bluuebunny/crossref_metadata_2025 huggingface dataset:
Chemical carcinogens
Authors: Oliveira Paula A.
Published: January 2016

The development of cancer associated with exposure to chemical carcinogens is a reality and existing knowledge of these cancers is based on epidemiological, in vivo, and in vitro studies. Chemical carcinogens are present virtually everywhere and humans can be exposed to these compounds in food, air, water, their environment, or their workplace. This chapter is concerned with the main types of exogenous chemical carcinogens, how they are classified and their modes of action, absorption, and metabolism, as well as the principal tests available for evaluating their carcinogenicity. Only exogenous chemicals are considered in this chapter, since exogenous chemical carcinogens may be the major contributors to human cancer.
Practice points for surgical oncology
Authors: Boelens Petra G. , van den Broek C.B.M. , van de Velde Cornelis J.H.
Published: January 2016

Cancer surgery remains the cornerstone of curative cancer treatment for most solid cancers. Staging, resectability and timing of surgery should be discussed in a multidisciplinary team. Complete resection offers the best prognosis at many stages. Anatomical planes of surgery need to be taught and respected to reduce locoregional recurrence rate. Age, comorbidities, and patient preferences are important to consider before surgical treatment is advised. Minimal invasive techniques have shown equivalence in oncologic outcome for certain cancer types and established benefits in short-term outcomes. A laparoscopic approach is even sometimes possible. It remains important to select patients for these techniques according to medical history, staging, and fitness. In specialized centres locally advanced disease can be treated by a multimodal approach. The quality of surgery can be improved using standardized audit structures to monitor and feed back on outcome of surgery such as resected margins, infectious complications, and disease-free and overall survival.
Multidisciplinary cancer care
Authors: Church David N. , Kerr Rachel , Kerr David J.
Published: January 2016

Over the last two decades, multidisciplinary team (MDT) working has become an integral part of cancer care in many healthcare systems in the Western world. MDT meetings were established as part of an effort to reduce the fragmented provision of cancer care, and to ensure that each patient receives a management plan based on expert consensus following consideration of all appropriate therapeutic options. Although limited, the available evidence indicates that MDT working is associated with improved patient outcomes, though the associated costs are significant. MDTs are likely to evolve over the coming years through the development of specific software tools to aid clinical decision-making, and through the incorporation of tumour genomics and the personalization of therapy this enables.
Design and analysis of clinical trials
Authors: Sargent Daniel , Shi Qian
Published: January 2016

This chapter addresses the statistical design and analysis of oncology clinical trials. Traditional trial designs are described by each of three phases—phase I, II, and III studies. It elaborates on the concepts of single-arm versus randomized (screening and selection) phase II trials. Critical aspects of randomized phase III studies are discussed, including randomization, stratification, blinding, and the intent-to-treat principle. Furthermore, the chapter introduces innovative designs, emphasizing the incorporation of biomarkers into the study design. Careful considerations of endpoints, essential to power and sample size when planning a study, are considered. In addition to discussing standard statistical analysis methods, we particularly discuss the critical element of controlling for multiple comparisons.
Health economic assessment of cancer therapy
Authors: Peppercorn Jeffrey
Published: January 2016

Our ability to deliver high-quality cancer care is increasingly influenced by our ability to understand and manage the costs of care. Though there are considerable differences in the ways healthcare is financed and administered in different nations, there is a common need to deliver high-quality care at sustainable costs. This chapter reviews recent estimates of the aggregate costs of cancer care, discusses methods for determining cost-effectiveness or value in cancer care, provides a framework for understanding the components of cost at the societal and individual levels, and discusses efforts to control cost while preserving or improving both quality and outcomes.
Cancer prevention
Authors: Goltz Sarah E.B. , Lob-Levyt Julian
Published: January 2016

This chapter describes the increasingly critical role of cancer vaccines in preventing, and potentially even treating, cancers in all resource settings. At this time, there are three cancer vaccines, two of which protect against cancer-causing viruses—hepatitis B virus (HBV) and the human papillomavirus (HPV); the third is an immunostimulant treatment virus for late-stage prostate cancer. Few advances in medicine and public health have had as substantial an impact on morbidity and mortality worldwide as vaccines. The potential public health impact of cancer vaccines is particularly significant in developing countries, where limited resources make prevention, screening, and disease management especially challenging. Numerous strategies are being employed to improve access to cancer vaccines in low- and middle-income settings. These efforts are beginning to demonstrate impact on cancer rates, indicating how innovative mechanisms may be used to expand access to HPV and other future cancer vaccines in the decades to come.
Familial cancer syndromes and genetic counselling
Authors: Lynch Henry T. , Snyder Carrie L. , Lynch Jane F.
Published: January 2016

Thanks to the veritably logarithmic advances in the molecular genetics of many emerging hereditary cancer syndromes, genetic counselling has become of paramount importance. It is a key element of the emerging concepts for patient education and management, which have become the clinical bedrock for diagnosis and management of hereditary cancer. Genetic counsellors have become proficient in the understanding of the complexities of molecular genetics in relation to hereditary cancer syndromes, demonstrating their ability both to supplement and replace the customary physician’s role in this overall process. We have used colorectal cancer, in particular Lynch syndrome, as a clinical genetic model based on the authors’ experience with diagnosis, DNA testing, and counselling of thousands of families for over four decades. Undoubtedly, the surface of the proverbial iceberg has barely been grazed in regard to the developments for the genetic counseling discipline.
Supportive and palliative care
Authors: Hui David , Bruera Eduardo
Published: January 2016

