bluuebunny/crossref_metadata_2025 huggingface dataset:
Facile development and structural investigations of HAp and HAp/Ta nanostructures: Photocatalytic activity against Turq blue GL dye
Authors: Manoj Murugesan , Mangalaraj Devanesan , Meena Palaniappan , Yuan Aihua
Published: November 2019

The rising awareness of the need for a healthy environment for living systems has led to an increasing demand for suitable catalyst materials for wastewater treatment. In this connection, in the present work, the catalyst materials Hydroxyapatite and Hydroxyapatite/Tantalum (HAp/Ta) core–shell nanostructured particles were prepared through a facile nanoprecipitation method without a surfactant, chelating agents and/or ligands. The prepared nanostructured particles were characterised with the help of several analytical techniques namely XRD, FESEM, TEM, EDS, FTIR, Raman, XPS and BET. The calculated average crystallite size of HAp was found to be 26 nm and the core–shell nanorod morphology was corroborated through FESEM and TEM technique. The average length and width were found to be 44 and 16 nm respectively. The specific surface area (SSA), microporous nature and pore volume were investigated through the N2 adsorption isotherm method. The photocatalytic activity of the prepared HAp and HAp/Ta core–shell nanostructured particles was investigated on frequently used dyeing industrial dyes Turq blue GL under UV irradiation. The recorded results evince that the HAp/Ta core–shell nanorods have more catalytic activity than pure HAp and can be used as a nanophotocatalyst for industrial waste water treatment process to curb water pollution and to protect the environment.
Structural and electronic properties of the iron pnictide compound EuFe2As2 from first principles
Authors: Omboga N K , Otieno C O
Published: November 2019

We report results of the electronic and mechanical structure properties of the iron pnictide compound EuFe2As2, at zero pressure. The open source computer code Quantum Espresso, which incorporates the Density Functional Theory (DFT), Pseudo Potentials (PP) and the Plane Wave (PW) were used to perform calculations from first principles. Projector-Augmented Wave (PAW) Pseudo Potentials were used in these calculations. The Density of States exhibits a sizeable superconducting gap and the band structure has no bandgap. Calculations were performed from scratch.
Impact of H2 gas on disruptive birefringence optical fibers with embedded Palladium particles for developing robust sensors
Authors: Aazi Mohamed , Kudinova Maryna , Kinet Damien , Auguste Jean-Louis , Delépine-Lesoille Sylvie , Mégret Patrice , Humbert Georges
Published: November 2019

Optical fiber sensors of hydrogen gas (H2) are conventionally based on the reaction of a sensitive material deposited on the surface of a fiber. Long-term applications of H2 monitoring require more robust configurations, less sensitive to the degradations of the sensitive layer. To overcome this issue, we develop disruptive polarisation-maintaining optical fibers composed of a sensitive material (Palladium, Pd) integrated into the silica cladding. We present the development of two Panda-type optical fibers with or without embedded Pd particles. These fibers have been fabricated for evaluating, through the measurement of the birefringence, the contribution of Pd particles on the detection of H2 gas. We have specially developed a gas chamber for measuring on-line the detection of H2 during its diffusion into the fiber. Dynamic comparisons between both fibers demonstrate the contribution of Pd particles resulting in a faster response time (of about 20 h for our experimental conditions). These results pave the way to the realization of robust optical fibers with enhanced sensitivity to H2 gas for developing sensing systems compatible with long-term hydrogen monitoring applications in extreme and harsh environments, such as radioactive waste repositories.
CRISPR/Cas9 technology: towards a new generation of improved CAR-T cells for anticancer therapies
Authors: Ureña-Bailén Guillermo , Lamsfus-Calle Andrés , Daniel-Moreno Alberto , Raju Janani , Schlegel Patrick , Seitz Christian , Atar Daniel , Antony Justin S , Handgretinger Rupert , Mezger Markus
Published: November 2019

Chimeric antigen receptor (CAR)-modified T cells have raised among other immunotherapies for cancer treatment, being implemented against B-cell malignancies. Despite the promising outcomes of this innovative technology, CAR-T cells are not exempt from limitations that must yet to be overcome in order to provide reliable and more efficient treatments against other types of cancer. The purpose of this review is to shed light on the field of CAR-T cell gene editing for therapy universalization and further enhancement of antitumor function. Several studies have proven that the disruption of certain key genes is essential to boost immunosuppressive resistance, prevention of fratricide, and clinical safety. Due to its unparalleled simplicity, feasibility to edit multiple gene targets simultaneously, and affordability, CRISPR/CRISPR-associated protein 9 system has been proposed in different clinical trials for such CAR-T cell improvement. The combination of such powerful technologies is expected to provide a new generation of CAR-T cell-based immunotherapies for clinical application.
Midget retinal ganglion cell dendritic and mitochondrial degeneration is an early feature of human glaucoma
Authors: Tribble James R , Vasalauskaite Asta , Redmond Tony , Young Robert D , Hassan Shoaib , Fautsch Michael P , Sengpiel Frank , Williams Pete A , Morgan James E
Published: November 2019

