bluuebunny/crossref_metadata_2025 huggingface dataset:
Family and relationships
Authors: Sivan Manoj , Phillips Margaret , Baguley Ian , Nott Melissa
Published: August 2019

This chapter covers the role of the family in caregiving after an individual has experienced a serious, sudden-onset illness that requires ongoing care. Family members require a range of supportive measures during the process of transition into a caregiving role. This may include emotional support, physical assistance with daily activities, and practical support and advocacy to navigate complex healthcare services. The chapter describes the caregiving role, and also different types of support required at different points of the rehabilitation process. Strains and burdens on those providing care are outlined, with support strategies described. Impacts on relationships including the biological, psychological, and social factors are covered.
Vocational rehabilitation
Authors: Sivan Manoj , Phillips Margaret , Baguley Ian , Nott Melissa
Published: August 2019

Work is important for the health and well-being of individuals, regardless of whether it is paid or unpaid employment. Employment is known to be a critical component of personal identity and personal growth, disability adjustment, social integration, and life satisfaction, in addition to economic self-sufficiency. In its broadest sense, work is ‘an activity involving mental or physical effort in order to achieve a result’. People with disabilities experience a significantly higher than average level of unemployment. This chapter defines and describes vocational rehabilitation techniques to reintegrate the patient into the community and workforce, interventions and assessment, and suitable workplace accommodations.
Orthotics
Authors: Sivan Manoj , Phillips Margaret , Baguley Ian , Nott Melissa
Published: August 2019

An orthosis is an externally applied device used to modify, support, or enhance the functional characteristics of a body segment. Other terminology used to describe orthoses includes splints, braces, and supports. Orthoses can be custom-made, or can be ordered ‘off the shelf’ as a prefabricated device, and can be fabricated from a variety of materials depending on the need for external support. The practice of orthotics can include selecting, prescribing, designing, fabricating, fitting, applying, and evaluating orthoses to achieve specific rehabilitation goals. This chapter covers various types of orthoses by body part and function, as well as recent advances in orthotics.
Wheelchairs and seating
Authors: Sivan Manoj , Phillips Margaret , Baguley Ian , Nott Melissa
Published: August 2019

Freedom of movement is an essential component of independence and mobility is closely associated with quality of life. People who have difficulty with independent walking often require a wheelchair to assist with mobility. The International Classification of Functioning, Disability and Health model can be used to guide the provision of wheelchairs and seating through consideration of the individual personal factors and preferences, environmental limitations, the person’s desired activities and participation in life roles, as well as the person’s health condition or impairments of body structure and function. This chapter describes the steps in prescribing a wheelchair, types of manual and powered wheelchairs, and specialized seating and positioning components.
Spinal cord injury
Authors: Sivan Manoj , Phillips Margaret , Baguley Ian , Nott Melissa
Published: August 2019

The term spinal cord injury (SCI) is often taken to denote damage to the spinal cord following trauma, with non-traumatic SCI treated as a separate condition in some services. The prognosis for SCI varies depending on aetiology. Often, survival for those with non-traumatic SCI is determined by the underlying diagnosis. Individuals with SCI have great capacity to maintain a good quality of life. Helping to make this a reality is one of the multiple challenges that SCI poses to the multidisciplinary team. Following inpatient rehabilitation, the key to independence and participation in previous life roles is access to good-quality information. Individuals should be kept informed of developments at all times and put in touch with the necessary range of professionals, not only with regard to their health, but also in social services, employment, and other spheres.
Multiple sclerosis
Authors: Sivan Manoj , Phillips Margaret , Baguley Ian , Nott Melissa
Published: August 2019

Multiple sclerosis (MS) is the commonest of the demyelinating CNS conditions and is the most frequent condition causing neurological disability in younger adults. It causes a combination of physical and cognitive disabilities, which, when combined with starting in young adult life and with an uncertain rate of progression, make it both challenging and responsive to rehabilitation. It is important to understand the criteria for diagnosis both to be able to discuss prognosis with patients and because symptoms may become apparent later which affect the diagnosis. It is more likely that rehabilitation medicine clinicians will see those with primary or secondary progressive MS than relapsing–remitting MS because the impact of disability tends to be greater and the current benefits from disease-modifying therapies less in progressive MS.
Neurodegenerative conditions
Authors: Sivan Manoj , Phillips Margaret , Baguley Ian , Nott Melissa
Published: August 2019

The neurodegenerative conditions (NDGCs) encompass a wide variety of neurological conditions, with varying signs, symptoms, age of onset, prognoses, and underlying pathologies. However, they share a number of features. The aims of this chapter are to describe the essentials of some of the more frequent NDGCs that are not covered elsewhere in this handbook, to indicate symptoms that are common features, and to provide an overview of some of the strategies that may be useful. The individual conditions are not described in depth; a textbook of neurology is recommended for this.
Prolonged disorders of consciousness
Authors: Sivan Manoj , Phillips Margaret , Baguley Ian , Nott Melissa
Published: August 2019

