bluuebunny/crossref_metadata_2025 huggingface dataset:
Antagonist Treatment for Opioid Use Disorder
Authors: Peglow Stephanie Lee , Moran Joshua , Keats Matthew
Published: September 2020

This chapter focuses on the use of oral and injectable extended-release naltrexone for opioid use disorder. The historical development of naltrexone and its pharmacology are discussed. The chapter presents the clinical application of initiating naltrexone therapy, including the transition to and from methadone and buprenorphine and the utility of the naloxone challenge test. The pros and cons of naltrexone are reviewed and compared to first-line agents: methadone and buprenorphine. In addition, the efficacy of different formulations of naltrexone is addressed. Last, this chapter reviews the use of naltrexone in special populations including in criminal justice, adolescents, pregnant or childbearing patients, and other vulnerable populations.
Pharmacotherapy for Opioid Use Disorders in Special Populations
Authors: Wright Tricia E.
Published: September 2020

Three populations are most at risk for opioid use disorder: adolescents, pregnant women, and those with comorbid psychological or psychiatric disorders. Opioid use disorders present throughout the life course of an individual, often developing during adolescence. For women, these disorders commonly occur during peak childbearing years. In addition, the twin vulnerabilities of genetics and adverse childhood events often interact to impart a greater chance for co-occurring psychiatric conditions. Caring for the pregnant woman, the adolescent, or the person with a co-occurring mental disorder presents special challenges. This chapter focuses on special considerations when treating opioid use disorders in these populations.
Pharmacology of Alcohol Use Disorder
Authors: Lemay Megan
Published: September 2020

Alcohol use disorder (AUD) is a common and costly disease. Alcohol withdrawal is a common complication of AUD. Alcohol withdrawal has primarily been managed in the inpatient setting, though evidence supports treatment in the outpatient setting for selected low-risk patients. Benzodiazepines are the gold standard medication class to prevent complications of alcohol withdrawal and may be given in symptom-triggered, fixed-schedule, and loading dose regimens. Medications for the treatment of AUD are effective and underutilized. There are three medications approved by the US Food and Drug Administration for AUD: naltrexone (available in short-acting oral and long-acting injectable formulations), acamprosate, and disulfiram. Naltrexone and acamprosate are preferred in most settings due to their efficacy and tolerability. Patients with moderate to severe AUD should be offered medication as part of their treatment plan along with a comprehensive history and physical, behavioral treatment, and mutual goal-setting. It is recommended that medications for AUD are continued for at least 6–12 months or until their risks outweigh their benefits. This chapter reviews the medication management of alcohol withdrawal and AUD in detail.
Pharmacotherapy for Smoking Cessation
Authors: Karam-Hage Maher , Gonzalez Roberto , Imad Damaj M.
Published: September 2020

Tobacco smoking is a major public health hazard, one responsible for more deaths than alcohol, drugs, car accidents, HIV, and fire combined. While on the decline, it continues to be a major problem that is feasible but difficult to remedy, in particular once an individual is addicted to nicotine. On the bright side, effective treatments are available although very few people are taking advantage of these tools. The standard of care and evidenced-based treatment consist of behavioral in conjunction with pharmacological therapy. In the United States, there are seven pharmacological agents approved for use as single agents, while for heavily addicted or recalcitrant smokers a combination of more than one agent may be needed. Nicotine replacement products offer a safe way to transition from the harm of smoking tobacco to using only medicinal doses of nicotine for a gradual transition to total abstinence. E-cigarettes can be seen as a less harmful alternative to smoking; however, little is known about their potential for harm on long-term use.
What Is “Evidence-Based” Treatment?
Authors: Stoltman Jonathan J. K. , Lander Laura R.
Published: September 2020

This chapter discusses the range of evidence for efficacy in evidence-based treatments for substance abuse disorders. The authors draw their information from both case reports and multisite randomized control trials, presenting both the controversies over evidence-based behavioral therapies and the reasons given for the utilization of less evidence-based behavioral treatments. The chapter also discusses the reasons for the lack of approval from the US Food and Drug Administration (FDA) for evidence-based pharmacotherapy treatments in substance use disorders and details the corresponding reasons for clinicians’ use of non-FDA-approved pharmacotherapies, all while stressing the importance of transparency and documentation.
Evidence-Based Behavioral Therapies for Substance Use Disorders
Authors: Polak Kathryn , Kelpin Sydney , Reisweber Jarrod , Svikis Dace S.
Published: September 2020

A variety of pharmacological and psychosocial interventions have demonstrated efficacy in the treatment of substance use disorders (SUDs). This chapter focuses on evidence-based behavioral and psychosocial interventions for the treatment of alcohol use disorder and other SUDs. Among the interventions discussed are screening, brief intervention, and referral to treatment (SBIRT); motivational interviewing (MI); cognitive behavioral therapy (CBT); and contingency management (CM). Additionally, one promising intervention for SUD, Transcending Self Therapy (TST), is spotlighted. The importance of comprehensive care is noted by the authors, as is the importance of recognizing gender differences in the selection of therapies and the need to address barriers to care for specific populations.
Evidence-Based Pharmacotherapy for Cocaine, Amphetamine, and Methamphetamine Use Disorders
Authors: Zhang Xuefeng , Kosten Thomas R.
Published: September 2020

