bluuebunny/crossref_metadata_2025 huggingface dataset:
Gene Teller: an extensible Alexa Skill for gene-relevant databases
Authors: Hill Jon D
Published: July 2020

Voice assistants have become increasingly embedded in consumer electronics, as the quality of their interaction improves and the cost of hardware continues to drop. Despite their ubiquity, these assistants remain underutilized as a means of accessing biological research data. Gene Teller is a voice assistant service based on the Alexa Skills Kit and Amazon Lambda functions that enables scientists to query for gene-centric information in an intuitive manner. It includes several features, such as synonym disambiguation and short-term memory, that enable a natural conversational interaction, and is extensible to include new resources. The underlying architecture, based on Simple Storage Service and Amazon Web Services Lambda, is cost efficient and scalable.

Availability and implementation

A publicly accessible version of Gene Teller is available as an Alexa Skill from the Amazon Marketplace at https://www.amazon.com/dp/B08BRD8SS8. The source code is freely available on GitHub at https://github.com/solinvicta/geneTeller.
OPA1 deficiency accelerates hippocampal synaptic remodelling and age-related deficits in learning and memory
Authors: Bevan Ryan J , Williams Pete A , Waters Caroline T , Thirgood Rebecca , Mui Amanda , Seto Sharon , Good Mark , Morgan James E , Votruba Marcela , Erchova Irina
Published: July 2020

A healthy mitochondrial network is essential for the maintenance of neuronal synaptic integrity. Mitochondrial and metabolic dysfunction contributes to the pathogenesis of many neurodegenerative diseases including dementia. OPA1 is the master regulator of mitochondrial fusion and fission and is likely to play an important role during neurodegenerative events. To explore this, we quantified hippocampal dendritic and synaptic integrity and the learning and memory performance of aged Opa1 haploinsufficient mice carrying the Opa1Q285X mutation (B6; C3-Opa1Q285STOP; Opa1+/−). We demonstrate that heterozygous loss of Opa1 results in premature age-related loss of spines in hippocampal pyramidal CA1 neurons and a reduction in synaptic density in the hippocampus. This loss is associated with subtle memory deficits in both spatial novelty and object recognition. We hypothesize that metabolic failure to maintain normal neuronal activity at the level of a single spine leads to premature age-related memory deficits. These results highlight the importance of mitochondrial homeostasis for maintenance of neuronal function during ageing.
The Small and Efficient Language Network of Polyglots and Hyper-polyglots
Authors: Jouravlev Olessia , Mineroff Zachary , Blank Idan A , Fedorenko Evelina
Published: July 2020

Acquiring a foreign language is challenging for many adults. Yet certain individuals choose to acquire sometimes dozens of languages and often just for fun. Is there something special about the minds and brains of such polyglots? Using robust individual-level markers of language activity, measured with fMRI, we compared native language processing in polyglots versus matched controls. Polyglots (n = 17, including nine “hyper-polyglots” with proficiency in 10–55 languages) used fewer neural resources to process language: Their activations were smaller in both magnitude and extent. This difference was spatially and functionally selective: The groups were similar in their activation of two other brain networks—the multiple demand network and the default mode network. We hypothesize that the activation reduction in the language network is experientially driven, such that the acquisition and use of multiple languages makes language processing generally more efficient. However, genetic and longitudinal studies will be critical to distinguish this hypothesis from the one whereby polyglots’ brains already differ at birth or early in development. This initial characterization of polyglots’ language network opens the door to future investigations of the cognitive and neural architecture of individuals who gain mastery of multiple languages, including changes in this architecture with linguistic experiences.
Dual Role of Rbpj in the Maintenance of Neural Progenitor Cells and Neuronal Migration in Cortical Development
Authors: Son Alexander I , Mohammad Shahid , Sasaki Toru , Ishii Seiji , Yamashita Satoshi , Hashimoto-Torii Kazue , Torii Masaaki
Published: July 2020

The development of the cerebral cortex is directed by a series of methodically precise events, including progenitor cell proliferation, neural differentiation, and cell positioning. Over the past decade, many studies have demonstrated the critical contributions of Notch signaling in neurogenesis, including that in the developing telencephalon. However, in vivo evidence for the role of Notch signaling in cortical development still remains limited partly due to the redundant functions of four mammalian Notch paralogues and embryonic lethality of the knockout mice. Here, we utilized the conditional deletion and in vivo gene manipulation of Rbpj, a transcription factor that mediates signaling by all four Notch receptors, to overcome these challenges and examined the specific roles of Rbpj in cortical development. We report severe structural abnormalities in the embryonic and postnatal cerebral cortex in Rbpj conditional knockout mice, which provide strong in vivo corroboration of previously reported functions of Notch signaling in neural development. Our results also provide evidence for a novel dual role of Rbpj in cell type-specific regulation of two key developmental events in the cerebral cortex: the maintenance of the undifferentiated state of neural progenitor cells, and the radial and tangential allocation of neurons, possibly through stage-dependent differential regulation of Ngn1.
Use of Drug-level Testing and Single-genome Sequencing to Unravel a Case of Human Immunodeficiency Virus Seroconversion on Pre-exposure Prophylaxis
Authors: Spinelli Matthew A , Lowery Brentton , Shuford Jennifer A , Spindler Jon , Kearney Mary F , McFarlane Jenny R , McDonald Cheryl , Okochi Hideaki , Phung Nhi , Kuncze Karen , Jee Kathryn , Johannessen DeeJay , Anderson Peter L , Smith Dawn K , Defechereux Patricia , Grant Robert M , Gandhi Monica
Published: July 2020