The term ‘consciousness’ refers to our brain’s capacity to provide an integrated, running commentary over our sensations and motivations for actions. The organic substrate underpinning ‘consciousness’ has not been identified. It is highly unlikely that any one structure plays a dominant role, and consciousness is probably best thought of as a massively distributed system within the brain. It is therefore highly susceptible to widespread, diffuse injuries of any aetiology. This chapter describes elements of consciousness, the difference between arousal and awareness, assessment of consciousness levels (conscious versus subconscious versus unconscious), and various rehabilitative techniques and treatment paradigms, including sensory stimulation, physical approaches, pharmaceutical, and brain stimulation.
Musculoskeletal problems of upper and lower limbs
Authors: Sivan Manoj , Phillips Margaret , Baguley Ian , Nott Melissa
Published: August 2019

This chapter first describes common musculoskeletal disorders of the upper limb, including adhesive capsulitis of the shoulder, glenohumeral joint arthritis, acromioclavicular joint arthritis, rotator cuff disease, tennis elbow/lateral epicondylalgia and golfer’s elbow/medial epicondylalgia, De Quervain’s tenosynovitis/intersection syndrome, Dupuytren’s contracture, carpal tunnel syndrome, and work-related upper limb disorders. It then goes on to describe common musculoskeletal disorders of the lower limb including osteoarthritis, greater trochanter pain syndrome, tendinopathy: patellar tendon/Achilles tendon/tibialis posterior tendon, plantar fasciopathy, and Morton’s neuroma. Management of symptoms and assessment of cases are all described and suggestions for further reading and useful websites are given.
Geriatric rehabilitation
Authors: Sivan Manoj , Phillips Margaret , Baguley Ian , Nott Melissa
Published: August 2019

Ageing is strongly associated with co-morbidities, frailty, and disability. The co-morbidity burden is tremendous with at least two-thirds of elderly people having three or more chronic diseases. More than a quarter of elderly patients are frail and a similar proportion have difficulties in activities of daily living, especially those older than 75 years. Physical frailty, sarcopenia, and the consequences of reduced mobility are specific areas that rehabilitation clinicians are well suited to assess and offer interventions for. Falls, and their association with minimal trauma fractures, are characteristic of the elderly and geriatric rehabilitation. This chapter describes assessment and rehabilitative interventions in older patients.
Amputee rehabilitation
Authors: Sivan Manoj , Phillips Margaret , Baguley Ian , Nott Melissa
Published: August 2019

Amputee rehabilitation involves the multidisciplinary assessment of all amputees and the resultant advice and therapy delivered. It is essential that treatment is delivered in a patient-centred manner and timely fashion. Amputee rehabilitation includes patients over a wide spectrum of ages—from a baby born with an upper or lower limb deformity or deficiency to an elderly patient with vascular disease and multiple medical comorbidities. Amputee rehabilitation is no longer concerned with only patients who are suitable for limb fitting. It is inclusive of all amputees and the specialist amputee multidisciplinary team should be able to provide valuable advice and therapy to all amputees
Functional and Psychosocial Consequences of Major Depressive Disorder
Authors: Greer Tracy L. , Joseph Jeethu K.
Published: August 2019

Depression is associated with profound personal and societal costs worldwide, in great part due to negative functional and psychosocial consequences. These consequences can range from minimally disruptive to life-altering, and they occur across a wide variety of life domains (e.g. home, work, school, social). Despite patient preference for the inclusion of functional outcomes as the desired endpoint of antidepressant treatment and goal for the achievement of wellness, functional outcomes are still infrequently measured. This is likely due, at least in part, to the wide variety of assessment tools that are available and lack of consensus definitions of functional recovery. This chapter reviews several measures that are available to assess functioning; describes the functional impairment associated with depression and related symptoms, such as cognition, sleep, and pain; and briefly discusses issues associated with treating disrupted functioning in depression. Future directions include the need to develop and utilize a consensus definition of functional recovery, as well as consistent incorporation of functional assessment in both clinical monitoring and research outcomes.
Major Depressive Disorder as a Disorder of Cognition
Authors: Kaser Muzaffer , Sahakian Barbara J.
Published: August 2019

Depression is one of the leading causes of disability worldwide. People who experience depression face difficulties in many areas of their daily living. Cognitive problems are commonly associated with depression and have significant impact on social and work functioning. The lack of treatments specifically aimed at improving cognition may lead to persistent cognitive dysfunction in depression, and this is a major factor in depression-related disability. In this chapter, we will discuss the case for formulating major depressive disorder as a disorder of cognition and motivation, and the interaction between the two. We will also highlight cognitive dysfunction as a target for treatment in depression.
The Assessment of Cognitive Dysfunction in Major Depressive Disorder
Authors: Harrison John E.
Published: August 2019