Cocaine use disorder is one of the important stimulants use disorders worldwide, and amphetamine/methamphetamine misuse is a growing epidemic. There are no pharmacotherapy treatments approved by the US Food and Drug Administration (FDA) available for these illnesses. Numerous treatments based on a variety of strategies from psychotherapy, pharmacotherapy, to neuromodulation have been tested to date. Clinical efficacy of the trialed treatments, including both negative and positive outcomes. are reviewed and discussed in this chapter. In summary, many agents and interventions showed promising therapeutic potential in preclinical and early phase clinical trials but eventually failed in later larger trials. Thus, behavioral interventions and supportive therapy focusing on detoxification, initial recovery, and relapse prevention remain the major therapeutic approach due to lack of targeted treatment. New strategies and models are urgently needed to develop effective treatments for these detrimental disorders.
Testing Hope
Authors: Snyder Jeremy
Published: September 2020

Chapter 5 examines human participation in phase I clinical trials for experimental cancer interventions and phase III clinical trials in low- and middle-income countries. In both cases, these participants may take part in these trials in the hope of accessing an experimental intervention that will improve their own health or that of their communities. Exploitation of hope is most likely to take place in these contexts when there is a confusion about the roles of researchers and the aims of clinical research such that participants misunderstand the likely outcomes of the trial for themselves or their communities. Researchers and their sponsors can contribute to this misunderstanding by not communicating the aims of clinical research clearly or by using the language of hope to encourage trial participation.
Introduction
Authors: Loebel J. Pierre , Savulescu Julian
Published: September 2020

This introductory chapter discusses the lack of a unifying theory in psychiatry. No generally accepted theory of mental illness exists, in part because there is little agreement on what the concepts ‘mental’ and ‘illness’ entail. Lacking such a theory, the profession has experienced internal divisiveness, uncertainty among applicants for training, and attacks from outside. Since the decline of nineteenth- and twentieth-century paradigms such as psychoanalysis and behaviourism, psychiatrists have been in search of one that acknowledges what is universally recognized, that is, that human beings function in a nexus comprising the psyche, the soma, and the social surround, and that each domain requires consideration when drawing up a psychiatric formulation and treatment plan. Thus, the biopsychosocial (BPS) paradigm proposed by George L. Engel in 1977 was adopted without much enquiry into details. This book presents a nascent, stronger version of the concept based on a growing body of genetic, epigenetic, and other evidence that encompasses a central, overlapping component to the Venn diagram description of the BPS conceptualization.
Minority report: Values, teamwork, and implementing biopsychosocial psychiatry
Authors: Fulford K.W.M. (Bill)
Published: September 2020

This chapter builds on a new approach to working with values in healthcare, called values-based practice, to explore the roles of values and teamwork in implementing the biopsychosocial model in psychiatry. This ‘minority’ humanities-led approach to the biopsychosocial model is complementary to the ‘majority’ scientific approach. In four main sections the chapter covers the underpinnings of the minority approach in an empirical study of the biopsychosocial model in multidisciplinary mental health teams, gives a brief introduction to values-based practice, provides examples of how values-based practice has been implemented in mental health, and notes some of the new resources for values-based implementation of biopsychosocial psychiatry to be found in developments in contemporary person-centred clinical care. The chapter concludes with a note on the challenge of pluralism for implementing biopsychosocial approaches in mental health. Further reading and web-based resources are included.
Objectification: Ethical and epistemic concerns about neurocentrism in psychiatry
Authors: Bublitz Jan Christoph
Published: September 2020

Objectification is a recurrent criticism of psychiatry. But what is it more precisely? In the absence of a general theory, this chapter draws on various strands in the history of ideas, including Marxism and feminism, to distil key features. Central to objectification is the disregard for subjectivity and the reduction of persons to bodies. These elements also characterize biological psychiatry. Neurobiological explanations of disorders are to some degree inherently insensitive for the mental, as they presuppose the ‘real’ problem lies at the neurobiological level. Neurointerventions fall short of engaging with the subjectivity of recipients through a second-person stance. Accordingly, neurobiological explanations and interventions tend to objectify persons. This claim does not presuppose dubious mind–brain dualisms and might be sustained to some extent even if some form of neuroreductionism were true. However, the current emphasis on neurobiology and the supposed primacy of the brain in explaining and treating disorders is unfounded. No more than an indeed exciting research hypothesis, it should neither guide treatment decisions nor their ethical evaluation.
Spanner in the Works or Cogs in a Wheel?
Authors: Callus Thérèse
Published: September 2020

