bluuebunny/crossref_metadata_2025 huggingface dataset:
Skin cancer
Authors: Allen Heidi
Published: May 2019

This chapter focuses on the management of skin cancer, exploring both malignant melanoma and non-melanoma skin cancer. The epidemiology of melanoma is covered, and risk factors are described. Management looks at both early-stage and widespread disease, including surgery, adjuvant drug therapy, and radiotherapy. There is further emphasis on recent developments in biological and immunotherapy treatments such as ipilimumab and nivolumab. Non-melanoma skin cancer is discussed, covering risk factors and presentation of these diseases and a summary of their management.
Teenage and young adult cancer
Authors: Sherbourne Karen
Published: May 2019

There is increasing recognition that teenagers and young adults (TYAs) are a distinct group from children and older adults and have their own unique needs. This chapter explores the particular issues that affect this group, including late diagnosis, psychosocial impact, family concerns, late effects of treatment, and end-of-life care issues. The role of primary treatment centres is discussed. This provides expertise in young persons' cancer and treatment and specialist support, including youth workers, clinical psychologists, and specialist nurses. Nursing support is explored, and helpful hints are given on how to manage and support patients in this group.
Pain management
Authors: Curtin John
Published: May 2019

Pain is described as being whatever the experiencing person says it is, and their perception of pain is determined by their mood and morale and the meaning of the pain for them. Cancer pain is common, and prevalence is related to the stage of the illness: 59% in patients undergoing treatment, and 64% in those with advanced disease. Pain is multi-causal and multidimensional, and a holistic, interdisciplinary approach to assessment is necessary, encompassing physical, psychological, social, and spiritual aspects of pain (together are ‘total pain’). A narrative approach to pain assessment is helpful, keeping the focus on the patient and their experience. Pain assessment tools can also be used to identify where pain is and how much it hurts. These include: pain body map, visual analogue scales (VAS), verbal rating scales (VRS), numerical rating scales (NRS), and Brief Pain Inventory (BPI). Classifications of pain include acute and chronic pain, nociceptive pain caused by the stimulation of nerve endings, and neuropathic pain caused by nerve dysfunction or compression. Analgesic drugs may be given according to the World Health Organization's pain relief ladder: step 1, non-opioid analgesics such as paracetamol and non-steroidal anti-inflammatory drugs; step 2, mild opioids like codeine with or without non-opioid analgesics; and step 3, strong opioids like morphine with or without non-opioid analgesics. Non-pharmacological interventions for pain management include transcutaneous electrical nerve stimulation (TENS), massage, distraction, relaxation, breathing exercises, comfort measures, and presence of the nurse. Effective communication at all stages of management is essential.
Symptom management at the end of life
Authors: Lund Susi
Published: May 2019

At the end of life, it is important to review all medications, and those required may be continued via a syringe driver if the person is unable to take them orally. The anticipation of needs and forward planning are important, having medications and resources available, ensuring all service providers are aware of the patient 24 hours a day and families have relevant contact numbers. Effective communication with the patient and family is essential, to manage expectations and ensure they understand what is being done and why. Care should always be planned in accordance with local and national guidelines in best practice in palliative and end-of-life care. Anticipatory prescribing of as-required medications for symptoms can help avoid distress. Respiratory secretions (death rattle) can cause noisy, rattling breathing that occurs when the dying person is unconscious and close to death and is unable to cough or clear secretions. This can be distressing to family members, and they will need support and information about the condition. Nursing care involves repositioning to aid drainage of secretions, frequent mouth care, and review of fluid input, and drugs may be used to reduce secretions. Terminal agitation is a state of agitation and distress at the end of life. This is a distressing experience, and it is most important to communicate effectively with the patient and family, maintaining dignity and privacy and providing a comforting professional presence. Sedation should be used with care and discretion, taking the wishes of the patient and family into account.
Crystal arthritis
Authors: Rome Keith , Roddy Edward
Published: May 2019

Many different crystal types can form in the body and potentially cause acute synovitis, chronic arthropathy, or periarticular syndromes. The most common and clinically relevant crystals are monosodium urate, the causative agent in gout, and calcium pyrophosphate, both of which commonly affect the foot and ankle. Foot involvement, particularly the first metatarsophalangeal joint, is the clinical hallmark of gout.
Juvenile idiopathic arthritis
Authors: Hendry Gordon
Published: May 2019

The impact of foot problems in adults with rheumatic and musculoskeletal diseases is generally well established. However, in contrast, the impact of foot problems in children with rheumatic diseases has received relatively little attention. Therefore this chapter provides an overview of the most common rheumatic disorder of childhood: juvenile idiopathic arthritis (JIA), with a focus on how it affects the foot, how it impacts on foot function, gait, and activities of daily living, and its associated assessment and management strategies. We acknowledge that other rheumatic disorders of childhood such as (but not limited to) juvenile systemic lupus erythematosus and dermatomyositis may occasionally present with foot-related impairments; however, these are less likely to affect the foot and ankle in the same way or to the same extent as JIA, and podiatrists are often less involved in management of these conditions. Therefore this chapter will focus on JIA, which frequently affects the foot and ankle and often requires podiatric contributions to the overall management strategies implemented by a multidisciplinary team.
Clinical assessment
Authors: Cherry Lindsey , Gates Lucy , Bowen Catherine
Published: May 2019