Accurately capturing an individual’s cognitive status is a key requirement for identifying levels of impairment in patients with central nervous system indications, including in those with diagnoses of major depressive disorders (MDD). This requirement extends to the determination of whether a therapeutic intervention has impacted cognition and, if so, the extent to which this has occurred. In this chapter we will consider these issues with respect to the assessment of cognition in patients with MDD. We begin with a review of performance on measures reported in recent meta-analyses and with a particular focus on their sensitivity to treatment effects. We proceed to a consideration of how best we might accurately capture levels of cognitive performance and the precautions required to reduce sources of measurement error. These methods will then be considered in the context of a recent case study of a treatment (vortioxetine) development programme. The issues explored in the context of assessing cognition in the vortioxetine programme are then considered in the context of screening for deficits in patients with MDD. We close the chapter with a summary and recommendations for the accurate assessment of cognition, as well as a brief consideration of how technological developments might aid this process.
Molecular Neurobiology of Cognitive Dysfunction in Major Depressive Disorder
Authors: Mills Natalie T. , Baune Bernhard T.
Published: August 2019

The neurobiology of cognitive dysfunction observed in major depressive disorder (MDD) involves changes in neurotransmitters, inflammatory markers, synaptic plasticity, and the hypothalamic–pituitary–adrenal (HPA) axis. In addition to the monoamines serotonin and dopamine, glutamate is also an important neurotransmitter for cognition. The importance of serotonin receptor subtypes for learning and memory has been shown through both preclinical and clinical studies. Elevated levels of proinflammatory cytokines, in particular tumour necrosis factor-alpha (TNF-α‎), interleukin (IL)-6, and IL-1β‎ have also been associated with cognitive changes in MDD. Genetic variation of the serotonin transporter gene SLC6A4, including polymorphisms of the 5-HTTLPR and STin2 genotypes, has been associated with performance on memory tasks in individuals with and without MDD. Variants of other genes involved in neurotransmission (such as the catechol-O-methyl transferase [COMT] gene), inflammation, and in HPA axis regulation, including the glucocorticoid receptor gene (NR3C1) and mineralocorticoid receptor gene (NR3C2), have also been associated with cognitive changes in MDD. Changes in gene expression, such as increased expression of TNF-α‎, have also been observed to correlate negatively with working memory and executive function observed in MDD. Since epigenetic pathways have shown a role in synaptic plasticity and neurogenesis, associated with changes in learning, memory, and depression-like activities seen in preclinical models, this implies possible relevance for human cognitive dysfunction in MDD as well.
Clinical Characteristics of Emotional-Cognitive Dysfunction in Major Depressive Disorder
Authors: Beblo Thomas , Dehn Lorenz B.
Published: August 2019

The experiences of sustained negative affect and diminished positive emotions are cardinal symptoms of major depressive disorder (MDD). They come with several emotional-cognitive dysfunctions, which contribute to the onset, maintenance, and recurrence of depression. Depressed patients show reduced approach motivation and increased avoidance motivation. Furthermore, there is evidence for a mood-congruent negative processing bias in MDD. Consequently, depressed patients preferentially attend to mood-congruent stimuli, recall more unpleasant than pleasant memories, and tend to interpret (ambiguous) information in a negative manner. Patients might also exhibit an elevated sensitivity to negative feedback. Depressive patients also show an altered thinking style referred to as rumination. Rumination implies repetitive thinking about the causes, consequences, and symptoms of one’s negative feelings. These emotional-cognitive dysfunctions characterize the contents and the way of thinking in MDD. In addition, as emotional-cognitive dysfunctions are closely related to information processing, they also impair cognitive performance of patients with MDD.
Neurocircuitries of Emotion Processing Affected in Major Depressive Disorder
Authors: Sankar Anjali , Fu Cynthia H.Y.
Published: August 2019

Impairments in processing emotions are a hallmark feature of depression. Advances in neuroimaging techniques have rapidly improved our understanding of the pathophysiology underlying major depression. In this chapter, we provide an overview of influential neural models of emotion perception and regulation and discuss the neurocircuitries of emotion processing that are affected. Major depression is characterized by impairments in widespread brain regions that are evident in the first episode. Models have sought to distinguish the neural circuitry associated with recognition of the emotion, integration of somatic responses, and monitoring of the affective state. In particular, there has been a preponderance of research on the neurocircuitries affected during processing of mood-congruent negative emotional stimuli in depression. While neuroimaging correlates have been investigated and models proposed, these findings have had limited clinical applicability to date. Novel methods such as multivariate pattern recognition applied to neuroimaging data might enable identification of reliable, valid, and robust biomarkers with high predictive accuracy that can be applied to an individual. Last, we discuss avenues for extension and future work.
The Neural Circuitry of Negative Bias, Oversensitivity to Negative Feedback, and Hyposensitivity to Reward in Major Depressive Disorder
Authors: Robinson Oliver J.
Published: August 2019

