bluuebunny/crossref_metadata_2025 huggingface dataset:
Variants of the guanine riboswitch class exhibit altered ligand specificities for xanthine, guanine, or 2′-deoxyguanosine
Authors: Hamal Dhakal Siddhartha , Panchapakesan Shanker S. S. , Slattery Paul , Roth Adam , Breaker Ronald R.
Published: May 2022

Significance

Numerous purines and their metabolic derivatives must be monitored for proper control of relevant metabolic pathways. In certain bacteria, some metabolic steps related to purine production or degradation are catalyzed by proteins whose production is under direct regulatory control by purine-sensing riboswitches. Four riboswitch classes selective for guanine, adenine, and 2′-deoxyguanosine (two classes) reported previously exploit a common architecture involving a three-stem junction. Here, we describe three additional classes based on this same scaffold that sense xanthine, guanine, or 2′-deoxyguanosine. Thus, some riboswitches can diversify their ligand-sensing and gene-control functions without the need to evolve entirely novel structures, which highlights a capability that could have also been exploited by ancient forms of life during the RNA World.
Orc6 is a component of the replication fork and enables efficient mismatch repair
Authors: Lin Yo-Chuen , Liu Dazhen , Chakraborty Arindam , Kadyrova Lyudmila Y. , Song You Jin , Hao Qinyu , Mitra Jaba , Hsu Rosaline Y. C. , Arif Mariam K. , Adusumilli Sneha , Liao Ting-Wei , Ha Taekjip , Kadyrov Farid A. , Prasanth Kannanganattu V. , Prasanth Supriya G.
Published: May 2022

Significance

Origin recognition complex (ORC) is required for the initiation of DNA replication. Unlike other ORC components, the role of human Orc6 in replication remains to be resolved. We identified an unexpected role for hOrc6, which is to promote S-phase progression after prereplication complex assembly and DNA damage response. Orc6 localizes at the replication fork, is an accessory factor of the mismatch repair complex, and plays a fundamental role in genome surveillance during S phase.
Discovery of potent BET bromodomain 1 stereoselective inhibitors using DNA-encoded chemical library selections
Authors: Modukuri Ram K. , Yu Zhifeng , Tan Zhi , Ta Hai Minh , Ucisik Melek Nihan , Jin Zhuang , Anglin Justin L. , Sharma Kiran L. , Nyshadham Pranavanand , Li Feng , Riehle Kevin , Faver John C. , Duong Kevin , Nagarajan Sureshbabu , Simmons Nicholas , Palmer Stephen S. , Teng Mingxing , Young Damian W. , Yi Joanna S. , Kim Choel , Matzuk Martin M.
Published: May 2022

Significance

BET bromodomain inhibition is therapeutic in multiple diseases; however, pan-BET inhibitors have induced significant myelosuppression and gastrointestinal toxicity, perhaps due to inhibition of both tandem bromodomains (BD) of all BET family members. However, selective inhibition of just the first BD (BD1) phenocopies pan-BET inhibitor activity in preclinical models of cancer, other diseases, and, for BRDT, in the testes for a contraceptive effect. Here, we leveraged our multibillion-molecule collection of DNA-encoded chemical libraries (DECLs) to identify BET BD1-selective inhibitors of specific chirality with high potency, stability, and good cellular activity. Our findings highlight the robustness and efficiency of the DECL platform to identify specific, potent protein binders that have promise as potential anticancer and anti-inflammatory agents and as male contraceptives.
Critical assessment 41: The strength of undeformed pearlite
Authors: Bhadeshia H. K. D. H. , Chintha A. R.
Published: May 2022

The dependence of the proof strength of undeformed pearlite on its interlamellar spacing is examined in detail, with a view to resolving the plethora of relationships that exist in the research literature. It is found by the analysis of published data that the Hall–Petch equation is best suited to explain the strength, not simply on the basis of empirical fit, but even when examined in a Bayesian framework. Furthermore, it is the only relationship that gives a physically meaningful value to the friction stress. The reasons why previous analyses have failed to resolve this issue are examined and explained. It is discovered that ferrite in interstitial-free iron is, at an identical length scale, stronger in yield than the ferrite within pearlite.
Contamination suppression of coupling glass during vacuum laser welding
Authors: Lee Yongki , Cheon Jason , Min Byung-Kwon , Kim Cheolhee
Published: May 2022

In vacuum laser welding, a laser beam is irradiated into a chamber through a coupling glass exposed to contamination. A conical protective system for the coupling glass is suggested, and contamination is analysed via simulation and experiments based on the conical component height and the gas flow rate. Stable descending flow is a key to suppressing the contamination, which affects the particle ascending velocity, horizontal deflection of particles and number of residual particles. The laser transmission area can be protected using a gas flow rate of 1.0 L min−1 or a cone height of 90 mm for the conical component. The conical protective system demonstrates excellent contamination suppression capability. The simulation-based approach can provide an effective design for the protective system.
‘Musical effort’ and ‘musical pleasantness’
Authors: Inguscio Bianca Maria Serena , Mancini Patrizia , Greco Antonio , Nicastri Maria , Giallini Ilaria , Leone Carlo Antonio , Grassia Rosa , Di Nardo Walter , Di Cesare Tiziana , Rossi Federica , Canale Andrea , Albera Andrea , Giorgi Andrea , Malerba Paolo , Babiloni Fabio , Cartocci Giulia
Published: May 2022

Objective

This pilot case-control study is aimed to estimate ‘musical effort’ and ‘musical pleasantness’ in adults normal hearing (NH) and Unilateral Cochlear Implant (UCI) users via neurophysiological indices and a cognitive-behavioural approach.

