bluuebunny/crossref_metadata_2025 huggingface dataset:
Stone disease
Authors: Biers Suzanne , Armenakas Noel , Lamb Alastair , Mark Stephen , Reynard John , Sullivan Mark , Turner Kevin , Turney Ben
Published: March 2020

This chapter covers the treatment options for kidney, ureteric, and bladder stones. It takes the reader through the diagnosis, presentation, and imaging, before detailing different treatments and management and diagnosis in difficult or uncommon situations.
Surgery for upper tract obstruction and other ureteric surgery
Authors: Biers Suzanne , Armenakas Noel , Lamb Alastair , Mark Stephen , Reynard John , Sullivan Mark , Turner Kevin , Turney Ben
Published: March 2020

This chapter covers pelvi-ureteric junction obstruction in adults, the management of ureteric strictures and retroperitoneal fibrosis, ureteric re-implantation, and repair of uteroceles. It contains patient position, the operative technique, outcomes, and complications.
Trauma to the genitourinary tract and other urological emergencies
Authors: Biers Suzanne , Armenakas Noel , Lamb Alastair , Mark Stephen , Reynard John , Sullivan Mark , Turner Kevin , Turney Ben
Published: March 2020

This chapter starts by describing the essentials in the initial evaluation of the trauma patient. It then goes on to explain how to manage renal, ureteric, bladder, testicular, penile, and scrotal injuries. It covers tissue transfer techniques in genital reconstructive surgery, anterior and posterior urethral injuries, pelvic fractures, paraphimosis, priapism, and testicular torsion.
Scrotal and penile surgery
Authors: Biers Suzanne , Armenakas Noel , Lamb Alastair , Mark Stephen , Reynard John , Sullivan Mark , Turner Kevin , Turney Ben
Published: March 2020

This chapter covers surgery of the scrotum and the penis. It gives indications, contraindications, and techniques for circumcision, meatotomy, hydrocele repair, vasectomy, orchidectomy, epididymectomy, and testicular and epididymal biopsy.
Uroradiological and other interventions
Authors: Biers Suzanne , Armenakas Noel , Lamb Alastair , Mark Stephen , Reynard John , Sullivan Mark , Turner Kevin , Turney Ben
Published: March 2020

This chapter covers uroradiological interventions in urology, including percutaneous nephrostomy, antegrade stent insertion, renovascular procedures, radiofrequency ablation, renal cryoablation, and varicocele and prostate embolization.
Surgery for disorders of erectile function, ejaculation, and seminal vesicles
Authors: Biers Suzanne , Armenakas Noel , Lamb Alastair , Mark Stephen , Reynard John , Sullivan Mark , Turner Kevin , Turney Ben
Published: March 2020

This chapter begins by covering the physiology of erections and ejaculation. It provides ways of evaluating erectile dysfunction and then surgical interventions, including vascular surgery and penile prosthesis. Finally, surgical treatment for Peyronie’s disease is covered.
Management of the neuropathic bladder
Authors: Biers Suzanne , Armenakas Noel , Lamb Alastair , Mark Stephen , Reynard John , Sullivan Mark , Turner Kevin , Turney Ben
Published: March 2020

A variety of neurological conditions are associated with abnormal bladder and sphincter function, e.g. spinal cord injury (SCI), spina bifida (myelomeningocele), and multiple sclerosis (MS). The bladder and sphincters of such patients are described as ‘neuropathic’. This chapter describes the clinical consequences with the neuropathic lower urinary tract, bladder management techniques, and cystoplasty. It also provides management of incontinence, recurrent urinary tract infections, and hydronephrosis. Finally, it also covers catheters and condoms and artificial urinary sphincters.
Paediatric urology
Authors: Biers Suzanne , Armenakas Noel , Lamb Alastair , Mark Stephen , Reynard John , Sullivan Mark , Turner Kevin , Turney Ben
Published: March 2020

