bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of the precipitated phase changes for Super304H heat resistant steel during shot time aging at 800°C
Authors: Tao Song , Zhiwu Wang
Published: August 2019

For analyzing the change trend of Super304H heat resistant steel steel precipitated phases, this article adopts the method of high temperature aging to simulate the material conditions during actual working environment. Super304H steel aged under 800 °C for short time 10 h, 20 and 30 h. And analyzed SEM morphology, precipitate phase statistics, composition changes of the original sample and the samples after aging. The results showed that the number of precipitated phase increased first, then decreased and then increased with the prolong of aging time, while the average size and area fraction of precipitated phase increased all the time. In the precipitated phase, Cr continued to increase while Ni decreased.
Fractional Hermite-Hadamard-type inequalities for interval-valued functions
Authors: Budak Hüseyin , Tunç Tuba , Sarikaya Mehmet
Published: August 2019

In this paper, we define interval-valued right-sided Riemann- Liouville fractional integrals. Later, we handle Hermite-Hadamard inequality and Hermite-Hadamard-type inequalities via interval-valued Riemann-Liouville fractional integrals.
Regulatory mechanisms for the axonal localization of tau protein in neurons
Authors: Iwata Minori , Watanabe Shoji , Yamane Ayaka , Miyasaka Tomohiro , Misonou Hiroaki
Published: August 2019

Tau is a microtubule (MT)-associated protein that is thought to be localized to the axon. However, its precise localization in developing neurons and mechanisms for the axonal localization have not been fully addressed. In this study, we found that the axonal localization of tau in cultured rat hippocampal neurons mainly occur during early neuronal development. Interestingly, transient expression of human tau in very immature neurons, but not in mature neurons, mimicked the developmental localization of endogenous tau to the axon. We therefore were able to establish an experimental model, in which exogenously expressed tau can be properly localized to the axon. Using this model, we obtained a surprising finding that the axonal localization of tau did not require stable MT binding. Tau lacking the MT-binding domain (MTBD) exhibited high diffusivity but localized properly to the axon. In contrast, a dephosphorylation-mimetic mutant of the proline-rich region 2 showed reinforced MT binding and mislocalization. Our results suggest that tight binding to MTs prevents tau from entering the axon and results in mislocalization in the soma and dendrites when expressed in mature neurons. This study therefore provides a novel mechanism independent of MTBD for the axonal localization of tau.
PACSIN2-dependent apical endocytosis regulates the morphology of epithelial microvilli
Authors: Postema Meagan M. , Grega-Larson Nathan E. , Meenderink Leslie M. , Tyska Matthew J.
Published: August 2019

Apical microvilli are critical for the homeostasis of transporting epithelia, yet mechanisms that control the assembly and morphology of these protrusions remain poorly understood. Previous studies in intestinal epithelial cell lines suggested a role for the F-BAR domain protein PACSIN2 in normal microvillar assembly. Here we report the phenotype of PACSIN2 KO mice and provide evidence that through its role in promoting apical endocytosis, this molecule plays a role in controlling microvillar morphology. PACSIN2 KO enterocytes exhibit reduced numbers of microvilli and defects in the microvillar ultrastructure, with membranes lifting away from rootlets of core bundles. Dynamin2, a PACSIN2 binding partner, and other endocytic factors were also lost from their normal localization near microvillar rootlets. To determine whether loss of endocytic machinery could explain defects in microvillar morphology, we examined the impact of PACSIN2 KD and endocytosis inhibition on live intestinal epithelial cells. These assays revealed that when endocytic vesicle scission fails, tubules are pulled into the cytoplasm and this, in turn, leads to a membrane-lifting phenomenon reminiscent of that observed at PACSIN2 KO brush borders. These findings lead to a new model where inward forces generated by endocytic machinery on the plasma membrane control the membrane wrapping of cell surface protrusions.
Integrating ab initio and template-based algorithms for protein–protein complex structure prediction
Authors: Vangaveti Sweta , Vreven Thom , Zhang Yang , Weng Zhiping
Published: August 2019

Motivation

Template-based and template-free methods have both been widely used in predicting the structures of protein–protein complexes. Template-based modeling is effective when a reliable template is available, while template-free methods are required for predicting the binding modes or interfaces that have not been previously observed. Our goal is to combine the two methods to improve computational protein–protein complex structure prediction.

Results

Here, we present a method to identify and combine high-confidence predictions of a template-based method (SPRING) with a template-free method (ZDOCK). Cross-validated using the protein–protein docking benchmark version 5.0, our method (ZING) achieved a success rate of 68.2%, outperforming SPRING and ZDOCK, with success rates of 52.1% and 35.9% respectively, when the top 10 predictions were considered per test case. In conclusion, a statistics-based method that evaluates and integrates predictions from template-based and template-free methods is more successful than either method independently.

Availability and implementation

ZING is available for download as a Github repository (https://github.com/weng-lab/ZING.git).

