bluuebunny/crossref_metadata_2025 huggingface dataset:
Application of neural network fitting for modeling the pneumatic networks bending soft actuator behavior
Authors: Salem Mohamed E M , Wang Qiang , Xu Ma Hong
Published: February 2022

Soft actuators have recently gained a lot of interests as an emerging topic, although complete methodologies for modeling soft actuators are still missing. Identifying and forecasting the behaviour of soft actuators is difficult due to the nonlinear behaviour of the materials used, the complicated geometries they form, and the wide range of motions they produce. In this paper, we demonstrated how to use neural network technology to describe the motion and produced force that the pneumatic network bending soft actuator can create at various input pressures. To confirm the results, three separate neural network models for three different modeling modes were constructed and evaluated with different input data sets. First, the dimension model, which deals with changes in the form and geometry of the soft actuator and their influence on its response at various pressure inputs. Second, the free force model, which simulates the motion of a soft actuator in free space without any external disturbances. Finally, the blocked force model, which may simulate a real-world soft actuator that is subjected to an external force. The input data sets were created with ABAQUS/CAE software, which replicates the behavior of the soft actuator and uses this data to train the neural network models.
Application of individualized differential expression analysis in human cancer proteome
Authors: Liu Yachen , Lin Yalan , Yang Wenxian , Lin Yuxiang , Wu Yujuan , Zhang Zheyang , Lin Nuoqi , Wang Xianlong , Tong Mengsha , Yu Rongshan
Published: February 2022

Liquid chromatography–mass spectrometry-based quantitative proteomics can measure the expression of thousands of proteins from biological samples and has been increasingly applied in cancer research. Identifying differentially expressed proteins (DEPs) between tumors and normal controls is commonly used to investigate carcinogenesis mechanisms. While differential expression analysis (DEA) at an individual level is desired to identify patient-specific molecular defects for better patient stratification, most statistical DEP analysis methods only identify deregulated proteins at the population level. To date, robust individualized DEA algorithms have been proposed for ribonucleic acid data, but their performance on proteomics data is underexplored. Herein, we performed a systematic evaluation on five individualized DEA algorithms for proteins on cancer proteomic datasets from seven cancer types. Results show that the within-sample relative expression orderings (REOs) of protein pairs in normal tissues were highly stable, providing the basis for individualized DEA for proteins using REOs. Moreover, individualized DEA algorithms achieve higher precision in detecting sample-specific deregulated proteins than population-level methods. To facilitate the utilization of individualized DEA algorithms in proteomics for prognostic biomarker discovery and personalized medicine, we provide Individualized DEP Analysis IDEPAXMBD (XMBD: Xiamen Big Data, a biomedical open software initiative in the National Institute for Data Science in Health and Medicine, Xiamen University, China.) (https://github.com/xmuyulab/IDEPA-XMBD), which is a user-friendly and open-source Python toolkit that integrates individualized DEA algorithms for DEP-associated deregulation pattern recognition.
Accelerated decline in white matter microstructure in subsequently impaired older adults and its relationship with cognitive decline
Authors: Shafer Andrea T. , Williams Owen A. , Perez Evian , An Yang , Landman Bennett A. , Ferrucci Luigi , Resnick Susan M.
Published: February 2022

Little is known about a longitudinal decline in white matter microstructure and its associations with cognition in preclinical dementia. Longitudinal diffusion tensor imaging and neuropsychological testing were performed in 50 older adults who subsequently developed mild cognitive impairment or dementia (subsequently impaired) and 200 cognitively normal controls. Rates of white matter microstructural decline were compared between groups using voxel-wise linear mixed-effects models. Associations between change in white matter microstructure and cognition were examined. Subsequently impaired individuals had a faster decline in fractional anisotropy in the right inferior fronto-occipital fasciculus and bilateral splenium of the corpus callosum. A decline in right inferior fronto-occipital fasciculus fractional anisotropy was related to a decline in verbal memory, visuospatial ability, processing speed and mini-mental state examination. A decline in bilateral splenium fractional anisotropy was related to a decline in verbal fluency, processing speed and mini-mental state examination. Accelerated regional white matter microstructural decline is evident during the preclinical phase of mild cognitive impairment/dementia and is related to domain-specific cognitive decline.
The Effect of a Second Dose of Measles Vaccine at 18 Months of Age on Nonaccidental Deaths and Hospital Admissions in Guinea-Bissau: Interim Analysis of a Randomized Controlled Trial
Authors: Berendsen Mike L T , Silva Isaquel , Balé Carlitos , Nielsen Sebastian , Hvidt Sophus , Martins Cesario L , Benn Christine S , Aaby Peter
Published: February 2022

Background

The world is set on the eradication of measles. Continuation of the measles vaccine (MV) after eradication could still reduce morbidity because the MV has so-called beneficial nonspecific effects. We evaluated the effect of a “booster” dose of the MV on overall severe morbidity.