Methods

7 NH and 7 UCI subjects underwent electroencephalographic (EEG) recording with two EEG indices, Approach Withdrawal (AW) and Workload (WI), and behavioural tests conducted during a forced-choice musical emotion recognition task performed in quiet and noise in two emotional conditions.

Results

Musical effort in terms of WI did not vary between conditions and groups. Inversely, for AW, statistically significant differences in noisy conditions were observed between groups, indicating a difficulty for the patients in discriminating the musical pleasantness in noise. However, self-reported data suggest the ability of UCI to cognitively evaluate the stimulus in terms of both auditory difficulty and pleasantness.

Conclusion

Findings suggest the possible relevance of the Cochlear Implant in supporting the patients’ effort in listening to music in noise, allowing a pleasant enjoyment in the quiet condition. Overall, this study appears worthy of interest and paves the way for further investigation by providing data on the neurophysiological perception of music.
Bayesian statistical inference using a regression in electrical impedance tomography
Authors: Lee Lia Jisoo , Graff Marie
Published: May 2022

In this paper, we present the formulation of Bayesian statistical inference with respect to a posterior distribution using a regression model. So the unknown parameter is set as the dependent variable and the data measurement is set as the independent variable of the regression model. The regression model is built using joint samples of the unknown parameter and the data measurements drawn from the related likelihood function and prior distribution. The regression fits an operator constructed from the so-called optimal approximation method. Naturally, the regression model defines an approximated posterior distribution and, in this regards, we call it the posterior approximated regression model (PARM). The feasibility of making Bayesian statistical inference using PARM is tested numerically. We consider the electrical impedance tomography Bayesian inverse problem on a two dimensional domain with benchmark examples. Results with varying levels of practicality and intuitive discussions are presented.
Enhanced nonlinear optical properties of reduced graphene oxide modified by Mn-doped semiconductor CdS nanoparticles as photonic materials
Authors: Yuan Xue , Wang Fangfang , Liang Yuning , Zhu Baohua , Gu Yuzong
Published: May 2022

Graphene has broad prospects for application in photonic devices. However, its zero-band gap limits its nonlinear optical (NLO) properties, and thus, its application. In this study, we synthesized reduced graphene oxide modified by Mn-doped semiconductor CdS nanoparticles (RGO/CdS:Mn) via a solvothermal method to study the development of NLO properties of graphene. The structures, morphologies and basic physical properties of RGO, CdS, RGO/CdS, and RGO/CdS:Mn were characterized. The third-order optical nonlinearities were tested by the Z-scan technique using a mode-locked Nd:YAG laser operating at 532 nm with a 30 ps pulse width. The results showed that the nonlinear susceptibility and saturation absorption of RGO/CdS:Mn were 15.3 and 26 times higher than those of RGO, respectively. The mechanism of the enhancement was analyzed based on the charge transfer between and within the components, and Mn doping produced trapping effect. The significantly improved optical nonlinearity of RGO/CdS:Mn lays a foundation for its applications in photonic devices.
Calculation of charge density wave phase diagram by interacting eigenmodes method
Authors: Park Changwon
Published: May 2022

Patterns and periods of charge density waves (CDWs) in transition metal dichalcogenides exhibit complex phase diagrams that depend on pressure, temperature, metal intercalation, or chalcogen alloying. The phase diagrams have been understood in the context of Landau free energy model which explains the lock-in behavior in the commensurate–incommensurate phase transition and rotational symmetry breaking (stripe phase) in CDW phase. Here, we present that our interatomic potential energy function has not only reproduced the above behaviors in the temperature-dependent phase diagram of monolayer H-TaSe2 without adjustable parameters, but also predict a new commensurate–commensurate phase transition. For the calculation, eigenmodes of the lattice potential were used for variables in the interatomic potential and CDWs are obtained as ground states of interacting eigenmodes. Unlike Landau model, the parameters in our potential energy function are directly calculated from first-principles. Our work explicitly shows how the aforementioned behaviors in CDW phase transition are related with the lattice anharmonicity.
Systematic synthesis of different-sized AgInS2/GaS
x
nanocrystals for emitting the strong and narrow excitonic luminescence
Authors: Thi Thu Huong Tran , Loan Nguyen Thu , Ung Thi Dieu Thuy , Tung Nguyen Thanh , Han HyukSu , Liem Nguyen Quang
Published: May 2022