Supplementary information

Supplementary data are available at Bioinformatics online.
Island Nation, US Territory and Contested Space: Territorial Status As a Social Determinant of Indigenous Health in Guam
Authors: Diaz Tressa P , Ka‘opua Lana Sue I , Nakaoka Susan
Published: August 2019

The United Nations and International Federation of Social Work affirm the right of all people to determine their political status, preserve their environments and pursue endeavours for well-being. This article focuses on CHamoru, Guam’s Indigenous people, and examines distal social determinants of health (SDOH) in the contested spaces of US territorial status and non-self-determining Indigenous nationhood. Published multi-disciplinary literature identified ways in which territorial status functions as an SDOH unique to non-self-determining Pacific Island nations. Indicated is the use of structural approaches that address mechanisms of US power and control, including economic policies that ‘defacto’ promote coca-colonisation and non-communicable diseases risk. Critical race theory centres race, colonisation and subversive narratives. In line with fourth-generation SDOH action-oriented research, we posit a CHamoru critical race theory model that weaves Indigenous, social work and public health perspectives. Lack of community input is a limitation of the current research. To assure relevance, the model will be vetted through community discussions. Our discussion guide may be tailored for other Indigenous communities. Social workers may play a meaningful role in promoting health equity through participatory action-oriented, cultural–political social work that upholds Indigenous self-determination and survivance in contested spaces.
Neurotoxic tau oligomers after single versus repetitive mild traumatic brain injury
Authors: Bittar Alice , Bhatt Nemil , Hasan Tasneem F , Montalbano Mauro , Puangmalai Nicha , McAllen Salome , Ellsworth Anna , Carretero Murillo Mariana , Taglialatela Giulio , Lucke-Wold Brandon , Logsdon Aric , Rosen Charles , Turner Ryan C , Kayed Rakez
Published: August 2019

Mild traumatic brain injury accounts for the majority of head injuries and has been correlated with neurodegeneration and dementia. While repetitive mild traumatic brain injury is highly correlated to neurodegeneration, the correlation of a single mild traumatic brain injury with neurodegeneration is still unclear. Because tau aggregates are the main form of mild traumatic brain injury induced pathology, toxic forms of tau protein most likely play a role in the development of post-mild traumatic brain injury neurodegeneration. Therefore, it becomes crucial to characterize the properties of soluble tau aggregates in single versus repetitive mild traumatic brain injury. Herein, we isolated tau oligomers from wild-type mice exposed to single or repetitive mild traumatic brain injury and characterized the tau aggregates at functional, biochemical and biophysical levels. We demonstrated that single versus repetitive mild traumatic brain injuries frequencies lead to the formation of different tau oligomeric polymorphisms. These polymorphisms express different long-term potentiation impairment potencies, toxicity potentials, morphologies and strain indicating properties. To our knowledge, this is the first evidence that soluble tau oligomers derived from single versus repetitive mild traumatic brain injuries form distinct polymorphisms that possibly correlate with the risk of neurodegeneration after mild traumatic brain injury.
Epigenetics of Inflammatory Bowel Disease: Unraveling Pathogenic Events
Authors: Mateos Beatriz , Palanca-Ballester Cora , Saez-Gonzalez Esteban , Moret Inés , Lopez Adrian , Sandoval Juan
Published: August 2019

Epigenetics has emerged as a new and promising field in recent years. Because there exists a need to find new biomarkers and improve diagnosis, prognosis, and drug response for inflammatory bowel diseases, the research on epigenetic biomarkers for molecular diagnostics encourages the translation of this field from the bench to the clinical practice. In this review, we present an overview of the current knowledge and its potential applicability of this emerging field in inflammatory bowel diseases.
Non-invasive in vivo imaging of acute thrombosis: development of a novel factor XIIIa radiotracer
Authors: Andrews Jack P M , Portal Christophe , Walton Tashfeen , Macaskill Mark G , Hadoke Patrick W F , Alcaide Corral Carlos , Lucatelli Christophe , Wilson Simon , Wilson Ian , MacNaught Gillian , Dweck Marc R , Newby David E , Tavares Adriana A S
Published: August 2019

Aims

Cardiovascular thrombosis is responsible a quarter of deaths annually worldwide. Current imaging methods for cardiovascular thrombosis focus on anatomical identification of thrombus but cannot determine thrombus age or activity. Molecular imaging techniques hold promise for identification and quantification of thrombosis in vivo. Our objective was to assess a novel optical and positron-emitting probe targeting Factor XIIIa (ENC2015) as biomarker of active thrombus formation.

Methods and results

Optical and positron-emitting ENC2015 probes were assessed ex vivo using blood drawn from human volunteers and passed through perfusion chambers containing denuded porcine aorta as a model of arterial injury. Specificity of ENC2015 was established with co-infusion of a factor XIIIa inhibitor. In vivo18F-ENC2015 biodistribution, kinetics, radiometabolism, and thrombus binding were characterized in rats. Both Cy5 and fluorine-18 labelled ENC2015 rapidly and specifically bound to thrombi. Thrombus uptake was inhibited by a factor XIIIa inhibitor. 18F-ENC2015 remained unmetabolized over 8 h when incubated in ex vivo human blood. In vivo, 42% of parent radiotracer remained in blood 60 min post-administration. Biodistribution studies demonstrated rapid clearance from tissues with elimination via the urinary system. In vivo,18F-ENC2015 uptake was markedly increased in the thrombosed carotid artery compared to the contralateral patent artery (mean standard uptake value ratio of 2.40 vs. 0.74, P < 0.0001).