Cases of seroconversion on pre-exposure prophylaxis (PrEP) should be carefully investigated, given their public health implications and rarity. We report a case of transmitted drug resistance causing seroconversion on PrEP in spite of high adherence, confirmed with dried blood spot and segmental hair drug-level testing and single-genome sequencing.
Atherosclerotic Cardiovascular Events in Patients Infected With Human Immunodeficiency Virus and Hepatitis C Virus
Authors: Tan Boun Kim , Chalouni Mathieu , Ceron Dominique Salmon , Cinaud Alexandre , Esterle Laure , Loko Marc Arthur , Katlama Christine , Poizot-Martin Isabelle , Neau Didier , Chas Julie , Morlat Philippe , Rosenthal Eric , Lacombe Karine , Naqvi Alissa , Barange Karl , Bouchaud Olivier , Gervais Anne , Lascoux-Combe Caroline , Garipuy Daniel , Alric Laurent , Goujard Cécile , Miailhes Patrick , Aumaitre Hugues , Duvivier Claudine , Simon Anne , Lopez-Zaragoza Jose-Luis , Zucman David , Raffi François , Lazaro Estibaliz , Rey David , Piroth Lionel , Boué François , Gilbert Camille , Bani-Sadr Firouzé , Dabis François , Sogni’ Philippe , Wittkop Linda , Boccara Franck ,   ANRS CO13 HEPAVIH study group
Published: July 2020

Background

An increased risk of cardiovascular disease (CVD) was reported in patients coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV), without identifying factors associated with atherosclerotic CVD (ASCVD) events.

Methods

HIV-HCV coinfected patients were enrolled in the Agence Nationale de Recherches sur le Sida et les hépatites virales (ANRS) CO13 HEPAVIH nationwide cohort. Primary outcome was total ASCVD events. Secondary outcomes were coronary and/or cerebral ASCVD events, and peripheral artery disease (PAD) ASCVD events. Incidences were estimated using the Aalen-Johansen method. Factors associated with ASCVD were identified using cause-specific Cox proportional hazards models.

Results

At baseline, median age of the study population (N = 1213) was 45.4 (interquartile range [IQR] 42.1−49.0) years and 70.3% were men. After a median follow-up of 5.1 (IQR 3.9−7.0) years, the incidence was 6.98 (95% confidence interval [CI], 5.19−9.38) per 1000 person-years for total ASCVD events, 4.01 (2.78−6.00) for coronary and/or cerebral events, and 3.17 (2.05−4.92) for PAD ASCVD events. Aging (hazard ratio [HR] 1.06; 95% CI, 1.01−1.12), prior CVD (HR 8.48; 95% CI, 3.14−22.91), high total cholesterol (HR 1.43; 95% CI, 1.11−1.83), high-density lipoprotein cholesterol (HR 0.22; 95% CI, 0.08−0.63), statin use (HR 3.31; 95% CI, 1.31−8.38), and high alcohol intake (HR 3.18; 95% CI, 1.35−7.52) were independently associated with total ASCVD events, whereas undetectable baseline viral load (HR 0.41, 95% CI, 0.18−0.96) was associated with coronary and/or cerebral events.

Conclusions

HIV-HCV coinfected patients experienced a high incidence of ASCVD events. Some traditional cardiovascular risk factors were the main determinants of ASCVD. Controlling cholesterol abnormalities and maintaining undetectable HIV RNA are essential to control cardiovascular risk.
Outcome of Dialysis-Requiring Acute Kidney Injury in Patients With Infective Endocarditis: A Nationwide Study
Authors: Petersen Jeppe Kofoed , Jensen Andreas Dalsgaard , Bruun Niels Eske , Kamper Anne-Lise , Butt Jawad Haider , Havers-Borgersen Eva , Chaudry Mavish S , Torp-Pedersen Christian , Køber Lars , Fosbøl Emil Loldrup , Østergaard Lauge
Published: July 2020

Background

Infective endocarditis (IE) may be complicated by acute kidney injury, yet data on the use of dialysis and subsequent reversibility are sparse.

Methods

Using Danish nationwide registries, we identified patients with first-time IE from 2000 to 2017. Dialysis-naïve patients were grouped into: those with and those without dialysis during admission with IE. Continuation of dialysis was followed 1 year postdischarge. Multivariable adjusted Cox proportional hazard analysis was used to examine 1-year mortality for patients surviving IE according to use of dialysis.

Results

We included 7307 patients with IE; 416 patients (5.7%) initiated dialysis treatment during admission with IE and these were younger, had more comorbidities and more often underwent cardiac valve surgery compared with nondialysis patients (47.4% vs 20.9%). In patients with both cardiac valve surgery and dialysis treatment (n = 197), 153 (77.7%) initiated dialysis on or after the date of surgery. The in-hospital mortality was 40.4% and 19.0% for patients with and without dialysis, respectively (P < .0001). Of those who started dialysis and survived hospitalization, 21.6% continued dialysis treatment within 1 year after discharge. In multivariable adjusted analysis, dialysis during admission with IE was associated with an increased 1-year mortality from IE discharge, hazard ratio = 1.64 (95% confidence interval, 1.21–2.23).