Patients with advanced cancer experience significant symptom burden as a result of disease progression, anti-neoplastic therapies and various psychosocial factors. Furthermore, they are often faced with complex decisions regarding information and communication. Palliative care is a professional specialty that specifically addresses patients’ and their families’ supportive care needs through validated assessments, evidence-based interventions, impeccable communication, and collaborative teamwork. Palliative care involvement is associated with improved symptom burden, quality of life, quality of care, satisfaction, and possibly survival and cost of care. In this chapter, we describe the structure, processes, and outcomes of palliative care, and discuss contemporary models of integration between oncology and palliative care. We will also discuss the latest insights into management of cancer pain, fatigue, and depression. Oncologists equipped with basic palliative care skills can deliver effective front-line supportive care. Patients in distress may also benefit from early referral to specialist palliative care teams.
Cancer survivorship and rehabilitation
Authors: Yung Rachel L. , Partridge Ann H.
Published: January 2016

A cancer diagnosis is often a life-changing event. Cancer survivorship has become an integral part of cancer care. Currently, two-thirds of patients survive at least five years after their cancer diagnosis and the proportion is increasing. Key components of survivorship care include: (1) surveillance for recurrence and screening for second primary cancers; (2) identification and management of long-term and late effects of the cancer and cancer treatments (3) improving modifiable health behaviours; and (4) care coordination. Late effects can be physical or psychosocial. Development of clinical practice guidelines that incorporate evidence-based recommendations is critical, as is further research to understand the full impact of cancer on patients’ lives.
Head and neck cancer
Authors: Chung Christine H. , Dietz Andreas , Gregoire Vincent , Guzzo Marco , Hamoir Marc , Leemans René , Lefebvre Jean-Louis , Licitra Lisa , El-Naggar Adel K. , O’Sullivan Brian , Tan Bing , Vandecaveye Vincent , Poorten Vincent Vander , Vermorken Jan , Williams Michelle D.
Published: January 2016

This chapter discusses head and neck cancers, and covers the epidemiology and molecular biology of head and neck cancer. Head and neck cancer is a heterogeneous disease and most commonly caused by tobacco and alcohol use, as well as high-risk human papillomavirus (HPV) infection. HPV-negative and -positive HNSCC are demographically, biologically and clinically distinct entities with more favourable outcomes associated with HPV-positive tumours of the oropharynx. Comprehensive genomic analyses show that more functional loss of tumour suppressors are present in HPV-negative tumours compared to HPV-positive tumours. Furthermore, HNSCC can be molecularly characterized into five subtypes. The challenges facing future investigations are efficient translation of these biological findings into clinically meaningful advancements in patient treatment.
Colorectal cancer
Authors: Boussioutas Alex , Fox Stephen , Nagtegaal Iris , Heriot Alexander , Knowles Jonathan , Michael Michael , Ngan Sam , Field Kathryn , Zalcberg John
Published: January 2016

This chapter covers colorectal cancer, and includes information on epidemiology, risk factors (chronic inflammation/inflammatory bowel disease, radiation, diet and lifestyle, post cholecystectomy, diabetes, obesity and insulin resistance, cigarette smoking, alcohol, ureterocolic anastamosis, and genetic risk factors, screening, and chemoprevention (aspirin, and NSAIDS), the molecular biology and pathology of colorectal cancer, colorectal carcinoma (location, pathologic prognostic markers, and predictive markers), surgical management (colonic cancer and inflammatory bowel disease, hereditary non-polyposis colonic cancer or HNPCC, presenting as an emergency, treatment of polyp or early cancers, liver and lung metastasis, peritoneal disease, results of surgery and treatment for colon cancer, medical management of early stage disease, adjuvant chemotherapy for stage III disease (T1-4, N1-2M0), adjuvant therapy of patients with resected stage II colon cancer, radiotherapy, multidisciplinary care and special groups, the role of allied teams, and surveillance and follow-up.
Gynaecological cancers
Authors: Pötter Richard , Liu Shujuan , Liu Bolin , Gouy Sebastien , Lax Sigurd , Leblanc Eric , Morice Philippe , Narducci Fabrice , Reinthaller Alexander , Schmid Maximilian Paul , Uzan Catherine , Wimberger Pauline
Published: January 2016

This chapter covers gynaecological cancers and includes information on cervical, endometrial, ovarian, and vaginal and vulval cancers. It also covers epidemiology, molecular biology and pathology. Surgical management focuses on risk adapted diagnostic and therapeutic procedures and includes laparoscopic lymph node and tumour surgery. The role of primary, adjuvant or neoadjuvant radiotherapy is described consisting of external beam therapy or (image guided) brachytherapy or combined treatment, also as concomitant radiochemotherapy. Medical management is outlined comprising cytotoxic chemotherapy, hormonal therapy and targeted drugs with their different role in neoadjuvant, adjuvant and primary treatment. Multidisciplinary management is described for complex cases of cervix, endometrium and ovarian cancer.
Neoplasms of the thymus
Authors: Bütof Rebecca , Denz Axel , Baretton Gustavo , Stöhlmacher-Williams Jan , Baumann Michael
Published: January 2016