In what circumstances should medical treatment decisions concerning a child be treated differently from any one of a myriad of important decisions that parents routinely make for their children without any state intervention? Who is best placed to make such decisions and on what basis? Why does conflict arise and how can it be minimized? This chapter deals with the sensitive and complex question of decision making for critically ill children. An analysis of the case law reveals that parents are generally believed to be the best-placed to make a shared decision with the medical team focusing on the child’s best interests. However, when conflict arises, it is necessary to seek court intervention. I examine how the framework of the child’s best interests includes consideration of what the child personally may want, yet this begs the question why is the judge’s interpretation of what the child would want any more valid than that of the parents or the doctors? Rejecting the claim that the court should only be involved when it is shown that the parents’ decision on the child’s treatment would cause harm to the child, I suggest framing the question as a ‘not against the child’s interests’ test, or what is ‘compatible’ with the child’s interests. This would alleviate the perception that it is a binary decision between a right and wrong choice, and better serve the overall objective of minimizing conflict. Focusing on how the decision is taken is ultimately just as important as who makes the decision.
Pandemic Planning after Covid-19
Authors: Danbury Christopher , Newdick Christopher , Keene Alex Ruck , Waldmann Carl
Published: September 2020

What happens when demand for intensive care exceeds the supply of beds available? Covid-19 has brought these questions to the fore in an exceptionally acute fashion, highlighting the multi-level response required. This chapter, written as the pandemic was developing in the spring of 2020, when the UK and, indeed, most of the world was in lockdown to minimize social interaction, addresses these dilemmas in three sections: (1) the nature and extent of the demand for intensive care and the government’s response to Covid-19 (up until April 2020), (2) the necessity for a procedural framework for decision making to promote transparency, fairness, and consistency, and (3) the models of clinical triage to achieve the best results.
Introduction
Authors: Elliott Perry , Lambiase Pier D. , Kumar Dhavendra
Published: September 2020

This chapter sets out the rationale for the second edition of this Oxford Specialist Handbook in Inherited Cardiac Disease, with the aim to describe the basic principles of clinical genetics where relevant to cardiology practice, with the advances in sequencing technologies since the previous edition included to aid diagnosis.
Genes, genome, and inheritance patterns
Authors: Elliott Perry , Lambiase Pier D. , Kumar Dhavendra
Published: September 2020

This chapter covers the fundamentals of genetics that underpins the basis of inherited cardiac diseases. It starts with the structure of DNA and genes, and the mechanisms of gene expression, including transcription and translation. It then goes on to alterations of the genetic code via mutations and polymorphisms, and the normal chromosomal structure and subsequent disorders. Mendelian inheritance is explained, including autosomal dominant, recessive, and X-linked categories. Multifactorial and polygenic inheritance, alongside its relevance to cardiovascular diseases that are not caused by single gene disorders, is covered. Finally, methods of non-traditional inheritance are also explained.
Mitochondrial cardiovascular diseases
Authors: Elliott Perry , Lambiase Pier D. , Kumar Dhavendra
Published: September 2020

This chapter begins by defining the mitochondrial genome, and the subsequent assessment of suspected mitochondrial DNA (mtDNA) disorders. The incidence and prevalence of cardiac involvement in mitochondrial disorders is covered, including the probably under-reporting of this. Different cardiovascular phenotypes associated with mitochondrial disease (arrhythmias, hypertrophic cardiomyopathy, Barth syndrome etc.) are all described, and then the clinical management of the diseases are explained. As there is no fixed treatment, pharmacological regimens to avoid, and other approaches are also included.
Dysregulation of synovial fibroblasts in rheumatoid arthritis
Authors: Crowley Thomas , Turner Jason D. , Filer Andrew , Clark Andy , Buckley Chris
Published: September 2020

Fibroblasts are ubiquitous stromal cells, with populations found in all organs. The traditional role of fibroblasts was thought to be mainly structural; making and modifying extracellular matrix. Taken together the ability of fibroblasts to produce and respond to many factors involved in the immune system indicates the degree to which they are involved in orchestrating the inflammatory response in rheumatoid arthritis (RA). This level of involvement demonstrates the importance of fibroblasts in inflammation and indicates the shift from transient to chronic inflammation in RA could be facilitated in part by synovial fibroblasts. This chapter explores the role of fibroblasts in RA.
Autoantibodies in rheumatoid arthritis
Authors: Huizinga Tom W.J.
Published: September 2020

Autoantibodies are a characteristic feature of autoimmune diseases. Although the exact pathogenetic role of autoantibodies is in general not known, they are very often useful for diagnostic purposes. Rheumatoid arthritis (RA) is a chronic autoimmune disease primarily affecting the joints. RA is a heterogeneous disease that encompasses several disease subsets with probable differences in underlying pathophysiology. Via a final common inflammatory pathway these different pathophysiological pathways might lead to a similar clinical presentation of arthritis. The best-known subdivision in RA is between autoantibody positive and autoantibody negative RA, which differ in both risk factors and clinical outcomes. This chapter focuses on the role of autoantibodies in the pathophysiology of RA. First, the relation between autoantibodies and known risk factors for RA will be discussed. Thereafter, the specific characteristics of the autoantibody response and the pathogenic potential of the different autoantibodies are reviewed.
Radiography in rheumatoid arthritis
Authors: Peterfy Charles , Conaghan Philip G. , Østergaard Mikkel
Published: September 2020