This chapter provides an overview of the importance and process for clinical assessment of the foot and ankle in rheumatology. A reference guide for obtaining a clinical history is provided, in addition to recommendations about considering psychosocial and footwear history. An overview of common screening techniques is provided, with particular reference to common serological and musculoskeletal assessment approaches. Specific examples of movement assessment are considered and the importance of clinical observation and palpation in rheumatic disease is noted in addition to the importance of understanding the complex and changing presentation of pain. Finally, insight about future research directions is provided. Overall, it is intended that readers of this chapter will find useful guidance and practical tips for use in a clinical environment.
Pathomechanics and gait analysis
Authors: Chapman Graham , Helliwell Philip
Published: May 2019

Gait analysis is the systematic study of human walking. This chapter summarizes currently available gait analysis techniques that are available to the clinician and researcher. Gait analysis can be used alongside clinical history and examination and other special investigations to gain a better understanding of the relationship between joint disease, impairment, and compensatory gait mechanisms. Abnormal pathology leads to abnormal biomechanics, and tools that demonstrate these changes can lead to insights into the effects of the disease on function, in disease progression, and the impact of physical treatments. Plantar pressure measurement techniques yield valuable information on structure and function and are probably the most likely tool to be used in clinical practice. Three-dimensional joint kinematic and kinetic analyses are more difficult to perform and interpret and are likely to remain largely research tools. Gait analysis techniques will drive experimental work to further advance core knowledge and inform future development of customized approaches to conservative therapies such as footwear and orthosis manufacture, as well as foot surgery.
Foot health management
Authors: Siddle Heidi , Hendry Gordon
Published: May 2019

This chapter will provide the reader with current evidence and the clinical strategies to improve the foot health management of patients with rheumatic and musculoskeletal diseases. The education of patients and health professionals will be key to implementing self-management early in the disease, together with the recognition of problems that require clinical intervention to improve the patient’s long-term outcomes. Unfortunately, there is still a lack of evidence to support many specific interventions, particularly for patients with connective tissue diseases. However, we can utilize increased understanding of the effects that these diseases have on the foot, together with clinical expertise, to manage symptoms and prevent damage and deformity.
Introduction to public health and public health economics
Authors: Edwards Rhiannon T. , Atenstaedt Robert
Published: May 2019

Chapter 1 opens with a historical perspective on the development of public health economics, presents a rationale for this book, and introduces the reader to what is known as public health or population health. This chapter introduces readers to the physical, environmental, and socioeconomic determinants of health and covers concepts such as social norms, ‘nudge’, ‘choice architecture’, and ‘assets-based approaches’ to public health. Strategies for prevention in public health developed by Geoffrey Rose are presented (Rose, 1985). Readers are then introduced to the three main questions in economics: what goods and services to produce, how to produce them, and how to distribute them. Readers are introduced to the economic costs of health harming behaviours such as alcohol misuse, the importance of the upstream approach across the life course and an introduction to the NICE reference case and the importance of study design in underpinning economic evaluation in public health.
The supply and demand of preventive goods and services and the need for economic analysis
Authors: Yeo Seow Tien , Lloyd-Williams Huw , Edwards Rhiannon T.
Published: May 2019

Chapter 2 introduces readers to micro-economic theory of utility, rational choice, and demand and supply. This chapter explains to readers why markets for healthcare goods and services fail and why this failure is so spectacular in the case of preventive goods and services. The chapter introduces readers to the need for economic evaluation in public health to guide the allocation of scarce public resources towards cost-effective prevention initiatives. This chapter goes on to explain the purpose of economic evaluation and its relationship to key concepts such as scarcity, choice, allocative efficiency, technical efficiency, and opportunity cost in health economics. With relevance to public health, readers are introduced to incremental cost-effectiveness ratios (ICERs), cost-effectiveness planes, and cost-effectiveness acceptability curves (CEACs), net monetary benefit (NMB), and their relationship to payer thresholds.
Synthesizing evidence for economic evaluations of public health interventions
Authors: Wu Olivia , Charles Joanna M. , Bray Nathan
Published: May 2019

Reviewing and synthesizing evidence is an important component of the toolkit of methods for the economic evaluation of PHIs. Chapter 4 provides readers with information about good practice in identifying relevant literature, judging the quality of relevant literature, and synthesizing evidence for economic evaluations of PHIs. Narrative synthesis has become a key focus in synthesizing complex PHIs. Readers are also introduced to the idea that logic (conceptual) models can be helpful in describing processes and hence outcomes. The chapter goes on to describe mixed-method reviews, realist synthesis, other forms of evidence synthesis, and equity considerations.
Identifying, measuring, and valuing outcomes within economic evaluations of public health interventions
Authors: McIntosh Emma
Published: May 2019