Glaucoma is characterized by the progressive dysfunction and loss of retinal ganglion cells. However, the earliest degenerative events that occur in human glaucoma are relatively unknown. Work in animal models has demonstrated that retinal ganglion cell dendrites remodel and atrophy prior to the loss of the cell soma. Whether this occurs in human glaucoma has yet to be elucidated. Serial block face scanning electron microscopy is well established as a method to determine neuronal connectivity at high resolution but so far has only been performed in normal retina from animal models. To assess the structure–function relationship of early human glaucomatous neurodegeneration, regions of inner retina assessed to have none-to-moderate loss of retinal ganglion cell number were processed using serial block face scanning electron microscopy (n = 4 normal retinas, n = 4 glaucoma retinas). This allowed detailed 3D reconstruction of retinal ganglion cells and their intracellular components at a nanometre scale. In our datasets, retinal ganglion cell dendrites degenerate early in human glaucoma, with remodelling and redistribution of the mitochondria. We assessed the relationship between visual sensitivity and retinal ganglion cell density and discovered that this only partially conformed to predicted models of structure–function relationships, which may be affected by these early neurodegenerative changes. In this study, human glaucomatous retinal ganglion cells demonstrate compartmentalized degenerative changes as observed in animal models. Importantly, in these models, many of these changes have been demonstrated to be reversible, increasing the likelihood of translation to viable therapies for human glaucoma.
Antipneumococcal Seroprotection Years After Vaccination in Allogeneic Hematopoietic Cell Transplant Recipients
Authors: Robin Christine , Bahuaud Mathilde , Redjoul Rabah , Jeljeli Mohamed , Leclerc Mathieu , Cabanne Ludovic , Beckerich Florence , Pautas Cécile , Maury Sébastien , Cordonnier Catherine
Published: November 2019

Background

International guidelines recommend vaccinating allogeneic hematopoietic cell transplant (HCT) recipients at 3 months after transplant, giving 3 doses of pneumococcal conjugate vaccine (PCV) followed by either a dose of 23-valent pneumococcal polysaccharide vaccine (PSV23) or a fourth PCV dose in the case of graft-versus-host disease (GvHD). However, the long-term immunity after this regimen is unknown, and there is no recommendation from 24 months after transplant regarding boosts. Our objective was to assess the antipneumococcal antibody titers and seroprotection rates of allogeneic HCT recipients years after different schedules of vaccination.

Methods

We assessed 100 adult HCT recipients a median of 9.3 years (range: 1.7–40) after transplant. All patients had received at least one dose of PCV and were assessed for antipneumococcal immunoglobulin G (IgG) antibody titers against the 7 serotypes shared by PCV7, PCV13, and PSV23. Sixty-six percent of the patients had been vaccinated according to the current guidelines.

Results

Considering an IgG titer ≥ 0.35 µg/mL as protective for each serotype, the seroprotection rate was 50% for 7/7 serotypes and 70% for 5/7 serotypes, with no differences between the different vaccination schedules. The lack of seroprotection was associated with a transplant performed not in complete remission or from a cord-blood unit, a relapse after transplant, or chronic GvHD at assessment.

Conclusion

Because only half of the vaccinated patients had long-term protection, pending prospective studies defining the best boost program after the initial one, we recommend the assessment of specific IgG titers starting from 24 months to decide for further doses.
Genomic background of a colistin-resistant and highly virulent MCR-1-positive Escherichia coli ST6395 from a broiler chicken in Pakistan
Authors: Mohsin Mashkoor , Azam Mariya , ur Rahman Sajjad , Esposito Fernanda , Sellera Fábio P , Monte Daniel F , Cerdeira Louise , Lincopan Nilton
Published: November 2019

The convergence of high virulence and multidrug resistance (MDR) in Gram-negative pathogens circulating at the human–animal interface is a critical public health issue. We hereby report the genomic characteristics and virulent behavior of a colistin-resistant Escherichia coli, serotype ONT:H26, belonging to ST6395, isolated from a healthy broiler in Pakistan. This strain harbored multiple antimicrobial resistance genes, including mcr-1.1 and blaCARB-2, besides cma (colicin M) and astA [heat-stable enterotoxin 1 (EAST1) toxin] virulence genes. In vivo experiments carried out with the Galleria mellonella infection model revealed that MCR-1-positive E. coli ST6395 killed 96.4% of the larvae at 18 hour post-infection. Interplay between resistance and virulence in clinically important pathogens could be a potential threat, representing a serious challenge to global public health.
A Motion of No Confidence: Leadership and Rebel Fragmentation
Authors: Doctor Austin C
Published: November 2019

Why do rebel organizations splinter into competing factions during civil war? To explain this outcome, I leverage variation in rebel leadership. I argue that rebel leaders draw on their pre-war experiences—i.e., their military and political experiences—to manage their organizations during conflict. These experiences bear unique patterns of rebel management and, thus, corresponding risks of fragmentation. Empirical evidence comes from a two-stage research design and original data featuring over 200 rebel leaders from 1989 to 2014. In the first stage, I estimate the probability of group fragmentation with a series of logistic regression models. In the second stage, I use Cox proportional-hazards models to estimate leadership effects on the rate of group fragmentation. Results indicate that variation in rebel leadership corresponds with unique risks of fragmentation. In particular, the results suggest that leaders with real military experience are best equipped to maintain group cohesion. This study offers insight into the processes by which rebel groups splinter into armed factions. In addition, it makes an important contribution to the broader discussion on the roles of structure and agency in shaping the dynamics of civil war.
Exposure Therapy for Eating Disorders
Authors: Black Becker Carolyn , Farrell Nicholas R. , Waller Glenn
Published: November 2019