Paediatric urology is a sub-specialty derived from urology and paediatric surgery. It is generally an elective surgical specialty with few acute conditions. Development of a good team incorporating a paediatric nephrologist, a radiologist, and a pathologist assists in the clinical diagnosis, management options, and follow-up. A paediatric anaesthetist and skilled experienced and compassionate nursing staff are essential to manage the children. This chapter covers the foreskin and circumcision, undescended testes and testis torsion, hypospadias, abnormalities of the urethra, ambiguous genitalia, and malignancies of the genitourinary tract.
Female urology and incontinence surgery
Authors: Biers Suzanne , Armenakas Noel , Lamb Alastair , Mark Stephen , Reynard John , Sullivan Mark , Turner Kevin , Turney Ben
Published: March 2020

This chapter covers female stress urinary incontinence and its management, including assessment, non-operative management, urethral bulking agents, artificial urinary sphincters, and different types of sling. It also describes modes of management for male stress urinary incontinence, pelvic organ prolapse, female urethral diverticulum, and the repair of vesicovaginal fistula.
Medicolegal aspects of urology
Authors: Biers Suzanne , Armenakas Noel , Lamb Alastair , Mark Stephen , Reynard John , Sullivan Mark , Turner Kevin , Turney Ben
Published: March 2020

This chapter covers the medicolegal aspects of urology. It starts with the reasons people sue surgeons, the factors that precipitate litigation, and steps a surgeon can do to prevent possible litigation (from referral letters and patient identification to good communication skills). Good record-keeping is described, as well as correct procedures for obtaining consent, including methods of explaining different treatment options succinctly and appropriately to the patient.
Paediatric Endocrinology and Diabetes
Authors: Butler Gary , Kirk Jeremy
Published: March 2020

The updated handbook of Paediatric Endocrinology and Diabetes is a comprehensive pocket-sized guide of areas of endocrinology and diabetes that clinicians are likely to encounter. Chapters are divided up into those that reflect a clinical problem (e.g. short stature, pubertal disorders, late effects, and obesity), a particular endocrine gland (e.g. adrenal and thyroid glands), plus chapters on endocrine testing and also management of endocrine emergencies. These are all set out in a logical and easily readable fashion; where appropriate, background embryology, anatomy, and physiology are provided, along with differential diagnosis, investigation, and also management, including tips gleaned over decades of clinical experience. The handbook is written for a broad clinical readership including students, doctors in training, and established consultants as well as nurses and allied health professionals.
Puberty and its disorders
Authors: Butler Gary , Kirk Jeremy
Published: March 2020

• Puberty is defined as the acquisition of secondary sexual characteristics, with a view to reproductive capability.

• Assessment of puberty can be done by Tanner stages or the puberty phases.

• Timing of pubertal onset and sequence of changes is carefully controlled.

• Premature sexual maturation:

◦ <8 years in girls; menarche <11 years

◦ <9 years in boys.

• Central precocious puberty or gonadotropin-dependent precocious puberty:

◦ hormone secretion is similar to normal puberty

◦ may be idiopathic, genetic, or secondary to central nervous system/pituitary tumour or insult

◦ treatment is with gonadotropin-releasing hormone analogues.

• Gonadotropin-independent precocious puberty (independent source of sex steroid, e.g. gonadal tumour):

◦ treatment should address the primary cause.

• Late puberty:

◦ pubertal events within the later normal range.

• Delayed onset of puberty:

◦ absence of secondary sexual characteristics:

■ >13 years in a girl

■ >14 years in a boy

• Central causes (low follicle-stimulating hormone (FSH)/luteinizing hormone (LH)):

◦ chronic illness

◦ eating disorders

◦ physiological

◦ hypogonadotropic hypogonadism.

• Peripheral causes (high FSH/LH):

◦ gonadal dysgenesis including chromosomal syndromes, e.g. Turner, Klinefelter

◦ gonadal damage including cancer treatments.

• Treatment:

◦ low-dose sex hormone to induce growth and secondary sexual characteristics

◦ recombinant FSH/LH to induce fertility potential.
Endocrine effects of other diseases and treatments
Authors: Butler Gary , Kirk Jeremy
Published: March 2020

• Survival rates for childhood cancer have doubled over the last 50 years.

• With improved numbers of survivors of childhood cancer (currently 1 in 715 young adults), late effects (including endocrine) of therapy are increasingly recognized.

• Endocrine late effects are found in 20–50% of patients (multiple in up to 20%) dependent on underlying malignancy, age, sex, and time elapsed since therapy.

