. We pooled relative risk (RR) and mean difference (MD) with 95% confidence interval (CI) for the binary endpoint of QT prolongation.

Results

We included 14 RCTs comprising 16 196 patients, of whom 8576 underwent therapy with CDK4/6i. An increased risk of QTc prolongation was associated with the use of CDK4/6i (RR = 2.35, 95% CI = 1.67 to 3.29, P < .001; I2 = 44%). Subgroup analyses revealed a significant increase in the QTc interval for the ribociclib and palbociclib cohorts. The ribociclib subgroup showed a relative risk of 3.12 (95% CI = 2.09 to 4.65, P < .001; I2 = 12%), whereas the palbociclib subgroup had a relative risk of 1.51 (95% CI = 1.05 to 2.15, P = .025; I2 = 0%).

Conclusion

Palbociclib was associated with QTc prolongation; however, the relative risk for any grade QTc was quantitively twice with ribociclib. Furthermore, grade 3 QTc prolongations were observed exclusively with ribociclib. These results are important for guiding clinical decision-making and provide reassurance regarding the overall safety profile of this drug class.
A Review of Force Health Protection Aspects of Lyme Disease in the U.S. Military
Authors: Melanson Vanessa R , Bateman Stacey L , Hering Kalei , Weiss Thomas J , Reilly James L , Davis Keeley T , Gramlich Victoria A , Jankovich Alexis , Daffin McKenzie , Hershfield Jeremy R , Barnhill Jason C
Published: September 2024

Introduction

Lyme disease (LD) is an underrated threat to the military that negatively impacts mission readiness. Lyme disease has traditionally been thought to only be a risk in an operational context, where training or deployments are frequently conducted in heavily wooded environments. However, this view diminishes risks posed by many off-duty outdoor recreational activities. Furthermore, although the Army introduced a permethrin factory-treated Army Combat Uniform in 2012, permethrin retention and subsequent protection have been shown to decrease significantly after 3 months of wear. Thus, although LD is a known health risk that threatens unit readiness, beyond using treated uniforms there has been little progress at the unit level to address this threat.

Materials and Methods

Focusing on a narrative review of LD and its impact on U.S. military force health protection, sources included DoD websites and policies, government press releases and information papers from sources like the CDC and FDA, and scholarly peer-reviewed journals with full-text access from the online databases EBSCOhost, MEDLINE, SCOUT, and Google Scholar. Searches included the following key words: LD and military, Army, etiology, epidemiology, incidence, treatments, post-treatment LD, and chronic LD. Articles were selected for review based on the relevance of their abstracts and titles.

Results

Although the incidence of LD appears to be increasing among service members, it is difficult to attribute this increase to military-related duties. Also, despite ongoing LD research specifically conducted and funded by the DoD, there are limited data on the mitigating effects of force education and permethrin-treated uniforms on the LD threat. Therefore, it is reasonable to conclude that LD negatively impacts military readiness and monetary costs diverted from other priorities.

Conclusion

Lyme disease poses a genuine threat to the health and careers of service members and is an often-overlooked disruptor to military operations. Simple, feasible prevention strategies that are tailored to high-risk geographic regions can be emphasized by military units to reduce the incidence of on-duty and off-duty cases. Additionally, there remains a critical need for new preventative and diagnostic measures for LD.