Exposure therapy is a core component of evidence-based treatments for eating disorders (EDs), including cognitive-behavioral therapy and family-based treatment. Despite this, existing treatment guides give relatively limited attention to the clinical issues associated with good implementation of exposure. This book is designed to augment a wide variety of treatment manuals by providing ED clinicians with practical advice for maximizing the effectiveness of exposure, regardless of which evidence-based treatment they use or the profession to which they belong. Written in an easy-to-understand format, this book not only translates the most up-to-date empirical research on exposure for EDs, it also extrapolates clinical advice from the anxiety disorders literature to help busy clinicians become more effective in treating EDs. Readers will walk away with a solid foundation in the theoretical underpinnings of exposure therapy, as well as an understanding of how to utilize this information to sell the rationale for exposure to their ED patients. Clinically rich chapters, with ample case material, demonstrate how to prepare to embark on exposure therapy with a wide range of ED patients, including those with anorexia nervosa, bulimia nervosa, binge-eating disorder, and avoidant/restrictive food intake disorder. Specific types of ED exposure are covered in detail, including exposure to food and eating, cue exposure for binge eating, weighing and weight exposure, body image exposure, emotion and interpersonally focused exposure, and novel forms of exposure for EDs. Clinicians also will walk away with strategies for overcoming obstacles to implementation of exposure therapy, including institutional resistance.
Eating Disorders
Authors: Becker Carolyn Black , Farrell Nicholas R. , Waller Glenn
Published: November 2019

Eating disorders are serious mental health disorders that are associated with significant morbidity and mortality. This chapter provides eating disorders clinicians with the necessary understanding of both the differences associated with specific ED diagnoses and the transdiagnostic features that commonly present across diagnoses. Many, if not all, of the common features can be targeted using exposure therapy, which is discussed in subsequent chapters. The authors specifically address the most common features of anorexia nervosa, bulimia nervosa, and binge-eating disorder, as well as avoidant/restrictive food intake disorder and other specified/unspecified eating disorders. Key transdiagnostic features of eating disorders, including eating-related fear and avoidance, body image disturbance, and binge eating, are addressed through a brief case study.
Body Image Exposure
Authors: Becker Carolyn Black , Farrell Nicholas R. , Waller Glenn
Published: November 2019

Body image disturbances play a central role in the development and maintenance of eating disorders and are maintained, in part, by body avoidance. Exposure-based strategies are effective in reducing the cognitive, affective, and behavioral features of body image disturbances. Mirror exposure is a body-focused treatment intervention that has amassed consistent empirical support in reducing body image distress. It is important to consider a number of factors when implementing mirror exposure, including the type of mirror exposure, how the patient should be dressed, and avoidance of excessive body checking. Functional assessment and collaboratively making decisions with the patient will address such issues in how to work with body avoidance (e.g., in relation to anxiety-provoking stimuli, such as mirrors and wearing “revealing” clothing items).
Delivering Psychological Services to Religious and Spiritual Clients
Authors: Magyar-Russell Gina
Published: November 2019

Spiritual and religious beliefs and practices in the United States are becoming increasingly diverse. This chapter reviews some of the fundamental problems and obstacles to providing culturally competent and compassionate mental health care to religious and spiritual clients, highlights the recent progress that has been made toward better serving the mental health needs of these clients, and provides a summary of best practices and future directions. Although religious and spiritual individuals continue to be underserved, there is increasing consensus among mental health professionals that religion and spirituality represent important cultural and clinical dimensions associated with treatment outcomes. As such, the field continues to work toward narrowing the gap in service delivery for religious and spiritual individuals seeking psychotherapy.
Dyspnea
Authors: Weaver Meaghann S.
Published: November 2019

This chapter defines dyspnea as a subjective sense of air hunger. Measurements for dyspnea, from validated scales to forms of subjective reporting, are discussed. A treatment summary is offered with a focus on pharmaceutical interventions and environmental comforts.
Law and Ethics of End-of-Life Care in Humanitarian Crises
Authors: Yacoub Natasha , Schwartz Lisa , Bezanson Kevin
Published: November 2019

This chapter explores the legal and ethical foundations for the inclusion of palliative care in humanitarian responses, as well as practical challenges in doing so. Despite overwhelming need, such care is not consistently integrated into domestic and international crisis responses. The first section demonstrates that international human rights and humanitarian law, often reflected in regional and domestic law, may require the provision of palliative care in conflict and natural disaster settings. The second section summarizes key ethical guidance to support the provision of palliative care in these scenarios. The third section explains the challenges identified by humanitarians in delivering end-of-life care. It highlights the trauma experienced by healthcare professionals who identify but are unable to meet the needs of patients who cannot be cured. The chapter concludes with practical recommendations to improve access to palliative care in humanitarian crises.
Cultural, Psychological, and Spiritual Dimensions of Palliative Care in Humanitarian Crises
Authors: Clark Peter Yuichi , Joseph Denah M. , Humphreys Jessi
Published: November 2019