Medical imaging is used to determine whether structural damage (bone erosion and/or articular cartilage loss) is present in the patient with rheumatoid arthritis. Conventional radiography is inexpensive, widely available, and relatively safe, and characteristic radiographic findings are part of the American College of Rheumatology (ACR) 1987 classification criteria, as well as the ACR/European League Against Rheumatism (EULAR) 2010 classification. Radiography can be helpful in differentiating RA from other joint conditions, such as psoriatic arthritis, osteoarthritis, and neoplasm. This chapter discussion outlines the technical and interpretative principles, as well as the challenges, associated with radiographic evaluation of RA, and points to ways of dealing with some of the most common pitfalls in routine clinical practice and research.
Rheumatoid arthritis and work
Authors: Verstappen Suzanne , Jones Cheryl , Houssien Abdullah , Galloway James
Published: September 2020

Loss of work due to rheumatic and musculoskeletal diseases (RMDs), including rheumatoid arthritis (RA), causes a major socioeconomic burden to society. In Europe, RMDs affect more than 4 million people with an estimated societal cost of 0.5–2% of the gross domestic product. The peak age of onset for both men and women is before the age of ~65 years, typically the age of retirement in most countries meaning most people who develop RA are of working age at diagnosis. For many people work is important, improving self-esteem and self-worth, and contributing to financial independence. This chapter will review the impact, including economic aspects, of RA on work, personal and environmental factors associated with work outcomes, and management of problems at work or work loss.
Occupational therapy
Authors: Hammond Alison , Adams Joanne , Prior Yeliz
Published: September 2020

People with rheumatoid arthritis can find it painful, tiring, and frustrating to perform their daily activities, work, family and social responsibilities, and leisure. While drug therapy has improved outcomes, many still experience limitations in their daily lives. Occupational therapy aims to: improve clients’ abilities to perform their activities and participate in their social roles; reduce pain and fatigue; improve or maintain physical function; improve or maintain psychological status; help people self-manage their condition successfully and adapt to changes in their lifestyle; achieve a healthy work and personal life balance. People with participation restrictions have poorer psychological and physical outcomes. Helping people participate in their roles, as and when they wish to, is an important part of rehabilitation to maximize clients’ quality of life. Occupational therapists use a wide range of educational, physical, social, psychological, and work-related interventions to help people live their lives as successfully as possible.
Self-management: A patient’s perspective
Authors: Voshaar Marieke M.J.H.
Published: September 2020

This chapter is written by an expert patient who works with medical professionals. It covers a personal experience of being diagnosed and the psychosocial effects that arose from this period of time. It highlights the requirements for self-management in terms of retaining autonomy, models the definitions of self-management, and discusses the outcomes of different approaches. All chronic illness support, including self-management programmes, require an ongoing relationship between the patient and provider, including considerations of individual barriers; therefore the necessity for both social and medical support for patients’ self-management is also discussed, including differing needs for people from marginalized backgrounds, and suggestions on improving programmes is deliberated.
Analgesics, opioids, and NSAIDs
Authors: Russell Mark D. , Sofat Nidhi
Published: September 2020

In this chapter, we discuss nociceptive treatment targets for pain in rheumatoid arthritis (RA), including non-steroidal anti-inflammatory drugs (NSAIDs). Sustained nociceptive input, as found in RA, can lead to changes in central pain processing. Nociceptive input is increased following local sensitization of peripheral nerves within the joint. Coupled with inflammation, it is known that major mediators of pain include neuropeptides (e.g. calcitonin gene-related peptide, CGRP) and neurotrophins such as nerve growth factor (NGF), each of which can also sensitize peripheral nerves. Immune cells within the central nervous system (CNS) directly contribute to developing central sensitization through the generation of cytokines such as IL-1. Interest has therefore grown in analgesics for RA pain that may target the CNS, including opiates and centrally acting analgesics. In this chapter, we discuss the scientific basis of pain in RA, followed by treatments currently widely used in clinical practice, including NSAIDs, opioids, and centrally acting analgesics.
Combination therapy in rheumatoid arthritis
Authors: Coumbe Ben G.T. , Nikiphorou Elena , Sokka-Isler Tuulikki
Published: September 2020

The therapeutic armamentarium available for treatment of rheumatoid arthritis (RA) has changed significantly over the past 30 years, transforming the therapeutic landscape and prognosis for a substantial proportion of patients with RA. Combination therapies represent an important therapeutic paradigm for management of rheumatoid arthritis. The rationale for combination therapies is clear and demonstrated to bring treatment benefit to patients achieving lower disease activity scores and reduced radiologic progression according to ‘treat-to-target’ principles. A rigorous evidence-based debate is required involving not only parameters related to disease activity scores and radiologic progression, but related to the cost-effectiveness analysis of using many of these newer agents compared to older csDMARDs. This chapter addresses the evidence related to the utilization of combination strategies for the management of RA as compared to monotherapy.
European biologics registers
Authors: Zink Angela , Strangfeld Anja
Published: September 2020