Chapter 6 explores the many challenges associated with identification, measurement, valuation, reporting, and presenting outcomes within economic evaluations of population health interventions and policies. Drawing on the vast literature in this area, existing guidelines, government recommendations, and methodological advances, this chapter will outline the current challenges, solutions, and suggestions. This chapter also introduces a number of research developments and new outcome measures particularly suited to public health intervention evaluation. These developments include the growing acceptance and relevance of broader measures of outcomes, greater use of ‘capability well-being’ as an outcome, and an increasing use of alternative reporting and presenting frameworks to accommodate these outcomes such as cost–consequence analysis, multi-criteria decision analysis, and social cost–benefit analysis.
Cost–utility analysis of public health interventions
Authors: Edwards Rhiannon T. , Winrow Eira
Published: May 2019

This chapter builds upon Chapters 2 and 6 by introducing the reader to the history and concepts of health-related quality of life, cost–utility analysis, quality-adjusted life years (QALYs), and payer thresholds. The aim of this chapter is to outline in more depth the role of applied cost–utility analyses in the economic evaluation of public health interventions. The chapter goes on to reproduce a paper by Owen and colleagues at the National Institute for Health and Care Excellence (NICE) in the United Kingdom. This paper shows that many public health interventions often have a cost per QALY considerably lower than the £20,000 payer threshold conventionally used by NICE in the United Kingdom.
The use of modelling approaches for the economic evaluation of public health interventions
Authors: Squires Hazel , Boyd Kathleen
Published: May 2019

This chapter considers the use of modelling for public health economic evaluation. The approach to decision analytic modelling within health economic evaluation is described and five key challenges relating to modelling public health interventions are highlighted: incorporating equity; extrapolating multi-component intervention effectiveness beyond study data; capturing relevant complex relationships and feedback loops of a dynamically complex system; modelling human behaviour; and capturing relevant non-health costs and outcomes and the relationship between individual and social determinants. The chapter describes current practice and the latest methodological research in these areas. It outlines two general approaches which could help to address these challenges by (i) adopting an iterative approach to the evaluation by using early-stage decision modelling to guide primary data collection, and (ii) a conceptual modelling framework to guide the model development process.
Return on investment, social return on investment, and the business case for prevention
Authors: Charles Joanna M. , Jones Alice , Lloyd-Williams Huw
Published: May 2019

This chapter describes social return on investment (SROI) analysis as a method to calculate a wider concept of value of an intervention from each £1 invested, across the ‘triple bottom line’ of economic, social, and environmental value. The method is underpinned by seven principles and can be considered a practical, stakeholder adaptation of cost–benefit analysis, although there are important differences between these two methods. This chapter outlines the method, providing an illustrative case study of applying SROI analysis to housing improvements to highlight each stage of the analysis and provide a worked example of the method. The merits and limitations of this relatively new method are also discussed, including reasons for the increased use of the approach for economic evaluation of PHIs. The role of SROI in producing a pragmatic business case for prevention is also discussed.
Vascular ultrasound
Authors: Bowra Justin , Loubani Osama , Atkinson Paul
Published: May 2019

Vascular ultrasound is accurate in the diagnosis of abdominal aortic aneurysm (AAA) and deep vein thrombosis (DVT) at or above the knee. B-mode ultrasound usually suffices to make or refute these diagnoses, although sometimes Doppler ultrasound is required. Vascular ultrasound can also assist in the diagnosis of aortic dissection, although it cannot be used to rule out dissection. Finally, vascular ultrasound is also used to image the inferior vena cava (IVC) to assist in the estimation of intravascular volume status in the shocked patient, usually in conjunction with a shock protocol.
Ultrasound and procedures
Authors: Jarman Bob , Hoffmann Beatrice , Al-Githami Miteb , Hardin John , Skoromovsky Elena , Durham Stuart , Lewis David , Atkinson Paul , Bowra Justin
Published: May 2019

Using ultrasound as an adjunct to a clinical procedure is widespread. This aspect of PoCUS has allowed clinicians to improve the speed and safety of a wide variety of procedures that are performed at the patient’s side, as well as in more traditional interventional environments. There is a large evidence base demonstrating improved safety when ultrasound is used to guide procedures, and this has resulted in widespread adoption by many specialties. Needle guidance to a specific target area is key to the majority of procedures. This chapter will describe the principles required for safe needle guidance and will outline the specific procedures where ultrasound can aid the clinician.
Education and simulation in point-of-care ultrasound
Authors: Olszynski Paul , Stander Melanie , Harris Tim , Tutschka Mark , Atkinson Paul
Published: May 2019

This chapter deals with some of the common questions surrounding training in point-of-care ultrasound (PoCUS)—how does a clinician achieve competence in PoCUS? What educational methods are the most appropriate for PoCUS? What applications should be taught? How can advanced skills be learnt? How can quality be assured and improved? How can low- and high-fidelity simulation help with skills training and maintenance and confidence building, as well as clinical integration and decision-making? Technology is evolving, advancing, and adapting to training needs. While there may be no universally accepted curriculum for training and assessment, a consensus is forming around core theories and practices.
Cardiovascular
Authors: Monaghan Tanya M. , Thomas James D.
Published: May 2019