Conclusion

In dialysis-naïve patients with IE, approximately 1 in 20 patients initiated dialysis treatment during admission with IE. Dialysis identified a high-risk group with an in-hospital mortality of 40% and an approximate 20% risk of continued dialysis. Those with dialysis during admission with IE showed worse long-term outcomes than those without.
Decision Making and Implementation of the First Public Sector Introduction of Typhoid Conjugate Vaccine—Navi Mumbai, India, 2018
Authors: Date Kashmira , Shimpi Rahul , Luby Stephen , N Ramaswami , Haldar Pradeep , Katkar Arun , Wannemuehler Kathleen , Mogasale Vittal , Pallas Sarah , Song Dayoung , Kunwar Abhishek , Loharikar Anagha , Yewale Vijay , Ahmed Danish , Horng Lily , Wilhelm Elisabeth , Bahl Sunil , Harvey Pauline , Dutta Shanta , Bhatnagar Pankaj
Published: July 2020

Background

Typhoid fever prevention and control efforts are critical in an era of rising antimicrobial resistance among typhoid pathogens. India remains one of the highest typhoid disease burden countries, although a highly efficacious typhoid conjugate vaccine (TCV), prequalified by the World Health Organization in 2017, has been available since 2013. In 2018, the Navi Mumbai Municipal Corporation (NMMC) introduced TCV into its immunization program, targeting children aged 9 months to 14 years in 11 of 22 areas (Phase 1 campaign). We describe the decision making, implementation, and delivery costing to inform TCV use in other settings.

Methods

We collected information on the decision making and campaign implementation in addition to administrative coverage from NMMC and partners. We then used a microcosting approach from the local government (NMMC) perspective, using a new Microsoft Excel–based tool to estimate the financial and economic vaccination campaign costs.

Results

The planning and implementation of the campaign were led by NMMC with support from multiple partners. A fixed-post campaign was conducted during weekends and public holidays in July–August 2018 which achieved an administrative vaccination coverage of 71% (ranging from 46% in high-income to 92% in low-income areas). Not including vaccine and vaccination supplies, the average financial cost and economic cost per dose of TCV delivery were $0.45 and $1.42, respectively.

Conclusion

The first public sector TCV campaign was successfully implemented by NMMC, with high administrative coverage in slums and low-income areas. Delivery cost estimates provide important inputs to evaluate the cost-effectiveness and affordability of TCV vaccination through public sector preventive campaigns.
Disease Prevention Not Decolonization: A Model for Fecal Microbiota Transplantation in Patients Colonized With Multidrug-resistant Organisms
Authors: Ghani Rohma , Mullish Benjamin H , McDonald Julie A K , Ghazy Anan , Williams Horace R T , Brannigan Eimear T , Mookerjee Siddharth , Satta Giovanni , Gilchrist Mark , Duncan Neill , Corbett Richard , Innes Andrew J , Pavlů Jiří , Thursz Mark R , Davies Frances , Marchesi Julian R
Published: July 2020

Fecal microbiota transplantation (FMT) yields variable intestinal decolonization results for multidrug-resistant organisms (MDROs). This study showed significant reductions in antibiotic duration, bacteremia, and length of stay in 20 patients colonized/infected with MDRO receiving FMT (compared with pre-FMT history, and a matched group not receiving FMT), despite modest decolonization rates.
The complex interplay between kidney injury and inflammation
Authors: McWilliam Stephen J , Wright Rachael D , Welsh Gavin I , Tuffin Jack , Budge Kelly L , Swan Laura , Wilm Thomas , Martinas Ioana-Roxana , Littlewood James , Oni Louise
Published: July 2020

Acute kidney injury (AKI) has gained significant attention following patient safety alerts about the increased risk of harm to patients, including increased mortality and hospitalization. Common causes of AKI include hypovolaemia, nephrotoxic medications, ischaemia and acute glomerulonephritis, although in reality it may be undetermined or multifactorial. A period of inflammation either as a contributor to the kidney injury or resulting from the injury is almost universally seen. This article was compiled following a workshop exploring the interplay between injury and inflammation. AKI is characterized by some degree of renal cell death through either apoptosis or necrosis, together with a strong inflammatory response. Studies interrogating the resolution of renal inflammation identify a whole range of molecules that are upregulated and confirm that the kidneys are able to intrinsically regenerate after an episode of AKI, provided the threshold of damage is not too high. Kidneys are unable to generate new nephrons, and dysfunctional or repeated episodes will lead to further nephron loss that is ultimately associated with the development of renal fibrosis and chronic kidney disease (CKD). The AKI to CKD transition is a complex process mainly facilitated by maladaptive repair mechanisms. Early biomarkers mapping out this process would allow a personalized approach to identifying patients with AKI who are at high risk of developing fibrosis and subsequent CKD. This review article highlights this process and explains how laboratory models of renal inflammation and injury assist with understanding the underlying disease process and allow interrogation of medications aimed at targeting the mechanistic interplay.
Seasonal rainfall in subtropical montane cloud forests drives demographic fluctuations in a Green-backed Tit population
Authors: Shiao Ming-Tang , Chuang Mei-Chen , Yuan Hsiao-Wei , Wang Ying
Published: July 2020