Negative affective bias is a core symptom of major depressive disorder (MDD) that promotes and upholds the debilitating negative mood state. This chapter reviews cognitive neuroscience research exploring negative affective bias and its underlying neural circuitry. It describes converging research across clinical populations and experimental manipulations in humans suggesting that cortical and subcortical brain regions, and their interactions as circuits, are responsible for tipping the scales of information processing away from rewards and towards threats. The ultimate balance of activity within these neural circuits may therefore be responsible for negative affective bias symptoms in MDD.
Networks of Cognitive Processes: Functional and Anatomical Correlates of Cognition, Emotions, and Social Cognition
Authors: Medaglia John D.
Published: August 2019

Networks of cognitive processes describe some of the key findings emerging from cognitive network neuroscience. Cognition is organized in distinct networks in the human brain. These cognitive networks interact via complex dynamics to process our environments and enact our decisions on the world. Within the emerging subdiscipline known as cognitive network neuroscience, we can connect classical neuroscience approaches to network science. This allows us to consider how major cognitive functions ranging from sensation to cognitive control and emotion are organized in the human brain. Through the lens of network neuroscience, we can enrich our understanding of normal and disordered cognitive function to be manifestations of processes and representations in ordered or disorded neural networks.
Emotional and Cognitive Consequences of Social Rejection: An Entry Door to Major Depression
Authors: Fossati Philippe , Hinfray Sophie , Fall Anna , Lemogne Cédric , Rotge Jean-Yves
Published: August 2019

Interpersonal factors are strong predictors of the onset and course of major depression. However, the biological and neural bases of interpersonal difficulties in major depression are unknown. In this chapter we describe a general homeostatic system that monitors the social acceptance of individuals. We show that this system is activated in response to actual or putative threats to social acceptance and signals of social rejection. Our model describes a cascade of cognitive, emotional, and behavioural consequences of social exclusion. The model emphasizes the role of specific regions—the subgenual anterior cingulate, the insula, and the default mode network—in the detection and regulation of social signals. Hence we propose that major depressive disorder is tightly linked to the processing of social exclusion and may represent a specific impairment in the homeostatic system that monitors social acceptance.
Psychological Interventions for Cognitive Dysfunction in Major Depressive Disorder
Authors: Woolf Claudia , Mowszowski Loren , Naismith Sharon
Published: August 2019

Major depressive disorders (MDD) are common and disabling, and are linked to functional impairment and increased mortality. While current treatments for MDD are moderately effective, ultimately up to one-third of patients do not achieve full remission. Interestingly, while affective symptoms of depression resolve with the resolution of a depressive episode, cognitive or neuropsychological impairment persists, and has been identified as one of the most prominent predictors of ongoing disability, reduced quality of life, and illness recurrence. Yet available treatments in MDD do not typically address neuropsychological dysfunction. Cognitive training, however, despite a small and heterogeneous evidence base, represents a promising and novel therapeutic intervention for neuropsychological impairment in MDD, which may yield neuropsychological, affective, and functional benefits.
Social Cognitive Deficits: Impact on Psychosocial Function and Novel Treatment Opportunities in Major Depressive Disorder
Authors: Weightman Michael , Baune Bernhard T.
Published: August 2019

This chapter examines current literature regarding the impact of social cognition on psychosocial functioning in major depressive disorder, as well as potential treatment opportunities. Impairments of social cognition influence psychosocial functioning in the key domains of social performance, emotional/empathic performance, general cognitive functioning, and quality of life. Multiple treatment modalities have been used to target these difficulties, including antidepressant medication, psychotherapeutic approaches, and procedural interventions. Studies assess treatment efficacy based on the impact on facial affect recognition, interpretation of affective pictures, theory of mind performance, and prosody. Many current therapies are shown to have a normalizing effect for accuracy of interpretation and reduction in underlying negative interpretative bias. In particular, certain antidepressants seem to correct facial affect recognition deficits, while several psychotherapeutic approaches appear well suited for addressing impaired theory of mind or mood-congruent interpretative biases.
Orthognathic surgery
Authors: Breeze Johno , Parmer Sat , McLeod Niall
Published: August 2019

This chapter contains eight clinical vivas on the subject of orthognathic surgery. This will provide candidates sitting the vivas component of the Oral and Maxillofacial Surgery FRCS examination with practical knowledge in the assessment and treatment of dentofacial disproportion, asymmetric, and congenital orthognathic cases. It will also provide insight for clinicians in allied specialties, such as otolaryngology and plastic surgery, in how to engage in a debate with a senior clinician in the contemporary management of such complex cases.
Skin cancer
Authors: Breeze Johno , Parmer Sat , McLeod Niall
Published: August 2019

This chapter contains eight clinical vivas on the subject of skin cancer surgery. This will provide candidates sitting the vivas component of the Oral and Maxillofacial Surgery FRCS examination with practical knowledge in the assessment and treatment of skin cancer presenting in the head, face, and neck region. It will also provide insight for clinicians in allied specialties, such as otolaryngology and plastic surgery, in how to engage in a debate with a senior clinician in the contemporary management of such complex cases.
Salivary gland disease
Authors: Breeze Johno , Parmer Sat , McLeod Niall
Published: August 2019