This chapter is about cardiovascular medicine, and covers mitral regurgitation, mitral stenosis, aortic regurgitation, aortic stenosis, mixed mitral valve disease, mixed aortic valve disease, tricuspid regurgitation, prosthetic valves, ventricular septal defect, atrial septal defect, hypertrophic cardiomyopathy, coarctation of the aorta, persistent ductus arteriosus, Fallot’s tetralogy, dextrocardia, infective endocarditis, and congenital heart disease diagrams.
Locomotor
Authors: Monaghan Tanya M. , Thomas James D.
Published: May 2019

This chapter concerns locomotive medicine, and covers rheumatoid arthritis, osteoarthritis, psoriatic arthritis, ankylosing spondylitis, Paget’s disease, tophaceous gout, Marfan’s syndrome, systemic sclerosis, vasculitis, systemic lupus erythematosus, rickets, Dupuytren’s contracture, trigger finger, and Charcot’s joint.
Rectal cancer and systemic therapy of colorectal cancer
Authors: Beets-Tan Regina , Glimelius Bengt
Published: May 2019

In rectal cancer treatment, surgery is most important. Dissection outside the mesorectal fascia, total mesorectal excision is required for cure in most cases; a local procedure is possible in the earliest tumours. Appropriate staging is required prior to treatment decision to stratify patients into risk groups. In early tumours surgery alone is sufficient whereas in intermediate cancers local recurrence rates are too high and preoperative radiotherapy is indicated. A short-course schedule is convenient, low toxic, although some prefer long-course chemoradiotherapy. The addition of a fluoropyrimidine enhances the radiotherapy. In locally advanced tumours preoperative chemoradiotherapy is required. The value of adjuvant chemotherapy in rectal cancer is controversial, particularly if preoperative chemoradiotherapy was used. Palliative chemotherapy prolongs life and improves well-being in patients with metastatic disease. Targeted drugs further improves the results to some extent. In some patients, chemotherapy may convert non-readily resectable metastases to resectable, and result in long-term cure.
Skin cancer: non-melanoma
Authors: Damian Diona L. , Scolyer Richard A. , Stevens Graham , Guminski Alexander , Thompson John F.
Published: May 2019

Non-melanoma skin cancer (NMSC) is the most common malignancy in fair-skinned populations. In Australia, NMSC is four times as common as all other cancers combined, with an incidence of ~1000 per 100 000 person-years. The incidence of NMSC has been gradually rising among Caucasian/white populations over the last few decades. The vast majority of NMSCs are basal cell carcinomas (BCCs), which rarely metastasize, or squamous cell carcinomas (SCCs), which do have metastatic potential, especially in immune-suppressed individuals. Because of their high frequency in the general population, and particularly in older people, NMSCs are likely to occur in many general oncology patients. Skin cancer risk can be additionally increased in oncology patients as a result of disease-induced immune suppression (e.g., non-Hodgkin’s lymphoma) or by a range of cancer treatments including iatrogenic immune suppression, radiation therapy arsenic, and BRAF inhibitors (if not given with a MEK inhibitor). In this chapter the aetiology, pathology, prognosis, and management of NMSCs are discussed.
Cancer of unknown primary site
Authors: Pavlidis Nicholas , Pentheroudakis George
Published: May 2019

This chapter covers cancer of unknown primary site (CUP), and includes information on epidemiology, molecular biology, pathology, and multidisciplinary management of clinicopathological subsets. Previously, these tumours were diagnosed and treated based on clinical presentation, light microscopy and clinical intuition. Today, the majority of cancers of unknown primary site are becoming less unknown, more accurately classified, and appropriately treated by the use of multiplex or genome-wide expression profiling platforms. These techniques allow for precise and correct knowledge of the true tumour origin, leading to more rational and effective treatment. However, there also may be genetic signatures that are primary-independent, pro-metastatic, and possibly CUP-specific.
Permanent pacemaker implantation
Authors: Mitchell Andrew , Ormerod Oliver
Published: May 2019

This chapter covers pacemaker implantation. Pre-procedure considerations such as the operative conditions and steps for patient preparations are outlined. The implantation procedure is discussed in detail, with visual aids to show the incision and pocket placement, techniques to improve the success of the operation, and different types of venous access. Advantages and disadvantages of different routes are summarized. Lead implantation is covered, from positioning, securing, and electrical testing. Connecting the generator and wound closure is followed by a description of post-procedure care. Alternative device types and sites and are outlined, with indications for choice. Finally, special considerations in the young patient are described.
Troubleshooting
Authors: Betts Timothy , Ormerod Julian
Published: May 2019

This chapter covers the common reasons why a pacemaker can fail to work, then provides methods for fixing each problem. Complications with high threshold have the diagnosis, cause, and treatment for lead displacement, lead fracture, lead insulation break, and exit block. Complications with oversensing have the diagnosis, cause, and treatment for T-wave oversensing, far-field sensing, myopotential inhibition, lead fracture, and pacing lead interaction with old leads. Undersensing covers generator failure, the end of life battery failure, and problems with a runaway pacemaker. Finally, other, yet rare, problems are described.
Damping rates and frequency corrections of Kepler LEGACY stars
Authors: Houdek G , Lund M N , Trampedach R , Christensen-Dalsgaard J , Handberg R , Appourchaux T
Published: May 2019