Thymic tumours are among the malignant diseases with very low incidence. Therefore clinical research and development of new treatment options pose an ongoing challenge. For treatment of thymomas the following methods are used: surgery, radiotherapy, chemotherapy, and targeted drugs. The optimal type and sequence of therapy depends on tumour stage, histological subtype, and general health condition of the patient. A complete surgical resection is still the mainstay of therapy. For patients with incomplete resection or in locally advanced stages adjuvant radio/chemotherapy is recommended. Neoadjuvant treatment approaches and novel targeted therapies are under investigation. Lifelong follow-up has to be preferred because of possible late recurrences.
Skin cancer: melanoma
Authors: Thompson John F. , Scolyer Richard A. , Kefford Richard F.
Published: January 2016

The development of cutaneous melanoma is attributed mainly to UV-induced DNA damage producing genetic mutations that make melanocytes capable of invasion and metastasis. Early diagnosis and surgical excision are the key to successful treatment. Breslow thickness, ulceration and mitotic rate are the most important prognostic factors. Histological examination of the ‘sentinel’ lymph node indicates prognosis with even greater accuracy, and is now routinely recommended for patients with melanomas ≥1.0 mm in Breslow thickness. Early complete regional node clearance in sentinel node-positive patients may improve melanoma-specific survival. Clinically involved nodes are best treated by surgery, as are isolated systemic metastases. However, new systemic therapies are achieving good short- to-medium term systemic disease control; these include BRAF and MEK inhibitors and immune check-point regulators (e.g. CTLA-4 inhibitors and agents targeting PD-1 and PDL-1). Radiotherapy, regional chemotherapy, topical therapies and intralesional therapies may also be effective in patients with metastatic melanoma.
Acute leukaemias
Authors: Fielding Adele K. , Mullighan Charles G. , Hoelzer Dieter , Stein Eytan M. , Zakout Ghada , Tallman Martin S. , Ofran Yishai , Rowe Jacob M. , Levine Ross L.
Published: January 2016

This chapter covers acute myeloid leukaemia (AML) and acute lymphoblastic leukaemia (ALL), and includes information on prognostic factors, current standard of care, basic biology, epidemiology, clinical presentation, diagnosis, pathophysiology, aetiology, and management. Although the majority of patients with acute myeloid leukaemia (AML) achieve complete remission with induction chemotherapy, relapse after achievement of clinical remission remains the most critical clinical challenge facing AML patients and clinicians today, with a pressing need to improve prognostication. Prognostic factors in acute lymphoblastic leukaemia is to stratify patients into good- and poor-risk groups and to adapt different treatment strategies accordingly. There are principally two phases to evaluating prognostic factors; the first is the patient characteristics at diagnosis and the second is the response to treatment.
Chronic leukaemias
Authors: Malhotra Hemant , Kumar Lalit , Malhotra Pankaj , Hiwase Devendra , Bhatia Ravi
Published: January 2016

Chronic Leukaemia, as contrasted to the acute luekemia, are slowly growing clonal malignancies of the hematopoietic system in which, even without active intervention, survival is possible for several years. In the past decade there have been several advances in the basic understanding of these diseases which have lead to improvement in survival of several decades in the majority of patients which is now being referred to as ‘operational cure’. This chapter covers the chronic leukaemias (chronic myeloid leukaemia (CML), chronic lymphocytic leukaemia (CLL), hairy cell leukaemia, prolymphocytic leukaemia, large granular lymphocytic leukaemia (LGL), and hairy cell leukaemia variant (HCL-v), including epidemiology, staging and diagnosis, molecular biology, pathology, medical management, disease monitoring, management of relapse/refraction, and future directions.
Myeloma
Authors: Pawlyn Charlotte , Davies Faith , Morgan Gareth
Published: January 2016

Myeloma is a haematological malignancy of plasma cells. Uncontrolled proliferation of plasma cells results in overproduction of monoclonal immunoglobulin and clinical disease is characterized by evidence of associated end-organ damage. Over 4500 patients are diagnosed in the UK each year, making it the second most common haematological malignancy. Our understanding of the molecular events underlying the pathogenesis of myeloma has dramatically increased over the last ten years and we now understand that myeloma is a heterogeneous disease with lesions in multiple different genes and pathways altering the normal development of plasma cells and leading to the oncogenic phenotype. Patient survival has concomitantly improved as a result of the development of novel therapies. Our current state of knowledge along with diagnostic approaches and treatment strategies are set out in this chapter.
Sarcomas of soft tissues and bone
Authors: Gronchi Alessandro , Dei Tos Angelo P. , Casali Paolo G.
Published: January 2016