Methods

We conducted a randomized controlled trial among children aged 17.5 to 48 months in Guinea-Bissau, where the MV is recommended only at 9 months of age. At the time of this interim analysis, 3164 children had been allocated 1:1 to a second dose of measles vaccine (MV2) at 18 months of age or to no vaccine. Severe morbidity (a composite outcome of nonaccidental deaths and hospital admissions) rate ratios (SMRRs) were calculated by Cox regression analysis censored for national oral polio vaccine (OPV) campaigns.

Results

There were no measles cases during the trial period. There were 43 nonaccidental deaths or hospital admissions during follow-up. Severe morbidity was 2.6 per 100 person-years in the MV2 group and 3.6 per 100 person-years among controls; hence, the estimated effect of MV2 on severe morbidity was 28% (SMRR, 0.72; 95% confidence interval [CI], .38–1.38). At 12 months of follow-up, the number needed to treat to prevent 1 severe morbidity event was 137 children. After OPV campaigns, the estimated effect of MV2 was reduced to 9% (SMRR, 0.91; 95% CI, .46–1.81).

Conclusions

MV2 may reduce nonmeasles severe morbidity by 28% (−38% to 62%), although this did not achieve statistical significance in this study. If significant in higher powered studies, this has major implications for child health, even after measles eradication.

Clinical Trials Registration

NCT02943681.
Bringing Transmission of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) to the Surface: Is There a Role for Fomites?
Authors: Katona Peter , Kullar Ravina , Zhang Kevin
Published: February 2022

Understanding the contribution of routes of transmission, particularly the role of fomites in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) transmission is important in developing and implementing successful public health infection prevention and control measures. This article will look at case reports, laboratory findings, animal studies, environmental factors, the need for disinfection, and differences in settings as they relate to SARS-CoV-2 transmission.
Effectiveness of Motivational Interviewing on contribution to self-care, self-efficacy, and preparedness in caregivers of patients with heart failure: a secondary outcome analysis of the MOTIVATE-HF randomized controlled trial
Authors: Locatelli Giulia , Zeffiro Valentina , Occhino Giuseppe , Rebora Paola , Caggianelli Gabriele , Ausili Davide , Alvaro Rosaria , Riegel Barbara , Vellone Ercole
Published: February 2022

Aims

Caregiver characteristics and behaviours are associated with patients’ and caregivers’ outcomes. However, there is scarce evidence on interventions aimed at improving caregiver contribution (CC) to patient self-care, caregiver self-efficacy, and caregiver preparedness in heart failure (HF). This study aims to evaluate the effect of Motivational Interviewing (MI) on CC to patient self-care, caregiver self-efficacy, and caregiver preparedness in HF.

Methods and results

This is a secondary outcome analysis of MOTIVATE-HF randomized controlled trial. Caregivers of patients with HF were randomized into three arms: Arm 1 (MI for patients), Arm 2 (MI for patients and caregivers), and Arm 3 (standard care). The intervention consisted of one MI session plus three telephone contacts. Data were collected at baseline and after 3, 6, 9, and 12 months. A total of 510 patient and caregiver (median age 54 years, 76% females) dyads were enrolled, 235 caregivers and 238 patients completed the study until 12 months. Caregiver contribution to self-care maintenance and management and caregiver preparedness significantly improved over time, but without significant differences among the three arms. At 9 months, caregiver self-efficacy improved more in Arm 2 than Arm 3 [difference: 8.36, 95% confidence interval (CI) (3.13; 13.59), P = 0.001]. This improvement remained significant also at linear mixed model [β^ = 1.39, 95% CI (0.02; 2.75), P = 0.046].

Conclusion

Motivational Interviewing did not improve CC to patient self-care and caregiver preparedness. However, it increased caregiver self-efficacy, which is known to be a powerful mediator of CC to self-care.

Registration

Clinicaltrials.gov: NCT02894502.
Is aortic valve-sparing root reimplantation (David-I) justified in cardiac redo surgery?
Authors: Beckmann Erik , Kaufeld Tim , Martens Andreas , Rudolph Linda , Krüger Heike , Natanov Ruslan , Haverich Axel , Shrestha Malakh Lal
Published: February 2022

OBJECTIVES

Aortic valve-sparing root reimplantation (AVSRR) is a complex procedure, which offers the benefit of preserving the native aortic valve. Cardiac redo surgery is complex and time-consuming, and it is not known if David procedure is safe or beneficial in this context.

METHODS

Between 1993 and 2019, we performed a total of 544 elective AVSRR operations at our centre. Patients were assigned to either group A (n = 30, redo) or group B (n = 514, first-time sternotomy).

RESULTS

Aortic cross-clamp time was higher in the redo group (173[62] vs 125[31], P < 0.001). Cardiopulmonary bypass time was higher in the redo group as well (250[78] vs 179[51], P < 0.001). There were significantly more concomitant total arch replacements in the redo group (43.3% vs 5.8%, P < 0.001) using the ‘beating heart’ technique (20.0% vs 1.9%, P < 0.001). In-hospital mortality was comparable in both groups (3.3% vs 1.8%, P = 0.44). The rates for perioperative complications in terms of permanent neurological deficit and rethoracotomy were comparable between the 2 groups, too. Follow-up was complete for 99.6% of all patients and comprised a total of 584 patient-years. The 1-, 5-, 10- and 15-year survival rates were 90%, 81%, 60% and 55%, in group A (redo) and 96%, 90%, 78% and 67% in group B (native, P = 0.16), respectively. The rates for freedom from valve-related reoperation at 1, 5, 10 and 15 years after initial surgery were 96%, 92%, 92% and 92% in group A (redo) and 97%, 92%, 87% and 84% in group B (native, P = 0.52), respectively.