Conclusion 

ENC2015 rapidly and selectively binds to acute thrombus in both an ex vivo human translational model and an in vivo rodent model of arterial thrombosis. This probe holds promise for the non-invasive identification of thrombus formation in cardiovascular disease.
Does isolated mitral annular calcification in the absence of mitral valve disease affect clinical outcomes after transcatheter aortic valve replacement?
Authors: Okuno Taishi , Asami Masahiko , Khan Faisal , Praz Fabien , Heg Dik , Lanz Jonas , Kassar Mohammad , Khalique Omar K , Gräni Christoph , Brugger Nicolas , Räber Lorenz , Stortecky Stefan , Valgimigli Marco , Windecker Stephan , Pilgrim Thomas
Published: August 2019

Aims 

Mitral annular calcification (MAC) has been associated with adverse outcomes in patients undergoing transcatheter aortic valve replacement (TAVR) but has been investigated in isolation of co-existent mitral regurgitation or mitral stenosis, which may represent important confounders. This study sought to investigate the effect of MAC with and without concomitant mitral valve disease (MVD) on clinical outcomes in patients treated with TAVR.

Methods and results 

Computed tomography (CT) and echocardiographic data in consecutive TAVR patients enrolled into a prospective registry were categorized according to presence or absence of severe MAC and significant MVD, respectively. A total of 967 patients with adequate CT and echocardiography data were included between 2007 and 2017. Severe MAC was found in 172 patients (17.8%) and associated with MVD in 87 patients (50.6%). Compared to TAVR patients without severe MAC or MVD, all-cause mortality at 1 year was significantly increased among patients with severe MAC in combination with MVD [adjusted hazard ratio (HRadj): 1.97, 95% confidence interval (CI): 1.12–3.44, P = 0.018] and patients with isolated MVD (HRadj: 2.33, 95% CI: 1.56–3.47, P < 0.001), but not in patients with isolated severe MAC in the absence of MVD (HRadj: 0.52, 95% CI: 0.21–1.33, P = 0.173).

Conclusion 

We found no effect of isolated MAC on clinical outcomes following TAVR in patients with preserved mitral valve function. Patients with MVD had an increased risk of death at 1 year irrespective of MAC.
Temporal trends in bleeding events in acute myocardial infarction: insights from the SWEDEHEART registry
Authors: Simonsson Moa , Wallentin Lars , Alfredsson Joakim , Erlinge David , Hellström Ängerud Karin , Hofmann Robin , Kellerth Thomas , Lindhagen Lars , Ravn-Fischer Annica , Szummer Karolina , Ueda Peter , Yndigegn Troels , Jernberg Tomas
Published: August 2019

Aims

To describe the time trends of in-hospital and out-of-hospital bleeding parallel to the development of new treatments and ischaemic outcomes over the last 20 years in a nationwide myocardial infarction (MI) population.

Methods and results

Patients with acute MI (n = 371 431) enrolled in the SWEDEHEART registry from 1995 until May 2018 were selected and evaluated for in-hospital bleeding and out-of-hospital bleeding events at 1 year. In-hospital bleeding increased from 0.5% to a peak at 2% 2005/2006 and thereafter slightly decreased to a new plateau around 1.3% by the end of the study period. Out-of-hospital bleeding increased in a stepwise fashion from 2.5% to 3.5 % in the middle of the study period and to 4.8% at the end of the study period. The increase in both in-hospital and out-of-hospital bleeding was parallel to increasing use of invasive strategy and adjunctive antithrombotic treatment, dual antiplatelet therapy (DAPT), and potent DAPT, while the decrease in in-hospital bleeding from 2007 to 2010 was parallel to implementation of bleeding avoidance strategies. In-hospital re-infarction decreased from 2.8% to 0.6% and out-of-hospital MI decreased from 12.6% to 7.1%. The composite out-of-hospital MI, cardiovascular death, and stroke decreased in a similar fashion from 18.4% to 9.1%.

Conclusion

During the last 20 years, the introduction of invasive and more intense antithrombotic treatment has been associated with an increase in bleeding events but concomitant there has been a substantial greater reduction of ischaemic events including improved survival.
A novel Sphingobacterium sp. RB, a rhizosphere isolate degrading para-nitrophenol with substrate specificity towards nitrotoluenes and nitroanilines
Authors: Samson Rachel , Bodade Ragini , Zinjarde Smita , Kutty Razia
Published: August 2019

Sphingobacterium sp. RB, a novel bacterial strain isolated from a soil sample, was able to utilize para-nitrophenol (PNP) as sole source of carbon and energy at high concentrations (1.0–5.0 mM). The culture completely degraded 3.0 mM PNP within 36 h with proportionate increase in biomass. With 5.0 mM PNP (700 ppm), 70% degradation was observed within 72 h of incubation. Scanning electron microscope images of the isolate in the presence and absence of PNP showed no significant morphological variations. Liquid chromatography–mass spectrometry analysis indicated that the biodegradation of PNP in this bacterium proceeded via the formation of 1,2,4-benzenetriol. Cells previously exposed to PNP (induced) were 30% more effective in degrading PNP. With catechol and phenol, such induction was not observed. Uninduced cells of Sphingobacterium sp. RB were capable of degrading a variety of other nitroaromatic compounds, including 2-nitroaniline, 2,4-dinitroaniline, 2-nitrotoluene, 3-nitrotoluene and 2,4-dinitrophenol, within 72 h, thus proving its candidacy as a potent bioremediation agent. To the best of our knowledge, this is the first report on a Sphingobacterium species degrading PNP via formation of 1,2,4-benzenetriol.
The correlation between microRNAs and Helicobacter pylori in gastric cancer
Authors: Dastmalchi Narges , Safaralizadeh Reza , Banan Khojasteh Seyed Mahdi
Published: August 2019