Over the last 15 years, the European biologics registers have greatly increased our knowledge of the safety and effectiveness of biologic therapies in daily practice. They have convincingly shown that tumour necrosis factor (TNF) inhibitors do not increase the overall risk of solid or lymphoproliferative tumours. However, a slight increase in the risk of skin cancer cannot be ruled out. A higher risk of serious infections compared to csDMARDs has been identified which has to be taken into account in clinical care. The registers have identified the great impact of uncontrolled high disease activity on the risks of myocardial infarction, stroke, and overall mortality which underlines the importance of tight disease control. By their clinical effectiveness, the biologic agents therefore have the potential to prevent adverse outcomes. Overall, a favourable benefit-risk profile of TNFi and other biological agents has been observed, with some specific precautions in defined patient groups.
Thinking about obstetric anaesthesia
Authors: Collis Rachel
Published: September 2020

The labour ward can be a stressful and demanding experience for all anaesthetists, junior and senior alike. Therefore, starting to working on a labour ward presents a number of new challenges to the novice obstetric anaesthetist, in an environment which many may not have spent any time visiting or working within since medical school. A helpful A–Z of survival is set out, where although no point is more important than the other, it is a useful tool to guide you through your first weeks or months. The chapter also offers resources to help with non-English speaking mothers and suggested advice of how to deal with difficult situations or behaviour. The principles of conducting audit, research and quality improvement work, which are an integral part of improving service delivery and facilitating efficient management of a high quality service, are also described.
Confidential Enquiries into Maternal Deaths
Authors: Lucas Nuala , Bamber James
Published: September 2020

The Confidential Enquiries into Maternal Deaths is the longest running audit of maternal mortality in the world. From its inception in 1952 to 2011, triennial reports have been published on the direct and indirect causes of maternal death, with salutatory messages from the care delivered to these mothers. Since 2011, the report has been published annually, to facilitate a more rapid response to emerging patterns of disease and prevent a time-lag in dissemination and learning from cases. The historical trend in causes of deaths is well-described, with mortality figures for the UK and the current themes in lessons learned. Despite this representing UK demographics and healthcare, many of the lessons learnt are applicable in healthcare settings around the world, including developing nations.
Non-regional labour analgesia
Authors: Turner Matthew , Lilley Graeme
Published: September 2020

Women may choose to deliver their baby in different places, e.g. obstetric-led units, midwife-led units, or at home, depending on their risk assessment and the mother’s own wishes. The way they manage their pain during labour will depend on where they deliver; however, it is essential that they are fully informed about the available options. This chapter explores the evidence base for both non-pharmacological and pharmacological options, e.g. complementary therapies, water immersion, TENS, inhalational analgesia, and systemic opioids. The use of patient-controlled analgesia (PCA) with ultra-short acting opioids, e.g. remifentanil, has been shown to be safe when used in a monitored environment and has high maternal satisfaction scores. The typical regimens and safe monitoring conditions for PCA remifentanil use are described.
Regional techniques in pregnancy
Authors: Collis Rachel , Harries Sarah
Published: September 2020

Regional analgesia is the most effective way of managing pain associated with labour, and the majority of operative deliveries are conducted under regional anaesthesia, with the woman awake. The importance of appropriate consent, documentation, monitoring, positioning, and conduct of regional procedures is described. Supporting illustrations offer the reader tips to overcome common difficulties during epidural, spinal, and CSE placement, as well as the management of bloody tap or accidental dural puncture. Current guidance on the absolute and relative contra-indications to a regional technique and the management of the woman on anti-coagulants is also outlined.
Postpartum review and problems
Authors: Harries Sarah
Published: September 2020

Postpartum review, at ~24 hours following delivery, is an essential duty of the obstetric anaesthesia team, to identify residual regional anaesthesia or complications associated with delivery or regional techniques. A method of maintaining an accurate database of procedures for all cases to aid follow-up is emphasized. This chapter covers the key issues and management of complications in the postpartum period, with a comprehensive section on the management of backache, neurological symptoms, and Red Flag signs indicating further investigation and referral for neurology or surgical management as the suggested next step. The symptoms, signs, and management of both recognized postdural puncture headache and headache presenting in the postpartum period are well described. Finally, the process of dealing with a complaint is outlined to aid the reader.
Embolic disease
Authors: Theron Abrie
Published: September 2020