Sarcomas are rare tumours that can arise from bone or a variety of soft tissues in a variety of body sites. Surgery is the treatment mainstay for localized disease. Margins of resection are contingent on accurate histologic diagnosis. Adjuvant chemotherapy is routinely employed in osteosarcoma and Ewing Sarcomas, while it is used only on an individualized basis in high-risk soft tissue sarcoma. Isolated lung metastases from either bone or soft tissue sarcoma are primarily treated by surgery, especially if the disease-free interval is long and the number limited. Otherwise chemotherapy is the first-line therapy and subsequent treatments are decided according to response and disease evolution. Treatment planning should include multidisciplinary consultation to determine optimal therapy, taking into consideration tumour histology, site, and extent of the disease, its natural history and sensitivity to available treatments, surgical challenges and, of course, quality of life.
Craniospinal malignancies
Authors: Plaha Puneet , Parry Allyson , Pretorius Pieter , Brada Michael , Ansorge Olaf , Blesing Claire
Published: January 2016

This chapter covers cancer of the central nervous system (CNS), including epidemiology and aetiology, classification, pathology and molecular genetics, clinical manifestation, neuroradiology, medical management, surgery for intracranial tumours, radiotherapy, chemotherapy, and clinical management of brain tumours. In addition, there are sections devoted to brain and spinal metastases, and primary tumours of the skull and spine. New concepts of molecular oncology for diagnosis and therapy are discussed. Brain cancers (gliomas) were amongst the first neoplasms subjected to systematic genomic and transcriptomic analysis that may guide individualized treatments. In addition to gliomas, rarer type of intracranial tumours are included, such as ependymomas, primitive neuroectodermal tumours, and pineal tumours are also covered.
Endocrine cancers
Authors: Weaver Andrew , Weetman Anthony P. , Gimm Oliver , Grossman Ashley , Sulentic Petra , Wiedenmann Bertram , Plöckinger Ursula , Pape Ulrich-Frank , Wass John , Rogers Angela , de Herder Wouter
Published: January 2016

This chapter covers endocrine cancers, including typical thyroid cancer as well as medullary thyroid carcinoma (MTC). Adrenal tumours, associated with Cushing's syndrome, and Conn's syndrome, associated with pituitary tumours, are discussed in detail. It includes information on epidemiology, clinical features, pathology, diagnosis, treatment, follow-up, and prognosis. It also covers special problems in pregnancy. Special attention is made to merging techniques in molecular oncology, which have led to biomarker-driven therapy of thyroid and pancreatic neuroendocrine tumours with biologic agents. For pancreatic neuroendocrine tumours, special attention is made to new imaging techniques and therapy for patients with syndrome associated with peptide hormone release.
Specialty Competencies in Forensic Psychology
Authors: Packer Ira K. , Grisso Thomas
Published: January 2016

Although Forensic Psychology was formally recognized as a specialty by the American Board of Professional Psychology in 1985 and by the American Psychological Association's Commission for the Recognition of Specialties and Proficiencies in Professional Psychology in 2001, its origins can be traced back to early applications of psychology to law during the time psychology was being differentiated from the more general field of philosophy. As it is currently applied, the specialty took organizational shape from the 1960s to the 1990s, and today forensic psychology is one of the most popular areas of specialization among emerging psychologists. The demand for forensic training, continuing education, and research is growing in many graduate level professional programs and at events sponsored by the American Psychology-Law Division of APA or the American Academy of Forensic Psychology. Therefore, the need for a comprehensive text focused on the competencies required in the specialty has never been greater. With Specialty Competencies in Forensic Psychology, this title provides a guide to understanding legal systems, evaluations, and consultations encountered in day-to-day forensic practice that is simultaneously sophisticated, scholarly, and user-friendly.
Definition of Forensic Psychology
Authors: Packer Ira K. , Grisso Thomas
Published: January 2016

This chapter begins by deconstructing the definition used for APA recognition of the specialty. It discusses the ways that the specialty of forensic psychology is different from, and similar to, other related professional fields, activities, and identities. This is followed by a brief history of the development of forensic psychology, from its roots in the late nineteenth century to its recognition by APA as a specialty in the early twenty-first century. Finally, it outlines the boundaries of forensic psychology in three ways: its unique knowledge base and skill sets, the problems that it addresses, and the populations that it serves.
Scientific Foundations of Forensic Psychology
Authors: Packer Ira K. , Grisso Thomas
Published: January 2016

This chapter discusses the conceptual and scientific bases for some important areas of research that inform forensic practice. Before proceeding, however, it is worthwhile to consider some core principles for applying scientific inquiry and methods in forensic evaluations.
Assessment Strategies
Authors: Packer Ira K. , Grisso Thomas
Published: January 2016

This chapter focuses on aspects of forensic assessment that are different from assessments in other specialties. It first discusses three general concepts that influence all parts of the forensic assessment process, before reviewing how those are applied to three parts of the assessment process: method selection, the data collection process, and communication of results.
Forensic Consultation
Authors: Packer Ira K. , Grisso Thomas
Published: January 2016

This chapter begins with a discussion of standards for providing written reports of forensic evaluations. It then discusses the competencies involved when forensic psychologists function as formal consultants.
Laws Relevant to the Practice of Forensic Psychology
Authors: Packer Ira K. , Grisso Thomas
Published: January 2016