This chapter contains eight clinical vivas on the subject of salivary gland disease. This will provide candidates sitting the vivas component of the Oral and Maxillofacial Surgery FRCS examination with practical knowledge in the assessment and treatment of obstructive, benign, and malignant salivary gland diseases. It will also provide insight for clinicians in allied specialties, such as otolaryngology and plastic surgery, in how to engage in a debate with a senior clinician in the contemporary management of such complex cases.
Cleft surgery
Authors: Breeze Johno , Parmer Sat , McLeod Niall
Published: August 2019

This chapter contains eight clinical vivas on the subject of cleft surgery. This will provide candidates sitting the vivas component of the Oral and Maxillofacial Surgery FRCS examination with practical knowledge in the assessment and treatment of presentations such as cleft lip and palate as well as modalities of treatment including types of cleft lip repair. It will also provide insight for clinicians in allied specialties, such as otolaryngology and plastic surgery, in how to engage in a debate with a senior clinician in the contemporary management of such complex cases.
Dentoalveolar surgery
Authors: Breeze Johno , Parmer Sat , McLeod Niall
Published: August 2019

This chapter contains eight clinical vivas on the subject of dentoalveolar surgery. This will provide candidates sitting the vivas component of the Oral and Maxillofacial Surgery FRCS examination with practical knowledge in the assessment of dentoalveolar pathology as well as surgical treatment including third molar extractions, coronectomy, and endodontics. It will also provide insight for clinicians in allied specialties, such as otolaryngology and plastic surgery, in how to engage in a debate with a senior clinician in the contemporary management of such complex cases.
Reconstructive head and neck surgery
Authors: Breeze Johno , Parmer Sat , McLeod Niall
Published: August 2019

This chapter contains eight clinical vivas on the subject of reconstructive maxillofacial surgery. This will provide candidates sitting the vivas component of the Oral and Maxillofacial Surgery FRCS examination with practical knowledge in reconstruction of mandibular and maxillary defects including free flap design and microvascular anastomosis. It will also provide insight for clinicians in allied specialties, such as otolaryngology and plastic surgery, in how to engage in a debate with a senior clinician in the contemporary management of such complex cases.
Miscellaneous
Authors: Breeze Johno , Parmer Sat , McLeod Niall
Published: August 2019

This chapter contains two clinical vivas on miscellaneous subjects for candidates sitting the vivas component of the Oral and Maxillofacial Surgery FRCS examination. One viva pertains to consent and the other to negligence, both important scenarios but ones which are generally only alluded to in the syllabus and not taught directly. It will also provide insight for clinicians in allied specialties, such as otolaryngology and plastic surgery, in how to engage in a debate with a senior clinician in the contemporary management of such complex cases.
Bow shocks, bow waves, and dust waves – III. Diagnostics
Authors: Henney William J , Arthur S J
Published: August 2019

Stellar bow shocks, bow waves, and dust waves all result from the action of a star’s wind and radiation pressure on a stream of dusty plasma that flows past it. The dust in these bows emits prominently at mid-infrared wavelengths in the range 8 to   60 $\mu$m. We propose a novel diagnostic method, the τ–η diagram, for analysing these bows, which is based on comparing the fractions of stellar radiative energy and stellar radiative momentum that is trapped by the bow shell. This diagram allows the discrimination of wind-supported bow shocks, radiation-supported bow waves, and dust waves in which grains decouple from the gas. For the wind-supported bow shocks, it allows the stellar wind mass-loss rate to be determined. We critically compare our method with a previous method that has been proposed for determining wind mass-loss rates from bow shock observations. This comparison points to ways in which both methods can be improved and suggests a downward revision by a factor of two with respect to previously reported mass-loss rates. From a sample of 23 mid-infrared bow-shaped sources, we identify at least four strong candidates for radiation-supported bow waves, which need to be confirmed by more detailed studies, but no strong candidates for dust waves.
V1005 Her: a solar-type shallow-contact binary in a triply fossil system
Authors: Zhu L-Y , Wang Z H , Tian X M , Li L J , Gao X
Published: August 2019

Four sets of complete multicolour light curves of the short-period solar-type eclipsing binary V1005 Her are presented. It is found that the depth of the primary minima in the light curves went deeper from 2013 to 2018, and then became shallower again in 2019, while those of the secondary minima were unchanged. The total-eclipse characteristics in the light curves enable us to determine reliable photometric solutions of this system. Our results from the detailed light-curve analysis show that V1005 Her is a W-type shallow-contact binary with spot activities. We have monitored this system for 7 yr and 22 new times of light minimum have been determined. Together with those collected from the literature, we investigate its Observed-Calculated O–C curve and detect a cyclic variation. Because of the insufficient energy, this cyclic change cannot be explained by magnetic activity cycles of the components even if it has high spots activities. The detected cyclic variation is more plausible as the results of the light-time effect due to the existence of a third body orbiting around the central binary. The minimal mass of the additional stellar companion is determined around 0.45 M⊙ in both circular orbit and eccentric orbit cases when a total mass of 1.2 M⊙ for the binary is adopted. This mass is larger than that of the less massive component of the central binary. It implies that the secondary body was not replaced by the third body during early stellar interactions, suggesting that it is a fossil system and keeps original dynamical information.
Constraining coherent low-frequency radio flares from compact binary mergers
Authors: Rowlinson A , Anderson G E
Published: August 2019

