bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deriving Specifications of Control Programs for Cyber Physical Systems
Authors: Burns Alan , Hayes Ian J , Jones Cliff B 
Published: February 2019

Abstract
Cyber physical systems (CPS) exist in a physical environment and comprise both physical components and a control program. Physical components are inherently liable to failure and yet an overall CPS is required to operate safely, reliably and cost effectively. This paper proposes a framework for deriving the specification of the software control component of a CPS from an understanding of the behaviour required of the overall system in its physical environment. The two key elements of this framework are (i) an extension to the use of rely/guarantee conditions to allow specifications to be obtained systematically from requirements (as expressed in terms of the required behaviour in the environment) and nested assumptions (about the physical components of the CPS); and (ii) the use of time bands to record the temporal properties required of the CPS at a number of different granularities. The key contribution is in combining these ideas; using time bands overcomes a significant drawback in earlier work. The paper also addresses the means by which the reliability of a CPS can be addressed by challenging each rely condition in the derived specification and, where appropriate, improve robustness and/or define weaker guarantees that can be delivered with respect to the corresponding weaker rely conditions.
Quantitative estimation of extravascular lung water volume and preload by dynamic 15O-water positron emission tomography
Authors: Nielsen Roni Ranghøj , Sörensen Jens , Tolbod Lars , Alstrup Aage Kristian Olsen , Iversen Peter , Frederiksen Christian Alcaraz , Wiggers Henrik , Jorsal Anders , Frøkier Jørgen , Harms Hendrik Johannes 
Published: February 2019

Abstract

Aims
Left ventricular filling pressure (preload) can be assessed by pulmonary capillary wedge pressure (PCWP) during pulmonary arterial catheterization (PAC). An emerging method [pulse indexed contour cardiac output (PICCO)] can estimate preload by global end-diastolic volume (GEDV) and congestion as extravascular lung water (EVLW) content. However, no reliable quantitative non-invasive methods are available. Hence, in a porcine model of pulmonary congestion, we evaluated EVLW and GEDV by positron emission tomography (PET). The method was applied in 35 heart failure (HF) patients and 9 healthy volunteers.

Methods and results
Eight pigs were studied. Pulmonary congestion was induced by a combination of beta-blockers, angiotensin-2 agonist and saline infusion. PAC, PICCO, computerized tomography, and 15O-H2O-PET were performed. EVLW increased from 521 ± 76 to 973 ± 325 mL (P < 0.001) and GEDV from 1068 ± 170 to 1254 ± 85 mL (P < 0.001). 15O-H2O-PET measures of EVLW increased from 566 ± 151 to 797 ± 231 mL (P < 0.001) and GEDV from 364 ± 60 to 524 ± 92 mL (P < 0.001). Both EVLW and GEDV measured with PICCO and 15O-H2O-PET correlated (r2 = 0.40, P < 0.001; r2 = 0.40, P < 0.001, respectively). EVLW correlated with Hounsfield units (HU; PICCO: r2 = 0.36, P < 0.001, PET: r2 = 0.46, P < 0.001) and GEDV with PCWP (PICCO: r2 = 0.20, P = 0.01, PET: r2 = 0.29, P = 0.002). In human subjects, measurements were indexed (I) for body surface area. Neither EVLWI nor HU differed between chronic stable HF patients and healthy volunteers (P = 0.11, P = 0.29) whereas GEDVI was increased in HF patients (336 ± 66 mL/m2 vs. 276 ± 44 mL/m2, P = 0.01).

Conclusion
The present study demonstrates that 15O-H2O-PET can assess pulmonary congestion and preload quantitatively. Hence, prognostic information from 15O-H2O-PET examinations should be evaluated in clinical trials.
NLRP7 and KHDC3L variants in Chinese patients with recurrent hydatidiform moles
Authors: Ji Mingliang , Shi Xiaohua , Xiang Yang , Cui Quancai , Zhao Jun 
Published: February 2019

Abstract

Objective
Recurrent hydatidiform moles are reportedly biparental complete moles and related to mutated NLRP7 and KHDC3L. This study was designed to identify mutations of gene NLRP7 and KHDC3L in biparental complete moles.