Montane birds are vulnerable to climate change. However, the mechanisms by which weather drives demographic processes in montane birds have seldom been investigated. We conducted a long-term study (2009–2019) on the Green-backed Tit (Parus monticolus), an insectivorous passerine, in the montane cloud forest of subtropical Taiwan. We explored the effects of weather variability on the productivity and survival of adult Green-backed Tits. Nest survival was negatively associated with seasonal rainfall during the breeding season (April–July) and was lower in early clutches than in late clutches. Higher typhoon-induced precipitation during the postbreeding period (July–September) was related to reduced adult survival, but neither summer temperature nor winter weather conditions were found to be related to adult bird survival. We developed a stochastic simulation model for Green-backed Tit population dynamics based on empirical data. We compared the simulated time-series and observed population growth rates (λ) and found that 80% (8/10 yr) of the observed λ fell within the 5th and 95th percentiles of the simulated data over the 10-yr period. Moreover, the simulated average (± standard deviation) of the geometric mean of λ over 10 yr (1.05 ± 0.07) was close to that observed from 2009 to 2019 (0.99), which provided confidence that the model effectively simulated the population growth rate of the Green-backed Tit. We conducted a sensitivity analysis for λ and found that juvenile and adult survival influenced by typhoon-induced rainfall were the greatest contributors to the variance in the growth rate of the Green-backed Tit population. With the onset of intensified seasonal precipitation associated with global warming, the population growth and density of Green-backed Tits will decline substantially. Our results suggest that under scenarios of high emissions of greenhouse gas, this local population of Green-backed Tits will not persist in the near future.
Family-Centered Care in the Transition to Early Hearing Intervention
Authors: Nickbakht Mansoureh , Meyer Carly , Scarinci Nerina , Beswick Rachael
Published: July 2020

This study aimed to explore and compare families’ and professionals’ perspectives on the implementation of family-centered care (FCC) (Moeller, Carr, Seaver, Stredler-Brown, & Holzinger, 2013) during the period between diagnosis of hearing loss (HL) and enrollment in early intervention (EI). A convergent mixed-methods study incorporating self-report questionnaires and semistructured in-depth interviews was used. Seventeen family members of children with HL and the 11 professionals who support these families participated in this study. The results suggested that the services engaged during the transition period partially adhered to the principles of FCC, including the provision of timely access to EI services and provision of emotional and social support. However, areas for improvement identified include strengthening family/professional partnerships, shared decision-making processes, collaborative teamwork, program monitoring, and consistency in the provision of information and support. Qualitative and quantitative research findings also indicated a lack of consistency in service provision during the transition period.
Management of ventricular electrical storm: a contemporary appraisal
Authors: Kowlgi Gurukripa N , Cha Yong-Mei
Published: July 2020

Ventricular electrical storm (VES) is a clinical scenario characterized by the clustering of multiple episodes of sustained ventricular arrhythmias (VA) over a short duration. Patients with VES are prone to psychological disorders, heart failure decompensation, and increased mortality. Studies have shown that 10–28% of the patients with secondary prevention ICDs can sustain VES. The triad of a susceptible electrophysiologic substrate, triggers, and autonomic dysregulation govern the pathogenesis of VES. The rate of VA, underlying ventricular function, and the presence of implantable cardioverter-defibrillator (ICD) determine the clinical presentation. A multi-faceted approach is often required for management consisting of acute hemodynamic stabilization, ICD reprogramming when appropriate, antiarrhythmic drug therapy, and sedation. Some patients may be eligible for catheter ablation, and autonomic modulation with thoracic epidural anesthesia, stellate ganglion block, or cardiac sympathetic denervation. Hemodynamically unstable patients may benefit from the use of left ventricular assist devices, and extracorporeal membrane oxygenation. Special scenarios such as idiopathic ventricular fibrillation, Brugada syndrome, Long and short QT syndrome, early repolarization syndrome, catecholaminergic polymorphic ventricular tachycardia, arrhythmogenic right ventricular cardiomyopathy, and cardiac sarcoidosis have been described as well. VES is a cardiac emergency that requires swift intervention. It is associated with poor short and long-term outcomes. A structured team-based management approach is paramount for the safe and effective treatment of this sick cohort.
Primary care visits can reduce the risk of potentially avoidable hospitalizations among persons with diabetes in France
Authors: Georgescu Vera , Green Anders , Jensen Peter B , Möller Sören , Renard Eric , Mercier Gregoire
Published: July 2020

Background

Diabetes is a frequent chronic condition, which can lead to costly complications if not managed well in the primary care setting. Potentially avoidable hospitalizations (PAH) are considered as an indirect measure of primary care. However, the association between primary care use and PAH in diabetic patients has not been investigated in France.

Methods

We investigate the association between primary care indicators and PAH at an individual level among persons with diabetes in a population-based cohort study on the French national health insurance database (EGB sample). PAH occurrence in 2013 was modeled as a function of primary care use and access, health status and socio-economic indicators over the exposure period 2011–12 using a cause-specific hazards model with death as a competing event.

Results

We included 25 293 diabetics in our cohort, among which 385 (1.5%) experienced at least 1 PAH in 2013. After adjustment on health status indicators, primary care use had a protective effect against PAH. Diabetic patients who had seen a general practitioner (GP) 10–14 times had a reduced hazard of PAH compared to less frequent encounters (HR=0.49, P<0.001). The effect size decreased when the number of encounters increased, suggesting a remaining confounding effect of health status.