• In addition to the tumour itself, the three main treatment modalities—surgery, radiotherapy, and chemotherapy—all cause late effects.

◦ Radiotherapy can be used either on its own, or following chemotherapy and/or surgery. It produces late effects via action on the:

■ pituitary/hypothalamus

■ endocrine gland itself

■ end organ such as bone.

■ Effects are dependent on site, total dose, and also regimen, e.g. single dose vs fractionated. They are also progressive and irreversible.

◦ Chemotherapy:

■ generally produces gonadal toxicity; with little effect on other endocrine glands (including pituitary/hypothalamus). Osteopenia/osteoporosis and dyslipidaemia are also described

■ damage dependent on type and dose, plus age at administration

■ effects may be reversible.

• Poor growth following cancer therapy is multifactorial:

◦ non-hormonal: poor nutrition, steroid therapy, direct bone/soft tissue damage

◦ hormonal: GH deficiency, delayed/premature puberty, hypothyroidism
Diabetes mellitus
Authors: Butler Gary , Kirk Jeremy
Published: March 2020

• Diabetes mellitus is a chronic hyperglycaemia state, caused by defects in:

◦ insulin secretion

◦ insulin action

◦ both.

• Type 1 diabetes accounts for ~95% of cases.

◦ Rising incidence in UK (25/100,000 children/year) now appears to be stabilizing.

◦ Peaks at younger age (4–6 years of age) and also puberty.

• Therapy:

■ With subcutaneous insulin (multiple daily injections, continuous subcutaneous insulin infusion (CSII) (less used now, twice- and thrice-daily mixtures)) to mimic physiological secretion, maintain euglycaemia, minimize hypoglycaemic episodes and diabetic ketoacidosis.

◦ Monitoring:

■ Minimum of five self-monitored blood glucose measurements a day recommended. Continuous glucose monitoring increasingly utilized, especially with CSII.

■ Overall control assessed using glycated haemoglobin.

• Outcome:

■ Clear evidence that good diabetic control associated with reduction in complications (micro- and macrovascular).

■ Screening recommended at an early stage to detect complications and prevent progression.

• Type 2 diabetes:

◦ Increasingly recognized in children/adolescents.

◦ Increased incidence in:

■ females

■ ethnic minorities

■ overweight/obese

■ those with family history.

◦ Part of metabolic syndrome: T2DM/insulin resistance, hypertension, hyperlipidaemia, cardiovascular disease, adrenarche/polycystic ovarian syndrome.

◦ A combination of insulin resistance and (relative) insulin deficiency; oral hypoglycaemics may be appropriate (at least initially).

• Other forms of diabetes (uncommon):

◦ Maturity-onset diabetes of the young (MODY):

■ autosomal dominant inheritance; dependent on type, variable

■ response to oral hypoglycaemics

■ development of microvascular complications.

◦ Association with syndromes, e.g. Wolfram, Walcott–Rallison, Prader–Willi syndrome.

◦ Cystic fibrosis-related diabetes:

■ not autoimmune in origin, due to combination of insulin deficiency/resistance

■ increasing incidence with age

■ treatment is with insulin.
Hypoglycaemia
Authors: Butler Gary , Kirk Jeremy
Published: March 2020

• Hypoglycaemia is defined as ‘A plasma glucose concentration low enough to cause symptoms and/or signs of impaired brain function’.

• Cut-offs are contentious, ranging from <2.2 to <4.0 mmol/L, and are dependent on age, diagnosis, and also availability/usage of alternative metabolic fuels such as ketones.

• May be transient or persistent, dependent on diagnosis.

• Causes broadly due to:

◦ decreased glucose including prematurity, inborn errors of metabolism, hypopituitarism, adrenal insufficiency (primary and secondary), and prolonged fasting

◦ increased glucose utilization including infant of diabetic mother, hyperinsulinaemia, perinatal asphyxia, and various syndromes, e.g. Beckwith–Wiedemann.

• Endocrine causes of hypoglycaemia include growth hormone deficiency, adrenal insufficiency (primary and secondary), and (?) hypothyroidism.

• Metabolic disorders cause hypoglycaemia via impaired:

◦ mobilization of glucose stores

◦ gluconeogenesis

◦ alternative energy sources

◦ liver function.