Venous thromboembolism is the leading direct cause of maternal death. Therefore an understanding of the risk factors, clinical presentation, appropriate investigations (i.e. echocardiogram, V/Q Scan, or CT pulmonary angiography) and the treatment options available for managing patients with suspected and confirmed pulmonary embolism (PE) are essential knowledge on an obstetric unit. The chapter includes information on anticoagulation treatment options and the management of life-threatening PE, when thrombolysis or pulmonary embolectomy may be indicated. Amniotic fluid embolism is discussed, reviewing aetiology, pathophysiology, clinical features, diagnosis, and supportive management. Finally air embolism is discussed, also looking at aetiology, pathophysiology, clinical features, diagnosis, and management, emphasizing, however, that prevention is key.
A full characterization of the supermassive black hole in IRAS 09149–6206
Authors: Walton D J , Alston W N , Kosec P , Fabian A C , Gallo L C , Garcia J A , Miller J M , Nardini E , Reynolds M T , Ricci C , Stern D , Dauser T , Harrison F A , Reynolds C S
Published: September 2020

We present new broad-band X-ray observations of the type-I Seyfert galaxy IRAS 09149–6206, taken in 2018 with XMM–Newton, NuSTAR, and Swift. The source is highly complex, showing a classic ‘warm’ X-ray absorber, additional absorption from highly ionized iron, strong relativistic reflection from the innermost accretion disc and further reprocessing by more distant material. By combining X-ray timing and spectroscopy, we have been able to fully characterize the supermassive black hole in this system, constraining both its mass and – for the first time – its spin. The mass is primarily determined by X-ray timing constraints on the break frequency seen in the power spectrum, and is found to be log [MBH/M⊙] = 8.0 ± 0.6 (1σ uncertainties). This is in good agreement with previous estimates based on the H α and H β line widths, and implies that IRAS 09149–6206 is radiating at close to (but still below) its Eddington luminosity. The spin is constrained via detailed modelling of the relativistic reflection, and is found to be $a^* = 0.94^{+0.02}_{-0.07}$ (90 per cent confidence), adding IRAS 09149–6206 to the growing list of radio-quiet active galactic nuclei (AGNs) that host rapidly rotating black holes. The outflow velocities of the various absorption components are all relatively modest (vout ≲ 0.03c), implying these are unlikely to drive significant galaxy-scale AGN feedback.
Classifying image sequences of astronomical transients with deep neural networks
Authors: Gómez Catalina , Neira Mauricio , Hernández Hoyos Marcela , Arbeláez Pablo , Forero-Romero Jaime E
Published: September 2020

Supervised classification of temporal sequences of astronomical images into meaningful transient astrophysical phenomena has been considered a hard problem because it requires the intervention of human experts. The classifier uses the expert’s knowledge to find heuristic features to process the images, for instance, by performing image subtraction or by extracting sparse information such as flux time-series, also known as light curves. We present a successful deep learning approach that learns directly from imaging data. Our method models explicitly the spatiotemporal patterns with deep convolutional neural networks and gated recurrent units. We train these deep neural networks using 1.3 million real astronomical images from the Catalina Real-Time Transient Survey to classify the sequences into five different types of astronomical transient classes. The TAO-Net (for Transient Astronomical Objects Network) architecture outperforms the results from random forest classification on light curves by 10 percentage points as measured by the F1 score for each class; the average F1 over classes goes from $45{{\ \rm percent}}$ with random forest classification to $55{{\ \rm percent}}$ with TAO-Net. This achievement with TAO-Net opens the possibility to develop new deep learning architectures for early transient detection. We make available the training data set and trained models of TAO-Net to allow for future extensions of this work.
Jet feedback and the photon underproduction crisis in simba
Authors: Christiansen Jacob F , Davé Romeel , Sorini Daniele , Anglés-Alcázar Daniel
Published: September 2020

We examine the impact of black hole jet feedback on the properties of the low-redshift intergalactic medium (IGM) in the simba simulation, with a focus on the Lyα forest mean flux decrement DA. Without jet feedback, we confirm the photon underproduction crisis (PUC) in which ΓH i at $z$ = 0 must be increased by 6 times over the Haardt & Madau value in order to match the observed DA. Turning on jet feedback lowers this discrepancy to ∼2.5 times, and additionally using the recent Faucher–Giguère background mostly resolves the PUC, along with producing a flux probability distribution function in accord with observations. The PUC becomes apparent at late epochs ($z \lesssim 1$) where the jet and no-jet simulations diverge; at higher redshifts simba reproduces the observed DA with no adjustment, with or without jets. The main impact of jet feedback is to lower the cosmic baryon fraction in the diffuse IGM from 39 per cent to 16 per cent at $z$ = 0, while increasing the warm-hot intergalactic medium (WHIM) baryon fraction from 30 per cent to 70 per cent; the lowering of the diffuse IGM content directly translates into a lowering of DA by a similar factor. Comparing to the older mufasa simulation that employs different quenching feedback but is otherwise similar to simba, mufasa matches DA less well than simba, suggesting that low-redshift measurements of DA and ΓH i could provide constraints on feedback mechanisms. Our results suggest that widespread IGM heating at late times is a plausible solution to the PUC, and that simba’s jet active galactic nucleus feedback model, included to quench massive galaxies, approximately yields this required heating.
Morphology of radio relics – I. What causes the substructure of synchrotron emission?
Authors: Domínguez-Fernández P , Brüggen M , Vazza F , Banda-Barragán W E , Rajpurohit K , Mignone A , Mukherjee D , Vaidya B
Published: September 2020