Methods
In this study, we have screened NLRP7 and KHDC3L mutations in five patients with recurrent moles and five with sporadic moles. Molar tissues and blood samples were collected from patients and their partners. Genotypes of the molar tissues were determined based on short tandem repeat polymorphism. The coding exons of NLRP7 and KHDC3L were sequenced.

Results
Two patients with recurrent moles had biparental complete moles, while all other patients had androgenetic complete moles. Three non-synonymous variants in NLRP7 (c.955 G>A, c.1280 T>C and c.1441 G>A) and one in KHDC3L (c.602 C>G) were identified in patients with recurrent moles. NLRP7 c.1441 G>A and c.1280 T>C were mutations found in the Chinese population, while c.1441 G>A was only detected in patients with biparental complete moles in this study.

Conclusions
Genotyping can be used to differentiate biparental complete moles from androgenetic moles and to predict the risk of recurrent moles in future pregnancies. NLRP7 c.1441 G>A may associate with biparental complete moles. Biparental complete moles exhibit genetic heterogeneity.
‘Mirages of an Intellectual Dreamland’? Ratio, Obiter and the Textualization of International Precedent
Authors: Ridi Niccolò 
Published: February 2019

Abstract
In recent years, various actors—states, judges and commentators alike—have taken issue with the way international adjudicators have approached precedent. Criticism has been levelled, in particular, to the phenomenon of ‘obiter dicta’ (observations that, though not necessary for the decision, are nonetheless included in it), which have been found to amount to a symptom of bad decision-making or, from the perspective of the adjudicator using them, bad precedent following. This article addresses this debate by resituating the issue within a more grounded discussion of the theory of precedent in international adjudication, providing an in-depth theoretical and empirical analysis of the practice, and seeks to frame it within in the broader phenomenon of ‘textualization’. By doing so, it strives to clarify the use, authority and ultimate function of obiter dicta, as well as of precedent in general, in international adjudication.
Pathogenesis of Acute Kidney Injury
Authors: Basile David P. , Padanilam Babu J. 
Published: February 2019

Abstract
Acute kidney injury represents a significant clinical disorder associated with a rapid loss of renal function following a variety of potential insults. This chapter reviews multiple issues related to the pathophysiology of AKI with an emphasis on studies from animal models. Early responses following kidney injury include impaired hemodynamic and bioenergetic responses. Reductions in renal ATP levels occur as a result of compromised fatty acid oxidation and impaired compensation by glycolysis. Sustained reductions in perfusion contribute to extension of AKI characterized by complex inflammatory and cellular injury responses, often leading to cell death. Concurrently, the kidney displays an elegant repair response, leading to successful recovery in most cases, characterized in part by epithelial cell growth, while maladaptive or incomplete recovery of tubules or capillaries can predispose the development of interstitial fibrosis and CKD progression.
Imaging of the Kidney
Authors: Wymer David C. , Wymer David T. G. 
Published: February 2019

Abstract
The focus of this chapter is the use of imaging in providing the information necessary to protect the kidney from insults (metabolic and physical) and when needed to evaluate effects of age related renal changes, drugs, treatments, and trauma on renal function. Imaging is an integral part in the evaluation of the renal patient. Radiology has a mandate to help provide a diagnosis while balancing the benefits of imaging against any potential adverse effect encountered in the imaging process. Major considerations in deciding on how to best image a given patient include radiation exposure, contrast allergies, potential contrast toxicity (including systemic effects such as NSF), psychological effects (such as claustrophobia), and renal trauma secondary to interventional procedures.
Slowing Progression of Chronic Kidney Disease
Authors: Pollack-Zollman Martine , Vassalotti Joseph A. 
Published: February 2019

Abstract
CKD progression is introduced broadly, including definitions to distinguish related conditions (such as rapid CKD progression from AKI), common pathways for loss of kidney function, as well as validated ESRD prediction models to risk stratify patients and populations. Interventions to slow CKD progression are hypertension control in the context of current blood pressure target controversies, use of RAAS blockade for hypertension with albuminuria (A3) or proteinuria, glycemic control in diabetes, diabetic kidney disease therapy with a focus on recent and ongoing interventional trials and alkali therapy for CKD metabolic acidosis. Other less evidenced-based treatments (retrospective and observational trials, as well as secondary outcomes of RCT) to slow CKD progression are also discussed. These include the folic acid supplementation in the deficient population, SGLT-2 inhibitors for type-2 diabetes, intervention for obstructive sleep apnea, prevention of AKI, early nephrology referral and implementation of the multi-disciplinary approach to slowing CKD progression.
Obstructive Uropathies
Authors: Deshpande Priya , Sharma Shuchita 
Published: February 2019