This paper presents for the first time the systematic synthesis of AgInS2 (AIS) nanocrystals (NCs) with different sizes of 2.6–6.8 nm just by controlling only the reaction temperature. The synthesis of AIS core NCs was carried out in 2 steps: (i) synthesis of Ag2S NCs and then (ii) partial exchange of Ag+ with In3+ in the template Ag2S NCs. For step (i), Ag2S NCs of different sizes were synthesized by reaction of the Ag and S precursors at different temperatures of 30 °C to 130 °C, for the same reaction time of 30 min. For step (ii), AIS NCs were created by the exchange of Ag+ with In3+ at 120 °C for 60 min. Finally, GaS
x
was shelled on AIS core NCs to produce the AgInS2/GaS
x
core/shell structures. The synthesized AIS/GaS
x
NCs demonstrate the clear excitonic absorptions and strong, narrow excitonic luminescence peaking at 530–606 nm depending on the size of AIS core NCs.
Generation of mode-locked thulium/holmium-doped fiber laser assisted by bismuthene/side polished fiber as saturable absorber
Authors: Ahmad Harith , Azali Nur Atikah , Bayang Leonard , Yusoff Norazriena
Published: May 2022

An all-fiber passively mode-locked laser is demonstrated near the 2.0 µm wavelength region utilizing thulium/holmium-doped fiber as the gain medium and bismuthene/side-polished fiber (SPF) as saturable absorber (SA). The effect of bismuthene concentration on the performance of the generated mode-locked lasers has also been investigated. In this work, bismuthene was obtained by the exfoliation of bismuth under the ultrasonication technique. Two different concentrations of bismuthene (10 and 20 mg ml−1) were prepared to coat the SPF and be further used as SA. Based on the experimental results, the SA with 10 mg ml−1 concentration of bismuthene induced the most stable mode-locked pulses with good performance. The 10 mg ml−1 bismuthene/SPF SA produced pulses at the center wavelength of 1932.69 nm with the 3 dB bandwidth of 2.59 nm and a signal-to-noise ratio value of 63 dB. The generated pulsed laser exhibits pulse energy of 421.3 pJ, peak power of 261.4 W, and average output power of 4.613 mW. Overall, this work reveals the potential of bismuthene/SPF as an SA for generating mode-locked laser pulses, which is useful in photonics applications.
Multiparticle natSr(γ,

) reactions induced with bremsstrahlung end-point energies of 55, 60, and 65 MeV *
Authors: Do Nguyen Van , Luan Nguyen Thanh , Xuan Nguyen Thi , Thanh Kim Tien , Hien Nguyen Thi , Kim Guinyun
Published: May 2022

This study measured the yields of the radionuclides 82Sr, 83(m+g)Sr, 85mSr, 85gSr, 87mSr, 81(g+0.976m)Rb,82mRb,83gRb,84(m+g)Rb, and 86(m+g)Rb produced in natSr(γ, xnyp) multiparticle reactions with bremsstrahlung end-point energies of 55, 60, and 65 MeV. The bremsstrahlung radiation was generated using the 100-MeV electron linear accelerator at the Pohang Accelerator Laboratory, Korea, and the reaction yields were derived from the induced activitiesmeasured using off-line γ-ray spectrometry. To obtain accurate experimental results, we performed the necessary γ-rayinterference corrections. The experimental results were compared with the theoretical predictions obtained usingthe TALYS-1.95 statistical nuclear model code. The calculations were performed using six different level-density models to ascertain which model best fitted the experimental results. The dependence of the reaction yield on the incident bremsstrahlung energy and on the number of nucleons emitted by the photonuclear reactions was also investigated.
Bio-Environmental preparation of Selenium Nanoparticle using Klebsiella Pneumonia and their Biomedical Activity
Authors: Hadi Soroor Mohammed , Aldujaili Nawfal Hussein
Published: May 2022

The aim of this study was to study the biomedical activity (biofilm by fluoresence microscope) and Characterization of Selenium NPs synthesized by klebsiella pneumonia. Different types of bacterial strains (S1-S35) aureus, were screened for biosynthesis of selenium NPs. Isolate S6 was selected as efficient isolate based on color change and antibacterial activity against the pathogenic bacteria, and it was diagnosed as klebsiella pneumonia depending on the morphology, microscopic examination and VITEK2 compact system. Characterization of bio-selenium NPs was performed using: UV-visible spectroscopy was used to characterize the synthesis of selenium NPs by Klebsiella pneumonia, with an absorption peak at 280 nm. The size and structure of the bioavailable selenium NPs were measured using an XRD occurring at 20°-26°. AFM analysis showed that the mean diameter of the bio-selenium NPs was 47. 18. Antibacterial activities have been studied for bio-selenium against pathogenic bacteria (B. cepacia, S. aureus, A. baumanni and E. coli).Biogenic Selenium expressed high significant antibiofilm activity with increasing concentration of Selenium NPs. DPPH reducing activity of nanoparticles which increased with increase concentration of biogenic Selenium NPs.
Synthesis and Characterization of TiO2 – Ag-Cellulose Nanocomposite and evaluation of photo catalytic degradation efficiency for Congo Red
Authors: Thamer Nidal Hassoun , Hatem Oraas Adnan
Published: May 2022

Photocatalytic degradation of toxic organic contaminants in aquatic environments is a cost-effective, efficient, and long-term solution for environmental restoration. The capacity to fine-tune the structures and compositions of photocatalysts is vital for optimizing photocatalytic decontamination processes, as is a deep understanding of the mechanisms that govern photocatalytic interfacial molecular changes. We created a ternary TiO2/Ag/cellulose nanocomposite particle by hydrothermal process that acts as a photocatalyst for the photodegradation of congo red CR dye into mineralized small molecules