Linear damping rates and modal frequency corrections of radial oscillation modes in selected LEGACY main-sequence stars are estimated by means of a non-adiabatic stability analysis. The selected stellar sample covers stars observed by Kepler with a large range of surface temperatures and surface gravities. A non-local, time-dependent convection model is perturbed to assess stability against pulsation modes. The mixing-length parameter is calibrated to the surface-convection-zone depth of a stellar model obtained from fitting adiabatic frequencies to the LEGACY observations, and two of the non-local convection parameters are calibrated to the corresponding LEGACY linewidth measurements. The remaining non-local convection parameters in the 1D calculations are calibrated so as to reproduce profiles of turbulent pressure and of the anisotropy of the turbulent velocity field of corresponding 3D hydrodynamical simulations. The atmospheric structure in the 1D stability analysis adopts a temperature–optical–depth relation derived from 3D hydrodynamical simulations. Despite the small number of parameters to adjust, we find good agreement with detailed shapes of both turbulent pressure profiles and anisotropy profiles with depth, and with damping rates as a function of frequency. Furthermore, we find the absolute modal frequency corrections, relative to a standard adiabatic pulsation calculation, to increase with surface temperature and surface gravity.
A new empirical method to estimate the molecular gas mass in galaxies
Authors: Concas Alice , Popesso Paola
Published: May 2019

We find a tight correlation between the dust extinction, traced by the Balmer Decrement (BD = H α/H β), the CO(1-0) line luminosity (LCO), and total molecular gas mass (MH2) in a sample of 222 local star-forming galaxies drawn from the xCOLD GASS survey. As expected, the galaxy disc inclination affects the correlation by inducing a saturation of the Balmer decrement on highly inclined galaxies. Once this effect is taken into account, LCO and MH2 can be expressed as a function of BD with a scatter of ∼0.3 dex. We do not find any dependence on galaxy size, mass, morphology, star formation activity, and gas metallicity. The correlation disappears if the atomic gas phase is considered. This is likely due to the fact that the region traced by the BD, the stellar disc, is much smaller than the HI disc.
LOMETS2: improved meta-threading server for fold-recognition and structure-based function annotation for distant-homology proteins
Authors: Zheng Wei , Zhang Chengxin , Wuyun Qiqige , Pearce Robin , Li Yang , Zhang Yang
Published: May 2019

The LOMETS2 server (https://zhanglab.ccmb.med.umich.edu/LOMETS/) is an online meta-threading server system for template-based protein structure prediction. Although the server has been widely used by the community over the last decade, the previous LOMETS server no longer represents the state-of-the-art due to aging of the algorithms and unsatisfactory performance on distant-homology template identification. An extension of the server built on cutting-edge methods, especially techniques developed since the recent CASP experiments, is urgently needed. In this work, we report the recent advancements of the LOMETS2 server, which comprise a number of major new developments, including (i) new state-of-the-art threading programs, including contact-map-based threading approaches, (ii) deep sequence search-based sequence profile construction and (iii) a new web interface design that incorporates structure-based function annotations. Large-scale benchmark tests demonstrated that the integration of the deep profiles and new threading approaches into LOMETS2 significantly improve its structure modeling quality and template detection, where LOMETS2 detected 176% more templates with TM-scores >0.5 than the previous LOMETS server for Hard targets that lacked homologous templates. Meanwhile, the newly incorporated structure-based function prediction helps extend the usefulness of the online server to the broader biological community.
Yosshi: a web-server for disulfide engineering by bioinformatic analysis of diverse protein families
Authors: Suplatov Dmitry , Timonina Daria , Sharapova Yana , Švedas Vytas
Published: May 2019

Disulfide bonds play a significant role in protein stability, function or regulation but are poorly conserved among evolutionarily related proteins. The Yosshi can help to understand the role of S–S bonds by comparing sequences and structures of homologs with diverse properties and different disulfide connectivity patterns within a common structural fold of a superfamily, and assist to select the most promising hot-spots to improve stability of proteins/enzymes or modulate their functions by introducing naturally occurring crosslinks. The bioinformatic analysis is supported by the integrated Mustguseal web-server to construct large structure-guided sequence alignments of functionally diverse protein families that can include thousands of proteins based on all available information in public databases. The Yosshi+Mustguseal is a new integrated web-tool for a systematic homology-driven analysis and engineering of S–S bonds that facilitates a broader interpretation of disulfides not just as a factor of structural stability, but rather as a mechanism to implement functional diversity within a superfamily. The results can be downloaded as a content-rich PyMol session file or further studied online using the HTML5-based interactive analysis tools. Both web-servers are free and open to all users at https://biokinet.belozersky.msu.ru/yosshi and there is no login requirement.
NetGO: improving large-scale protein function prediction with massive network information
Authors: You Ronghui , Yao Shuwei , Xiong Yi , Huang Xiaodi , Sun Fengzhu , Mamitsuka Hiroshi , Zhu Shanfeng
Published: May 2019