Helicobacter pylori infection and H. pylori-related gastric inflammation can be considered as the most significant promoter of gastric cancer (GC). Recent investigations have evaluated the regulatory function of microRNAs (miRNAs) in H. pylori pathogenesis and H. pylori-related diseases, especially GC. The present study reviewed the correlation between miRNAs and H. pylori in gastrointestinal diseases. Furthermore, the current review highlighted the role of H. pylori pathogen and some H. pylori-related virulence factors in the deregulation of various miRNAs, especially oncogenic miRNAs (miRs) and their associated molecular pathways. Among the related studies, some have focused on the effects of H. pylori infection on regulatory networks of miRs, while others have highlighted the effects of alterations in the expression level of miRs in H. pylori-related diseases. The connectivity between miRNAs and H. pylori is regulated by various molecular pathways and different molecular targets of miRNAs.
A Manin–Mumford Theorem for the Maximal Compact Subgroup of a Universal Vectorial Extension of a Product of Elliptic Curves
Authors: Jones Gareth , Schmidt Harry
Published: August 2019

We study the intersection of an algebraic variety with the maximal compact subgroup of a universal vectorial extension of a product of elliptic curves. For this intersection we show a Manin–Mumford-type statement. This answers some questions posed by Corvaja–Masser–Zannier, which arose in connection with their investigation of the intersection of an algebraic curve with the maximal compact subgroup of various algebraic groups. In particular they proved that these intersections are finite for universal vectorial extensions of elliptic curves. Using Khovanskii’s zero-estimates combined with a stratification result of Gabrielov–Vorobjov and recent work of the authors, we obtain effective bounds for this intersection that only depend on the degree of the algebraic variety and the dimension of the group. As a corollary, we obtain new uniform results of Manin–Mumford type for additive extensions of certain abelian varieties.
Universal Behavior of the Corners of Orbital Beta Processes
Authors: Cuenca Cesar
Published: August 2019

There is a unique unitarily-invariant ensemble of $N\times N$ Hermitian matrices with a fixed set of real eigenvalues $a_1> \dots > a_N$. The joint eigenvalue distribution of the $(N-1)$ top-left principal submatrices of a random matrix from this ensemble is called the orbital unitary process. There are analogous matrix ensembles of symmetric and quaternionic Hermitian matrices that lead to the orbital orthogonal and symplectic processes, respectively. By extrapolation, on the dimension of the base field, of the explicit density formulas, we define the orbital beta processes. We prove the universal behavior of the virtual eigenvalues of the smallest $m$ principal submatrices, when $m$ is independent of $N$ and the eigenvalues $a_1> \dots > a_N$ grow linearly in $N$ and in such a way that the rescaled empirical measures converge weakly. The limiting object is the Gaussian beta corners process. As a byproduct of our approach, we prove a theorem on the asymptotics of multivariate Bessel functions.
Staphylococcus aureus from hospital-acquired pneumonia from an Italian nationwide survey: activity of ceftobiprole and other anti-staphylococcal agents, and molecular epidemiology of methicillin-resistant isolates
Authors: Antonelli Alberto , Giani Tommaso , Coppi Marco , Di Pilato Vincenzo , Arena Fabio , Colavecchio Olga Lorenza , Conte Viola , Santerre Henriksen Anne , Rossolini Gian Maria ,   MRSA-HAP Study Group, Principe Luigi , Pagani Elisabetta , Galanti Irene , Scarparo Claudio , Vaggelli Guendalina , Mencacci Antonella , Orecchioni Francesca , Fontana Carla , Labonia Maria , Bianco Gabriele , Sambri Vittorio , Campanile Floriana , Bielli Alessandra
Published: August 2019

Objectives

To determine the prevalence of Staphylococcus aureus from hospital-acquired pneumonia (HAP) in Italy and the susceptibility to ceftobiprole and comparators of MSSA and MRSA isolates. A secondary objective was to characterize the clonality and acquired resistance and virulence genes of MRSA.

Methods

Consecutive non-replicate isolates from HAP were collected from 13 laboratories distributed across Italy, from January to May 2016. Antimicrobial susceptibility testing was performed by broth microdilution, and results were interpreted according to the EUCAST breakpoints. All MRSA isolates were subjected to WGS using an Illumina platform. Clonality and resistance and virulence gene content were investigated with bioinformatics tools.

Results

Among 333 isolates from HAP, S. aureus was the third most common pathogen (18.6%). The proportion of MRSA was 40.3%. Susceptibility to ceftobiprole was 100% for MSSA and 95.5% for MRSA. Lower susceptibility rates of 78.4% and 94.6% in MSSA and 36.4% and 12.1% in MRSA isolates were observed for erythromycin and levofloxacin, respectively. The MRSA from HAP mostly belonged to clonal complex (CC) 22 (47.0%), CC5 (25.8%) and CC8 (15.2%), with a minority of other lineages (ST1, ST6, ST7, ST30, ST152 and ST398). Acquired resistance and virulence genes in most cases exhibited a clonal distribution. The three ceftobiprole-resistant isolates exhibited an MIC of 4 mg/L and belonged to ST228-MRSA-I of CC5.