High-resolution radio observations of cluster radio relics often show complex spatial and spectral features. However, it is not clear what these features reveal about the underlying magnetic field properties. We performed three-dimensional magnetohydrodynamical simulations of merger shock waves propagating through a magnetized, turbulent intracluster medium. Our model includes the diffusive shock acceleration (DSA) of cosmic ray electrons, their spatial advection and energy losses at run-time. With this set-up we can investigate the relation between radio substructure and pre-shock plasma conditions in the host cluster. We find that upstream turbulence plays a major role in shaping the properties of radio relics produced downstream. Within the assumption of DSA, we can reproduce the observed discrepancy between the X-ray derived Mach number of shocks, and the Mach number inferred from radio spectra. Our simulated spectral index maps and profiles across the radio relic also suggest that the standard deviation of the upstream magnetic field must be relatively small ($\sigma _B\le 1 \, \mu$G) in order to reproduce observations and therefore radio relics can potentially constrain the distribution of magnetic fields in galaxy clusters outskirts.
Development of aptamer-based inhibitors for CRISPR/Cas system
Authors: Zhao Jing , Inomata Rika , Kato Yoshio , Miyagishi Makoto
Published: September 2020

The occurrence of accidental mutations or deletions caused by genome editing with CRISPR/Cas9 system remains a critical unsolved problem of the technology. Blocking excess or prolonged Cas9 activity in cells is considered as one means of solving this problem. Here, we report the development of an inhibitory DNA aptamer against Cas9 by means of in vitro selection (systematic evolution of ligands by exponential enrichment) and subsequent screening with an in vitro cleavage assay. The inhibitory aptamer could bind to Cas9 at low nanomolar affinity and partially form a duplex with CRISPR RNA, contributing to its inhibitory activity. We also demonstrated that improving the inhibitory aptamer with locked nucleic acids efficiently suppressed Cas9-directed genome editing in cells and reduced off-target genome editing. The findings presented here might enable the development of safer and controllable genome editing for biomedical research and gene therapy.
Mobile, Remote, and Individual Focused: Comparing Breath Carbon Monoxide Readings and Abstinence Between Smartphone-Enabled and Stand-Alone Monitors
Authors: Tuck Breanna M , Karelitz Joshua L , Tomko Rachel L , Dahne Jennifer , Cato Patrick , McClure Erin A
Published: September 2020

Introduction

Newly available, smartphone-enabled carbon monoxide (CO) monitors are lower in cost than traditional stand-alone monitors and represent a marked advancement for smoking research. New products are promising, but data are needed to compare breath CO readings between smartphone-enabled and stand-alone monitors. The purpose of this study was to (1) determine the agreement between the mobile iCO (Bedfont Scientific Ltd) with two other monitors from the same manufacturer (Micro+ pro and Micro+ basic) and (2) determine optimal, monitor-specific, cotinine-confirmed abstinence cutoff values.

Methods

Adult (≥18) smokers (n = 26) and nonsmokers (n = 21) provided three breath CO samples (using three different monitors) in each of 10 sessions, and urine cotinine was measured for gold standard determination of abstinence. CO comparisons (N = 437) were analyzed using regression-based Bland–Altman Analysis of Agreement; receiver operating characteristics curves were used to determine optimal abstinence cutoffs.

Results

Bland–Altman analyses indicated that the iCO monitor provided higher CO results than both Micro+ monitors. Sensitivity and specificity analyses showed that the optimal CO cutoff for determining abstinence was <3 ppm for the Micro+ pro (88% sensitivity, 93% specificity) and Micro+ basic (83% sensitivity, 98% specificity), but was higher for the iCO (<6 ppm; 73% sensitivity, 100% specificity).

Conclusions

Relative to both Micro+ monitors, the smartphone-enabled iCO provided systematically higher CO values and required a higher cutoff to reliably determine smoking abstinence. This does not indicate that CO values obtained using the iCO are not valid; instead, these results suggest that monitor-specific abstinence cutoffs are needed to ensure accurate bioverification of smoking status.

Implications

Results from this study indicate that CO values from the smartphone-enabled iCO should not be used interchangeably with the stand-alone Micro+ pro and Micro+ basic, particularly when lower CO values (<10 ppm) are critical (ie, determination of abstinence vs confirming smoking status for study inclusion). Optimal CO cutoffs recommended for determining abstinence on Micro+ and iCO monitors are at <3 and <6 ppm, respectively.
Epidemiology and Risk Factors Associated With Mortality in Consecutive Patients With Bacterial Bloodstream Infection: Impact of MDR and XDR Bacteria
Authors: Santoro Antonella , Franceschini Erica , Meschiari Marianna , Menozzi Marianna , Zona Stefano , Venturelli Claudia , Digaetano Margherita , Rogati Carlotta , Guaraldi Giovanni , Paul Mical , Gyssens Inge C , Mussini Cristina
Published: September 2020

Background

 Mortality related to bloodstream infections (BSIs) is high. The epidemiology of BSIs is changing due to the increase in multidrug resistance, and it is unclear whether the presence of multidrug-resistant (MDR) organisms, per se, is an independent risk factor for mortality. Our objectives were, first, to describe the epidemiology and outcome of BSIs and, second, to determine the risk factors associated with mortality among patients with BSI.