Automated function prediction (AFP) of proteins is of great significance in biology. AFP can be regarded as a problem of the large-scale multi-label classification where a protein can be associated with multiple gene ontology terms as its labels. Based on our GOLabeler—a state-of-the-art method for the third critical assessment of functional annotation (CAFA3), in this paper we propose NetGO, a web server that is able to further improve the performance of the large-scale AFP by incorporating massive protein-protein network information. Specifically, the advantages of NetGO are threefold in using network information: (i) NetGO relies on a powerful learning to rank framework from machine learning to effectively integrate both sequence and network information of proteins; (ii) NetGO uses the massive network information of all species (>2000) in STRING (other than only some specific species) and (iii) NetGO still can use network information to annotate a protein by homology transfer, even if it is not contained in STRING. Separating training and testing data with the same time-delayed settings of CAFA, we comprehensively examined the performance of NetGO. Experimental results have clearly demonstrated that NetGO significantly outperforms GOLabeler and other competing methods. The NetGO web server is freely available at http://issubmission.sjtu.edu.cn/netgo/.
PRECOG: PREdicting COupling probabilities of G-protein coupled receptors
Authors: Singh Gurdeep , Inoue Asuka , Gutkind J Silvio , Russell Robert B , Raimondi Francesco
Published: May 2019

G-protein coupled receptors (GPCRs) control multiple physiological states by transducing a multitude of extracellular stimuli into the cell via coupling to intra-cellular heterotrimeric G-proteins. Deciphering which G-proteins couple to each of the hundreds of GPCRs present in a typical eukaryotic organism is therefore critical to understand signalling. Here, we present PRECOG (precog.russelllab.org): a web-server for predicting GPCR coupling, which allows users to: (i) predict coupling probabilities for GPCRs to individual G-proteins instead of subfamilies; (ii) visually inspect the protein sequence and structural features that are responsible for a particular coupling; (iii) suggest mutations to rationally design artificial GPCRs with new coupling properties based on predetermined coupling features.
Web 3DNA 2.0 for the analysis, visualization, and modeling of 3D nucleic acid structures
Authors: Li Shuxiang , Olson Wilma K , Lu Xiang-Jun
Published: May 2019

Web 3DNA (w3DNA) 2.0 is a significantly enhanced version of the widely used w3DNA server for the analysis, visualization, and modeling of 3D nucleic-acid-containing structures. Since its initial release in 2009, the w3DNA server has continuously served the community by making commonly-used features of the 3DNA suite of command-line programs readily accessible. However, due to the lack of updates, w3DNA has clearly shown its age in terms of modern web technologies and it has long lagged behind further developments of 3DNA per se. The w3DNA 2.0 server presented here overcomes all known shortcomings of w3DNA while maintaining its battle-tested characteristics. Technically, w3DNA 2.0 implements a simple and intuitive interface (with sensible defaults) for increased usability, and it complies with HTML5 web standards for broad accessibility. Featurewise, w3DNA 2.0 employs the most recent version of 3DNA, enhanced with many new functionalities, including: the automatic handling of modified nucleotides; a set of ‘simple’ base-pair and step parameters for qualitative characterization of non-Watson–Crick double-helical structures; new structural parameters that integrate the rigid base plane and the backbone phosphate group, the two nucleic acid components most reliably determined with X-ray crystallography; in silico base mutations that preserve the backbone geometry; and a notably improved module for building models of single-stranded RNA, double-helical DNA, Pauling triplex, G-quadruplex, or DNA structures ‘decorated’ with proteins. The w3DNA 2.0 server is freely available, without registration, at http://web.x3dna.org.
Remodeling and destabilization of chromosome 1 pericentromeric heterochromatin by SSX proteins
Authors: Traynor Sofie , Møllegaard Niels Erik , Jørgensen Mikkel G , Brückmann Nadine H , Pedersen Christina B , Terp Mikkel G , Johansen Simone , Dejardin Jerome , Ditzel Henrik J , Gjerstorff Morten F
Published: May 2019

Rearrangement of the 1q12 pericentromeric heterochromatin and subsequent amplification of the 1q arm is commonly associated with cancer development and progression and may result from epigenetic deregulation. In many premalignant and malignant cells, loss of 1q12 satellite DNA methylation causes the deposition of polycomb factors and formation of large polycomb aggregates referred to as polycomb bodies. Here, we show that SSX proteins can destabilize 1q12 pericentromeric heterochromatin in melanoma cells when it is present in the context of polycomb bodies. We found that SSX proteins deplete polycomb bodies and promote the unfolding and derepression of 1q12 heterochromatin during replication. This further leads to segregation abnormalities during anaphase and generation of micronuclei. The structural rearrangement of 1q12 pericentromeric heterochromatin triggered by SSX2 is associated with loss of polycomb factors, but is not mediated by diminished polycomb repression. Instead, our studies suggest a direct effect of SSX proteins facilitated though a DNA/chromatin binding, zinc finger-like domain and a KRAB-like domain that may recruit chromatin modifiers or activate satellite transcription. Our results demonstrate a novel mechanism for generation of 1q12-associated genomic instability in cancer cells.
Genetic and genomic alterations differentially dictate low-grade glioma growth through cancer stem cell–specific chemokine recruitment of T cells and microglia
Authors: Guo Xiaofan , Pan Yuan , Gutmann David H
Published: May 2019