This chapter examines the complex psychological, sociocultural, and spiritual dynamics that arise when offering palliative care during humanitarian crises. It asserts the importance of being aware of one’s unconscious beliefs, biases, and assumptions, while advocating for cultural awareness, curiosity, and humility when engaging with those impacted by crises. It encourages readers to consider common dilemmas in cross-cultural caregiving situations. It also reviews factors that can increase psychological morbidities, stress resilience, principles of psychological first aid (PFA), and grief and bereavement, including a description of the types of loss people experience and how they may cope with grief. The chapter ends by discussing spirituality as a vital dimension of human experience, principles of spiritual first aid (SFA), and the essential accompanying that marks spiritual care in disaster situations.
Strasbourg, Heidelberg, and New Orleans: 1935–1942
Authors: Miller Craig A.
Published: November 2019

DeBakey travels to Europe for a year to study and train with the famed French surgeon Rene Leriche and his German counterpart Martin Kirschner. DeBakey becomes a trusted assistant to Leriche. In Germany, he admires the disciplined surgery teams, and their efficiency influences DeBakey’s later development of his own surgical program. He joins the faculty at Tulane, and he and Ochsner compose ground-breaking papers on abdominal infections and, especially, the link between smoking and lung cancer. After Pearl Harbor, Tulane mobilizes its medical staff as a General Hospital. DeBakey is, however, deemed “essential” and can neither enlist or be drafted.
Washington, D.C. and New Orleans: 1942–1948
Authors: Miller Craig A.
Published: November 2019

DeBakey is made Consultant in the Surgeon General’s Office, participating in personnel assignments, modernization of equipment, and much writing. Military red tape vexes his efforts to prevent a repeat of the medical lessons learned during World War I, and the soldiers suffer as trench foot reappears. Auxiliary Surgical Groups are formed for front-line surgery. DeBakey tours the armies in Europe, compiling data for scientific analysis. After the war, DeBakey remains in uniform for a year, is appointed to a full Colonel and other positions of importance, and returns to New Orleans a figure well-known to leaders in American medicine and politics.
Epilogue
Authors: Miller Craig A.
Published: November 2019

The Epilogue provides a description of Dr. Michael E. DeBakey’s funeral and interment and a brief summation of his accomplishments and his legacy of advancements in medical technology and patient care. Also provided is a brief account of DeBakey’s surviving family members.
The Decline and Fall of Dynamic Psychiatry
Authors: Horwitz Allan V.
Published: November 2019

After psychiatry’s ascendancy during the two decades after World War II ended, the profession entered its most troubled period. From the emergence of the anti-psychiatry movement in the mid-1960s through the resurrection of a biomedical model in the DSM-III in 1980, the field endured a time of continual crisis. The general culture shed its earlier infatuation with analytic ideas and turned sharply against the discipline. The medical profession, biologically oriented psychiatrists, and third-party insurers, too, came to reject psychodynamic approaches. The National Institute of Mental Health as well discarded its initial psychosocial emphasis in favor of a strong biological focus. Another government agency, the Food and Drug Administration, forced drug companies to stop advertising their products as remedies for general distress and mandated that they show efficacy in treating specific diseases. The high pedestal that dynamic psychiatry rested on in the postwar period swiftly crumbled.
The Successes and Failures of the DSM Revolution
Authors: Horwitz Allan V.
Published: November 2019

Forty years after the DSM-III diagnostic revolution, the fundamental dilemmas that have perennially confronted psychiatry (and other mental health professions) remain unresolved. Neuroscientific and epidemiologic findings show that the current DSM system poorly characterizes the nature of mental disorder. Contrary to the intentions of the researchers who developed the DSM-III, its conditions have tremendous internal heterogeneity, artificial comorbidity, and an inability to separate contextually appropriate from dysfunctional symptoms. These inadequacies led the DSM-5 Task Force to propose fundamental changes in the categorical system that was at the heart of these problems. Yet, the pathway they choose to remedy the situation—the introduction of dimensions—would have made these problems even worse. The American Psychiatric Association assembly and board of trustees rejected this premature upheaval in psychiatric diagnosis. The DSM-5, however, did implement other changes, in particular, the abolition of the bereavement exclusion to the diagnosis of major depression, which exacerbated the confusion between normality and pathology. Despite the intentions of its developers, the DSM-5 did not improve understandings of mental disorder.
Acute Subdural Hematoma
Authors: McGahan Benjamin , Toop Nathaniel , Shah Varun , McGregor John
Published: November 2019

Acute subdural hematomas are collections of acute blood in the subdural space. They usually present as a result of significant head trauma. They can occur spontaneously in relationship to an underlying hemorrhagic lesion such as tumor, arteriovenous malformation, or aneurysm. They are more likely to be associated with cortical injury than the epidural hematoma. Neurological symptoms on presentation are related to the underlying brain injury and/or mass effect. Acute subdural blood on CT scan is hyperdense, in a crescent shape, along the inner dural surface. Emergent surgical intervention via craniotomy is indicated in patients with at least 10 mm in thickness or at least 5 mm shift, or elevated ICP, or pupillary dilatations suggesting herniation, or progression of deficit based on the Glasgow Coma Score. Conservative management of small acute subdural hematomas may be done in select situations that include proper ICU monitoring for ICP elevations and neurological deteriorations.
Concussion
Authors: Mathews Amy A. , Bell Kathleen R.
Published: November 2019