CONCLUSIONS

Despite significantly more concomitant total arch replacements in the redo group, early mortality was comparable in both groups. We conclude that AVSRR can be performed in redo cardiac surgery without compromising the early postoperative outcome. Careful patient assessment and selection are mandatory when evaluating patients with a history of previous cardiac surgery for David procedure.
Dominant Local Rings and Subcategory Classification
Authors: Takahashi Ryo
Published: February 2022

We introduce a new notion of commutative noetherian local rings, which we call dominant. We explore fundamental properties of dominant local rings and compare them with other local rings. We also provide several methods to get a new dominant local ring from a given one. Finally, we classify resolving subcategories of the module category $\operatorname {\textsf {mod}} R$ and thick subcategories of the derived category $\textsf {D}^{b}(R)$ and the singularity category $\textsf {D}^{sg}(R)$ for a local ring $R$ whose certain localizations are dominant local rings. Our results recover and refine all the known classification theorems described in this context.
Comparison of the prevalence and molecular characteristics of fosA3 and fosA7 among Salmonella isolates from food animals in China
Authors: Wang Dong , Fang Liang-Xing , Jiang Yu-Wei , Wu De-Shu , Jiang Qi , Sun Ruan-Yang , Wang Min-Ge , Sun Jian , Liu Ya-Hong , Liao Xiao-Ping
Published: February 2022

Objectives

To investigate the prevalence and molecular characteristics of fosA3 and fosA7 among Salmonella isolates.

Methods

Five hundred and fifty-one Salmonella isolates collected from food animals in China during 2016–19 were screened for fos genes. The drug resistance, serovars, clonal relationships and genetic environments of fosA were compared between fosA7- and fosA3-positive Salmonella.

Results

A relatively high prevalence of fosA7 (9.26%) and fosA3 (6.53%) was identified. fosA3 was associated with high-level fosfomycin resistance (≥512 mg/L), while fosA7 conferred relatively low-level resistance that was independent of the presence of glucose-6-phosphate. Additionally, fosA7 could facilitate Salmonella survival under oxidative stress. Both fosA3 and fosA7 were found in diverse serovars and STs, but segregated into distinct groups. The fosA3-positive Salmonella Typhimurium/Salmonella Indiana strains showed close genetic relationships, while fosA7-positive Salmonella Meleagridis/Salmonella Agona/Salmonella Derby showed a relatively high degree of whole-genome sequence heterogeneity. fosA3 was located on conjugative IncHI2 plasmids or chromosomes, while fosA7 was strictly chromosomal. Furthermore, two strains carried large chromosomal fosA7 regions within genomic islands. The fosA3 and fosA7 contigs from our isolates and the NCBI could be segregated into four primary and distinct genomic backbones. IS26 and the antibiotic resistance genes (ARGs) blaCTX-M, blaTEM-1B and rmtB were frequently adjacent to fosA3, while fosA7-carrying contigs generally lacked mobile elements and ARGs.

Conclusions

fosA3 and fosA7 were the primary factors contributing to reduced fosfomycin susceptibility, to different degrees, in these Salmonella isolates. The distinct distributions and molecular characteristics of fosA7 and fosA3 indicated that their origin and evolution in Salmonella were most likely distinct.
A Phase III multicentre, randomized, double-blind trial to evaluate the efficacy and safety of oral contezolid versus linezolid in adults with complicated skin and soft tissue infections
Authors: Zhao Xu , Huang Haihui , Yuan Hong , Yuan Zhengyu , Zhang Yingyuan
Published: February 2022

Objectives

Contezolid is a novel oxazolidinone antibacterial agent for managing infections caused by aerobic and anaerobic Gram-positive bacteria including methicillin-resistant strains. A Phase III, multicentre, randomized, double-blind, active-controlled trial evaluated the efficacy and safety of contezolid versus linezolid in adults with complicated skin and soft tissue infections (cSSTIs).

Methods

Adult patients with cSSTI were randomized in a ratio of 1:1 to receive contezolid 800 mg or linezolid 600 mg q12h for 7–14 days. Clinical cure rate and safety were assessed at the test of cure (TOC) visit in the full analysis set (FAS) and clinical evaluable (CE) population. Non-inferiority was defined as a lower limit of the 95% CI around the treatment difference of clinical cure rates greater than −10%. Chinadrugtrials.org.cn registration identifier: CTR20150855.