• Hyperinsulinaemic hypoglycaemia presents with increased glucose requirements (>8 mg/kg/minute) and non-ketotic hypoglycaemia. Diagnosis confirmed by demonstrating raised/detectable insulin/C-peptide during hypoglycaemia. Genotyping may assist with not only diagnosis but direct therapy (medical and surgical).
Adrenal gland disorders
Authors: Butler Gary , Kirk Jeremy
Published: March 2020

• The fetal adrenal gland has an additional cortex which atrophies after birth.

• Postnatally, there are three zones to the cortex:

◦ glomerulosa producing mineralocorticoids

◦ fasciculata producing cortisol

◦ reticularis producing androgens.

• Adrenarche is a maturation process from age 6 years with an increase in androgens.

• Acute adrenal crisis presents with:

◦ low sodium

◦ high potassium

◦ cortisol low/undetectable.

• ACTH raised in primary causes, low in secondary.

• Primary insufficiency may be congenital dysplasia (adrenal hypoplasia congenita) and enzyme blocks: congenital adrenal hyperplasia (CAH).

• Acquired causes include autoimmune adrenalitis (Addison’s disease) and tuberculosis.

• Secondary insufficiency arises due to adrenocorticotropic hormone deficiency from hypopituitarism (congenital or acquired).

• CAH, e.g. 21-hydroxylase deficiency (commonest), can present with virilization of a newborn female, hyperandrogenism, or salt-wasting adrenal crisis.

• Iatrogenic treatment is commonest cause of adrenal steroid excess.

• Other causes are adrenal adenoma/carcinoma (Cushing syndrome) or pituitary adenoma (Cushing disease).
Thyroid gland disorders
Authors: Butler Gary , Kirk Jeremy
Published: March 2020

• The thyroid gland produces all of the T4 and 20% of T3.

• Congenital hypothyroidism is caused by:

◦ anatomical defects: agenesis/dysgenesis, ectopic, sublingual

◦ inborn errors of thyroid hormone metabolism

◦ secondary (pituitary thyroid-stimulating hormone (TSH)) or tertiary (hypothalamic thyrotropin-releasing hormone) deficiency

◦ iodine deficiency (commonest cause worldwide of hypothyroidism, patients are usually euthyroid).

• Genetic causes are rare.

• In most countries worldwide, newborn TSH screening is performed at 0–5 days of age. Treatment with l-thyroxine is (usually) lifelong.

• Neonatal thyrotoxicosis due to transplacental passage of thyroid-stimulating immunoglobulins (TSIs) from mothers with thyrotoxicosis/Graves’ disease and may require antithyroid drugs (ATDs).

• Acquired autoimmune hypothyroidism in children and adolescents:

◦ is caused by lymphocytic infiltration of the thyroid gland (Hashimoto’s disease/thyroiditis)

• raised thyroid peroxidase antibodies are diagnostic

• treatment is with l-thyroxine.

• Hyperthyroidism (Graves’ disease, Hashimoto’s stimulatory phase (Hashitoxicosis)):

◦ is caused by autoantibodies to the TSH receptor (TSI, or TRAbthyrotropin receptor antibody)

◦ the first-line drug of choice is the ATD carbimazole

◦ thyroidectomy or radioiodine treatment can be considered for drug-resistant cases or after relapse.

• Thyroid cancer is rare in childhood and adolescence, usually presenting with a nodule, but can be part of the multiple endocrine neoplasia syndromes.
Calcium, vitamin D, and bone disorders
Authors: Butler Gary , Kirk Jeremy
Published: March 2020

• Calcium metabolism is complex and dependent upon parathyroid hormone (PTH), calcitonin, and vitamin D3.

• Bone mineralization is dependent on normal health, diet growth, and puberty.

• Osteoporosis or osteopenia is a loss of total bone content, due to:

◦ decreased bone formation

◦ increased bone resorption.

• Osteomalacia is a defect in bone mineralization.

• Osteogenesis imperfecta is the most common cause of primary osteoporosis (although rare).

• Bisphosphonates can be used to reduce symptoms.