The diagnosis, evaluation, and management of concussion requires a systematic and thorough approach. In the acute setting, providers should effectively screen for concomitant injuries as well as address presenting symptoms of concussion. Concussed individuals may experience a number of somatic, cognitive, behavioral, and affective changes that require timely management. Concussion management also requires the ability to provide appropriate education and guidance as individuals return to activity. Although a majority of individuals who sustain a concussion improve within weeks, certain individuals may require continued treatment for persistent symptoms. Evidence regarding the long-term sequelae of concussion and cumulative trauma is still being developed, but it is important for the concussion provider to be able to counsel individuals about potential complications of concussion and preventative measures.
Traumatic Anterior Cranial Fossa CSF Leaks
Authors: Khanna Omaditya , Garzon-Muvdi Tomas , Garcia Hermes , Schmidt Richard F. , Evans James J. , Farrell Christopher J.
Published: November 2019

Traumatic CSF leaks are reported to complicate 10–30% of skull base fractures. CSF rhinorrhea or otorrhea may be clinically apparent but in patients with less obvious leaks, β‎2-transferrin evaluation is the most sensitive and specific confirmatory test to establish the diagnosis of CSF leakage. High-resolution CT effectively identifies the majority of skull base fractures and sites of CSF leakage. Adjunctive imaging modalities such as CT cisternography and magnetic resonance cisternography may be used for further evaluation. Most traumatic CSF leaks of the anterior cranial fossa resolve spontaneously with conservative management including bedrest, head elevation, and avoidance of activities that increase intracranial pressure. The risk of meningitis increases significantly with persistent CSF leakage beyond 1 week, and intervention in the form of CSF diversion or surgical closure of the leak should be pursued. Prophylactic antibiotics have not been shown to decrease the risk of meningitis in patients with traumatic CSF leaks.
Seizures in the Setting of Trauma
Authors: Hefton Sara
Published: November 2019

This chapter on seizures in the setting of trauma reviews the risk factors for seizures after traumatic brain injury (TBI), their medical prophylaxis, and their management using a case study to illustrate salient points. Differentiation of early and late posttraumatic seizures is discussed. Pathogenesis, incidence, and risk factors for early and late posttraumatic seizures are reviewed, as is posttraumatic epilepsy. Appropriate prophylactic antiepileptic drugs (AEDs) are discussed, as well as the management of seizures and status epilepticus in the setting of TBI. Prognosis and anticipated outcomes are considered.
Common methods of presentation
Authors: Corbridge Rogan , Steventon Nicholas
Published: November 2019

This chapter provides diagnostic flow charts for common methods of presentation to the ear, nose, and throat (ENT) clinic. Common symptoms are explored in relation to coexisting symptoms, and then a diagnosis is derived from the appropriate examination findings. Each diagnosis is then referenced to the relevant section in the book for a discussion of further management.
The external ear
Authors: Corbridge Rogan , Steventon Nicholas
Published: November 2019

Conditions affecting the outer ear are discussed, including congenital abnormalities, infections, trauma, and malignancy. Methods of ear wax removal and their advantages and disadvantages are tabulated. Management of the serious infection of necrotizing otitis externa usually affecting patients with diabetes is outlined. Skin cancer affecting the skin of the pinna and its treatment are listed. The rare condition of carcinoma of the external auditory canal, its classification, and treatment planning are documented.
The inner ear
Authors: Corbridge Rogan , Steventon Nicholas
Published: November 2019

Conditions affecting the inner ear are delineated. Sensorineural hearing loss and its aetiologies are explored in reference to age-related hearing loss, noise-induced hearing loss, syndromic problems, and auditory neuropathy spectrum disorder. Causes of vertigo related to peripheral vestibular dysfunction are discussed, including vestibular migraine. Management of temporal bone fractures and their sequelae are explored. Methods of hearing rehabilitation are described.
The neck
Authors: Corbridge Rogan , Steventon Nicholas
Published: November 2019

This chapter outlines the anatomy of the neck. The investigation of neck lumps is described. Congenital neck lumps, including branchial cleft abnormalities, are tabulated. The management of neck infections and neoplastic conditions affecting the lymph nodes of the neck are discussed.
Ward care
Authors: Corbridge Rogan , Steventon Nicholas
Published: November 2019

This chapter outlines aspects of ward care of patients from the preoperative period, post-operative management, and discharge planning. The care of myocutaneous flaps, tracheostomy tubes, fluid balance, and nutrition are discussed. Deep vein thrombosis prophylaxis, along with managing anticoagulation, is described.
Pain Pathways
Authors: Schumacher Mark , Hogans Beth B.
Published: November 2019