Abstract
Obstructive Uropathy remains an important cause of acute kidney injury. The etiology of obstructive uropathy can be very variable ranging from extrinsic compression of the urinary tract by tumors or surrounding structures to intraluminal obstruction by crystals and stones. Patients with obstructive uropathy manifest symptoms based on the area of obstruction within the urinary tract. Flank pain, hematuria, and suprapubic discomfort are some of the associated symptoms. The diagnosis of obstructive uropathy requires a high index of suspicion and, depending on its nature, can be confirmed clinically and/or with an imaging modality. Prompt diagnosis and treatment with effective relief of obstruction is important in preventing long-term and permanent damage to the kidneys.
Acute Kidney Injury from Therapeutic Agents
Authors: Knicely Daphne , Choi Michael J. , Thavarajah Sumeska 
Published: February 2019

Abstract
Many agents, which are crucial for diagnostic and therapeutic purposes, are associated with nephrotoxicity and acute kidney injury. The nephrotoxicity often becomes the limiting factor for use of these agents, and, in some cases, there are no alternative agents. This chapter reviews the common classes of agents that are associated with nephrotoxicity (contrast, intravenous immunoglobulin, aminoglycosides, vancomycin, amphotericin, and nonsteroidal anti-inflammatory drugs). The mechanisms of nephrotoxicity from these agents as well various patient risk factors associated with nephrotoxicity are examined, and potential strategies to try to prevent acute kidney injury are reviewed. There are many therapeutic agents that cause renal toxicity that often become the limiting factor in the agent’s use. Often, there are no alternative agents available, so recognition of the risk factors for nephrotoxicity and incorporation of preventative measures are critical.
Immunological Agents in the Treatment of Glomerulonephritis
Authors: Farouk Samira , Winston Jonathan 
Published: February 2019

Abstract
Glomerulonephritis is an important cause of end-stage renal disease worldwide, and treatment strategies have evolved over the past several decades. Immunosuppressive therapies compromise the majority of available therapeutic options. Glucocorticoids, first studied in glomerular disease patients in 1957, remains a first-line therapy for most glomerular diseases. The decision of which cocktail of immunosuppressive therapies to prescribe is not only driven by data but also by patient characteristics and adverse effect profiles. Though the majority of current therapeutic options are globally immunosuppressive therapies, more targeted and less toxic therapies are being developed and tested in clinical trials. An understanding of the mechanisms and efficacy of each of these immunological agents in various glomerular diseases is critical for the nephrologist.
NSAIDs and the Kidney
Authors: Chan Lili , Kim Tonia 
Published: February 2019

Abstract
NSAIDs are among the most commonly prescribed medications in the United States. NSAID associated kidney disease presents in various ways including ischemic acute kidney injury, nephrotic syndrome, and analgesic nephropathy. Elderly patients and patients who are also on diuretics and/or renin angiotensin aldosterone system blockade are at higher risk of developing NSAIDs associated kidney disease. Additionally, NSAIDs negatively impact blood pressure. Unfortunately, there is no currently effective therapy for the prevention of NSAIDS associated kidney disease. Proposed preventative strategies are discussed.
Chemotherapeutic Agents and the Kidney
Authors: Selamet Umut , Hanna Ramy M. , Rastogi Anjay , Abudayyeh Ala 
Published: February 2019