The morphology, size and crystalline structure of the TiO2 – Ag – Cellulose nanocomposite were investigated by scaning electron microscopy SEM, transmission electron microscopy (TEM) and X-ray diffraction XRD respectively. Surface functional groups were analyzed using FTIR analysis. Specific surface area of the composite was characterized by BET-BJH analysis and the elemental composition of the composite was study using EDX analysis. Interestingly, the prepared TiO2 – Ag – Cellulose nanocomposites showed high catalytic degradation activity for CR dye. The photocatalytic degradation of the azo dye was monitored spectrophotometrically, a high degradation efficiency 81,76 % under visible radiation were obtained for composite after 120 min of reaction compared to 30% for pure TiO2.
Electrical and aerodynamic characteristics of sliding discharge based on a microsecond pulsed plasma supply
Authors: ZHAO Taifei , ZHANG Qian , ZHENG Borui , LIU Yuanpeng , JIN Yuanzhong , CHEN Quanlong
Published: May 2022

Plasma flow control technology has broad prospects for application. Compared with conventional dielectric barrier discharge plasma actuators (DBD-PA), the sliding discharge plasma actuator (SD-PA) has the advantages of a large discharge area and a deflectable induced jet. To achieve the basic performance requirements of light weight, low cost, and high reliability required for UAV (Unmanned Aerial Vehicle) plasma flight experiments, this work designed a microsecond pulse plasma supply that can be used for sliding discharge plasma actuators. In this study, the topology of the primary circuit of the microsecond pulse supply is determined, the waveform of the output terminal of the microsecond pulse plasma supply is detected using the Simulink simulation platform, and the design of the actuation voltage, the pulse frequency modulation function and the construction of the hardware circuit are achieved. Using electrical diagnosis and flow field analysis, the actuation characteristics and flow characteristics of sliding discharge plasma under microsecond pulse actuation are studied, the optimal electrical actuation parameters and flow field characteristics are described.
Guidelines for Domestic Violence and Child Custody Litigation
Authors: Pisarra David
Published: May 2022

A growing body of social science literature has shown that children who witness abuse between their parents, known as domestic violence or intimate partner violence, are at risk for developing severe behavioral and psychological problems. Accusations of domestic violence are now taken seriously within the family court system. It is expected that the custody rights of offending parents will be curtailed when such accusations have merit. However, determining the merits of a particular set of accusations is difficult because of vague and contradictory legal statutes, poorly informed evaluators and mediators whose decisions too often reflect bias or prevailing political interests rather than empirical research findings, and the adversarial process in which these cases are litigated. In this chapter, a practicing family law attorney addresses these issues and suggests, from his experience, how custody determinations can be improved so that the best interests of children are indeed served.
Risk-Needs-Responsivity-Informed Approaches to Batterer Intervention Treatment
Authors: Roberts Amie
Published: May 2022

This chapter describes the standard components of batterer intervention programs, alternatives to the most common approaches, and which treatment modalities to avoid for offenders of intimate partner violence. The chapter focuses on treatment standards from Washington State, including rules for behavioral assessments, treatment plans, a standardized cognitive-behavioral treatment curriculum, and core competencies for treatment completion. The risk-need-responsivity model is explained in depth, including how it is used in the assessment process, treatment planning, and treatment delivery in the programs of Washington State.
Therapy
Authors: Craig Errol
Published: May 2022

Since the days of the ancient Greek physician Galen, physicians approached The Itch as a disease requiring systemic or internal treatment. Topical treatments were frowned upon as they were thought to drive the malady back into the body preventing its full cure. Thus standard therapies would often include bloodletting, purges, or a variety of ingestible concoctions of dubious repute. Irrespective of the approach used, many early treatments for scabies likely carried some degree of toxicity. In some instances they could confer adverse effects far worse than The Itch itself. Currently used topical medications such as permethrin, a chrysanthemum derivative, have an excellent cure rate. However, they must be used properly to be effective. Reasons for treatment failure are discussed. Scabies cases can be classified as confirmed, clinical, or suspected according to a set of consensus criteria. This chapter describes this algorithm, as well as the variety of treatments for scabies, including their origin and development. Oral treatment with ivermectin, a relatively new modality, is additionally discussed.
The Neurological Examination, the Epilepsies, an International Platform, and Dissolution, 1880–1884
Authors: Greenblatt Samuel H.
Published: May 2022

In later Victorian society one of the most dreaded neurological conditions was syphilis, especially the ‘lightening’ pains of its tertiary stage. The modern neurological examination was just then taking shape, partly as an effort to find diagnostic tools to distinguish syphilis from other conditions. In 1875 Erb and Westphal separately introduced the phenomena of deep tendon reflexes, which were brought to Jackson’s attention by his friend Thomas Buzzard, and by Grainger Stewart, starting with the knee jerk. In the early 1880s two other major themes for Jackson were: (1) integration of the pathophysiologies of ‘genuine’ epilepsy and ‘epileptiform’ seizures; and (2) further application of dissolution to the analysis of epileptic states, especially postictal events. At the International Medical Congress in London, August 1881, Jackson restricted his subject to epileptiform convulsions. In his Croonian Lectures at the Royal College of Physicians in 1884 he spoke more broadly ‘On the evolution and dissolution of the nervous system’. There he attributed focal epileptiform seizures to his middle cerebral level and genuine epileptic seizures to his highest level.
Conclusion
Authors: Greenblatt Samuel H.
Published: May 2022