This chapter focuses on the laws related to the practice of psychology, with particular emphasis on those issues that directly impact forensic practitioners. It begins with a broad discussion of laws pertaining to confidentiality and privilege of communications to psychologists as well as their applicability to forensic evaluations. It then discusses expert witness testimony, including issues of qualifications of experts, criteria for acceptance of expertise by the court, and liability issues related to expert testimony. The chapter concludes with a discussion of interjurisdictional practice, which is particularly relevant to forensic psychologists who may have specialized expertise in a particular area and are retained to work on cases in states in which they are not licensed.
First Report of Fruit Rot of Ridge Gourd (Luffa acutangula) Caused by Sclerotium rolfsii
Authors: Kousik Chandrasekar S. , Ikerd Jennifer , Mandal Mihir
Published: January 2016

Ridge gourd is a specialty cucurbit vegetable cultivated in the United States on a small scale for select markets. We report the infection of ridge gourd fruit by Sclerotium rolfsii (teleomorph: Athelia rolfsii). This appears to be the first report of Sclerotium rot of ridge gourd. In fields with history of S. rolfsii, the gourds should be grown on trellis to prevent fruit contact with wet soil. Several fungicides are available to manage S. rolfsii and may have to be applied if and when needed.

Accepted for publication 12 January 2016. Published 14 January 2016.
Survival of Microsclerotia of Calonectria pseudonaviculata and C. henricotiae Exposed to Sanitizers
Authors: Shishkoff Nina
Published: January 2016

Discrete microsclerotia of C. pseudonaviculata from culture were treated with eight commercially available sanitizers (ZeroTol 2.0, Oxidate, Sanidate, X3, Greenshield, and Lysol Concentrate at maximum label rates, plus 70% Ethanol and 0.6% sodium hypochlorite) to determine effective methods of disinfestation of nursery beds and benches. Ethanol proved most effective, killing microsclerotia in less than 5 min. ZeroTol, 10% bleach, and 70% ethanol were used in comparison tests of microsclerotia of C. pseudonaviculata and C. henricotiae. Microsclerotia of C. henricotiae were found to be more sensitive regardless of size. This finding, along with other research that has found differences in fungicide sensitivity and thermotolerance between the two species, suggests that differences between the species should be elucidated.

Accepted for publication 8 January 2016. Published 14 January 2016.
Effect of Foliar Fungicides on Hail-damaged Corn
Authors: Sisson Adam J. , Kandel Yuba R. , Robertson Alison E. , Hart Chad E. , Asmus Amy , Wiggs Stith N. , Mueller Daren S.
Published: January 2016

To test if fungicide applied to hail-injured corn improves yield and reduces disease, we simulated hail at VT and R2 growth stages for three years at three Iowa locations for a total of five site years. Hail damage was simulated using a string trimmer or an ice-propelling machine and non-hail controls were included. Estimated defoliation ranged from 5 to 51%, along with ear and stalk injury. After hail events, Headline AMP fungicide (pyraclostrobin + metconazole) was applied at an “immediate” or “deferred” timing (averaging 3 and 8 days afterwards, respectively). A non-fungicide treated control was included in hailed and non-hail control plots. Hail injury reduced fungal foliar disease compared to plants without hail injury, although overall disease severity was low during this study. Hail events at VT or R2 decreased yield compared to control plots (P = 0.1). Fungicide application did not provide yield-increasing plant health benefits after VT and R2 hail, at either “immediate” or “deferred” timing. While yield differences were not statistically significant, a cost/benefit analysis showed deferred fungicide application after VT hail, and immediate and deferred applications after VT for non-hail plots did provide positive economic returns. Results will help inform decisions about fungicide use in hail-damaged corn when foliar diseases are not present at high levels.

Accepted for publication 7 January 2016. Published 13 January 2016.
The Role of Hybridization in the Evolution and Emergence of New Fungal Plant Pathogens
Authors: Stukenbrock Eva H.
Published: January 2016

Hybridization in fungi has recently been recognized as a major force in the generation of new fungal plant pathogens. These include the grass pathogen Zymoseptoria pseudotritici and the powdery mildew pathogen Blumeria graminis triticale of triticale. Hybridization also plays an important role in the transfer of genetic material between species. This process is termed introgressive hybridization and involves extensive backcrossing between hybrid and the parental species. Introgressive hybridization has contributed substantially to the successful spread of plant pathogens such as Ophiostoma ulmi and O. novo-ulmi, the causal agents of Dutch elm disease, and other tree pathogens such as the rust pathogen Melampsora. Hybridization occurs more readily between species that have previously not coexisted, so-called allopatric species. Reproductive barriers between allopatric species are likely to be more permissive allowing interspecific mating to occur. The bringing together of allopatric species of plant pathogens by global agricultural trade consequently increases the potential for hybridization between pathogen species. In light of global environmental changes, agricultural development, and the facilitated long-distance spread of fungal plant pathogens, hybridization should be considered an important mechanism whereby new pathogens may emerge. Recent studies have gained insight into the genetics and biology of fungal hybrids. Here I summarize current knowledge about hybrid speciation and introgressive hybridization. I propose that future studies will benefit greatly from the availability of large genome data sets and that genome data provide a powerful resource in combination with experimental approaches for analyses of hybrid species.
Sex-biased gene expression inDrosophila melanogasteris constrained by ontogeny and genetic architecture
Authors: Ingleby FC , Webster CL , Pennell TM , Flis I , Morrow EH
Published: January 2016