Abstract
Chemotherapeutic agents have toxicities that extend beyond their therapeutic effect on malignant cells, and the kidneys are involved in the metabolism of these agents. Kidney toxicity delay the elimination of anticancer drugs from the body and increase the risk of systemic toxicity. Conventional chemotherapeutics generally cause direct renal tubular injury and electrolyte wasting syndromes. Newer cancer treatments include targeted therapy and immunotherapy. Targeted therapy, especially the drugs that target vascular endothelial growth factor, disrupt the crosstalk between podocytes and endothelial cells of the glomerulus resulting in a spectrum of glomerular diseases. On the other hand, immune checkpoint inhibitors release the break on the immune system and can cause immune-mediated tubulointerstitial nephritis and glomerulonephritis similar to autoimmune diseases. This chapter summarizes nephrotoxicity profiles of some of the common conventional chemotherapeutics as well as newer anticancer agents.
Thrombotic Microangiopathies
Authors: Kaufman Lewis 
Published: February 2019

Abstract
The thrombotic microangioapathy (TMA) syndromes are characterized by concomitant occurrence of severe thrombocytopenia, microangiopathic hemolytic anemia, and ischemic end organ dysfunction often of the kidneys. While several of their features overlap in terms of clinical presentation, the pathophysiology and underlying causes of each form of primary TMA are quite unique. Over the last decade, researchers’ understanding of these underlying causes has accelerated dramatically, providing transformative approaches to the way patients with these disorders are diagnosed, followed, stratified, and treated. These targeted approaches have led to rapidly evolving patient outcomes including the development of novel therapeutic approaches to prevent and treat kidney disease in these patients.
Kidney Disease in HIV Infection and Treatment
Authors: Wyatt Christina M. 
Published: February 2019

Abstract
HIV-positive individuals are at increased risk of kidney disease as a result of HIV-related kidney disease, toxicity of antiretroviral therapy, and accelerated progression of comorbid kidney disease. Because of the broad spectrum of disease, kidney biopsy should be considered in all HIV-positive individuals who present with kidney disease. While an effective combination antiretroviral therapy has substantially reduced the incidence of HIV-associated nephropathy, antiretroviral therapy appears to have less impact on immune-complex kidney disease and comorbid kidney diseases. The management of kidney disease in HIV-positive individuals is complicated by unique drug–drug interactions and drug effects on creatinine-based estimates of kidney function.
Urinary incontinence and female urology
Authors: Reynard John , Brewster Simon F , Biers Suzanne , Neal Naomi Laura 
Published: February 2019

Abstract
All aspects of female and male urinary incontinence assessment, investigation, and management are outlined. Definitions of incontinence are provided, with a review of the epidemiology, risk factors, and management of stress urinary incontinence (SUI), post-prostatectomy (male) incontinence, overactive bladder syndrome (OAB), mixed urinary incontinence, and incontinence in older populations. Conservative, drug, and surgical therapies are explored, including bulking agents, synthetic mid-urethral tapes, colposuspension, autologous fascial slings, and artificial urinary sphincters (AUS) for female SUI, and urethral slings and AUS for male incontinence, and botulinum toxin, ileocystoplasty, and sacral nerve stimulation for OAB. Clear management pathways are included which are supported by the International Continence Society, with guideline recommendations from the National Institute for Health and Care Excellence and European Association of Urology. Vesicovaginal fistula, urethral diverticulum, and pelvic organ prolapse (POP), are illustrated, and controversies including the use of mesh in POP and incontinence surgery, and anticholinergic drug burden in OAB are discussed.
Miscellaneous urological diseases of the kidney
Authors: Reynard John , Brewster Simon F , Biers Suzanne , Neal Naomi Laura 
Published: February 2019

Abstract
This chapter covers miscellaneous diseases of the kidney and outlines their presentation, investigations, and management. This includes renal cysts, calyceal diverticulum, medullary sponge kidney, and cystic disease (acquired renal cystic disease and autosomal dominant polycystic kidney disease, including the aetiology and associated disorders). Adult vesicoureteric reflux and pelviureteric junction obstruction are discussed alongside informative and representative images, together with their management. Embryological abnormalities are covered in detail, including horseshoe kidney, ectopic kidney, renal agenesis, malrotation, and duplication. The investigation and management of each anomaly are included.
Infertility
Authors: Reynard John , Brewster Simon F , Biers Suzanne , Neal Naomi Laura 
Published: February 2019