This chapter will attempt to define the most important elements of Jackson’s neurological paradigm as they survived into the mid-twentieth century, versus those that did not become part of his legacy. His hierarchical/evolutionary outlook, derived from Spencer, is well recognized, as is its corollary, dissolution. Jackson also adopted Spencer’s idea of a ‘physiological unit’ and combined it with Lockhart Clarke’s microscopic demonstration of neural ‘cells’ and (separate) ‘fibres’. Thus, from the mid-1860s Jackson thought about neurophysiological events at the histological (‘minute’) level. This modern element in his thought has been completely unrecognized. In fact, it was the basis of his dynamic conception of brain localization. It supported his lifelong effort to establish a unitary pathophysiology for all types of epileptic seizures, including temporal lobe epilepsy, which he called ‘uncinate fits’. Jackson’s conception of localized epileptic seizures was also fundamental to the establishment of modern ‘brain surgery’. Through the work of Charles Sherrington it played a significant role in the twentieth century’s paradigm for neurophysiology. His views on aphasia have been superseded, but their dynamism was recognized and praised by the preanalytic Sigmund Freud, who probably was also influenced by Jackson’s conception of psycho-physical parallelism (‘Concomitance’). Freud’s ‘regression’ was based on Jackson’s ‘dissolution’. Some Jacksonian ideas that did not survive were: ‘lowest level fits’, which were actually decerebrate posturing (demonstrated in cats by Sherrington); migraine and vertigo as epileptic phenomena; his theories of language processing in aphasia (pre-Wernicke); the neurology of subjective-objective; and the anatomical details of his postulated three levels of cerebral organization.
Am I losing my mind?
Authors: Kristan Angela M. , Santos Elizabeth J.
Published: May 2022

Mild cognitive impairment (MCI) represents a syndrome of objective cognitive change without significant functional impairment. When assessing for MCI, subjective memory complaints need to be evaluated with objective measures and correlated with functional abilities. When MCI is present, it is important to look for reversible, treatable conditions like sleep disorders, medication or substance effects, mood and anxiety disorders, or medical and neurologic conditions. Clinicians should be vigilant for potential progression of mild neurocognitive changes into a major neurocognitive disorder. There is no established treatment for MCI, but patients should be followed on a regular basis and prescribed a brain-healthy lifestyle.
A telling triad of symptoms
Authors: Du Fanny Huynh , Hess Robert T. , Huege Steve
Published: May 2022

Normal pressure hydrocephalus (NPH) is a relatively rare cause of dementia but one that is important to recognize as it is potentially reversible. NPH should be considered in older patients with gait disturbance and either cognitive deficits or urinary incontinence. Brain imaging with magnetic resonance imaging (MRI) or computed tomography (CT) shows disproportionate ventriculomegaly, although this is a common finding in the elderly and not specific for NPH, and so it should be coupled with improvement of gait and other clinical symptoms following cerebrospinal fluid removal to help to confirm the diagnosis and predict response to shunting. Comorbidities that can exacerbate dementia, gait disturbance, and urinary incontinence should be thoroughly assessed.
Life is not worth living
Authors: Asghar-Ali Ali , Lavingia Richa
Published: May 2022

Older adults are at high risk of attempting and completing suicide, particularly those with psychiatric illnesses, multiple medical comorbidities, previous suicide attempts, functional impairment, recent psychosocial stressors, and social isolation. Older White men have one of the highest risks of attempting and completing suicide. The most common method of suicide among older adults is the use of firearms, followed by poisoning. When assessing suicidality, clinicians should identify risk and protective factors; ask about suicidal ideation, past attempts, suicide plans, and intent to complete suicide; determine the patient’s suicide risk level and appropriate intervention; and document the rationale for this determination. Underlying mood disorders, substance use and chronic pain are particularly important risk factors to identify in later life. Suicide safety planning should involve a systematic, collaborative approach.
He is frightened of things that he sees
Authors: Farheen Arshiya Syeda , Tampi Deena J. , Tampi Rajesh R.
Published: May 2022

Parkinson’s disease (PD) psychosis is a common condition and is associated with increased morbidity, mortality, and caregiver burden. Symptoms may include delusions and hallucinations, with one common example being paranoid accusations about a spouse’s infidelity. An initial work-up should rule out other medical causes and medication effects. Decreasing the number and dosage of dopaminergic medications used to treat PD may improve or alleviate the psychotic symptoms but may also worsen motor function. Antipsychotics can be used to treat symptoms, but with the risk of also worsening the motor symptoms of PD. Pimavanserin is a serotonin receptor inverse agonist that is approved by the U.S. Food and Drug Administration to treat psychosis associated with PD.
Introduction
Authors: Rega Paul P.
Published: May 2022

The Introduction presents four disaster case histories demonstrating that no two disasters are alike. They all present nuances and challenges that require recognition and attention to minimize morbidity and mortality. The chapter emphasizes the fact if there is one commonality it is that all disasters are local and must be managed locally, at least in the early stages. Definitions and examples of simple, complex, and catastrophic disasters are presented with the admonition that with the development of climate change, disasters of the future will be even more challenging. A rationale for the chapters of the book is also presented.
Pile-up on the pike: First in
Authors: Rega Paul P.
Published: May 2022