Conclusions

S. aureus is an important cause of HAP in Italy. Ceftobiprole exhibited good in vitro activity against S. aureus isolated from HAP, including MRSA. A trend to replacement of ST228 with ST22 was noticed compared with previous studies.
Subgroup analysis of Japanese patients in a Phase 3 study of atezolizumab in advanced triple-negative breast cancer (IMpassion130)
Authors: Iwata Hiroji , Inoue Kenichi , Kaneko Koji , Ito Yoshinori , Tsugawa Koichiro , Hasegawa Ayumi , Nakagawa Shintaro , Kuratomi Hiroyasu , Tamura Kenji
Published: August 2019

Background

In the randomised Phase 3 IMpassion130 trial, atezolizumab combined with nab-paclitaxel (atezo + nab-P) in 902 patients with triple-negative breast cancer (TNBC) showed prolonged progression-free survival (PFS) in both the intention-to-treat (ITT) population and programmed death-ligand 1 (PD-L1)–positive subgroup compared with placebo plus nab-P (plac + nab-P). This study assessed the efficacy and safety of atezo + nab-P in the IMpassion130 Japanese subpopulation.

Methods

Eligible patients had unresectable locally advanced or metastatic TNBC previously untreated with chemotherapy for metastatic disease. Patients were randomised 1:1 to receive either atezo + nab-P or plac + nab-P. Co-primary endpoints were investigator-assessed PFS and overall survival (ITT population and PD-L1–positive subgroup). These were also assessed in the Japanese subpopulation.

Results

There were 65 Japanese patients (34 atezo + nab-P; 31 plac + nab-P). The PD-L1–positive subgroup included 25 patients (12 atezo + nab-P; 13 plac + nab-P). Median PFS was 7.4 months (atezo + nab-P) versus 4.6 months (plac + nab-P; hazard ratio [HR], 0.47; 95% CI, 0.25–0.90). In the PD-L1–positive subgroup, median PFS was 10.8 months (atezo + nab-P) versus 3.8 months (plac + nab-P; HR, 0.04; 95% CI, <0.01–0.35). Safety results in the Japanese subgroup were consistent with those in the overall population. The Japanese subgroup had a lower incidence of adverse events leading to treatment withdrawal than the overall population. More patients in the atezo + nab-P arm had neutrophil count decreases and stomatitis than patients in the plac + nab-P arm.

Conclusions

Atezo + nab-P efficacy in Japanese patients was consistent with the overall IMpassion130 population. No new safety signals were observed, and tolerability was consistent with that of the overall population.
One Parent, Three Parents: Judges and Ontario’s All Families Are Equal Act, 2016
Authors: Leckey Robert
Published: August 2019

This article studies judges’ early treatment of a new law on parentage and assisted reproduction. During decades of legislative inaction, Ontario’s judges adapted the law to evolving familial practices, at times boldly. A legislative overhaul in 2016, aiming to recognize all children’s families equally and inclusively, raised the question whether judges would adopt a more restrained role post-reform. In two early cases, where the new conditions for automatic recognition of a parental arrangement were unmet, the judges emphasized the intention of involved adults. Closely reading the legislation, the article presents bases for deciding the cases otherwise and for reducing their potential to incentivize litigation. Where the legislature has set out a broad range of accessible paths to parentage, even judges who champion family diversity may have reasons to stick to those paths. For legislative drafters, the difficulty of anticipating the variety of contemporary forms of family may counsel against purporting to limit judicial discretion. Ontario’s experience also favours including transitional measures in major reform.
Structural Causes of Stupor and Coma
Authors: Posner Jerome B. , Saper Clifford B. , Schiff Nicholas D. , Claassen Jan
Published: August 2019

Chapters 3 is the first of two chapters to discuss pathophysiology and specific causes of structural injury to the brain that result in defects of consciousness. It divides structural lesions causing coma into compressive and destructive lesions. It further indicates that lesions could be supratentorial, compressing, or destroying the diencephalon and upper midbrain, or infratentorial, directly affecting the pons and cerebellum. A physician attempting to determine the cause of coma resulting from a structural lesion must establish, first, the site of the lesion, determining whether the lesion is supratentorial or infratentorial, and, second, whether the lesion is causing its symptoms by compression or destruction or both.
Brain Death
Authors: Posner Jerome B. , Saper Clifford B. , Schiff Nicholas D. , Claassen Jan
Published: August 2019

This chapter considers the issue of brain death. The cornerstone of the diagnosis of brain death is a careful and sure clinical neurologic examination. In addition, a thorough evaluation of clinical history, neuroradiologic studies, and laboratory tests needs to be carried out to rule out potential confounding variables. The diagnosis of brain death rests on two major and indispensable tenets. The first is that the cause of brain nonfunction must be inherently irreversible. The second is that the vital structures of the brain necessary to maintain consciousness and independent vegetative survival are damaged beyond all possible recovery. It looks at how to determine that brain death has occurred. It goes on to outline the clinical signs for brain death. The chapter also looks at the differences between brain death and prolonged coma. Finally, it explains the management of the brain dead patient.
Deprescribing in Psychiatry
Authors: Gupta Swapnil , Miller Rebecca , Cahill John D.
Published: August 2019

This chapter introduces the concept of deprescribing in psychiatry, along with the rationale for its importance. Emerging from geriatric medicine, the reduction or stopping of medications in psychiatry goes beyond deciding which, when, and how to decrease a medication to also encompass psychological and social considerations. Settings for deprescribing, along with the involved ethics, are also touched upon. Deprescribing is placed in the context of recovery-oriented care as a broad-ranging intervention encompassing the complexity of decision-making and the doctor–patient relationship. The chapter sets the foundation for the rest of the book, laying out the rationale, structure, and goals of the text.
Deprescribing Antidepressant Medications in Major Depressive Disorder
Authors: Gupta Swapnil , Miller Rebecca , Cahill John D.
Published: August 2019