Conclusions

For the first time in France, this study shows a protective effect of the number of GP encounters against PAH at an individual level and highlights the importance of a frequent monitoring of diabetic patients in the primary care setting to prevent PAH occurrence.
Statistical rock physics inversion of elastic and electrical properties for CO2 sequestration studies
Authors: Ayani Mohit , Grana Dario
Published: July 2020

We present a statistical rock physics inversion of the elastic and electrical properties to estimate the petrophysical properties and quantify the associated uncertainty. The inversion method combines statistical rock physics modeling with Bayesian inverse theory. The model variables of interest are porosity and fluid saturations. The rock physics model includes the elastic and electrical components and can be applied to the results of seismic and electromagnetic inversion. To describe the non-Gaussian behaviour of the model properties, we adopt non-parametric probability density functions to sample multimodal and skewed distributions of the model variables. Different from machine learning approach, the proposed method is not completely data-driven but is based on a statistical rock physics model to link the model parameters to the data. The proposed method provides pointwise posterior distributions of the porosity and CO2 saturation along with the most-likely models and the associated uncertainty. The method is validated using synthetic and real data acquired for CO2 sequestration studies in different formations: the Rock Springs Uplift in Southwestern Wyoming and the Johansen formation in the North Sea, offshore Norway. The proposed approach is validated under different noise conditions and compared to traditional parametric approaches based on Gaussian assumptions. The results show that the proposed method provides an accurate inversion framework where instead of fitting the relationship between the model and the data, we account for the uncertainty in the rock physics model.
Business Law 2020-2021
Authors: Slorach J. Scott , Ellis Jason
Published: July 2020

Business Law provides practical, up-to-date coverage of company, partnership, taxation, and insolvency law, plus all relevant aspects of EU law. The title provides all of the relevant material needed to understand the latest legal developments affecting business law transactions. Coverage of the Companies Act 2006 is fully integrated and given prominence, mirroring the emphasis that business law courses place on this central piece of legislation. Additional emphasis has been placed on taxation and business accounts. Examples are used throughout the volume, which helps readers to contextualise their learning effectively. Updated statutory references allow for the cross-referencing to appropriate primary sources, and the interpretation of such sources. The volume looks at partnerships, companies, taxation, insolvency, and other topics such as choice of business medium, limited liability partnerships, sale of a business, and shareholder agreements.
17. Income tax: sole traders and partnerships
Authors: Slorach J. Scott , Ellis Jason
Published: July 2020

This chapter considers the taxation of income earned from a trade or profession. It covers the basic system of taxation; taxable profits for business; the basis of assessment; losses under the income tax system; and income tax liability of partnerships.
28. Limited liability partnerships
Authors: Slorach J. Scott , Ellis Jason
Published: July 2020

This chapter first discusses the key elements of limited liability partnerships (LLPs). It then considers the factors influencing choice of LLP. There are two instances where the question of choosing an LLP arises: as part of a business start-up or where an existing partnership is considering conversion. When considering LLPs, it should always be remembered that their resemblance to traditional partnerships is an exception rather than a rule, and that it is better to think of them as corporate structures.
20. Assessment guidance
Authors: Abbey Robert , Richards Mark
Published: July 2020

This chapter considers the process by which students are required to demonstrate their knowledge and abilities on property law and practice-the subject assessment or examination itself. It presents some hints and tips to enhance and improve examination technique.
7. Obtaining Identification Evidence
Authors: Hannibal Martin , Mountford Lisa
Published: July 2020

This chapter considers the following: the dangers of eye-witness identification; how identification evidence is obtained by the police during the police investigation; the pre-trial safeguards contained in the identification procedures under Code D of the Police and Criminal Evidence Act 1984 (PACE); the admissibility of eye-witness evidence obtained in breach of Code D; obtaining fingerprints, intimate and non-intimate samples at the police station; DNA evidence and identification evidence given by expert witnesses.
10. The Law and Practice Relating to Court Bail
Authors: Hannibal Martin , Mountford Lisa
Published: July 2020

This chapter explains the practice and procedure of court bail. It examines the grounds upon which bail might be refused; the factors a court can have regard to when deciding whether bail should be granted; the procedure at a contested bail application; appeals against bail decisions; and bail and Article 5 of the European Convention on Human Rights 1950 (ECHR 1950).
13. Crown Court Proceedings Pre-Trial
Authors: Hannibal Martin , Mountford Lisa
Published: July 2020

This chapter deals with pre-trial practices and procedures of indictable-only offences. It covers sending indictable-only cases to the Crown Court under s. 51 Crime and Disorder Act 1998 (CDA 1998); preparing for the preliminary hearing in the Crown Court; preparing for trial on indictment; pre-trial disclosure issues and defence statements; instructing counsel; and pre-trial hearings including the Plea and Trial Preparation Hearing (PTPH).
15. The Burden of Proof
Authors: Hannibal Martin , Mountford Lisa
Published: July 2020

This chapter explains the rules governing the legal and evidential burdens of proof that decide which party has the responsibility of proving a fact in issue to the court. It then discusses the degree of persuasiveness the evidence must attain to satisfy the appropriate standard of proof including the test for a successful submission of no case to answer and considers the human rights issues in those exceptional situations where the accused has the legal burden of proof. For both the prosecution and the defence, the rules that allocate the burden of proof and the degree of proof are fundamental to the outcome of a case at trial.
20. Private Privilege
Authors: Hannibal Martin , Mountford Lisa
Published: July 2020

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.
21. Sentencing Procedure and the General Principles of Sentencing
Authors: Hannibal Martin , Mountford Lisa
Published: July 2020