The chapter discusses a “simple” disaster on the highway that involves a multiple vehicular accident. The author explores how to determine if the accident scene is safe and what the next steps should be. Important factors to be considered are the events, who is involved, the location, the approximate number of vehicles involved, weather and road conditions, and obvious ongoing or potential hazards.
The hospital disaster committee: A challenge, a curse, or both?
Authors: Rega Paul P.
Published: May 2022

This chapter discusses the role of the hospital disaster committee and how serving on it can provide a valuable emergency medicine perspective on mass casualties. The chapter covers what the immediate priorities should be for a new committee member, which are understanding the disaster response and recovery cycle, reading the hospital’s disaster manual, learning the hospital’s incident command structure, taking two FEMA courses (“Introduction to the Incident Command System” and “Introduction to the National Incident Management Structure”), and reviewing the hospital’s hazards vulnerability analysis, which enumerates the specific threats that may occur in the community. The chapter ends by discussing mass gathering medicine, which is a subspecialty within disaster medicine.
My home, my castle—I hope!
Authors: Rega Paul P.
Published: May 2022

This chapter explores the concept of a family disaster plan, which contains a hazard vulnerability analysis and what to do in emergency situations including external chemical/radioactive release, earthquakes, or floods. The chapter also addresses evacuation plans and routes, home escape routes, first aid, food and water, communications, documents, insurance, and more. It details the contents that should be part of a disaster kit for adults, babies and children, and pets. A list of tools and supplies important to have on hand in case of a disaster is given. The chapter also addresses methods for water decontamination and general food considerations.
Calcium handling
Authors: Alexander Cherry , Smith Godfrey , Myles Rachel
Published: May 2022

Heart failure is a heterogeneous clinical syndrome which is accompanied by a variety of phenotypic changes, many of which have been linked to abnormalities in the intracellular calcium (Ca2+) signal. These range from mechanical dysfunction, usually characterized by reduced systolic contractile function, to electrophysiological dysfunction including QT interval prolongation, increased incidence of ventricular premature beats, and arrhythmic sudden cardiac death. In ventricular myocardial cells, intracellular Ca2+ ion fluxes govern the translation of the depolarizing signal into mechanical contraction, a process termed excitation–contraction (E–C) coupling. Abnormalities of intracellular Ca2+ handling are thought to underlie both mechanical and electrophysiological dysfunction in failing myocardium. This chapter summarizes the events involved in normal E–C coupling and describes the changes observed in heart failure, with particular focus on the changes reported in remodelled ventricular myocardium. Changes in intracellular Ca2+ signalling in other cardiac cell types, such as atrial cardiomyocytes and Purkinje fibre cells, may also be crucial to the final heart failure phenotype, but less is known about pathological changes in these tissues, and therefore these are only mentioned briefly.
The failing cardiomyocyte
Authors: Földes Gábor , Lyon Alexander R. , Harding Sian E.
Published: May 2022

The biology of the failing cardiomyocyte is a complex interaction of a number of abnormal pathophysiological processes involving signalling pathways, intracellular ionic fluxes, intercellular communications, oxidative stress, impaired mitochondrial energetics, altered structural morphology, abnormal reactivation of foetal gene expression patterns, and activation of cell death pathways. The crosstalk between these pathways is complex, and positive feedback between the different systems leads to the vicious cycle of deterioration of mechanical function and cell survival that characterizes the phenotype of the failing cardiomyocyte. Identifying and targeting critical nodal points and master regulatory systems may identify novel therapeutic strategies that can recover multiple elements of the failing phenotype and translate into meaningful clinical benefits for patients with heart failure.
Prognostication
Authors: Simpson Joanne , Gardner Roy S.
Published: May 2022

This chapter describes the prognostication of heart failure. Heart failure is a frequently progressive condition, although after commencing treatment patients usually reach a period of clinical ‘stability’, the duration of which varies between individuals. Most patients, if they do not suffer from sudden death, will ultimately deteriorate with refractory heart failure symptoms leading up to their death. Identifying such patients is one of the great challenges of heart failure management. Decisions regarding appropriateness and timing of scarce treatments—such as cardiac transplantation or mechanical circulatory support—or the need for end-of-life care can be aided by repeated prognostic assessment. As the one-year mortality following cardiac transplantation is ~15.5%, the selection of candidates for cardiac transplantation is therefore determined by identifying those patients whose annual mortality from heart failure exceeds this rate and who might therefore benefit prognostically from advanced therapy. Prognostic assessment of chronic heart failure can be made by a number of methods, including evaluation of univariable predictors, as well as by multivariable clinical models.
Anxiety and depression
Authors: Maddison Anna , Sharp John
Published: May 2022

Living with heart failure puts an increased burden on a patient’s psychological well-being, increasing their risk of mental health difficulties. This chapter examines the co-occurrence of anxiety and depression in the heart failure population. Both the physiological and psychological associations of anxiety and depression with heart failure are explored, demonstrating why they are so often intertwined. Evidence of significantly higher prevalence rates of anxiety and depression in the heart failure population than general public indicate the need for increased awareness and identification of psychological distress. Identification tools are presented alongside evidence for the recommended models of care, management and treatment of anxiety and depression in heart failure.
Therapeutic control of fluid balance in chronic heart failure
Authors: Clark Andrew L. , Coletta Alison P. , Cleland John G. F.
Published: May 2022