This chapter describes the specific considerations for decision-making surrounding the deprescribing of antidepressants. The chapter discusses how to arrive at a risk–benefit ratio that considers the pros and cons of deprescribing antidepressants, common clinical presentations of withdrawal symptoms and their management, and the possible steps that may be taken to prevent a recurrence of a depressive episode, including the use of nonpharmacological interventions. Antidepressants are among the most frequently prescribed psychotropic medications and are prescribed in an ongoing way that may be contrary to current guidelines. Commonly encountered decision points are discussed and illustrated with relevant case examples provided at the end of the chapter.
Concluding Thoughts and Future Directions
Authors: Gupta Swapnil , Miller Rebecca , Cahill John D.
Published: August 2019

This chapter summarizes and emphasizes the key elements of deprescribing, including developing and maintaining a strong therapeutic alliance, open communication, shared decision making, and a tolerance of uncertainty. The chapter also discusses future directions for research, such as receptor neuroimaging to investigate psychotropic withdrawal syndromes and the consolidation of patient narratives of medication discontinuation. Recommendations for integrating deprescribing into clinical practice, such as the development of tools and algorithms, reminders in electronic health records, and the setting up of “deprescribing clinics” or deprescribing consultation services are also discussed. Finally, the authors provide suggestions for the training of medical students, psychiatry residents, and other prescribers in the process of deprescribing.
Respiratory therapy techniques
Authors: Waldmann Carl , Rhodes Andrew , Soni Neil , Handy Jonathan
Published: August 2019

This chapter discusses respiratory therapy techniques and includes discussion on oxygen therapy, discussion of intermittent positive pressure ventilation and description of ventilators, modes of ventilation, adjusting the ventilator, barotrauma, and weaning techniques. The chapter also discusses high-frequency ventilation, airway pressure release ventilation, as well as positive end-respiratory pressure, continuous positive airway pressure ventilation, recruitment manoeuvres, prone position ventilation, non-invasive positive pressure ventilation, extracorporeal membrane oxygenation, cricothyroidotomy, tracheostomy, aftercare of the patient with a tracheostomy, chest drain insertion, pleural aspiration, flexible bronchoscopy, chest physiotherapy, humidification, and heart–lung interactions.
Respiratory monitoring
Authors: Waldmann Carl , Rhodes Andrew , Soni Neil , Handy Jonathan
Published: August 2019

This chapter discusses respiratory monitoring and includes discussion on pulmonary function tests in critical illness (including discussion on monitoring mechanical ventilation, monitoring the weaning process, and a summary), end-tidal CO2 monitoring (capnography, capnometry, measurement techniques, volumetric capnography, clinical applications of capnography, the shape of the volumetric capnogram), pulse oximetry (clinical applications, limitations, physical risks, recent advances), and monitoring transpulmonary pressure (physiological background, oesophageal pressure as a surrogate of pleural pressure, oesophageal pressure measurement, elastance-derived measurement, direct measurement, clinical use of oesophageal pressure, oesophageal pressure to guide therapy in acute respiratory distress syndrome, transpulmonary pressure to study the effects of spontaneous breathing during assisted ventilation, patient–ventilator asynchrony).
Fluids
Authors: Waldmann Carl , Rhodes Andrew , Soni Neil , Handy Jonathan
Published: August 2019

Fluid therapy is probably one of the most common interventions in intensive care medicine, after administration of oxygen. Fluids are drugs. The choice of the type of fluid, the dose, indications, and side-effects are crucially important. This chapter discusses fluids and includes discussion on crystalloids, colloids, sodium bicarbonate (including discussion on common indications for sodium bicarbonate administration, potential and theoretical dangers of sodium bicarbonate administration, sodium bicarbonate preparations, and sodium bicarbonate in dialysate fluids), and blood (describing laboratory testing for coagulopathy and blood components commonly available in the UK).
Haematological disorders
Authors: Waldmann Carl , Rhodes Andrew , Soni Neil , Handy Jonathan
Published: August 2019

This chapter discusses haematological disorders and includes discussion on bleeding disorders (including acquired bleeding disorders and inherited bleeding disorders), anaemia in critical care (including discussion on pathogenesis, consequences of anaemia, approach to the investigation of anaemia, classification of anaemia, measures to minimize blood loss in the intensive care unit [ICU], and erythropoietin). It also covers sickle cell anaemia (transfusion in sickle cell anaemia, including hyperhaemolysis, acute chest syndrome, and pulmonary hypertension in sickle cell disease), haemolysis (haemolytic conditions particularly relevant to critical care), disseminated intravascular coagulation, neutropenic sepsis (including persistent fever or inadequate clinical response, fungal infections, empirical antifungal therapy, viral infections, granulocyte-colony stimulating factor, and granulocytes for neutropenia). Finally, the chapter discusses haematological malignancies in the ICU (neutropenia and neutropenic sepsis, tumour lysis syndrome, hyperviscosity syndromes, hyperleukocytosis, haemorrhagic complications, haematopoietic stem cell transplant, graft versus host disease, and corticosteroids) and coagulation monitoring.
Death and dying
Authors: Waldmann Carl , Rhodes Andrew , Soni Neil , Handy Jonathan
Published: August 2019