• Hypocalcaemia (<2.2 mmol/L) can be caused by:

◦ primary hypoparathyroidism

◦ PTH resistance syndromes

◦ hypomagnesaemia

◦ vitamin D deficiency

◦ activating mutations of calcium-sensing receptor gene (CASR)

◦ autoimmune (may occur as part of polyglandular syndrome)

◦ metabolic disease.

• Albright’s hereditary osteodystrophy (AHO):

◦ is a family of PTH resistance syndromes caused by abnormalities in function of the GS-α‎ part of the G protein-coupled PTH receptor (GNAS1 gene).

◦ Treatment is with 1α‎-hydroxyvitamin D3 (alfacalcidol). Oral calcium supplements may be needed.

• Hypercalcaemia is rare in infancy and childhood; calcium >2.65 mmol/L usually detected by chance. Caused by:

◦ neonatal primary hyperparathyroidism: homozygous inactivating mutations of the CASR gene

◦ Williams syndrome, with mild hypercalcaemia is a feature in 20%

◦ vitamin D excess.

• Rickets can present with:

◦ symptoms and signs of hypocalcaemia

◦ muscle weakness

◦ metaphyseal flaring

◦ bowed legs

◦ rickety rosary.

• Treatment is with vitamin D3 or D2.

• Other genetic forms of rickets are rare.
Gender incongruence
Authors: Butler Gary , Kirk Jeremy
Published: March 2020

• Gender dysphoria is a disassociation with birth gender and identification with the opposite gender.

• The diagnosis needs to be made by an experienced mental health practitioner in accord with the Endocrine Society and World Professional Association for Transgender Health guidelines.

• Most presenting in childhood are less likely to go onto physical treatment, whereas the majority of adolescents may wish to socially and physically transition.

• Appropriate help and support should only be provided by an integrated medical and psychological/mental health team working in collaboration, with a psychosocial assessment preceding the medical review.

• Initial medical assessment should be supportive only. A physical diagnostic approach is not required, and it is not considered similar to a disorder of sex development.

• Counselling about fertility loss is required.

• Endocrine supportive treatment is with gonadotropin-releasing hormone analogues initially.

• Cross-sex hormone/gender-affirming hormone therapy may be considered after further counselling.

• Surgical gender reassignment is carried out in adulthood only after additional detailed counselling.
Endocrine emergencies
Authors: Butler Gary , Kirk Jeremy
Published: March 2020

• This chapter is intended to be brief, providing readily accessible information required in an endocrine emergency in an infant, child, or adolescent.

• Endocrine emergencies are rare but because of this they are usually unexpected.

• Always take a few moments to assess the situation.

• Getting the clinical signs and obtaining the right biochemical samples at the time is often the key to getting the correct diagnosis and management.

• The theory and background about each problem are dealt with in the relevant chapter.

• The key endocrine emergencies are:

• diabetic ketoacidosis

• hypoglycaemia

• adrenal insufficiency

• hypocalcaemia

• hypercalcaemia

• acute diabetes insipidus

• syndrome of inappropriate antidiuretic hormone secretion

• hyperthyroid crisis

• hypothyroid coma

• unclear sex (ambiguous genitalia—disorders of sex development).
Sepsis
Authors: Malhas Laith , Daniels Ron
Published: March 2020

This chapter is centred on a case study on sepsis. This topic is one of the key challenging areas in critical care medicine and one that all intensive care staff will encounter. The chapter is based on a detailed case history, ensuring clinical relevance, together with relevant images, making this easily relatable to daily practice in the critical care unit. The chapter is punctuated by evidence-based, up-to-date learning points, which highlight key information for the reader. Throughout the chapter, a topic expert provides contextual advice and commentary, adding practical expertise to the standard textbook approach and reinforcing key messages.
Acute heart failure
Authors: Krepska Amy , Murphy Deirdre
Published: March 2020

This chapter is centred on a case study on acute heart failure. This topic is one of the key challenging areas in critical care medicine and one that all intensive care staff will encounter. The chapter is based on a detailed case history, ensuring clinical relevance, together with relevant images, making this easily relatable to daily practice in the critical care unit. The chapter is punctuated by evidence-based, up-to-date learning points, which highlight key information for the reader. Throughout the chapter, a topic expert provides contextual advice and commentary, adding practical expertise to the standard textbook approach and reinforcing key messages.
Acute respiratory failure
Authors: Bryant Catherine , Shah Sanjoy
Published: March 2020