This chapter explains the procedure on passing sentence and the general principles that govern a court’s decision when passing sentence. It discusses the role of the Crow Prosecution Service (CPS) on sentence; the procedure on sentencing; hierarchy of sentences; sentencing aims; the basis of sentencing under the Criminal Justice Act 2003; Sentencing Council for England and Wales; sentencing guidelines in the Crown Court; how the defence solicitor assesses the seriousness of an offence; Magistrates’ Court Sentencing Guidelines (MCSGs); the importance of the pre—sentence report, personal offender mitigation; discount for timely guilty pleas; the Crown Court’s sentencing powers; victim impact statements; and taking other offences into consideration.
10. Taxation of sole proprietors and partnerships
Authors: Seymour Jennifer , Firth Clare , Crompton Lucy , Fox Helen , Seabridge Frances , Wigglesworth Susan , Smart Elizabeth
Published: July 2020

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.
13. Entitlement to the estate
Authors: Seymour Jennifer , Firth Clare , Crompton Lucy , Fox Helen , Seabridge Frances , Wigglesworth Susan , Smart Elizabeth
Published: July 2020

This chapter discusses the law underlying the entitlement to a person’s property on his or her death. It considers the law of ‘testate succession’ where the deceased has left a will; the law of ‘intestate succession’ if there is no will, or if any will left by the deceased is not wholly effective to dispose of their estate; the law governing devolution of property not passing under the terms of the deceased’s will or the operation of the intestacy rules; and the law enabling members of the family or dependants of the deceased to make claims for provision against the estate.
Regulation, diversity and function of MECP2 exon and 3′UTR isoforms
Authors: Rodrigues Deivid Carvalho , Mufteev Marat , Ellis James
Published: July 2020

The methyl-CpG-binding protein 2 (MECP2) is a critical global regulator of gene expression. Mutations in MECP2 cause neurodevelopmental disorders including Rett syndrome (RTT). MECP2 exon 2 is spliced into two alternative messenger ribonucleic acid (mRNA) isoforms encoding MECP2-E1 or MECP2-E2 protein isoforms that differ in their N-termini. MECP2-E2, isolated first, was used to define the general roles of MECP2 in methyl-deoxyribonucleic acid (DNA) binding, targeting of transcriptional regulatory complexes, and its disease-causing impact in RTT. It was later found that MECP2-E1 is the most abundant isoform in the brain and its exon 1 is also mutated in RTT. MECP2 transcripts undergo alternative polyadenylation generating mRNAs with four possible 3′untranslated region (UTR) lengths ranging from 130 to 8600 nt. Together, the exon and 3′UTR isoforms display remarkable abundance disparity across cell types and tissues during development. These findings indicate discrete means of regulation and suggest that protein isoforms perform non-overlapping roles. Multiple regulatory programs have been explored to explain these disparities. DNA methylation patterns of the MECP2 promoter and first intron impact MECP2-E1 and E2 isoform levels. Networks of microRNAs and RNA-binding proteins also post-transcriptionally regulate the stability and translation efficiency of MECP2 3′UTR isoforms. Finally, distinctions in biophysical properties in the N-termini between MECP2-E1 and E2 lead to variable protein stabilities and DNA binding dynamics. This review describes the steps taken from the discovery of MECP2, the description of its key functions, and its association with RTT, to the emergence of evidence revealing how MECP2 isoforms are differentially regulated at the transcriptional, post-transcriptional and post-translational levels.
Angiographic patency after robotic beating heart totally endoscopic coronary artery bypass grafting facilitated by automated distal anastomotic connectors
Authors: Balkhy Husam H , Nathan Sandeep , Torregrossa Gianluca , Kitahara Hiroto , Nisivaco Sarah , McCrorey Mackenzie , Patel Brooke
Published: July 2020

OBJECTIVES

Robotic totally endoscopic coronary artery bypass (TECAB) on the beating heart has been facilitated in our experience using distal coronary anastomotic connectors. In this study, we retrospectively reviewed graft patency in all robotic TECAB patients who underwent formal angiography at our current institution over a 5-year period.

METHODS

Between July 2013 and June 2018, 361 consecutive patients underwent robotic beating-heart TECAB. Of these patients, 121 had a follow-up angiogram, which assessed graft patency. Eighty-four patients had an angiogram as part of planned hybrid procedures and 37 patients underwent an unplanned angiogram for clinical indications. Retrospective analysis of angiographic patency and clinical outcomes was performed.

RESULTS

The mean Society of Thoracic Surgeons predicted risk of mortality was 1.8%. Single-vessel bypass was performed in 40 (33%) patients and multivessel grafting in 81 (67%). Average flow (ml/min) and pulsatility index in the grafts was 74.7 ± 39.1 and 1.42 ± 0.52, respectively. The number of grafts evaluated was 204 (130 left internal mammary artery and 74 right internal mammary artery grafts). The median time to angiography was 1.0 and 16.0 months and graft patency was 98% and 91% in the hybrid and non-hybrid groups, respectively. Overall graft patency was 95.6% (left internal mammary artery = 96%; right internal mammary artery = 93%). Left internal mammary artery to left anterior descending artery graft patency was 97%. Clinical follow-up was available for 316 (88%) patients at mean 22.5 ± 15.1 months. Freedom from major adverse cardiac events at 2 years was 92%.