Results

Clinical cure rates at TOC indicated non-inferiority of contezolid 800 mg to linezolid 600 mg q12h for patients in the FAS with clinical evaluation, FAS, and CE populations: 92.8% (271/292) versus 93.4% (284/304) (difference −0.6%, 95% CI: −4.7% to 3.5%), 81.4% (271/333) versus 84.5% (284/336) (difference −3.1%, 95% CI: −8.8% to 2.6%) and 90.5% (267/295) versus 90.1% (282/313) (difference 0.4%, 95% CI: −4.3% to 5.1%). Contezolid and linezolid showed similar efficacy for the cSSTIs caused by methicillin-susceptible or methicillin-resistant Staphylococcus aureus. Contezolid demonstrated significant lower incidence of leucopenia (0.3% versus 3.4%) and thrombocytopenia (0% versus 2.3%) than linezolid. The frequency of treatment-emergent adverse events was comparable between the two groups.

Conclusions

Contezolid 800 mg q12h is as effective as linezolid for treatment of cSSTIs in adults, but safer than linezolid in terms of haematological abnormalities.
Experience and design: Case studies
Authors: Arbib Michael A.
Published: February 2022

This chapter offers two case studies of the architectural design processes to present design as an exercise of the imagination rooted in memories emerging from prior experience. The case studies emphasize how their specific memories influenced the creativity of each architect in different ways. Neuroscience does not limit the styles of different designers. Jørn Utzon’s design of the Sydney Opera House was informed by experience in both boat-building and as a yachtsman that offered him a fresh perspective on how to develop the site on Bennelong Point on Sydney Harbour. Other inspiration came from Mayan and Chinese temples in which a building was erected above a pedestal, and clouds or the roof in some sense floated above the building. Frank Gehry’s design of the Guggenheim Museum Bilbao exemplifies how sketching and model-making make intuitions explicit in a way that can be the basis both for self-discovery and for teamwork. Crucially, the current sketch may not only provide ideas for further development but also reveal quirks that had not been consciously derived but that nonetheless suggest ideas to enrich or modify the design.
Understanding the Pathophysiology of Withdrawal Syndromes
Authors: Fava Giovanni A.
Published: February 2022

Continued drug treatment with antidepressant medications may stimulate processes that run counter to the initial acute effects of a drug. The oppositional model of tolerance may explain loss of treatment efficacy during maintenance treatment and the fact that some side effects tend to occur only after a certain time. These processes may also direct the illness into a treatment-unresponsive course, including manifestations of bipolar disorder or paradoxical reactions. When drug treatment ends, oppositional processes no longer encounter resistance, resulting in the potential onset of new withdrawal symptoms, persistent postwithdrawal disorders, hypomania, resistance to treatment if it is reinstituted, and refractoriness.
The Role of Clinical Assessment
Authors: Fava Giovanni A.
Published: February 2022

In the setting of guided antidepressant medication discontinuation, standard diagnostic criteria (DSM-5) need to be integrated by a specific clinimetric approach geared to data gathering, organization of findings, and formulation of treatment plans that is not usually performed in practice. In addition to the customary clinical assessment, clinimetric elements related to treatment history and staging, the assessment of current clinical state, macroanalysis, and the monitoring of progress of tapering and discontinuation are necessary for translating assessment into clinical decisions, and are outlined in the chapter. The author argues that such an assessment is necessary for an informed decision and is particularly important when the clinician and the prescriber are not the same person.
Second Psychotherapeutic Module
Authors: Fava Giovanni A.
Published: February 2022

This chapter describes the cognitive-behavioral component of the psychotherapeutic module. Cognitive-behavioral therapy generally follows explanatory therapy and antidepressant tapering (not necessarily full discontinuation), and comes before well-being therapy. However, there are situations when it may also precede explanatory therapy and medication tapering; for example, in cases where antidepressant drugs were used in anxiety disorders, obsessive-compulsive illness, or post-traumatic stress disorder without any concurrent or previous psychotherapeutic approach. The cognitive-behavioral strategy is based on the use of a structured diary, cognitive restructuring, homework assignments, and lifestyle suggestions. Explanatory therapy, if needed, is continued.
Third Psychotherapeutic Module
Authors: Fava Giovanni A.
Published: February 2022

The third psychotherapeutic module introduces Well-Being Therapy (WBT)—a short-term psychotherapeutic strategy that emphasizes self-observation of psychological well-being, with the use of a structured diary, cognitive restructuring of interfering thoughts and/or behaviors through cognitive-behavioral techniques, and homework assignments (such as pursuing optimal experiences). WBT may have an important role in counteracting psychological vulnerabilities that may ensue with discontinuation of antidepressant medications. Through the use of WBT, flourishing and resilience can be promoted, leading to a positive evaluation of one’s self, a sense of continuous growth and development, the belief that life is purposeful and meaningful, quality relations with others, the capacity to manage effectively one’s life, and a sense of self-determination.
Introduction
Authors: McQuellon Richard P. , Cowan Michael A.
Published: February 2022