Methods

 This research used a single-center retrospective observational study design. Patients were identified through microbiological reports. Data on medical history, clinical condition, bacteria, antimicrobial therapy, and mortality were collected. The primary outcome was crude mortality at 30 days. The relationships between mortality and demographic, clinical, and microbiological variables were analyzed by multivariate analysis.

Results

 A total of 1049 inpatients were included. MDR bacteria were isolated in 27.83% of patients, where 2.14% corresponded to an extremely drug-resistant (XDR) isolate. The crude mortality rates at days 7, 30, and 90 were 12.11%, 25.17%, and 36.13%, respectively. Pitt score >2, lung and abdomen as site of infection, and XDR Pseudomonas aeruginosa were independent risk factors for 7-, 30-, and 90-day mortality. Charlson score >4, carbapenem-resistant Klebsiella pneumoniae, and XDR Acinetobacter baumannii were independent risk factors for 30- and 90-day mortality. Infection by XDR gram-negative bacteria, Charlson score >4, and immunosuppression were independent risk factors for mortality in patients who were stable at the time of BSI.

Conclusions

 BSI is an event with an extreme impact on mortality. Patients with severe clinical condition are at higher risk of death. The presence of XDR gram-negative bacteria in blood is strongly and independently associated with patient death.
Microbiology of Bloodstream Infections in Children After Hematopoietic Stem Cell Transplantation: A Single-Center Experience Over Two Decades (1997–2017)
Authors: Heston Sarah M , Young Rebecca R , Hong Hwanhee , Akinboyo Ibukunoluwa C , Tanaka John S , Martin Paul L , Vinesett Richard , Jenkins Kirsten , McGill Lauren E , Hazen Kevin C , Seed Patrick C , Kelly Matthew S
Published: September 2020

Background

Bloodstream infections (BSIs) occur frequently after hematopoietic stem cell transplantation (HSCT). We examined the microbiology of BSI in pediatric HSCT recipients over a 2-decade period at our institution to inform empirical antimicrobial prescribing and infection prevention strategies.

Methods

We conducted a retrospective cohort study of children (<18 years) who underwent HSCT at Duke University between 1997 and 2015. We used recurrent-event gap-time Cox proportional hazards models to determine the hazards of all-cause and cause-specific BSI according to HSCT year. We compared the median time to BSI by causative organism type and evaluated for temporal trends in the prevalence of antibiotic resistance among causative organisms.

Results

A total of 865 BSI occurred in 1311 children, including 412 (48%) Gram-positive bacterial, 196 (23%) Gram-negative bacterial, 56 (6%) fungal, 23 (3%) mycobacterial, and 178 (21%) polymicrobial BSI. The hazard of all BSIs did not change substantially over time during the study period, but the hazard of fungal BSIs declined over time during the study period (P = .04). Most fungal BSIs (82%) occurred in the first 100 days after HSCT, whereas mycobacterial BSIs occurred later after HSCT than BSIs caused by other organisms (P < .0001). The prevalence of vancomycin resistance among BSIs caused by Enterococcus faecium increased during the study period (P = .0007). The risk of 2-year mortality in children was increased with BSI (P = .02), Gram-negative bacterial BSI (P = .02), and fungal BSI (P < .0001).

Conclusions

Despite expanded practices for BSI prevention over the past several decades, the incidence of BSI remains high in pediatric HSCT recipients at our institution. Additional strategies are urgently needed to effectively prevent BSIs in this high-risk population.
The Prevalence of “Pure” Lumbar Zygapophysial Joint Pain in Patients with Chronic Low Back Pain
Authors: MacVicar John , MacVicar Ann Marguerite , Bogduk Nikolai
Published: September 2020

Background

Estimates of the prevalence of lumbar zygapophysial joint (Z joint) pain differ in the literature, as do case definitions for this condition. No studies have determined the prevalence of “pure” lumbar Z joint pain, defined as complete relief of pain following placebo-controlled diagnostic blocks.

Objective

The objective of this study was to estimate the prevalence of “pure” lumbar Z joint pain.

Methods

In a private practice setting, 206 patients with possible lumbar Z joint pain underwent controlled diagnostic blocks using one of two protocols: placebo-controlled comparative blocks and fully randomized, placebo-controlled, triple blocks.

Results

In the combined sample, the prevalence of “pure” lumbar Z joint pain was 15% (10–20%).

Conclusions

The prevalence of “pure” lumbar Z joint pain is substantially and significantly less than most of the prevalence estimates of lumbar Z joint pain reported in the literature.