CONCLUSIONS

In this consecutive series of patients undergoing formal angiography after robotic single and multivessel TECAB, we found satisfactory graft patency and 2-year clinical outcomes. Longer-term follow-up is warranted.
A Study in First-Episode Psychosis Patients: Does Angiotensin I-Converting Enzyme Activity Associated With Genotype Predict Symptom Severity Reductions After Treatment With Atypical Antipsychotic Risperidone?
Authors: Nani João V , Dal Mas Caroline , Yonamine Camila M , Ota Vanessa K , Noto Cristiano , Belangero Sintia I , Mari Jair J , Bressan Rodrigo , Cordeiro Quirino , Gadelha Ary , Hayashi Mirian A F
Published: July 2020

Background

Our previous studies showed increased angiotensin I-converting enzyme (ACE) activity in chronic schizophrenia patients compared with healthy control (HC) volunteers, and the relevance of combining ACE genotype and activity for predicting schizophrenia was suggested.

Methods

ACE activity was measured in plasma of ACE insertion/deletion (I/D) genotyped HC volunteers (n = 53) and antipsychotic-naïve first-episode psychosis (FEP) patients (n = 45) assessed at baseline (FEB-B) and also after 2 months (FEP-2M) of treatment with the atypical antipsychotic risperidone.

Results

ACE activity measurements showed significant differences among HC, FEP-B, and FEP-2M groups (F = 5.356, df = 2, P = .005) as well as between HC and FEP-2M (post-hoc Tukey’s multiple comparisons test, P = .004). No correlation was observed for ACE activity increases and symptom severity reductions in FEP as assessed by total Positive and Negative Syndrome Scale (r = −0.131, P = .434). FEP subgrouped by ACE I/D genotype showed significant ACE activity increases, mainly in the DD genotype subgroup. No correlation between ACE activity and age was observed in FEP or HC groups separately (r = 0.210, P = .392), but ACE activity level differences observed between these groups were influenced by age.

Conclusions

The importance of measuring the ACE activity in blood plasma, associated with ACE I/D genotyping to support the follow-up of FEP patients, did not show correlation with general symptom amelioration in the present study. However, new insights into the influence of age and I/D genotype for ACE activity changes in FEP individuals upon treatment was demonstrated.
Joint Eigenfunctions for the Relativistic Calogero–Moser Hamiltonians of Hyperbolic Type. III. Factorized Asymptotics
Authors: Hallnäs Martin , Ruijsenaars Simon
Published: July 2020

In the two preceding parts of this series of papers, we introduced and studied a recursion scheme for constructing joint eigenfunctions $J_N(a_+, a_-,b;x,y)$ of the Hamiltonians arising in the integrable $N$-particle systems of hyperbolic relativistic Calogero–Moser type. We focused on the 1st steps of the scheme in Part I and on the cases $N=2$ and $N=3$ in Part II. In this paper, we determine the dominant asymptotics of a similarity-transformed function $\textrm{E}_N(b;x,y)$ for $y_j-y_{j+1}\to \infty $, $j=1,\ldots , N-1$ and thereby confirm the long-standing conjecture that the particles in the hyperbolic relativistic Calogero–Moser system exhibit soliton scattering. This result generalizes a main result in Part II to all particle numbers $N>3$.
Cystatin C and Urine Albumin to Creatinine Ratio Predict 5-Year Mortality and Cardiovascular Events in People Living With HIV
Authors: Chazot Robin , Botelho-Nevers Elisabeth , Mariat Christophe , Frésard Anne , Cavalier Etienne , Lucht Frédéric , Delanaye Pierre , Maillard Nicolas , Gagneux-Brunon Amandine
Published: July 2020

Background

Identifying people with HIV (PWH) at risk for chronic kidney disease, cardiovascular events, and death is crucial. We evaluated biomarkers to predict all-cause mortality and cardiovascular events, and measured glomerular filtration rate (mGFR) slope.

Methods

Biomarkers were measured at enrollment. Baseline and 5-year mGFR were measured by plasma iohexol clearance. Outcomes were a composite criterion of all-cause mortality and/or cardiovascular events, and mGFR slope.

Results

Of 168 subjects, 146 (87.4%) had undetectable HIV load. Median follow-up was 59.1 months (interquartile range, 56.2–62.1). At baseline, mean age was 49.5 years (± 9.8) and mean mGFR 98.9 mL/min/1.73m2 (± 20.6). Seventeen deaths and 10 cardiovascular events occurred during 5-year follow-up. Baseline mGFR was not associated with mortality/cardiovascular events. In multivariable analysis, cystatin C (hazard ratio [HR], 5.978; 95% confidence interval [CI], 2.774–12.88; P < .0001) and urine albumin to creatinine ratio (uACR) at inclusion (HR, 1.002; 95% CI, 1.001–1.004; P < .001) were associated with mortality/cardiovascular events. Area under receiver operating curve of cystatin C was 0.67 (95% CI, .55–.79) for mortality/cardiovascular event prediction. Biomarkers were not associated with GFR slope.

Conclusions

uACR and cystatin C predict all-cause mortality and/or cardiovascular events in PWH independently of mGFR.
Efficacy of human-simulated exposures of meropenem/vaborbactam and meropenem against OXA-48 β-lactamase-producing Enterobacterales in the neutropenic murine thigh infection model
Authors: Gill Christian M , Asempa Tomefa E , Nicolau David P
Published: July 2020

Objectives

Despite vaborbactam lacking inhibitory activity against OXA-48, approximately a third of OXA-48-harbouring Enterobacterales test susceptible to meropenem/vaborbactam due to its higher breakpoint than meropenem alone. The present study evaluated the efficacy of human-simulated exposures of meropenem/vaborbactam against OXA-48-harbouring Enterobacterales in the neutropenic murine thigh model.