Background

One of the clinical hallmarks of low-grade gliomas (LGGs) arising in children with the neurofibromatosis type 1 (NF1) cancer predisposition syndrome is significant clinical variability with respect to tumor growth, associated neurologic deficits, and response to therapy. Numerous factors could contribute to this clinical heterogeneity, including the tumor cell of origin, the specific germline NF1 gene mutation, and the coexistence of additional genomic alterations. Since human specimens are rarely acquired, and have proven difficult to maintain in vitro or as xenografts in vivo, we have developed a series of Nf1 mutant optic glioma mouse strains representing each of these contributing factors.

Methods

Optic glioma stem cells (o-GSCs) were generated from this collection of Nf1 genetically engineered mice, and analyzed for their intrinsic growth properties, as well as the production of chemokines that could differentially attract T cells and microglia.

Results

The observed differences in Nf1 optic glioma growth are not the result of cell autonomous growth properties of o-GSCs, but rather the unique patterns of o-GSC chemokine expression, which differentially attract T cells and microglia. This immune profile collectively dictates the levels of chemokine C-C ligand 5 (Ccl5) expression, the key stromal factor that drives murine Nf1 optic glioma growth.

Conclusions

These findings reveal that genetic and genomic alterations create murine LGG biological heterogeneity through the differential recruitment of T cells and microglia by o-GSC–produced chemokines, which ultimately determine the expression of stromal factors that drive tumor growth.
Lattice and spin dynamics in multiferroic BiFeO3 and RMnO3
Authors: Song Yan , Xu Ben , Nan Ce-Wen
Published: May 2019

The multiferroic materials BiFeO3 and RMnO3 exhibit coexisting magnetic order and ferroelectricity, and provide exciting platforms for new physics and potentially novel devices, where intriguing interplay between phonons and magnons exists. In this review, we paint a complete picture of bulk BiFeO3 together with orthorhombic and hexagonal RMnO3 (R includes rare-earth elements and yttrium) by summarizing the dynamics of spin and lattice and their magnetoelectric coupling, as well as the methods of controlling these characteristics under non-equilibrium conditions, from experimental and simulation perspectives.
Prescribing Prevalence, Effectiveness, and Mental Health Safety of Smoking Cessation Medicines in Patients With Mental Disorders
Authors: Taylor Gemma M J , Itani Taha , Thomas Kyla H , Rai Dheeraj , Jones Tim , Windmeijer Frank , Martin Richard M , Munafò Marcus R , Davies Neil M , Taylor Amy E
Published: May 2019

Objective

We conducted a prospective cohort study of the Clinical Practice Research Database to estimate rates of varenicline and nicotine replacement therapy (NRT) prescribing and the relative effects on smoking cessation, and mental health.

Methods

We used multivariable logistic regression, propensity score matched regression, and instrumental variable analysis. Exposure was varenicline or NRT prescription. Mental disorders were bipolar, depression, neurotic disorder, schizophrenia, or prescriptions of antidepressants, antipsychotics, hypnotics/anxiolytics, mood stabilizers. Outcomes were smoking cessation, and incidence of neurotic disorder, depression, prescription of antidepressants, or hypnotics/anxiolytics. Follow-ups were 3, 6, and 9 months, and at 1, 2, and 4 years.

Results

In all patients, NRT and varenicline prescribing declined during the study period. Seventy-eight thousand four hundred fifty-seven smokers with mental disorders aged ≥18 years were prescribed NRT (N = 59 340) or varenicline (N = 19 117) from September 1, 2006 to December 31, 2015. Compared with smokers without mental disorders, smokers with mental disorders had 31% (95% CI: 29% to 33%) lower odds of being prescribed varenicline relative to NRT, but had 19% (95% CI: 15% to 24%) greater odds of quitting at 2 years when prescribed varenicline relative to NRT. Overall, varenicline was associated with decreased or similar odds of worse mental health outcomes than NRT in patients both with and without mental disorders, although there was some variation when analyses were stratified by mental disorder subgroup.

Conclusions

Smoking cessation medication prescribing may be declining in primary care. Varenicline was more effective than NRT for smoking cessation in patients with mental disorders and there is not clear consistent evidence that varenicline is adversely associated with poorer mental health outcomes.