Chapter 1 describes the anatomic organization of the nervous system elements dedicated to sensing and perceiving pain: the so-called pain pathways or nociceptive processing system. This is a small part of the human nervous system that has a large impact on self-preservation as well as the potential to attenuate quality of life. The pain system is divided into four functional subsystems: transduction, dedicated to encoding information about noxious stimuli into the form of action potentials; transmission, which functions to carry pain information from distal structures such as toes to the spinal cord and brain; perception, which engages multiple areas of the cortex as well as subcortical structures to create an integrated awareness of pain; and modulation, which involves several different brain and spinal structures to potentially increase and decrease sensitivity and responses to painful stimulation. The development of the pain system is discussed in detail. This chapter provides the foundation for Chapter 2, which focuses on the relevant neurotransmitters and molecular signaling events involved in the major aspects of pain system functioning. Understanding pain structural pathways will often provide unique insight into a patient’s pain experience, provide clues regarding the cause of a patient’s pain, and yield insights into potentially effective treatments.
Impact of Pain on the Individual and Others
Authors: Arnstein Paul , Keating Megan
Published: November 2019

Chapter 3 describes how pain is a powerful stressor that aids in surviving an injury and how the resultant physiologic stressors put vulnerable patients at risk for pulmonary, renal, gastrointestinal, metabolic, and psychosocial complications. The timeliness and efficacy of pain control contribute to health outcomes. Of the estimated 30% of adults who develop chronic pain, these individuals face increased risk for an impoverished, premature death. Pain is a biopsychosocial experience that undermines health, activities, and enjoyment of life. Unless assessed and treated properly, pain devalues important things in the life of the sufferer, often leading down a path to disability and despair. Pain is always a combined physical, mental, and social experience that often partially responds to properly targeted therapy. Disparities are common in the way pain is managed and may relate to factors at the patient, provider, organizational, or payer levels. Thus, healthcare professionals who interact with people experiencing pain have a duty to dampen the biopsychosocial impact of pain to help them think, feel, and do better. Given potential harm related to analgesics or invasive treatments, ethical practices involve advocating for delivering personalized treatments, with vigilant monitoring to avoid potential harm.
Standard Systemic Analgesic Agents
Authors: Matthews Michele L. , Kematick Benjamin S.
Published: November 2019

Chapter 9 addresses drugs used for pain management. These drugs are categorized as standard systemic analgesic agents, including nonopioid and opioid analgesics, and other, neuromodulating, agents that are addressed in subsequent chapters. There is significant variability in individual response to standard systemic analgesics, and choice of therapy should foremost include patient-specific considerations balancing efficacy with tolerability. Acetaminophen is widely recommended for various acute and chronic pain syndromes and is generally considered safe when taken within therapeutic doses. Nonsteroidal anti-inflammatory drugs (NSAIDs) are versatile analgesics and are commonly utilized for general mild to moderate pain. NSAIDs are the most widely used analgesics today. Opioids are effective for severe pain, such as pain from acute trauma, postsurgical pain, and cancer pain, but require intense monitoring for side effects. All opioids cause sedation, constipation, nausea, and somnolence and can cause respiratory depression, physical dependence, and death. Opioids are available in both short-acting and extended-release or long-acting formulations. Like NSAIDs, opioids should be used at the lowest dose for the shortest duration of time when possible.
Neuromodulating Agents
Authors: Hogans Beth B.
Published: November 2019

Chapter 10 explores the variety and mechanisms of medications used for chronic and neuropathic pain. In patients with chronic and neuropathic pain, these medications can and do serve as the primary medication with efficacy. To call these agents “adjuvant” is, therefore, incorrect, despite longstanding custom. The neuromodulating medications discussed here include pain-active anticonvulsants, including gabapentinoids, pain-active antidepressants, local anesthetics, and other neuroactive agents. The medications are divided based on drug class and mechanism in order to facilitate rational combination of medications from different classes when treating patients with neuropathic or chronic pain that does not respond sufficiently to a single agent.
Interventional Techniques and Surgical Management of Pain
Authors: Young Mark , Rubens Andrew , Barreveld Antje M.
Published: November 2019

Chapter 11 describes many of the most common interventional and surgical procedures performed in the field of chronic pain medicine. They are discussed in a cranial to caudal pattern, and this is done not only for logical arrangement but also to highlight the breadth of procedures that are utilized in practice. Interventional and surgical pain management techniques using image or landmark guidance may provide diagnostic and therapeutic relief for patients suffering from pain. Performed by formally trained and experienced proceduralists, interventions, in conjunction with other multimodal strategies such as medications, physical therapy, and behavioral therapies, can be useful techniques for helping patients achieve improved function and pain relief. Benefits may be short or longer term, depending on the interventional strategy utilized. Indications, evidence, and risks must be considered when choosing the most appropriate interventional options for a patient.
Common Chronic Pain Problems
Authors: Hogans Beth B.
Published: November 2019

Chapter 16 addresses several common chronic pain-associated conditions. Utilizing the comprehensive, multimodal, evidence-based approach to assisting patients in planning for pain self-management, the chapter describes common chronic pain-associated conditions, including those of the head, such as chronic tension headache, temporomandibular joint disorder, and chronic migraine; the spine, such as chronic neck and low back pain; the appendicular musculoskeletal system, such as hip, knee, and shoulder pain; common neuropathic pain conditions, such as diabetic peripheral neuropathy; and common compressive neuropathies, such as carpal tunnel syndrome and ulnar neuropathy. The conditions are presented in terms of common characteristics, pathophysiologic features, and the basic approach to treatment.
Infectious Disease Clinical Research Program: Building the Bench
Authors: Coles Christian , Ottolini Martin G
Published: November 2019