This chapter discusses death and dying, and includes discussion on confirming death using neurological criteria (brainstem death), withdrawing and withholding treatment, organ donation after brain death (DBD), and organ donation after circulatory determination of death (DCD). Death is common in the intensive care unit (ICU) and it is important to identify patients whose condition meets the criteria for brainstem death testing as well as patients where continued treatment is not considered to be in their overall best interests. Confirming death using neurological criteria allows the relatives to be presented with the certainty of a diagnosis of death whether organ donation is possible or not. Decisions to withraw treatment are common in the ICU and are associated with approximately 50% of all deaths in the ICU. The decision is made by the multidisciplinary team in consultation with the patient’s relatives and taking into account the patient’s values and preferences. In both situations the possibility of organ donation should be considered and explored, and, when it is a possibility, it should be routinely offered to the relatives as an end-of-life care option.
Thoracostomy Tubes and Mediastinal Drains
Authors: Ternes Tyler H.
Published: August 2019

The Thoracostomy and Mediastinal Drains chapter addresses a group of medical devices used to drain intrathoracic collections of fluid or air. A chest (thoracostomy) tube is a broad term used for a variety of hollow catheters used for pleural drainage. Occasionally, the drain is placed in the mediastinum, and in these instances the term mediastinal drain is preferred. Thoracostomy tubes are typically placed in the pleural space for treatment of pneumothorax or pleural fluid. Tube sizes range from 6F to 40F, depending on the clinical scenario. Small catheters are often placed with Seldinger technique, whereas larger tubes are usually placed with blunt dissection. The tube is typically directed towards the apex in the setting of pneumothorax and towards the posterior base for treatment of pleural fluid collections. When interpreting radiographs following chest tube placement, the radiologist should ensure that the tube and sideport are positioned within the pleural space or the desired anatomic location. It is also imperative to exclude intraparenchymal or intrafissural tube placement and tube kinking.
Atelectasis, Pneumonia, and Aspiration
Authors: Little Brent P. , Henry Travis S.
Published: August 2019

Atelectasis and pneumonia are commonly encountered in the inpatient setting, particularly in the intensive care units (ICUs) where patients are intubated and seriously ill, and often subject to variety of co-morbidities. The two entities are often confused as they have overlapping imaging appearances and may coexist. Atelectasis represents incomplete expansion of the lung parenchyma, with associated loss of volume –whereas pneumonia is an infection of the parenchyma and not typically associated with volume loss. Recognition of the characteristic imaging findings of these diseases allows a confident diagnosis to be made in many cases, and a helpful differential diagnosis to be offered in others. Clues to lobar or total lung atelectasis include volume loss, mediastinal shift, fissural and hilar displacement, and a homogeneous opacity with straight borders obscuring adjacent structures (e.g., hemidiaphragm or heart border). Pneumonia may manifest with many different patterns – often nonspecific for a given organism; however, the pattern may help to narrow the differential diagnostic considerations. Aspiration most commonly manifests with dependent centrilobular nodules and/or consolidation. Chest radiographs may change rapidly in patients affected by aspiration or the more severe forms of atelectasis (i.e. lobar or whole lung) and the patient’s symptoms typically change just as rapidly, frequently developing hypoxemia and respiratory distress. While atelectasis in the inpatient setting is a common finding, outpatients who present with lobar atelectasis should be suspected to have an obstructing tumor until proven otherwise (except for patients with CF or asthma).
Chest Trauma: Nonvascular Injuries
Authors: Raptis Constantine
Published: August 2019

In the setting of trauma, thoracic injuries are third in frequency after injuries to the head and extremities. While the greatest source of mortality in the setting of thoracic trauma is vascular injury, nonvascular injuries are much more common and can result in substantial morbidity and mortality, complicating overall case management. This section will focus on non vascular injuries that may be seen in the setting of trauma involving the lungs, diaphragm, mediastinum, thoracic skeleton, heart and pleura. Findings in both blunt and penetrating trauma will be highlighted.
Pulmonary Infections
Authors: Martínez-Jiménez Santiago
Published: August 2019

Pneumonia can be classified as: community-acquired pneumonia (CAP), hospital-acquired pneumonia (HAP), ventilator-associated pneumonia (VAP), healthcare-associated pneumonia (HCAP), and pneumonia in immunosuppressed patients. Although the above are similar pathologically, they are very different from a clinical perspective. Chest radiography is often performed to support the diagnosis and to determine the extent of involvement prior to the onset of therapy. Radiography should not be performed in the short term in patients who are improving clinically as it can lead to the misdiagnosis of treatment failure. Chest radiography in patients treated for pneumonia should only be obtained before 4-6 weeks after the onset of therapy if there is a failure of clinical response or if complications of pneumonia are clinically suspected. The majority of pneumonias will resolve after 6 weeks of appropriate antibiotic therapy.
Introduction to the Immunocompromised Patient
Authors: Martínez-Jiménez Santiago
Published: August 2019

Evaluation of neoplastic and infectious diseases in immunocompromised patients and their complications is difficult. Knowledge of the type of immunodeficiency remains the best tool for the formulation of an appropriate and timely diagnosis. Several strategies are helpful when interpreting imaging studies of patient with potential immune compromise. If the patient is HIV (+), correlation with the CD4 lymphocyte count is imperative as different diseases occur at the various CD4 count levels. When a patient’s HIV status is unknown and imaging findings suggest an HIV-related disease, the clinician should be encouraged to actively search for pertinent risk factors, and HIV testing should be offered. Likewise, correlation with the medical chart is also critical in the assessment of all other immunocompromised patients: congenital immunosupression, diabetes, transplantation, preexisting lung disease (e.g. asthma and COPD). The following chapters emphasize imaging findings as correlated with clinical and laboratory abnormalities in a variety of common immunodeficiencies.
Lung Cancer: Lymphadenopathy and Extrapulmonary Involvement
Authors: Benson Ryo E. C.
Published: August 2019