The themes of mortal time and healing conversation with patients and their caregivers are introduced. Mortal time refers to the disturbing psychological experience of encountering mortality when diagnosed with cancer. Yet, it can be discussed in a life-giving manner. New developments in cancer medicine have changed the landscape of mortal time. These developments include additional treatment options for patients with advanced cancer, increasing recognition of the importance of interpersonal skills training for health care professionals, and additional resources for patients to learn how to communicate effectively with their medical team. There is growing reliance on family caregivers for delivering medical care in the home. More treatment options can mean extended periods in mortal time. It is possible to live gracefully with the possibility of death as the meaning of life comes into focus through the lens of mortality. The book has three major sections. In part I, the ways people experience mortal time are articulated. In part II, the basic elements of healing conversation are described with an emphasis on the hope that can spring from talking with a trusted companion. In Part III, the topic is guidance for caregivers and recognition healing conversation as a source of hope. Living with mortality can herald the birth of possibility for both patients and caregivers.
Genetics and Molecular Aspects of Gastrointestinal Motility Disorders
Authors: Camilleri Michael
Published: February 2022

Studying rare genetic and molecular diseases of gut motility provides an understanding of their underlying mechanisms and may provide insights on the mechanisms or management of more common illnesses. For example, constipation affects 1 in 5 people 65 years or older and 1 in 10 people younger than 65 years, and slow-transit constipation or colonic inertia is responsible for approximately 10% of referrals of patients with constipation to gastroenterologists and, among all patients with constipation, is the cause in probably 1%. Insights on the pathophysiology and mechanisms of constipation are provided by studying Hirschsprung disease, mitochondrial cytopathy, or multiple endocrine neoplasia type 2B. These diseases are used to illustrate the congenital diseases of the enteric neuromuscular apparatus.
Gastrointestinal Motility: Control Mechanisms and Pathogenesis of Disordered Function
Authors: Camilleri Michael
Published: February 2022

This chapter addresses the normal gastrointestinal (GI) motor functions and the underlying control mechanisms and how these are deranged to result in disorders of motor function. The focus of the chapter is the pathogenesis of dysmotility.
Neuromuscular Disorders Causing Gut Dysmotility
Authors: Camilleri Michael
Published: February 2022

Gut dysmotility results from disorders of gut muscle (myopathic disorders), disorders of the myenteric plexus and electrical syncytial cells that function as pacemakers (enteric disorders), and diseases of the extrinsic pathways (neuropathic disorders). Some diseases affect both intrinsic and extrinsic neural control. This chapter addresses how to identify extrinsic neurologic disorders, briefly discusses the gut motility presentations in neurologic diseases, and provides examples of classic or syndromic neurologic diseases that include gut dysmotility.
Implications of Pharmacogenomics for Irritable Bowel Syndrome
Authors: Camilleri Michael
Published: February 2022

Visceral sensation is one of the important mechanisms that are upregulated, a process resulting in hypersensitivity in functional gastrointestinal disorders. However, it is also relevant when other mechanisms, such as inflammation or altered motor function, result in signaling the abnormal functions such as stasis or accelerated transit from the gut to the brain. Thus, it is important to understand the physiologic basis of visceral sensation. The factors influencing visceral sensation are the neural pathways and transmitters, viscus compliance and tone, sex, level of attention, and unpleasantness of the sensation.
Gastrointestinal Physiologic and Motility Problems in Older Persons: Constipation, Irritable Bowel Syndrome, and Diverticulosis
Authors: Camilleri Michael
Published: February 2022

Aging affects motor and sensory functions throughout the gut. In the pharynx and esophagus, the changes can result in dysphagia and aspiration. As people age, swallow is slower as a result of abnormalities in the oral phase of swallowing, reduced lingual propulsive force, dry mouth with diminished pharyngeal lubrication, and delayed upper esophageal sphincter opening. Aging also affects functional reserve of the proximal esophagus, anus, and pelvic floor and leads to motility disturbances in older persons, manifesting mainly as high dysphagia, constipation, and fecal incontinence, especially in the presence of prior obstetric damage. Older patients may have reversible, nonmalignant disease and can be restored to health through proper management.
A Pragmatic Guide to Shared Decision Making
Authors: Walter Jennifer K. , Fiks Alexander G.
Published: February 2022

There has been inadequate penetrance of shared decision making (SDM) into clinical practice due to several barriers, including clinician skill in utilizing it. Using the case of an adolescent with advanced cancer, this chapter articulates the pragmatic skills needed to engage in SDM with pediatric patients and families. Theoretical foundations for the pragmatic skills are offered and a set of pragmatic skills are described in detail. These skills include (1) the provision of medical information that informs the need for a decision, (2) the recognition that there is more than one acceptable choice a patient can make, (3) the need to describe the different treatment options, (4) the elicitation of family questions or concerns, (5) the elicitation of family values, (6) determination of the extent of clinician involvement in decision making, (7) recommendation by the clinical team if desired by the family, and finally, (8) making a plan for follow-up.
Central nervous system
Authors: Erridge Sara C. , Thompson Gerard , Summers David
Published: February 2022

This chapter covers a wide range of tumours arising in the CNS and includes orbital tumours alongside those in the brain and spinal cord. The most common malignant tumours to arise in the CNS are metastases from solid tumours in particular breast and lung. Primary brain tumours range from benign growths such as meningioma to highly malignant glioblastoma. Primary CNS lymphoma is also included. The mainstay of diagnosis in CNS tumours is CT but far more detail around anatomical site and adjacent structures will be seen on MRI. Treatment will be either surgery when MR, often with functional sequences, is widely used to aid localisation and resection and radiotherapy (often with chemotherapy. Radiotherapy planning is based on CT but registered MR images are important to optimise treatment volume and organ at risk definition.
Soft tissue sarcomas
Authors: Brothwell Morag , Prewett Sarah , Horan Gail , Gerety Emma-Louise
Published: February 2022