Abstract
Male factor infertility is outlined in an easily digestible format to provide clear information on this sometimes less familiar topic, starting with the basics of male reproductive physiology, the hypothalamic–pituitary–testicular axis, and spermatogenesis. This chapter includes a review of the aetiologies of abnormal sperm counts (with particular emphasis on azoospermia and oligospermia), relevant clinical assessment, and key male factor infertility investigations such as semen analysis, hormone measurement, karyotying, imaging, and testicular biopsy. The chapter explains the management options for the infertile male and couple, including information on the different assisted reproductive techniques. The chapter covers additional important clinical and exam topics, including varicoceles, indications for repair in males of different ages, red flag signs that should trigger further investigation, and the treatment options of embolization and surgical repair. The fourth edition also includes the addition of new material exploring the pros and cons of vasectomy and vasectomy reversal.
Sexual health
Authors: Reynard John , Brewster Simon F , Biers Suzanne , Neal Naomi Laura 
Published: February 2019

Abstract
This andrology chapter covers the physiology of erection and ejaculation and expands on the evaluation and treatment of erectile dysfunction (ED), including the use of drugs (phosphodiesterase type-5 inhibitors or PDE-5I), intracavernosal injections, and insertion of penile prosthesis. The evaluation and treatment of Peyronie’s disease with Nesbitt or Lue procedure are explained. Ejaculatory dysfunction is covered, including the topics of retrograde, premature, delayed and absent ejaculation, and anorgasmia. The topical subjects of late-onset hypogonadism (LOH) and general male hypogonadism are examined in detail, with a clear description of testosterone replacement therapy. Gonococcal and non-gonococcal urethritis evaluation is laid out with current treatment guidelines.
Urological problems in pregnancy
Authors: Reynard John , Brewster Simon F , Biers Suzanne , Neal Naomi Laura 
Published: February 2019

Abstract
Important physiological changes to the urinary tract during pregnancy are examined, including physiological hydronephrosis of pregnancy and reduction in creatinine levels due to glomerular hyperfiltration. Changes in the anatomy contribute to an increased risk of urinary incontinence and lower urinary tract symptoms. Consequent urinary stasis contributes to a higher risk of urinary tract infection and pyelonephritis, which can contribute to preterm birth, and hence the importance of treating asymptomatic bacteriuria in the pregnant woman. Special attention may be given to the use of antibiotics in the different trimesters of pregnancy, and this is summarized in the chapter. The common diagnostic dilemmas of loin pain and hydronephrosis in pregnancy are debated, and guidance given on evaluation. Other essential urological issues that arise in pregnancy are reviewed, including the management of pregnant patients with previous urinary tract reconstruction, placenta accreta, and the problem of urinary retention after childbirth.
Genetic Consultations in the Newborn
Authors: Clark Robin D. , Curry Cynthia J. 
Published: February 2019

Abstract
This book was written to assist clinicians who care for newborns with congenital abnormalities in their diagnosis, genomic testing, and management. The goal was to make the evaluation of common neonatal anomalies and genetic syndromes accessible and understandable. In addition, the book may serve as an initial guide for practitioners in areas in which clinical genetic expertise is not readily available. As the book was being written, the testing paradigm shifted to a genomic approach: Chromosome analysis gave way to microarrays, and single gene testing was largely replaced by gene panels and exome sequencing. Thus, this book, which was initially intended as a clinical primer, of necessity became a resource for gene-based information as well.
Diaphragmatic Hernia
Authors: Clark Robin D. , Curry Cynthia J. 
Published: February 2019

Abstract
This chapter reviews background information about the incidence, risk factors, genetics, family history, recurrence risk, and epidemiology of isolated and syndromic diaphragmatic hernia. The chapter reviews the typical multifactorial inheritance pattern of isolated sporadic diaphragmatic hernia and its low recurrence risk, which is distinct from more complex single gene disorders. The discussion on the differential diagnosis of diaphragmatic hernia summarizes other intrathoracic disorders that can give a similar radiographic appearance. The common genetic causes of diaphragmatic hernia are discussed including chromosome anomalies (aneuploidy, mosaic tetrasomy 12p, recurrent copy number variants), and Mendelian disorders that include malformations in other organ systems and overgrowth conditions. The chapter gives recommendations for evaluation and management. A clinical case presentation features a large for gestational age infant with diaphragmatic hernia and bitemporal alopecia caused by Pallister–Killian syndrome.