Currently, diuretics are the most important family of treatments for patients with heart failure and one of the most under-researched. Diuretic management resides firmly in the era of opinion-based medicine, perhaps because it is nigh on impossible to manage the congestion without them. Now that tools for measuring congestion have improved and are widely available for clinical practice, we should investigate how to use diuretics more effectively. The introduction of diuretics, particularly loop diuretics, revolutionized the management of fluid retention. Observational studies show that patients who do not require treatment with loop diuretics have a much better prognosis than those who do, and that higher doses of loop diuretics are strongly associated with a worse prognosis. Such findings have led to recommendations that the dose and use of diuretics for heart failure should be minimized. However, more careful analyses of the data suggest that the use and dose of loop diuretics is merely a surrogate marker for the severity of congestion and that it is the congestion that is lethal. This argues that a sufficient dose of diuretic to control congestion effectively should be used.
Sodium–glucose co-transporter-2 inhibitors
Authors: Lee Matthew M. Y. , Docherty Kieran F. , Jhund Pardeep S.
Published: May 2022

This chapter studies the use of aldosterone antagonists, also known as Mineralocorticoid Receptor Antagonists (MRAs), in chronic heart failure (CHF). Overall, the results for aldosterone blockade in CHF due to left ventricular systolic dysfunction (LVSD) — now called heart failure with reduced ejection fraction (HF-REF) — have been very impressive with three large, undoubtedly positive results. These are the Randomized Aldactone Evaluation Study (RALES study); the Eplerenone Post-acute MI Heart failure Efficacy and Survival Study (EPHESUS) study; and the Eplerenone in Mild Patients Hospitalisation and Survival Study in Heart failure (EMPHASIS-HF) study. Importantly, there are no neutral or negative studies for aldosterone blockade in HF-REF. As a result, all CHF guidelines recommend MRAs as third line drugs after angiotensin converting enzyme inhibitors (ACEIs) and beta-blockers.
Ivabradine
Authors: Cowie Martin R.
Published: May 2022

The cells of the sinoatrial (SA) node generate a cyclical change in their resting membrane potential that drives them towards the threshold that triggers an action potential. The spontaneous depolarization current is a combined Na+/K+ inward current, termed the I
funny current (I
(f)). It is voltage-regulated and activated by hyperpolarization at around –40/–45 mV, at which point Na+ and K+ enter the SA cell, stopping the repolarization and facilitating the depolarization process. The I
(f) current channel closes briefly at the very beginning of the action potential, but when the cell hyperpolarizes again the channel is activated and the cycle continues.
Monitoring
Authors: Cowie Martin R. , Harper Andrew R. , Singhal Arvind
Published: May 2022

This chapter addresses the importance of monitoring in heart failure management. Heart failure is typically a chronic syndrome with the risk of episodic deterioration that requires adjustment of therapy and/or admission to hospital. International guidelines recommend that patients are enrolled in a disease management programme to help ensure that they receive appropriate multi-professional input to their treatment, education, and monitoring. The chapter identifies the key elements of monitoring: including what and who should be monitored, the frequency of monitoring, and the different methods of monitoring. Patients are becoming more actively involved in their care, with self-monitoring and management achievable for many, with appropriate professional support. Advances in digital technologies look promising, but require robust assessment to ensure that integration of such technologies improves the outcome and/or experience of care.
The future
Authors: Gardner Roy S. , McDonagh Theresa A. , Clark Andrew L.
Published: May 2022

This chapter looks at some of the approaches in the pipeline for heart failure. Heart failure continues to be an exciting field for healthcare professionals, and is no longer a diagnosis of despair for patients. Even though therapy has advanced considerably, new innovations continue to come forward and offer further hope to patients. The renin–angiotensin–aldosterone system (RAAS) can now be modulated at all stages of the pathway, and RAAS inhibition is still key to the management of chronic heart failure. The most promising advances in manipulating the RAAS probably lie with evermore selective mineralocorticoid receptor antagonists, and the use of agents that can prevent or treat hyperkalaemia. The chapter then considers the failure of expensive vasodilators in patients with acute heart failure to alter clinical or hard end-points. It also examines modulation of cardiac contractility, myocyte function, and mitochondrial function. The success of cardiac resynchronization therapy and implantable defibrillators has also generated a huge interest in the potential of device therapy.
Developing end of life literacy through public education
Authors: Patterson Rebecca M. , Hazelwood Mark A.
Published: May 2022

This chapter uses ‘end of life literacy’ as an umbrella term to refer broadly to the collection of knowledge, skills, experiences, attitudes, opportunities, and behaviours that enable an individual to plan for, deal with, and support others through the difficult times that can come with dying, death, loss, and care. It focuses particularly on the role that educating the public can play in supporting the development of end of life literacy. Different aims, modes, and examples of education are reviewed, and a case is made for the key role of education within public health approaches to palliative care.
Clinical practice methods combined with community resources
Authors: Kingston Helen , Millington-Sanders Catherine , Abel Julian
Published: May 2022