The presence and detectability of coherent radio emission from compact binary mergers (containing at least one neutron star) remains poorly constrained due to large uncertainties in the models. These compact binary mergers may initially be detected as short gamma-ray bursts or via their gravitational wave emission. Several radio facilities have developed rapid response modes enabling them to trigger on these events and search for this emission. For this paper, we constrain this coherent radio emission using the deepest available constraints for GRB 150424A, which were obtained via a triggered observation with the Murchison Widefield Array. We then expand this analysis to determine the properties of magnetar merger remnants that may be formed via a general population of binary neutron star mergers. Our results demonstrate that many of the potential coherent emission mechanisms that have been proposed for such events can be detected or very tightly constrained by the complementary strategies used by the current generation of low-frequency radio telescopes.
ModelTest-NG: A New and Scalable Tool for the Selection of DNA and Protein Evolutionary Models
Authors: Darriba Diego , Posada David , Kozlov Alexey M , Stamatakis Alexandros , Morel Benoit , Flouri Tomas
Published: August 2019

ModelTest-NG is a reimplementation from scratch of jModelTest and ProtTest, two popular tools for selecting the best-fit nucleotide and amino acid substitution models, respectively. ModelTest-NG is one to two orders of magnitude faster than jModelTest and ProtTest but equally accurate and introduces several new features, such as ascertainment bias correction, mixture, and free-rate models, or the automatic processing of single partitions. ModelTest-NG is available under a GNU GPL3 license at https://github.com/ddarriba/modeltest , last accessed September 2, 2019.
Regulation of La/SSB-dependent viral gene expression by pre-tRNA 3′ trailer-derived tRNA fragments
Authors: Cho Hee , Lee Wooseong , Kim Geon-Woo , Lee Seung-Hoon , Moon Jae-Su , Kim Minwoo , Kim Hyun Seok , Oh Jong-Won
Published: August 2019

tRNA-derived RNA fragments (tRFs) have emerged as a new class of functional RNAs implicated in cancer, metabolic and neurological disorders, and viral infection. Yet our understanding of their biogenesis and functions remains limited. In the present study, through analysis of small RNA profile we have identified a distinct set of tRFs derived from pre-tRNA 3′ trailers in the hepatocellular carcinoma cell line Huh7. Among those tRFs, tRF_U3_1, which is a 19-nucleotide-long chr10.tRNA2-Ser(TGA)-derived trailer, was expressed most abundantly in both Huh7 and cancerous liver tissues, being present primarily in the cytoplasm. We show that genetic loss of tRF_U3_1 does not affect cell growth and it is not involved in Ago2-mediated gene silencing. Using La/SSB knockout Huh7 cell lines, we demonstrate that this nuclear-cytoplasmic shuttling protein directly binds to the 3′ U-tail of tRF_U3_1 and other abundantly expressed trailers and plays a critical role in their stable cytoplasmic accumulation. The pre-tRNA trailer-derived tRFs capable of sequestering the limiting amounts of La/SSB in the cytoplasm rendered cells resistant to various RNA viruses, which usurp La/SSB with RNA chaperone activity for their gene expression. Collectively, our results establish the trailer-derived tRF-La/SSB interface, regulating viral gene expression.
Maternal Smoking and Hospital Treatment During Pregnancy
Authors: Wallin Hanna P , Gissler Mika , Korhonen Päivi E , Ekblad Mikael O
Published: August 2019

Introduction

Previous research suggests that young maternal age, smoking, hospitalization during a previous pregnancy, and poor self-rated health could be risk factors for prenatal hospitalization.

Methods

The objective of this retrospective observational register study was to investigate if maternal smoking during pregnancy is associated with mother’s need for hospital treatment during pregnancy. The study population consists of all singleton pregnancies (n = 961 127) in 1999–2015 in Finland. Information on maternal smoking was received from the Medical Birth Register in three classes: nonsmoker, quit smoking in the first trimester, and continued smoking throughout the pregnancy. These data were linked with the Hospital Discharge Register data and analyzed according to ICD-10 chapters.

Results

10.7% of women continued to smoke after the first trimester. After adjusting for confounding factors women in both smoking groups had more hospital treatment compared with nonsmokers. Especially outpatient treatment was more common among mothers who continued to smoke compared to those who quit smoking in the first trimester in several ICD-10 chapters. Compared to non-smokers, aOR for mental and behavioral disorders (F00–F99) was 2.14 (95% confidence interval 2.00–2.30) in the quit smoking group and 3.88 (3.71–4.06) in the continued smoking group. Similarly, aOR for respiratory diseases (J00–J99) was 1.26 (1.15–1.39) and 1.61 (1.52–1.71), respectively and aOR for genitourinary diseases (N00–N99) was 1.10 (1.03–1.17) and 1.29 (1.23–1.35), respectively. Some similar findings were made also in inpatient care. Some similar findings were made also in inpatient care.