Soft tissue sarcomas are usually initially identified by ultrasound for superficial lesions or computed tomography for deep lesions. Lesions identified with suspicious features or above a certain size require further assessment with magnetic resonance imaging (MRI). MRI imaging provides superior soft tissue contrast for characterization of the sarcoma. However, biopsy is usually required for definitive histological diagnosis. Biopsy may commonly require the use of ultrasound or CT, to target the region most likely to yield a positive diagnosis. MRI also has a crucial role in following treatment response, surgical planning, and post-surgical follow-up. Computed tomography is used routinely to detect metastatic disease for staging. The emerging role of nuclear medicine will also be discussed in the chapter.
Palliative medicine in the intensive care unit
Authors: Einav Sharon , Cherny Nathan I. , Curtis J. Randall
Published: February 2022

Despite best efforts, a substantial proportion of patients admitted to intensive care units (ICUs) die either during care or after a trial of intensive supportive therapy that fails to improve the patient’s well-being and these patients often have palliative care needs that should be addressed. Patients who ultimately survive an ICU stay may also have important palliative care needs. In the ICU, the duality of hope and death challenges clinicians, family members of desperately ill patients, and sometimes the patients themselves. Given the high severity of illness, it is incumbent upon intensive care practitioners to develop the skills and promote creation of a therapeutic environment that can effectively deal with humane care for patients with serious illness. This is reflected in a growing medical literature, the development of clinical standards, and in a new research agenda addressing the needs of intensive care patients, their families, and the clinicians caring for them. This chapter reviews these developments and outlines frameworks for care strategies, symptom management, and quality improvement initiatives.
Palliative care in the emergency department
Authors: George Naomi , Grudzen Corita
Published: February 2022

The emergency department provides immediate access to medical care for patients and families in crisis. As the proportion of elderly in our population continues to increase, complications related to advanced illness will drive increasing numbers of patients with palliative care needs to the emergency department for care. In addition to immediately life-threatening situations, severe physical symptoms, psychological distress, caregiver burdens, and unrecognized psychological or spiritual crises can overwhelm patients or their caregivers, who come to the emergency department hoping for relief from their suffering. When treating patients with serious illness, emergency clinicians must rapidly assess the situation at hand, provide time-sensitive clinical interventions, and engage in effective and efficient communication pertaining to often complex and charged topics. This chapter addresses several of the essential clinical skills for effective primary palliative care in the emergency department, including care of the imminently dying patient, as well as care of patients who are seriously ill who are not yet facing a terminal event. Essential skills include rapid identification of patients with palliative care needs, efficiently establishing treatment goals and a treatment pathway, titration of medications for symptom emergencies, skilful and empathic death disclosure, and a structured approach to involving family presence during resuscitation efforts.
Medical rehabilitation and the palliative care patient
Authors: Cole Andrew M.
Published: February 2022

Everybody values functional independence as a principal determinant of quality of life, and patients receiving palliative care and their caregivers are no exception. Rehabilitation techniques, interventions, and strategies can offer much to meet the needs of patients with advanced disease. The first section of this chapter describes relevant rehabilitation services available in hospitals and ambulatory settings for palliative care patients. The next section reviews the importance of early, goal-directed rehabilitation interventions for individuals receiving palliative care. Some in-depth examples of rehabilitation interventions are given that can improve function for patients with advanced disease processes, specifically in areas of frailty, deconditioning, and neurological impairment. This also includes the important areas of caregiver training and support. The final section reviews challenges to the effective use of rehabilitation strategies in palliative care settings, without tolerating therapeutic nihilism for these patients.
Non-opioid analgesics
Authors: Sjøgren Per , Elsner Frank , Kaasa Stein
Published: February 2022

Non-opioid analgesics encompass the non-steroidal anti-inflammatory drugs (NSAIDs) and paracetamol (acetaminophen). The NSAIDs include acetylsalicylic acid (aspirin), dipyrone (metamizole), and numerous other drugs in diverse classes. The NSAIDs have potent anti-inflammatory, analgesic, and antipyretic activities, and are among the most widely used drugs worldwide. In palliative medicine, they represent the first step of the World Health Organization’s analgesic ladder used for mild pain and they are an important supplement to opioids and adjuvant drugs at higher steps of the ladder. The disadvantages of non-opioid analgesics include a ceiling effect for pain relief and the risk of side effects. NSAIDs are associated with an increased risk of adverse gastrointestinal, renal, and cardiovascular effects and hepatotoxicity can result from overdosing with paracetamol. Dipyrone treatment may involve the risk of agranulocytosis. This chapter describes the clinical pharmacology of NSAIDs, their classification, molecular mechanisms of action, and adverse effects.
Adjuvant analgesics
Authors: Portenoy Russell K. , Ahmed Ebtesam , Patel Mona
Published: February 2022