This chapter is centred on a case study on respiratory failure. This topic is one of the key challenging areas in critical care medicine and one that all intensive care staff will encounter. The chapter is based on a detailed case history, ensuring clinical relevance, together with relevant images, making this easily relatable to daily practice in the critical care unit. The chapter is punctuated by evidence-based, up-to-date learning points, which highlight key information for the reader. Throughout the chapter, a topic expert provides contextual advice and commentary, adding practical expertise to the standard textbook approach and reinforcing key messages.
Early management of multi-trauma
Authors: Rehn Marius , Lockey David J.
Published: March 2020

This chapter is centred on a case study on multi-trauma and describes the patient pathway from the incident scene through to rehabilitation. This topic is one of the key challenging areas in critical care medicine and one that all intensive care staff will encounter. The chapter is based on a detailed case history, ensuring clinical relevance, making this easily relatable to daily practice in the critical care unit. The chapter is punctuated by evidence-based, up-to-date learning points, which highlight key information for the reader. Throughout the chapter, a topic expert provides contextual advice and commentary, adding practical expertise to the standard textbook approach and reinforcing key messages.
Multiple organ support in an ageing population
Authors: Oliver Matt , Murray Dave
Published: March 2020

This chapter is centred on a case study on multiorgan support in the ageing population. This topic is one of the key challenging areas in critical care medicine and one that all intensive care staff will encounter. The chapter is based on a detailed case history, ensuring clinical relevance, together with relevant images, making this easily relatable to daily practice in the critical care unit. The chapter is punctuated by evidence-based, up-to-date learning points, which highlight key information for the reader. Throughout the chapter, a topic expert provides contextual advice and commentary, adding practical expertise to the standard textbook approach and reinforcing key messages.
Sedation and delirium
Authors: Pathmanathan Nim , Nixon Paul
Published: March 2020

This chapter is centred on a case study of sedation and delirium. This topic is one of the key challenging areas in critical care medicine and one that all intensive care staff will encounter. The chapter is based on a detailed case history, ensuring clinical relevance, together with relevant images, making this easily relatable to daily practice in the critical care unit. The chapter is punctuated by evidence-based, up-to-date learning points, which highlight key information for the reader. Throughout the chapter, a topic expert provides contextual advice and commentary, adding practical expertise to the standard textbook approach and reinforcing key messages.
Acute-on-chronic liver failure
Authors: Pirani Tasneem , Wendon Julia
Published: March 2020

This chapter is centred on a case study on acute-on-chronic liver failure. This topic is one of the key challenging areas in critical care medicine and one that all intensive care staff will encounter. The chapter is based on a detailed case history, ensuring clinical relevance, together with relevant images, making this easily relatable to daily practice in the critical care unit. The chapter is punctuated by evidence-based, up-to-date learning points, which highlight key information for the reader. Throughout the chapter, a topic expert provides contextual advice and commentary, adding practical expertise to the standard textbook approach and reinforcing key messages.
Acute pancreatitis and renal replacement therapy
Authors: Lobo Clinton , Gupta Kim , Thomas Matt
Published: March 2020

This chapter is centred on a case study on pancreatitis and renal replacement therapy. This topic is one of the key challenging areas in critical care medicine and one that all intensive care staff will encounter. The chapter is based on a detailed case history, ensuring clinical relevance, together with relevant images, making this easily relatable to daily practice in the critical care unit. The chapter is punctuated by evidence-based, up-to-date learning points, which highlight key information for the reader. Throughout the chapter, a topic expert provides contextual advice and commentary, adding practical expertise to the standard textbook approach and reinforcing key messages.
Prolonged mechanical ventilation and delayed weaning
Authors: Murphy Patrick B. , Hart Nicholas
Published: March 2020

This chapter is centred on a case study on long-term ventilation and weaning. This topic is one of the key challenging areas in critical care medicine and one that all intensive care staff will encounter. The chapter is based on a detailed case history, ensuring clinical relevance, together with relevant images, making this easily relatable to daily practice in the critical care unit. The chapter is punctuated by evidence-based, up-to-date learning points, which highlight key information for the reader. Throughout the chapter, a topic expert provides contextual advice and commentary, adding practical expertise to the standard textbook approach and reinforcing key messages.
Pandemic planning and critical care
Authors: Gabriel Lucinda , Farrar Jeremy
Published: March 2020