Conclusions

Women who smoke during pregnancy seem to require more hospital care for various reasons. These findings emphasize the importance of actions for smoking cessation during pregnancy and women should be encouraged to quit as early as possible.

Implications

Maternal smoking during pregnancy is associated with greater rates of both outpatient and inpatient hospital care during pregnancy. Women who quit smoking had a similar risk for hospital care during pregnancy with nonsmokers in certain diagnosis chapters, which is very motivational and could be used as an informational tool in prenatal clinics to encourage smoking cessation as it is never too late to quit smoking during pregnancy.
Implementing a Comprehensive Hepatitis C Virus (HCV) Clinic Within a Human Immunodeficiency Virus Clinic: A Model of Care for HCV Microelimination
Authors: Rizk Christina , Miceli Janet , Shiferaw Bethel , Malinis Maricar , Barakat Lydia , Ogbuagu Onyema , Villanueva Merceditas
Published: August 2019

Background

Among the 1.2 million people with human immunodeficiency virus (HIV) in the United States, 25% are coinfected with hepatitis C virus (HCV). The availability of effective direct acting antivirals (DAAs) makes the goal of HCV elimination feasible, but implementation requires improvements to the HCV treatment cascade, especially linkage to and initiation of treatment in underserved populations.

Methods

In this retrospective review, a cohort of patients receiving care at a hospital-based HIV clinic in New Haven, Connecticut (January 1, 2014–March 31, 2017) with chronic HCV infection not previously treated with DAAs were followed longitudinally. Patients were referred to a colocated multidisciplinary team. Standardized referral and treatment algorithms and electronic medical record templates were developed, monthly meetings were held, and a registry was created to review progress.

Results

Of 173 patients, 140 (80.9%) were 50–70 years old, 115 (66.5%) were male, 99 (57.2%) were African American, 43 (24.9%) were white, and 23 (13.3%) were Hispanic. Comorbidities included the following: cirrhosis (25.4%), kidney disease (17.3%), mental health issues (60.7%), alcohol abuse (30.6%), and active drug use (54.3%). Overall, 161 (93.1%) were referred, 147 (85%) were linked, 122 (70.5%) were prescribed DAAs, and 97 (56.1%) had sustained viral response at 12 weeks posttreatment or cure (SVR12). Comparison between those with SVR12 and those unsuccessfully referred, linked, or treated, showed that among those not engaged in HCV care, there was a higher proportion of younger (mean age 54.2 vs 57 years old, P = .022), female patients (P = .001) and a higher frequency of missed appointments.

Conclusions

Establishing a colocated HCV clinic within an HIV clinic resulted in treatment initiation in 70.5% of patients and SVR12 in 56.1%. This success in a hard-to-treat population is a model for achieving microelimination goals set by the World Health Organization.
First Human Trial of Stem Cell Transplantation in Complex Arrays for Stroke Patients Using the Intracerebral Microinjection Instrument
Authors: Zhang GuangZhu , Cunningham Miles , Zhang HongTian , Dai YiWu , Zhang Ping , Ge GuangZhi , Wang BeiBei , Bai MiaoChun , Hazel Thomas , Johe Karl , Xu RuXiang
Published: August 2019

BACKGROUND

In preclinical studies, the Intracerebral Microinjection Instrument (IMI) has demonstrated the ability to deliver therapeutics within the brain in 3-dimensional arrays from a single overlying penetration while incurring minimal localized trauma.

OBJECTIVE

To evaluate the safety and performance of the IMI in its first use in humans to deliver stem cells in complex configurations within brain regions affected by ischemic injury.

METHODS

As part of a phase 1 study, 3 chronically hemiparetic motor stroke patients received intracerebral grafts of the therapeutic stem cell line, NSI-566, using the IMI and its supporting surgical planning software. The patients were 37 to 54 yr old, had ischemic strokes more than 1 yr prior to transplantation, and received Fugl-Meyer motor scale scores of 17-48 at screening. During a single surgical procedure, patients received several neural grafts (42 ± 3) within the peri-infarct region targeted strategically to facilitate neural repair.

RESULTS

The IMI enabled multiple cellular deposits to be safely placed peripheral to stroke lesions. The procedure was well tolerated, recovery was uneventful, and there occurred no subsequent complications. The IMI performed reliably throughout the procedures without evident targeting errors. One year after transplantation, all 3 subjects displayed significant clinical improvement, and imaging analysis demonstrated occupation of infarct cavities with new tissue without tumor formation.

CONCLUSION

IMI technology permits unprecedented numbers of injections to be tactically placed in 3-dimensional arrays safely and reliably in human subjects.