In the management of pain associated with serious illness, ‘adjuvant analgesics’ are usually administered in conjunction with opioid therapy in an effort to improve outcomes when an opioid does not provide satisfactory relief with tolerable side effects. They may be divided into categories, including multipurpose drugs, and drugs used selectively for neuropathic pain, bone pain, or pain due to bowel obstruction. These drugs are selected for a trial based on limited data available and clinical experience. Multipurpose drugs may be considered for any type of pain. The most useful include corticosteroids and analgesic antidepressants. For neuropathic pain, conventional first-line agents are gabapentinoids, analgesic antidepressants, and corticosteroids. Corticosteroids and bisphosphonates are used commonly for bone pain. The indications and dosing strategies for these drugs are evolving as scientific evidence and clinical experience grow.
Aetiology, classification, assessment, and treatment of the anorexia-cachexia syndrome
Authors: Baracos Vickie , Watanabe Sharon M.
Published: February 2022

Anorexia-cachexia is a heterogeneous and multifactorial syndrome most likely driven by systemic inflammation, neuroendocrine activation, and tumour-derived mediators. Key diagnostic features include reduced appetite, weight loss, and muscle wasting. Key clinical problems include facilitation of food intake without resort to artificial nutritional support, and muscle wasting that cannot be completely arrested/reversed even with such intervention. Assessment should cover domains such as body stores of energy and protein, food intake, performance status, and factors resulting in excess catabolism. Intervention should be early rather than late, informed by the assessment process and focused on a multimodal approach (nutrition, exercise, and pharmacological agents). This chapter aims to discuss these issues and provide (a) the reader with some background principles to classification, (b) a simple approach to patient assessment and a robust algorithm for basic multimodal treatment, and (c) an overview of the evidence base for different pharmacological interventions.
Cough and other pulmonary symptoms
Authors: Tse Doris , Chan Kin-Sang
Published: February 2022

Respiratory symptoms other than breathlessness are prevalent in palliative care patients suffering from cancer or chronic lung disease, including chronic obstructive pulmonary disease, bronchiectasis, and cystic fibrosis. Cough may cause physical and psychological morbidity with impaired quality of life. In chronic obstructive pulmonary disease, chronic cough and sputum are associated with disease progression and poorer prognosis. Recommendations on the symptomatic treatment of cough are based on limited evidence in palliative care settings, expert consensus, and studies involving other patients with chronic cough. Novel antitussive agents are being developed with more understanding of the role of ion channels in cough mechanism. Airway hypersecretion due to chronic inflammation and infection is common in chronic lung disease and the use of mucoactive agents may have a modest benefit on acute exacerbations and quality of life. Massive hypersecretion as in bronchorrhoea is uncommon, but can be distressing with no standard treatment. The choice of managing the patient with malignant pleural effusion includes repeated thoracocentesis, pleurodesis, or an intrapleural catheter, depending on the patient’s predicted survival and other factors. Haemoptysis is often alarming to patients and their families. History taking, physical examination, and a chest radiograph are informative, and guide the treatment plan in most of the patients. Other imaging and invasive interventions should be carefully considered in patients when evaluating whether it is feasible to stop massive bleeding from a localized site.
Oral care
Authors: Davies Andrew N.
Published: February 2022

Oral problems are common in patients with advanced cancer as well as in other groups of patients with life-limiting illnesses (and more generally in patients with chronic illness). Oral problems may be related to direct (‘anatomical’) effect of the primary disease, indirect (‘physiological’) effect of the primary disease, treatment of the primary disease, direct/indirect effect of a coexisting disease, treatment of the coexisting disease, or combinations of these factors. The successful management of oral problems involves adequate assessment, appropriate treatment, and adequate reassessment. In some cases, the most appropriate treatment for a patient with advanced cancer is the same treatment that would be given to a patient with early cancer (or no cancer). Thus, intensive treatment of the oral problem often results in the best palliation of the oral problem. It is not justified to withhold treatment on the grounds that the patient has advanced cancer; however, it may be justified to amend treatment (when appropriate).
Depression, demoralization, and suicidality
Authors: Kissane David W.
Published: February 2022

The development of clinical depression is common during palliative care, adversely affects quality of life and adherence to medical treatments, yet regrettably can pass unrecognized. Screening for distress as the sixth vital sign is therefore highly recommended. Demoralization is another form of distress where low morale and poor coping are associated with hopelessness, helplessness and pointlessness of continued life, and may lead to suicidal thinking. As the mental condition deteriorates, comorbid states of anxiety, depression, and demoralization become more likely. Rates of suicide are increased with advanced cancer and poor symptom control. Fortunately, combined treatment with medication and counselling is effective in ameliorating depression, demoralization, and suicidality. Meta-analyses of psychotherapy trials confirm clear benefits, with behavioural activation, supportive, interpersonal, and cognitive behavioural therapies all making contributions. Group, couple, and family therapies optimize support for all involved. All members of the multidisciplinary team contribute to the active treatment of depression, demoralization, and the prevention of suicide.
Dementia
Authors: Widera Eric , Talebreza Shaida , Bernacki Rachelle E.
Published: February 2022