The role of physicians in the U.S. Armed Forces is diverse, encompassing a wide array of skills and responsibilities to provide superior healthcare to their patients and to advance military medicine. In addition to healthcare delivery and medical education, military physicians are engaged in public health, operational medicine, and cutting-edge medical research. Thus, clinical research is a crucial component of Graduate Medical Education (GME) and supports critical thinking (knowledge, skills, and abilities) and the development of leadership skills among U.S. military physicians. The Infectious Disease Clinical Research Program (IDCRP) education mission was established in 2005 with the overall goal of supporting the development and training of the next generation of clinical researchers in infectious diseases and related public health disciplines in the Armed Forces using several strategies, including didactic learning, mentored research, and research engagement. Through involvement in the IDCRP, infectious disease fellows, residents (e.g., surgical, internal medicine, and pediatrics), and Master of Public Health (MPH) students have continued their education and gained valuable skills related to clinical research. Trainees either conduct research with IDCRP mentors or participate in IDCRP-led practicum experiences, with research projects ranging from epidemiologic studies to microbiological assessments. Consistent with the needs of the Military Health System (MHS), and in accordance with Accreditation Council for Graduate Medical Education goals, the IDCRP provides opportunities for medical and graduate students, residents, and infectious disease fellows to conduct mentored research within the MHS, as well as gain important leadership skills in the conduct of clinical research. Overall, IDCRP continues to further infectious disease research through the support and education of the next generation of active-duty infectious disease researchers in the MHS.
Opportunities and Obstacles in the Prevention of Skin and Soft-Tissue Infections Among Military Personnel
Authors: Millar Eugene V , Schlett Carey D , Law Natasha N , Whitman Timothy J , Ellis Michael W , Tribble David R , Bennett Jason W
Published: November 2019

Introduction

Skin and soft-tissue infections (SSTIs) are an important cause of infectious disease morbidity among military populations. Due to the high direct and indirect costs associated with SSTIs, particularly with methicillin-resistant Staphylococcus aureus (MRSA) infections, there remains a critical need for the development and evaluation of SSTI prevention strategies among high-risk military personnel. Herein, we review efforts of the Infectious Disease Clinical Research Program (IDCRP) related to the prevention of SSTIs in the military.

Methods

The IDCRP of the Uniformed Services University has conducted clinical research protocols on SSTI epidemiology and prevention among military personnel since 2009. Observational studies have examined the epidemiology of Staphylococcus aureus colonization and SSTI in training and deployment settings. Two randomized controlled trials of personal hygiene strategies for SSTI prevention at Marine Corps Base Quantico (Virginia) and Fort Benning (Georgia) were performed. Lastly, two vaccine trials have been conducted by the IDCRP, including a Phase 2 S. aureus vaccine trial (currently ongoing) among military trainees.

Results

Military recruits and deployed personnel experience an intense and prolonged exposure to S. aureus, the major causative agent of SSTI. The burden of S. aureus colonization and SSTI is particularly high in military trainees. Hygiene-based trials for S. aureus decolonization among military trainees were not effective in reducing rates of SSTI. In January 2018, the IDCRP initiated a Phase 2 S. aureus vaccine trial among the US Army Infantry training population at Fort Benning.

Conclusions

In the military, a disproportionate burden of SSTIs is borne by the recruit population. Strategies relying upon routine application of agents for S. aureus decolonization have not been effective in preventing SSTIs. A novel S. aureus vaccine candidate is being currently evaluated in a military training population and may represent a new opportunity to prevent SSTIs for the military.
Rapid and ultrasensitive digital PCR (dPCR) profiling of EGFRvIII in tumor cells and tissues
Authors: Saxena Deeksha , Sheikh Saad , Kao Gary , Binder Zev A , Alonso-Basanta Michelle , O’Rourke Donald M , Nasrallah MacLean P , Dorsey Jay F
Published: November 2019

Background

Amplification of the epidermal growth factor receptor (EGFR) gene is commonly found in glioblastoma (GBM). About 57% GBM overexpresses EGFR and are associated with tumor progression, poor prognosis, and shorter life expectancy. Molecular profiling of solid tumors usually takes several weeks and may be biased by intrinsic tumor heterogeneity.

Methods

The unique sequence created by the fusion of exon 1 and exon 8 in EGFRvIII was used to guide the design of primers and a Minor Groove Binder (MGB) probe. Extracted total RNA was reverse transcribed and pre-amplified by PCR, followed by detection of the EGFRvIII mutation by dPCR.

Results

The lowest limit of quantification of our EGFRvIII assay was 0.003%. The EGFRvIII variant was identified in patient-derived glioma neurosphere cell lines, xenograft mouse model, and patient-derived tumor specimens. The overall workflow can be accomplished within 24 hours. In certain samples, EGFRvIII was detected when next-generation sequencing was unable to identify the variant. This finding highlights the ability of the dPCR assay to identify EGFRvIII mutations in heterogeneous solid tumors such as GBM in a rapid fashion by profiling samples from spatially distinct areas of tumors from the same patient.