This advanced methodology can optimize the benefits of novel therapeutics by enabling versatile 3-dimensional intracerebral targeting.
Comparative Phosphoproteomic Analysis Reveals a Decay of ABA Signaling in Barley Embryos during After-Ripening
Authors: Ishikawa Shinnosuke , Barrero Jos� M , Takahashi Fuminori , Nakagami Hirofumi , Peck Scott C , Gubler Frank , Shinozaki Kazuo , Umezawa Taishi
Published: August 2019

Abscisic acid (ABA) is a phytohormone and a major determinant of seed dormancy in plants. Seed dormancy is gradually lost during dry storage, a process known as ‘after-ripening’, and this dormancy decay is related to a decline in ABA content and sensitivity in seeds after imbibition. In this study, we aimed at investigating the effect of after-ripening on ABA signaling in barley, our cereal model species. Phosphosignaling networks in barley grains were investigated by a large-scale analysis of phosphopeptides to examine potential changes in response pathways to after-ripening. We used freshly harvested (FH) and after-ripened (AR) barley grains which showed different ABA sensitivity. A total of 1,730 phosphopeptides were identified in barley embryos isolated from half-cut grains. A comparative analysis showed that 329 and 235 phosphopeptides were upregulated or downregulated, respectively after ABA treatment, and phosphopeptides profiles were quite different between FH and AR embryos. These results were supported by peptide motif analysis which suggested that different sets of protein kinases are active in FH and AR grains. Furthermore, in vitro phosphorylation assays confirmed that some phosphopeptides were phosphorylated by SnRK2s, which are major protein kinases involved in ABA signaling. Taken together, our results revealed very distinctive phosphosignaling networks in FH and AR embryos of barley, and suggested that the after-ripening of barley grains is associated with differential regulation of phosphosignaling pathways leading to a decay of ABA signaling.
A Darwinian Uncertainty Principle
Authors: Gascuel Olivier , Steel Mike
Published: August 2019

Reconstructing ancestral characters and traits along a phylogenetic tree is central to evolutionary biology. It is the key to understanding morphology changes among species, inferring ancestral biochemical properties of life, or recovering migration routes in phylogeography. The goal is 2-fold: to reconstruct the character state at the tree root (e.g., the region of origin of some species) and to understand the process of state changes along the tree (e.g., species flow between countries). We deal here with discrete characters, which are “unique,” as opposed to sequence characters (nucleotides or amino-acids), where we assume the same model for all the characters (or for large classes of characters with site-dependent models) and thus benefit from multiple information sources. In this framework, we use mathematics and simulations to demonstrate that although each goal can be achieved with high accuracy individually, it is generally impossible to accurately estimate both the root state and the rates of state changes along the tree branches, from the observed data at the tips of the tree. This is because the global rates of state changes along the branches that are optimal for the two estimation tasks have opposite trends, leading to a fundamental trade-off in accuracy. This inherent “Darwinian uncertainty principle” concerning the simultaneous estimation of “patterns” and “processes” governs ancestral reconstructions in biology. For certain tree shapes (typically speciation trees) the uncertainty of simultaneous estimation is reduced when more tips are present; however, for other tree shapes it does not (e.g., coalescent trees used in population genetics).
Effect of Mootral—a garlic- and citrus-extract-based feed additive—on enteric methane emissions in feedlot cattle
Authors: Roque Breanna M , Van Lingen Henk J , Vrancken Hilde , Kebreab Ermias
Published: August 2019

Enteric methane (CH4) production is the main source of greenhouse gas emissions from livestock globally with beef cattle contributing 5.95% of total global greenhouse gas emissions. Various mitigation strategies have been developed to reduce enteric emissions with limited success. In vitro studies have shown a reduction in CH4 emissions when using garlic and citrus extracts. However, there is paucity of data regarding in vivo studies investigating the effect of garlic and citrus extracts in cattle. The objective of this study was to quantitatively evaluate the response of Angus × Hereford cross steers consuming the feed additive Mootral, which contains extracts of both garlic and citrus, on CH4 yield (g/kg dry matter intake [DMI]). Twenty steers were randomly assigned to two treatments: control (no additive) and Mootral supplied at 15 g/d in a completely randomized design with a 2-wk covariate and a 12-wk data collection periods. Enteric CH4 emissions were measured using the GreenFeed system during the covariate period and experimental weeks 2, 6, 9, and 12. CH4 yield (g/kg DMI) by steers remained similar in both treatments for weeks 2 to 9. In week 12, there was a significant decrease in CH4 yield (23.2%) in treatment compared to control steers mainly because the steers were consuming all the pellets containing the additive. However, overall CH4 yield (g/kg DMI) during the entire experimental period was not significantly different. Carbon dioxide yield (g/kg DMI) and oxygen consumption (g/kg DMI) did not differ between treatments during the entire experimental period. DMI, average daily gain, and feed efficiency also remained similar in control and supplemented steers. The in vivo results showed that Mootral may have a potential to be used as a feed additive to reduce enteric CH4 production and yield in beef cattle but needs further investigation under various dietary regimen.