Sexual dimorphism is predicted to be constrained by the underlying genetic architecture shared between the sexes and through ontogeny, but whole-transcriptome data for both sexes across genotypes and developmental stages are lacking. Within a quantitative genetic framework, we sequenced RNA fromDrosophila melanogasterat different developmental stages to examine sex-biased gene expression and how selection acts upon it. We found evidence that gene expression is constrained by both univariate and multivariate shared genetic variation between genes, sexes and developmental stages, but may be resolved by differential splicing. These results provide a comprehensive picture of how conflict over sexual dimorphism varies through development and clarifies the conditions under which it is predicted to evolve.
Evolutionary stability of jointly evolving traits in subdivided populations
Authors: Mullon Charles , Keller Laurent , Lehmann Laurent
Published: January 2016

The evolutionary stability of quantitative traits depends on whether a population can resist invasion by any mutant. While uninvadability is well understood in well-mixed populations, it is much less so in subdivided populations when multiple traits evolve jointly. Here, we investigate whether a spatially subdivided population at a monomorphic equilibrium for multiple traits can withstand invasion by any mutant, or is subject to diversifying selection. Our model also explores the among traits correlations arising from diversifying selection and how they depend on relatedness due to limited dispersal. We find that selection favours a positive (negative) correlation between two traits, when the selective effects of one trait on relatedness is positively (negatively) correlated to the indirect fitness effects of the other trait. We study the evolution of traits for which this matters: dispersal that decreases relatedness, and helping that has positive indirect fitness effects. We find that when dispersal cost is low and the benefits of helping accelerate faster than its costs, selection leads to the coexistence of mobile defectors and sessile helpers. Otherwise, the population evolves to a monomorphic state with intermediate helping and dispersal. Overall, our results highlight the importance of population subdivision for evolutionary stability and correlations among traits.
The genetic Allee effect: A unified framework for the genetics and demography of small populations
Authors: Lucque Gloria M. , Vayssade Chloé , Facon Benoît , Guillemaud Thomas , Courchamp Franck , Fauvergue Xavier
Published: January 2016

The Allee effect is a theoretical model predicting low growth rates and the possible extinction of small populations. Historically, studies of the Allee effect have focused on demography. As a result, underlying processes other than the direct effect of population density on fitness components are not generally taken into account. There has been heated debate about the potential of genetic processes to drive small populations to extinction, but recent studies have shown that such processes clearly impact small populations over short time scales, and some may generate Allee effects. However, as opposed to the ecological Allee effect, which is underpinned by cooperative interactions between individuals, genetically driven Allee effects require a change in genetic structure to link the decline in population size with a decrease in fitness components. We therefore define the genetic Allee effect as a two-step process whereby a decrease in population size leads to a change in population genetic structure, and in turn, to a decrease in individual fitness. We describe potential underlying mechanisms, and review the evidence for this original type of component Allee effect, using published examples from both plants and animals. The possibility of considering demogenetic feedback in light of genetic Allee effects clarifies the analysis and interpretation of demographic and genetic processes, and the interplay between them, in small populations.
Pathologic gene network rewiring implicates PPP1R3A as a central cardioprotective factor in pressure overload heart failure
Authors: Cordero Pablo , Parikh Victoria N. , Erbilgin Ayca , Shang Ching , Smith Kevin S. , Dewey Frederick , Zaleta Kathia , Morley Michael , Brandimarto Jeff , Glazer Nicole , Pavlovic Aleksandra , Moravec Christine , Tang Wilson H. , Viterna Jamie , Malloy Christine , Hannenhalli Sridhar , Li Hongzhe , Ritter Scott , Li Mingyao , Connolly Andrew , Hakonarson Hakon , Lusis Aldons J. , Margulies Kenneth B. , Depaoli-Roach Anna A. , Montgomery Stephen , Wheeler Matthew T. , Cappola Thomas , Ashley Euan A.
Published: January 2016

Heart failure is a leading cause of mortality, yet our understanding of the genetic interactions underlying this disease remains incomplete. Here, we harvested 1352 healthy and failing human hearts directly from transplant center operating rooms, and obtained genome-wide genotyping and gene expression measurements for a subset of 313. We built failing and non-failing cardiac regulatory gene networks, revealing important regulators and cardiac expression quantitative trait loci (eQTLs).PPP1R3Aemerged as a novel regulator whose network connectivity changed significantly between health and disease. Time-course RNA sequencing afterPPP1R3Aknock-down validated network-based predictions of metabolic pathway expression, increased cardiomyocyte size, and perturbed respiratory metabolism. Mice lackingPPP1R3Awere protected against pressure-overload heart failure. We present a global gene interaction map of the human heart failure transition, identify new cardiac eQTLs, and demonstrate the discovery potential of disease-specific networks through the description ofPPP1R3Aas a novel central protective regulator in heart failure.
Reversiblechair↔skewconformational interconversion of 1,3,2-dioxaphosphorinane ring in the solid state
Authors: Ślepokura Katarzyna Anna
Published: January 2016