+This chapter is centred on a case study on pandemic planning. This topic is one of the key challenging areas in critical care medicine and one that all intensive care staff will encounter. The chapter is based on a detailed case history, ensuring clinical relevance, together with relevant images, making this easily relatable to daily practice in the critical care unit. The chapter is punctuated by evidence-based, up-to-date learning points, which highlight key information for the reader. Throughout the chapter, a topic expert provides contextual advice and commentary, adding practical expertise to the standard textbook approach and reinforcing key messages.
Organ donation and transplantation
Authors: Ray Andrew , Manara Alex
Published: March 2020

This chapter is centred on a case study on organ donation and transplantation. This topic is one of the key challenging areas in critical care medicine and one that all intensive care staff will encounter. The chapter is based on a detailed case history, ensuring clinical relevance, together with relevant images, making this easily relatable to daily practice in the critical care unit. The chapter is punctuated by evidence-based, up-to-date learning points, which highlight key information for the reader. Throughout the chapter, a topic expert provides contextual advice and commentary, adding practical expertise to the standard textbook approach and reinforcing key messages.
An excessively massive thick disc of the enormous edge-on lenticular galaxy NGC 7572
Authors: Kasparova Anastasia V , Katkov Ivan Yu , Chilingarian Igor V
Published: March 2020

Galactic discs are known to have a complex multilayer structure. An in-depth study of the stellar population properties of the thin and thick components can elucidate the formation and evolution of disc galaxies. Even though thick discs are ubiquitous, their origin is still debated. Here we probe the thick disc formation scenarios by investigating NGC 7572, an enormous edge-on galaxy having R25 ≈ 25 kpc and Vrot ≈ 370 km s−1, which substantially exceeds the Milky Way size and mass. We analysed DECaLS archival imaging and found that the disc of NGC 7572 contains two flaring stellar discs (a thin and a thick disc) with similar radial scales. We collected deep long-slit spectroscopic data using the 6 m Russian BTA telescope and analysed them with a novel technique. We first reconstructed a non-parametric stellar line-of-sight velocity distribution along the radius of the galaxy and then fitted it with two kinematic components accounting for the orbital distribution of stars in thin and thick discs. The old thick disc turned out to be 2.7 times as massive as the intermediate-age thin component, 1.6 × 1011 M⊙ versus 5.9 × 1010 M⊙, which is very unusual. The different duration of the formation epochs evidenced by the [Mg/Fe] values of +0.3 and +0.15 dex for the thick and thin discs respectively, their kinematics, and the mass ratio suggest that in NGC 7572 we observe a rapidly formed very massive thick disc and an underdeveloped thin disc, whose growth ended prematurely due to the exhaustion of the cold gas likely because of environmental effects.
Loop-closure kinetics reveal a stable, right-handed DNA intermediate in Cre recombination
Authors: Shoura Massa J , Giovan Stefan M , Vetcher Alexandre A , Ziraldo Riccardo , Hanke Andreas , Levene Stephen D
Published: March 2020

In Cre site-specific recombination, the synaptic intermediate is a recombinase homotetramer containing a pair of loxP DNA target sites. The enzyme system's strand-exchange mechanism proceeds via a Holliday-junction (HJ) intermediate; however, the geometry of DNA segments in the synapse has remained highly controversial. In particular, all crystallographic structures are consistent with an achiral, planar Holliday-junction (HJ) structure, whereas topological assays based on Cre-mediated knotting of plasmid DNAs are consistent with a right-handed chiral junction. We use the kinetics of loop closure involving closely spaced (131–151 bp) loxP sites to investigate the in-aqueo ensemble of conformations for the longest-lived looped DNA intermediate. Fitting the experimental site-spacing dependence of the loop-closure probability, J, to a statistical-mechanical theory of DNA looping provides evidence for substantial out-of-plane HJ distortion, which unequivocally stands in contrast to the square-planar intermediate geometry from Cre-loxP crystal structures and those of other int-superfamily recombinases. J measurements for an HJ-isomerization-deficient Cre mutant suggest that the apparent geometry of the wild-type complex is consistent with temporal averaging of right-handed and achiral structures. Our approach connects the static pictures provided by crystal structures and the natural dynamics of macromolecules in solution, thus advancing a more comprehensive dynamic analysis of large nucleoprotein structures and their mechanisms.
Social Housing Fraud in England
Authors: Pass Mark
Published: March 2020