Dementia is caused by a variety of disorders that result in a progressive loss of both cognitive and functional abilities. Despite the heterogeneity of disorders, there is a common set of problems that patients and families face living with this syndrome. Pain, eating difficulties, depression, apathy, and behavioural symptoms are common. As the disease progresses to the advanced stages, the different disorders share a common functional trajectory that includes persistently severe disability with complete dependence on others for basic activities of daily living. Care for individuals with dementia should involve a number of important palliative interventions. Advance care planning should occur early on in the disease process as it is anticipated that an individual will lose capacity to make medical and financial decisions at some point in their illness; specialized programmes for end of life care, such as hospice, should be considered for all patients with advanced dementia.
History and Management
Authors: Goss Rachel , McMaster Emma , Rennie Stephanie
Published: February 2022

This chapter contains 22 different history and management sample cases for the Fellowship of the Royal College of Emergency Medicine (FRCEM) Objective Structured Clinical Examination (OSCE). In this chapter, candidates are provided with the opportunity to go beyond simply taking a history to incorporating advanced communication skills and the knowledge and application of up-to-date guidelines. The cases reflect a range of common presentations that are pertinent to the Royal College of Emergency Medicine curriculum and that are seen in real-life emergency departments. Each case contains instructions for the candidate and the patient actor, as well as a sample mark scheme breakdown and mark scheme. Key learning points are highlighted after each case.
Practical Skills and Procedures
Authors: Goss Rachel , McMaster Emma , Rennie Stephanie
Published: February 2022

This chapter contains ten different sample cases of practical skills for the Fellowship of the Royal College of Emergency Medicine (FRCEM) Objective Structured Clinical Examination (OSCE). In this chapter, candidates are expected to be able to perform or teach a variety of procedures. Key concepts are common to all practical procedure stations and are taught in this chapter. Additional marks will be gained for communication skills, knowledge, and application of up-to-date guidelines. The cases reflect a range of common presentations that are pertinent to the Royal College of Emergency Medicine (RCEM) curriculum and that are seen in real-life emergency departments. Each case contains instructions for the candidate and the patient actor, as well as a sample mark scheme breakdown and a mark scheme. Key learning points are highlighted after each case.
A cytosine base editor toolkit with varying activity windows and target scopes for versatile gene manipulation in plants
Authors: Xiong Xiangyu , Li Zhenxiang , Liang Jieping , Liu Kehui , Li Chenlong , Li Jian-Feng
Published: February 2022

CRISPR/Cas-derived base editing tools empower efficient alteration of genomic cytosines or adenines associated with essential genetic traits in plants and animals. Diversified target sequences and customized editing products call for base editors with distinct features regarding the editing window and target scope. Here we developed a toolkit of plant base editors containing AID10, an engineered human AID cytosine deaminase. When fused to the N-terminus or C-terminus of the conventional Cas9 nickase (nSpCas9), AID10 exhibited a broad or narrow activity window at the protospacer adjacent motif (PAM)-distal and -proximal protospacer, respectively, while AID10 fused to both termini conferred an additive activity window. We further replaced nSpCas9 with orthogonal or PAM-relaxed Cas9 variants to widen target scopes. Moreover, we devised dual base editors with AID10 located adjacently or distally to the adenine deaminase ABE8e, leading to juxtaposed or spaced cytosine and adenine co-editing at the same target sequence in plant cells. Furthermore, we expanded the application of this toolkit in plants for tunable knockdown of protein-coding genes via creating upstream open reading frame and for loss-of-function analysis of non-coding genes, such as microRNA sponges. Collectively, this toolkit increases the functional diversity and versatility of base editors in basic and applied plant research.
Dual versus Administrative Federalism: Origins and Evolution of Two Models
Authors: Mueller Sean , Fenna Alan
Published: February 2022

Federations have traditionally divided powers either along policy lines, in which case a dual system results, or along functional lines with the central government legislating and the constituent units implementing, in which case a system of administrative federalism results. Although this distinction is widely used, we know little of its specific origins, the degree to which it accurately portrays federal practice today, or even its implications. This article examines the origins and traces the evolution of these two models in six federations since their formation: the United States, Switzerland, Canada, Australia, Germany, and India. Two questions are addressed. First, what explains the choice for either the one or the other type, and is administrative federalism really sui generis to Germany, as often argued in the literature? And second, how have they evolved over time and has there been a convergence?
Public Opinion, Federalism, and Level of Governmental Intervention: Perceptions of Law Enforcement Response to the 2020 George Floyd Protests
Authors: Kolcak Burcu , McCabe Katherine T
Published: February 2022

In June 2020, President Trump issued an executive order calling for the deployment of federal law enforcement agents to protests against police brutality. Several mayors across the country objected to this unilateral deployment of federal force as unconstitutional. In an online survey experiment, we test whether the public stands against this type of federal power aggrandizement by evaluating how approval of federal intervention in protests changes depending on whether it is requested by local mayors or directed by the presidential administration. The results show that the public is responsive to the level of government directing the action. Respondents are significantly less approving of the use of federal forces when it is directed by the federal executive branch. However, not all subgroups respond equally to the manipulation. The treatment effects vary significantly by respondent partisanship, trust in government, and perceptions of the importance of federalism.