β-NH4[(MeO)2cDHAP] (where cDHAP is cyclic dihydroxyacetone phosphate) has been investigated by X-ray crystallography in the temperature range 350–100 K. Three reversible single-crystal-to-single-crystal phase transitions have been examined and four phases (high-, room-, medium- and low-temperature phase, HTP, RTP, MTP and LTP, respectively) have been structurally determined: HTP (at 350 K,P21/a,Z= 24), RTP (290 K, P \overline{1},Z= 12), MTP (205 K,P21/a,Z= 4) and LTP (100 K, P \overline{1},Z= 24). Various puckering modes of the 1,3,2-dioxaphosphorinane ring of the organic cyclic phosphate anion have been revealed in the crystal:chairandskew. Thechair↔skewring flipping, which has been shown to take place during the phase transitions, results in various populations ofskewandchairconformers in different phases. The flexibility in the coordination geometry of ammonium cations is considered to assist in the conformational flexibility of the dioxaphosphorinane ring.
A double stranded metal–organic assembly accommodating a pair of water trimers in the host cavity and catalysing Glaser coupling
Authors: Pradhan Subhashis , Moon Dohyun , John Rohith P.
Published: January 2016

A supramolecular compound,catena-poly{[Cu2(1,3-μ2-(1a))2(μ2-ter)2(H2O)2]n·(6H2O)n} (1) has been synthesized using (1a) [(1a=N1,N3,N5-trimethyl-N1,N3,N5-tris((pyridin-4-yl)methyl)-1,3,5-benzene tricarboxamide] and terephthalate (ter) as the pillaring unit by self-assembly. The terephthalate units are connected by copper(II) ions forming a single strand, while a pair of such strands are then linked by (1a)viatwo pyridyl terminal arms bound to copper(II) nodes on either side forming a one-dimensional double stranded assembly propagating along thecaxis. The compound crystallizes in theFdd2 space group. The cavity created in the interior of this double strand assembly trap six water molecules and are stabilized by hydrogen bonding with the host. The arrangement of the pair of acyclic water trimers in isolated cavities of (1) is such that it resembles a closed-bracket-like formation. The Hirshfeld surface analysis of (1) reveals the presence of strong intermolecular hydrogen-bonding interactions between one-dimensional ladder-like units and with the water trimer in the host cavity. The copper(II)-containing coordination polymer also acts as an efficient catalyst for the Glaser–Hay homo-coupling reaction.
A multi-manned assembly line balancing problem with classified teams: a new approach
Authors: Yilmaz Hamid , Yilmaz Mustafa
Published: January 2016

Purpose

– Within team-oriented approaches, tasks are assigned to teams before being assigned to workstations as a reality of industry. So it becomes clear, which workers assemble which tasks.

Design/methodology/approach

– Team numbers of the assembly line can increase with the number of tasks, but at the same time, due to physical situations of the stations, there will be limitations of maximum working team numbers in a station. For this purpose, heuristic assembly line balancing (ALB) procedure is used and mathematical model is developed for the problem.

Findings

– Well-known assembly line test problems widely used in the literature are solved to indicate the effectiveness and applicability of the proposed approach in practice.

Originality/value

– This paper draws attention to ALB problem in which workers have been assigned to teams in advance due to the need for specialized skills or equipment on the line for the first time.
Exploratory analysis of the pathway towards operationalizing resilience in transportation infrastructure management
Authors: Mostafavi Ali , Inman Alex
Published: January 2016

Purpose

– The purpose of this paper is to explore the pathway toward operationalizing resilience in management of transportation infrastructure.

Design/methodology/approach

– The research approach includes a comprehensive survey of the State Transportation Agencies (STA) in the USA. The information collected from the survey is analyzed using statistical analysis to explore the determinants of operationalizing resilience in transportation infrastructure management.

Findings

– The results reveal that the current practices of STA need improvement in terms of pre-disaster vulnerability and exposure analysis as well as pre-disaster retrofit and betterment efforts. A pathway toward this end is identified with the major components being: funding availability, integration of efforts across different units, use of risk and vulnerability assessment approaches, and use of resilience indices.

Practical/implications

– The pathway, along with the other findings, enhances the understanding of the status quo, drivers, and barriers toward operationalizing resilience in transportation infrastructure management. Such an understanding is critical for infrastructure agencies to better adapt and enhance the resilience of their assets in response to various stressors such as the impacts of climate change as well as natural disasters.

Originality/value

– The study presented in this paper is the first of its kind to identify the pathway toward operationalizing resilience in transportation infrastructure management.
Safety of a Four‐factor Prothrombin Complex Concentrate Versus Plasma for Vitamin K Antagonist Reversal: An Integrated Analysis of Two Phase IIIb Clinical Trials
Authors: Milling Truman J. , Refaai Majed A. , Sarode Ravi , Lewis Brandon , Mangione Antoinette , Durn Billie L. , Harman Amy , Lee Martin L. , Goldstein Joshua N.
Published: January 2016

Objectives

Clinicians often need to rapidly reverse vitamin K antagonists (VKAs) in the setting of major hemorrhage or urgent need for surgery. Little is known about the safety profile of the traditional reversal agent, plasma, or the newly approved agent, four‐factor prothrombin complex concentrate (4F‐PCC), in a randomized setting. This is an integrated analysis of safety data from two clinical trials that evaluated 4F‐PCC versus plasma for the treatment of patients requiring rapid VKA reversal for acute major bleeding or prior to an urgent surgical/invasive procedure.