Conclusions

In this study, we developed a highly sensitive digital PCR (dPCR) platform and leveraged our assay to detect the variant III alteration of EGFR (EGFRvIII) and amplified EGFR in patient-derived glioma neurosphere cell lines, orthotopic xenograft GBM mouse models, and patient-derived tumor specimens in less than 24 hours from minute quantities of starting material.
Mechanical and biological properties of Ti–(0–25 wt%)Nb alloys for biomedical implants application
Authors: Zhang Yuqing , Sun Danni , Cheng Jun , Tsoi James Kit Hon , Chen Jiang
Published: November 2019

Binary titanium–niobium (Ti–Nb) alloys have recently been attracted due to low Young’s moduli and non-toxic properties. This study explores the influence of low Nb content (0–25 wt%) on the comprehensive parameters of tensile stress–strain relationships (ultimate strength (σUTS), yield strength (σ0.2) and elastic modulus (E)), surfaces properties (Vickers microhardness, surface roughness (Ra), water contact angle (WCA), X-ray diffraction (XRD) and scanning electron microscopy (SEM)), corrosion resistance (in artificial saliva and lactic acid) and biological properties (cytotoxicity and alkaline phosphatase activity of MC3T3-E1 pre-osteoblasts) of Ti–xNb alloys (x = 5, 10, 15, 20 and 25 wt%), with using commercially pure grade 2 titanium (cp-Ti) as control. XRD results shown that all the Ti–xNb alloys comprised α + β Ti alloy phases, such that the β phase increased correspondingly with the increased amount of Nb in the alloy, as well as the reduction of E (69–87 GPa). Except Ti–5Nb, all other Ti–xNb alloys showed a significantly higher hardness, increased σUTS and σ0.2, and decreased WCA compared with cp-Ti. No corrosion was detected on Ti–xNb alloys and cp-Ti in artificial saliva and lactic acid solutions. The cytotoxicity of Ti–xNb alloys was comparable to that of cp-Ti in MC3T3-E1 pre-osteoblasts without interference from differentiation behaviour, but the proliferation rate of the Ti–5Nb alloy was lower than other groups. In overall, binary Ti–(10–25 wt%)Nb alloys are promising candidate for orthopaedic and dental implants due to their improved mechanical properties and comparable biological performance, while Ti–5Nb should be used with caution.
‘Room to Rhyme’: Heaney, Arts Policy and Cultural Tradition in Northern Ireland 1968–1971
Authors: Carville Conor
Published: November 2019

Drawing on extensive research in Arts Council and government archives in Belfast and the collections of Seamus Heaney’s manuscripts, this essay reconstructs for the first time Northern Irish state cultural policy at the height of the crisis years 1968–1972. It also examines the response of a major poet to this policy, through a genetic mapping of the complex development of Heaney’s poem ‘The Last Mummer’, between 1969 and its publication in 1972. The poem refers to the mumming plays practiced at Christmas when troupes of young men, or ‘Rhymers’ would enter and perform in the houses of both communities in the North. This practice also informed ‘Room to Rhyme’, the Arts Council sponsored 1968 tour of several towns in Northern Ireland by Heaney and Michael Longley and the folk musician Davy Hammond. The make-up of the performers on the tour, the itinerary and accompanying booklet, suggest a deliberate attempt on the part of the Arts Council Northern Ireland to assert a role for itself, and for culture, in the political thaw of the time. In the years immediately after the tour, however, major confrontations between civil rights marches and police, widespread sectarian rioting and ultimately troops on the streets, resulted in even more extreme polarization in the North. As this essay shows, Heaney’s manuscripts from this period provide a valuable resource for the examination of the relationship between poetry, the public sphere and notions of cultural tradition in early 1970s Northern Ireland.
Increased monohexosylceramide levels in the serum of established rheumatoid arthritis patients
Authors: Miltenberger-Miltenyi Gabriel , Cruz-Machado Ana Rita , Saville Jennifer , Conceição Vasco A , Calado Ângelo , Lopes Inês , Fuller Maria , Fonseca João Eurico
Published: November 2019

Objectives

To identify serum sphingolipids that could act as candidate biomarkers in RA.

Methods

We performed lipidomic analyses in the serum of 82 participants: 19 established RA patients, 18 untreated early RA patients, 13 untreated early arthritis patients not fulfilling the classification criteria for RA, 12 established SpA patients and 20 controls. We compared the lipid levels from the different patient groups with the control group through multiple-regression analyses controlling for age at diagnosis, gender and medication (cDMARDs and corticoids).

Results

Established RA patients had significantly increased levels of sphingosine, monohexosylceramide and ceramide compared with controls, when controlling for age and gender. Monohexosylceramide levels remained significantly increased when additionally controlling for medication. On the contrary, SpA patients had significantly decreased levels of ceramide, in both analyses.

Conclusion

We observed a detectable increase in the levels of certain sphingolipids in the serum of established RA patients when compared with controls, in line with previous observations in the synovial fluid. Such findings provide further evidence that sphingolipids may play a key role in the pathophysiology of RA.