The public health approach to end of life helps health and social care professionals to remain focused on what adds to quality of life and how to make the most of the remaining life. It acknowledges the vital role of the community and in particular the network of family and friends that mean so much. Through this lens, teams can focus on what is needed to create a culture and society which supports good end of life care for both the person that is dying and for those who care about them. Clinician understanding and active promotion of the supportive networks of family, neighbours, and friends help ensure holistic, comprehensive, and reliable care. The primary carer and caring network is a focus for support, as well as for the individual who is dying. Practice and emotional support are both needed. Professionals cannot provide all elements of this care. This chapter examines how a compassionate community approach can be integrated with routine clinical care, ensuring that the experiences of death, dying, loss, and caregiving are based around the community, with medical care fitting in as needed, rather than medical care being a dominating feature. The chapter uses the example of putting this approach into action in the market town of Frome in Somerset, in the South West of England, through the efforts of Frome Medical Practice, and also examines how the Daffodil Standards for end of life care support this approach, with particular reference to primary care.
The evidence of the importance of informal care networks
Authors: Leonard Rosemary , Horsfall Debbie
Published: May 2022

Informal care networks are an essential ingredient for building and binding compassionate communities. They usually consist of a functional subset of people’s existing social networks; however, compassionate communities can provide additional people and resources. These networks provide a number of benefits. They can help people to die in the place of their choice; deal with the complex, demanding, and emotional work of caring; replace the burden of caring with positive experiences; have flow-on benefits to the community; facilitate better use of formal services; and assist with grief and bereavement. Four methods of presenting care networks are presented: descriptive maps drawn by researchers or clinicians, participatory network mapping, computer-generated maps, and statistical analysis. Three case studies illustrate some diversity in the way informal care networks operate. Social network analysis enhanced by discussion from the network revealed the size and composition of networks, their formation, their activities, and the significance of their location.
Controlled repositioning and primary osteoplasty as a treatment option for the management of unstable slipped capital femoral epiphysis
Authors: Venkatadass K. , Durga Prasad V. , Sangeet G. , Rajasekaran S.
Published: May 2022

The ideal management of an unstable slipped capital femoral epiphysis (SCFE) is still controversial. The currently available options are in-situ screw fixation with delayed corrective osteotomy, closed reduction and screw fixation and anatomic reduction by modified Dunn’s procedure (MDP). We present the results of our technique of controlled re-positioning (CRP) with primary osteoplasty in which the epiphysis is repositioned to the preacute slip stage and a mini-open osteoplasty is done in the same sitting to avoid later femoro-acetabular impingement. We had 27 unstable slips which presented to our institution between 2015 and 2019, of which nine were treated with the above technique, and the rest 18 were treated with MDP. All of them were followed up for a minimum of 1 year. The mean intraoperative flexion-internal rotation before osteoplasty was −21.1° (−5° to −40°), which improved to +22.8° (+15° to +30°). Pre- and post-operative mean head-neck angles were 46.5° and 18.3°, respectively, with a decrease of 28.2°. At the final follow-up, the mean alpha angle was 45.1° and the mean head-neck offset ratio was 0.26. None of the patients had avascular necrosis or chondrolysis. The technique of CRP, screw fixation and primary osteoplasty is a viable treatment option for a subset of patients with unstable SCFEs. But, the decision is made intraoperatively and the parents need to be counselled about the need for an alternative procedure if repositioning is unsuccessful. Level of evidence: level IV – case series.
Competency Assessment in Focused Cardiac Ultrasound—Can the Use of Sequential Testing Help Tailor Training Requirements?
Authors: Walker Humphrey G. M. , McKenzie Dean P. , Brooks Kyle S.
Published: May 2022

OBJECTIVES:

Varying numbers of scans are required by different professional bodies before focused cardiac ultrasound (FCU) competence is assumed. It has been suggested that innovation in the assessment of FCU competence is needed and that competency assessment needs to be more individualized. We report our experience of how the use of sequential testing may help personalize the assessment of FCU competence.

DESIGN:

This was a planned exploratory reanalysis of previously prospectively collected data. FCU was performed sequentially by an intensive care trainee and expert on the same patient. Assessment of left ventricular (LV) function by the trainee and expert was compared. Sequential testing methods were used in the analysis of this data to see if they could be used to help in the assessment of competence. Each trainee had completed a 38-hour teaching program and a logbook of 30 scans prior to enrollment.

SETTING:

Tertiary Australian not for profit private academic hospital.

MEASUREMENTS AND MAIN RESULTS:

Two hundred seventy paired echocardiograms were completed by seven trainees. For trainees to achieve greater than 90% accuracy in correctly assessing LV function when compared with an expert, a variable number of scans were required. This ranged from 13 to 25 (95% CI, 13–25) scans. Over the study period, the ability to correctly identify LV function was maintained, and it appeared there was no degradation in skill.

CONCLUSIONS:

Using the Sequential Probability Ratio Test demonstrates a variable number of scans were required to show greater than 90% accuracy in the assessment of LV function. As such, the use of sequential testing could help individualize competency assessments in FCU. Additionally, our data suggests that over a 6-month period, echocardiographic skill is maintained without any formal teaching or feedback. Further work assessing the utility of this method based on larger samples is required.