Implications

Patients with mental disorders were less likely to be prescribed varenicline than NRT. We triangulated results from three analytical techniques. We found that varenicline was more effective than NRT for smoking cessation in patients with mental disorders. Varenicline was generally associated with similar or decreased odds of poorer mental health outcomes (ie, improvements in mental health) when compared with NRT. We report these findings cautiously as our data are observational and are at risk of confounding.
Forensic Medicine And Female Victimhood In Victorian And Edwardian England*
Authors: Bates Victoria
Published: May 2019

Mistrust of women has been an enduring feature of trials for sexual offences, both historically and in the present day, but is not a transhistorical phenomenon. This article explores the late-Victorian and Edwardian courts, in which there was a renewed tendency to question female respectability and to judge complainants for failing adequately to resist a man’s sexual advances. Scholars have identified broad social trends that led to greater interrogation of female sexual behaviour during this period, but there remains limited understanding of the mechanisms by which these concerns entered the courtroom. This article focuses on the rise of a medico-legal framework for investigating sexual violence as one such mechanism. Drawing upon newspaper reports and court cases from Middlesex, Somerset, Gloucestershire and Devon in the period 1850–1914, it shows that medical witnesses often implicitly reinforced social models of ‘real’ victimhood — which excluded many complainants — through their testimony on female chastity and resistance. Forensic medicine operated as an important, and increasingly unique, bridge between English social change and local courts.
Exploring mechanisms for spring bloom evolution: contrasting 2008 and 2012 blooms in the southwest Pacific Ocean
Authors: Chiswell Stephen M , Safi Karl A , Sander Sylvia G , Strzepek Robert , Ellwood Michael J , Milne Angela , Boyd Philip W
Published: May 2019

Observations from two research cruises made in 2008 and 2012 to east of New Zealand are put into context with satellite data to contrast and compare surface chlorophyll a evolution in the two years in order to explore mechanisms of phytoplankton bloom development in the southwest Pacific Ocean. In 2008, surface chlorophyll a largely followed the long-term climatological cycle, and 2008 can be considered a canonical year, where the autumn bloom is triggered by increasing vertical mixing at the end of summer and the spring bloom is triggered by decreasing vertical mixing at the end of winter. In contrast, 2012 was anomalous in that there was no autumn bloom, and in early spring there were several periods of sustained increase in surface chlorophyll a that did not become fully developed spring blooms. (In this region, we consider spring blooms to occur when surface chlorophyll a exceeds 0.5 mg m-3). These events can be related to alternating episodes of increased or decreased vertical mixing. The eventual spring bloom in October was driven by increased ocean cooling and wind stress (i.e. increased mixing) and paradoxically was driven by mechanisms considered more appropriate for autumn rather than spring blooms.
The Effect of Minimum Wages on Low-Wage Jobs*
Authors: Cengiz Doruk , Dube Arindrajit , Lindner Attila , Zipperer Ben
Published: May 2019

We estimate the effect of minimum wages on low-wage jobs using 138 prominent state-level minimum wage changes between 1979 and 2016 in the United States using a difference-in-differences approach. We first estimate the effect of the minimum wage increase on employment changes by wage bins throughout the hourly wage distribution. We then focus on the bottom part of the wage distribution and compare the number of excess jobs paying at or slightly above the new minimum wage to the missing jobs paying below it to infer the employment effect. We find that the overall number of low-wage jobs remained essentially unchanged over the five years following the increase. At the same time, the direct effect of the minimum wage on average earnings was amplified by modest wage spillovers at the bottom of the wage distribution. Our estimates by detailed demographic groups show that the lack of job loss is not explained by labor-labor substitution at the bottom of the wage distribution. We also find no evidence of disemployment when we consider higher levels of minimum wages. However, we do find some evidence of reduced employment in tradeable sectors. We also show how decomposing the overall employment effect by wage bins allows a transparent way of assessing the plausibility of estimates.
The diversity of labor market institutions and entrepreneurship
Authors: Dilli Selin
Published: May 2019

Substantial literature demonstrates that flexible labor market institutions promote entrepreneurial activity. We re-evaluate this finding by considering the complementarity between institutions as advocated by the varieties of capitalism literature. We study the relevance of labor market regulations, wage-setting institutions and social security, and their complementarity for different types of entrepreneurial activity in 19 European countries and the USA. Two findings stand out. First, the four distinct bundles of labor market institutions characterizing Europe support different forms of entrepreneurial activity, and that innovative entrepreneurial activity also exists in less-flexible and -regulated labor market arrangements. Second, the relationships between single labor market institutions and entrepreneurial activity vary across the four institutional constellations. Therefore, to promote entrepreneurship in Europe, there is a need for tailored reform strategies that consider the diversity of the institutional constellations.
Absolute income inequality and rising house prices
Authors: Goda Thomas , Stewart Chris , Torres García Alejandro
Published: May 2019

Income inequality and house prices have risen sharply in developed countries during 1975–2010. In line with theoretical models, we argue that this co-movement is no coincidence, but that inequality has driven up house prices on the grounds that it raises the aggregate demand for housing. Our results suggest that absolute inequality and house prices in most Organisation for Economic Co-operation and Development (OECD) countries were positively correlated and cointegrated, whereas relative inequality and mean income were not significant long-run determinants. This finding indicates that the surge in OECD house prices in part can be explained by a top-income-induced increase in housing demand, and that it is important to consider the interaction of rising mean income and its relative distribution when studying potential correlates of house prices. Moreover, our results confirm previous findings that the short-term real interest rate also is an important correlate of house prices.