Methods

Twenty-six isolates [OXA-48 (n = 24) and KPC (n = 2)] were evaluated. MICs were conducted in triplicate per CLSI. Mice received human-simulated regimens of meropenem/vaborbactam, meropenem or vehicle for 24 h. Mice were inoculated with ∼1 × 107 cfu/mL in each thigh 2 h prior to dosing and both thighs were harvested at 24 h. Efficacy was assessed using mean log10 cfu/thigh at 24 h and the achievement of 1 log10 reduction relative to 0 h control as an established surrogate marker predictive of success for serious infections.

Results

Meropenem/vaborbactam MICs ranged from 1 to 64 mg/L. The mean inoculum at 0 h was 5.77 ± 0.26 compared with 8.26 ± 1.53 for controls at 24 h. As anticipated for KPCs, meropenem/vaborbactam resulted in enhanced mean ± SD change in bacterial density (−1.10 ± 0.26), compared with meropenem (1.45 ± 0.88). Vaborbactam did not enhance mean ± SD change against OXA-48 isolates compared with meropenem (−0.44 ± 1.29 and −0.43 ± 1.36, respectively). For OXA-48-harbouring isolates with meropenem/vaborbactam MICs ≥16 (n = 5), 8 (n = 5), 4 (n = 9) and ≤2 (n = 5) mg/L, 0%, 0%, 44% and 60% of isolates achieved the target reduction ≥1 log10 with either agent, respectively.

Conclusions

These data highlight that meropenem/vaborbactam and meropenem humanized exposures in vivo resulted in similar, albeit poor, activity against OXA-48-producing Enterobacterales despite susceptible MICs per EUCAST and CLSI interpretation. As a result, caution is warranted when treating meropenem/vaborbactam-susceptible Enterobacterales without a genotypic profile.
The Effects of High-Altitude Windborne Migration on Survival, Oviposition, and Blood-Feeding of the African Malaria Mosquito, Anopheles gambiae s.l. (Diptera: Culicidae)
Authors: Sanogo Zana L , Yaro Alpha S , Dao Adama , Diallo Moussa , Yossi Ousman , Samaké Djibril , Krajacich Benjamin J , Faiman Roy , Lehmann Tovi
Published: July 2020

Recent results of high-altitude windborne mosquito migration raised questions about the viability of these mosquitoes despite ample evidence that many insect species, including other dipterans, have been known to migrate regularly over tens or hundreds of kilometers on high-altitude winds and retain their viability. To address these concerns, we subjected wild Anopheles gambiae s.l. Giles mosquitoes to a high-altitude survival assay, followed by oviposition (egg laying) and blood feeding assays. Despite carrying out the survival assay under exceptionally harsh conditions that probably provide the lowest survival potential following high altitude flight, a high proportion of the mosquitoes survived for 6- and even 11-h assay durations at 120- to 250-m altitudes. Minimal differences in egg laying success were noted between mosquitoes exposed to high altitude survival assay and those kept near the ground. Similarly, minimal differences were found in the female’s ability to take an additional bloodmeal after oviposition between these groups. We conclude that similar to other high-altitude migrating insects, mosquitoes are able to withstand extended high-altitude flight and subsequently reproduce and transmit pathogens by blood feeding on new hosts.
Growth, phenology and N-utilization by invasive populations of Gunnera tinctoria
Authors: Mantoani Maurício Cruz , González Alberto Benavent , Sancho Leopoldo García , Osborne Bruce Arthur
Published: July 2020

Aims

Gunnera tinctoria is an unusual N-fixing plant species that has become invasive worldwide, generally in environments with a low evaporative demand and/or high rainfall. Amongst the many mechanisms that may explain its success as an introduced species, a contrasting phenology could be important but this may depend on an ability to grow and utilize nutrients under sub-optimal conditions. We examined whether G. tinctoria has an advantage in terms of a contrasting phenology and N-fixing capability, in comparisons with Juncus effusus, the native species most impacted by G. tinctoria invasions.

Methods

We made phenological assessments on a weekly or bi-weekly basis on long-established populations on Achill Island, Ireland, during 2016–2017. Data on leaf and inflorescence number, total leaf area, light interception and above-ground biomass were collected alongside measurements of soil temperature, moisture and oxidation–reduction potential. The significance of N-fixing ability for supporting seasonal growth was assessed using δ 15N isotopic assessments, together with in situ acetylene reduction measurements.

Important Findings

The timing of the initiation of growth of G. tinctoria and J. effusus varied between 2016 and 2017, with the earlier emergence and expansion of leaves of G. tinctoria, and the largest above-ground biomass associated with higher water availability. The early growth of G. tinctoria was dependent on preformed structures, with maximum canopy development occurring in late May, prior to that of J. effusus. Whilst N-fixation was observed in March, this made a more significant contribution to growth during the later stages of canopy development. Based on δ 15N isotopic analyses, early growth was predominantly associated with N-remobilization from the rhizomes, whilst seedlings were largely reliant on N-fixation. This emphasizes the importance of nutrient mobilization for early growth and shows that the importance of an N-fixing capability may vary developmentally, as well as during different stages of the invasion process.