Lymphadenopathy and extrapulmonary involvement may be presenting manifestations of advanced lung cancer. Central tumors such as squamous cell carcinomas and small cell carcinomas often exhibit ipsilateral hilar and mediastinal lymphadenopathy. Metastatic lymphadenopathy may exhibit subtle findings on radiography but is readily identified on CT, MRI and PET-CT. Lymphadenopathy in the setting of lung cancer portends a poorer prognosis compared with lung cancer without lymph node involvement. The differential diagnosis includes reactive lymphadenopathy from infection, granulomatous lymphadenopathy from sarcoidosis and malignant lymphadenopathy from metastatic disease and lymphoma. Advanced lung cancer may exhibit extrapulmonary involvement as the first manifestation of disease. Central lung cancers may directly invade the mediastinum and its organs and vessels. Peripheral lung cancers may invade the adjacent chest wall structures. Pleural and pericardial involvement may also occur and often manifests with effusion. Metastases to upper abdominal organs may be identified on chest CT. PET-CT allows identification of distant metastases.
Bronchial Carcinoids and Bronchial Gland Carcinomas
Authors: Benson Ryo E. C.
Published: August 2019

Bronchial carcinoid and bronchial gland carcinomas are rare airway-related thoracic malignancies. Carcinoid is a neuroendocrine neoplasm and comprises 1-2 % of primary lung cancers. Affected patients are younger than those with lung cancer, and may present with signs and symptoms of airway obstruction including cough, hemoptysis, wheezing, and recurrent pulmonary infection. Carcinoid typically manifests as a central nodule or mass and may cause post obstructive atelectasis or pneumonia. On imaging these lesions are usually well marginated pulmonary nodules or masses and may be completely endobronchial, partially endobronchial or may abut an airway. Typical carcinoid often exhibits an indolent behavior and carries a good prognosis with complete surgical excision. Atypical carcinoid is similar to typical carcinoid on imaging but has a more aggressive behavior and may be associated with metastatic intrathoracic lymphadenopathy. Bronchial gland carcinomas include adenoid cystic carcinoma (ACC) and mucoepidermoid carcinoma (MEC). ACC is the second most common primary tracheal malignancy and manifests as an endoluminal tracheal nodule or as circumferential tracheal narrowing. MEC typically affects segmental bronchi and may be indistinguishable from carcinoid on imaging. Although these lesions may exhibit an indolent course, they are locally invasive malignancies, and affected patients have a variable prognosis.
Bronchiectasis
Authors: Milliron Bethany , Little Brent P. , Henry Travis S.
Published: August 2019

Bronchiectasis represents irreversible bronchial dilatation. It can be focal or diffuse, and usually results from chronic infection, proximal airway obstruction, or a congenital bronchial abnormality. Traction bronchiectasis refers to irregular bronchial dilatation in the setting of surrounding pulmonary fibrosis. Patients with cystic fibrosis have a progressively worsening clinical course, with recurrent pneumonias and chronic airway colonization. Even with lung transplantation and modern antibiotic therapies, average life expectancy of cystic fibrosis patients remains limited to young adulthood. Non-cystic fibrosis related bronchiectasis can cause chronic cough and recurrent lung infection. Pulmonary function testing often reveals evidence of obstruction. Treatment of patients with mild to moderate bronchiectasis involves supportive care with bronchodilators, antibiotics, and other medical therapy. Surgical resection is uncommon, and usually reserved for cases of significant bronchiectasis limited to a single region of the lungs (such as a particular lobe or segment).
Amyloidosis
Authors: Martínez Felipe
Published: August 2019

Amyloidosis is a group of disorders characterized by over expression and extracellular deposition of amyloid with resultant organ dysfunction. The disease produces significant morbidity and mortality and its prevalence is increasing. Amyloidosis becomes clinically significant when organ function is impaired either due to loss of normal cell structure or mass effect from accumulating amyloid. The current classification of amyloidosis is based on the different types of fibrillar proteins which define organ involvement and disease manifestations. The heart is the most commonly involved organ in the chest, and progressive systolic dysfunction in a patient with ventricular hypertrophy is common. Pulmonary involvement is relatively rare and is more common in the localized form of the disease. There are systemic and localized forms of the disease, with systemic disease being more common. High resolution computed tomography (HRCT) is the modality of choice to evaluate patients with suspected tracheopulmonary amyloidosis. Cardiac MRI is the imaging modality of choice for evaluating patients with suspected amyloid cardiomyopathy.
Sarcoidosis
Authors: Bueno Juliana
Published: August 2019

Sarcoidosis is a systemic disease of unknown etiology, characterized by noncaseating epithelioid cell granulomas. Patients with sarcoidosis are frequently asymptomatic and may be diagnosed incidentally because of an abnormal imaging study. Sarcoidosis is a diagnosis of exclusion that warrants pathological confirmation in all cases. The distribution of granulomas in the lungs is characteristic and correlates with imaging findings; non-necrotizing granulomas classically exhibit a perilymphatic distribution. On chest radiography, the presence of bilateral hilar and right paratracheal lymphadenopathy, particularly in a young asymptomatic patient, should raise the possibility of sarcoidosis. On CT, a perilymphatic distribution (peribronchovascular, subpleural, septal) of abnormalities in the appropriate clinical context is highly specific for sarcoidosis.