Methods

This descriptive analysis comprised adverse event (AE) data from two phase IIIb, randomized, controlled trials. The bleeding and surgical studies were performed across 36 and 33 sites, respectively, in nine countries, with the integrated analysis comprising 388 patients (4F‐PCC, n = 191; plasma, n = 197) aged ≥ 18 years, who required VKA reversal due to major bleeding or prior to an urgent surgical/invasive procedure. Patients received either 4F‐PCC, containing nonactivated factors II, VII, IX, and X and proteins C and S (Beriplex/Kcentra, CSL Behring) or plasma, both dosed according to baseline international normalized ratio and body weight. Patients were also to receive vitamin K1. AEs and serious AEs (SAEs) were assessed up to days 10 and 45, respectively.

Results

The proportion of patients with AEs (4F‐PCC, 115/191 [60.2%]; plasma, 124/197 [62.9%]) and SAEs (4F‐PCC, 54/191 [28.3%]; plasma, 49/197 [24.9%]) was similar between groups. The proportion of patients with thromboembolic events was also similar between groups (4F‐PCC, 14/191 [7.3%]; plasma, 14/197 [7.1%]). There were 13 (6.8%) deaths in the 4F‐PCC group and 13 (6.6%) in the plasma group. Fluid overload events occurred in more patients in the plasma group than the 4F–PCC group (25 [12.7%] and 9 [4.7%], respectively).

Conclusions

These safety data represent the largest controlled assessment of a 4F‐PCC to date. For patients requiring urgent VKA reversal, 4F‐PCC had a safety profile similar to that of plasma (AEs, SAEs, thromboembolic events, and deaths), but was associated with fewer fluid overload events.
Are All Stroke Patients Eligible for Fast Alteplase Treatment? An Analysis of Unavoidable Delays
Authors: Choi Philip M. C. , Desai Jamsheed A. , Kashyap Devika , Stephenson Caroline , Kamal Noreen , Vogt Sheldon , Bohm Victoria , Suddes Michael , Bugbee Erin , Hill Michael D. , Demchuk Andrew M. , Smith Eric E.
Published: January 2016

Objectives

The National Quality Forum recently endorsed a performance measure for time to intravenous thrombolytic therapy which allows exclusions for circumstances in which fast alteplase treatment may not be possible. However, the frequency and impact of unavoidable patient reasons for long door‐to‐needle time (DNT), such as need for medical stabilization, are largely unknown in clinical practice. As part of the Hurry Acute Stroke Treatment and Evaluation‐2 (HASTE‐2) project, we sought to identify patient and systems reasons associated with longer DNT.

Methods

From June 2012 to June 2013 we collected data on DNT and potential reasons for delays from 102 consecutive patients presenting directly to the emergency department who were treated with alteplase within 4.5 hours of symptom onset.

Results

Mean age was 71 years, 56/113 (54%) were women, median NIH Stroke Scale score was 13, and median DNT was 53 minutes. Potential delays were noted in 59/102 (58%), of which 31/102 (31%) were unavoidable patient‐related or eligibility reasons. Median DNT was longer when patient‐related or eligibility reasons for delay were present (60 minutes) than when absent (45 minutes, p = 0.005). Multivariable modeling showed that need for urgent medical stabilization, presentation with seizure and inability to confirm eligibility were associated with 35%–50% longer DNT times.

Conclusions

Up to 31% of patients have delays due to medical or eligibility‐related causes that may be legitimate reasons for providing alteplase later than the benchmark time of 60 minutes.
Evaluating the Impact of Clinical Decision Tools in Pediatric Acute Gastroenteritis: A Population‐based Cohort Study
Authors: Bahm Allison , Freedman Stephen B. , Guan Jun , Guttmann Astrid
Published: January 2016

Objective

Acute gastroenteritis (AGE) is a leading cause of pediatric emergency department (ED) visits. Despite evidence‐based guidelines, variation in adherence exists. Clinical decision tools can enhance evidence‐based care, but little is known about their use and effectiveness in pediatric AGE. This study sought to determine if the following tools—1) pathways/order sets, 2) medical directives for oral rehydration therapy (ORT) or ondansetron, and 3) printed discharge instructions—are associated with AGE admission and ED revisits.

Methods

This was a retrospective population‐based cohort study of all children 3 months–18 years with an AGE ED visit in Ontario, Canada, from 2008 to 2010, using linked survey and health administrative databases. Logistic regression models associating clinical decision tools (CDTs) with hospitalizations and revisits controlling for hospital and patient characteristics were employed.

Results

Of the 57,921 patient visits during the study period, there were 2,401 hospitalizations (4.2%). A total of 55,520 patients were discharged from the ED, with 2,378 (4.3%) experiencing a 72‐hour return visit. In adjusted models, none of the tools were significantly associated with admission. Medical directive for ORT was associated with lower return visit rates (adjusted odds ratio [aOR] = 0.86, 95% confidence interval [CI] = 0.79–0.94] and printed discharge instructions with higher return visits (aOR = 1.33, 95% CI = 1.08–1.65); pathways/order sets and medical directives for ondansetron had no association.

Conclusions

Admissions in children with AGE are not associated with the presence of CDTs. While ORT medical directives are associated with lower ED revisits, printed discharge instructions have the opposite effect. The simple presence/absence of decision support tools does not guarantee improved clinical outcomes.