Social tenancy fraud is believed to cost UK taxpayers an estimated £1.8 billion annually, based upon estimates of prevalence and cost from over 5 years ago. Despite this, there is currently no centrally collected or published data on social tenancy fraud. The aim of this research was to investigate the amount of social tenancy frauds investigated, detected and prosecuted by local authorities in England. This was undertaken by means of documentary analysis, following Freedom of Information requests to the 198 local authorities who hold social housing stock. The research confirmed the findings of previous studies, that social tenancy fraud is a particular problem within London, as well as being increasingly detected in other urban areas. It was found that the amount of social tenancy fraud detected nationally has increased significantly in recent years, doubling since 2009. It is unclear, however, whether this indicates that social tenancy fraud is a growing problem or if the response has improved. This research has also identified a myriad of avenues in which further research would be of value, especially with respect to local government transparency which this research has found, despite recent initiatives, to be lacking.
Lymphopenia in primary Sjögren’s syndrome is associated with premature aging of naïve CD4+ T cells
Authors: Fessler Johannes , Fasching Patrizia , Raicht Andrea , Hammerl Sabrina , Weber Jennifer , Lackner Angelika , Hermann Josef , Dejaco Christian , Graninger Winfried B , Schwinger Wolfgang , Stradner Martin H
Published: March 2020

Objective

To investigate peripheral lymphopenia, a frequent finding in primary Sjögren’s syndrome (pSS) associated with higher disease activity and increased mortality.

Methods

Prospective, cross-sectional study of consecutive patients with pSS (n = 66) and healthy controls (n = 181). Lymphocyte subsets were analysed by flow cytometry, naïve (CD45RA+) and memory (CD45RO+) CD4+ T cells were purified by MACS technology. In vitro proliferation and senescence-associated β-galactosidase (SABG) were assessed by flow cytometry. Telomere length and TCR excision circles (TREC) were measured by real-time PCR. Telomerase activity was analysed according to the telomeric repeat amplification protocols (TRAP).

Results

In pSS, lymphopenia mainly affected naïve CD4+ T cells. We noted a lower frequency of proliferating naïve CD4+ T cells ex vivo and decreased homeostatic proliferation in response to IL-7 stimulation in vitro. Furthermore, naïve CD4+ T cells exhibited signs of immune cell aging including shortened telomeres, a reduction in IL-7R expression and accumulation of SABG. The senescent phenotype could be explained by telomerase insufficiency and drastically reduced levels of T-cell receptor excision circles (TRECs), indicating a history of extensive post-thymic cell division. TRECs correlated with the number of naïve CD4+ T cells linking the extend of earlier proliferation to the inability to sustain normal cell numbers.

Conclusion

In pSS, evidence for increased proliferation of naïve CD4+ T cells earlier in life is associated with a senescent phenotype unable to sustain homeostasis. The lack of naïve CD4+ T cells forms the basis of lymphopenia frequently observed in pSS.
Validity and reliability of a sensor-based electronic spinal mobility index for axial spondyloarthritis
Authors: Gardiner Philip V , Small Dawn , Muñoz-Esquivel Karla , Condell Joan , Cuesta-Vargas Antonio , Williams Jonathan , Machado Pedro M , Garrido-Castro Juan L
Published: March 2020

Objective

To evaluate the validity and reliability of inertial measurement unit (IMU) sensors in the assessment of spinal mobility in axial spondyloarthritis (axSpA).

Methods

A repeated measures study design involving 40 participants with axSpA was used. Pairs of IMU sensors were used to measure the maximum range of movement at the cervical (Cx) and lumbar (Lu) spine. A composite IMU score was defined by combining the IMU measures. Conventional metrology and physical function assessment were performed. Validation was assessed considering the agreement of IMU measures with conventional metrology and correlation with physical function. Reliability was assessed using intra-class correlation coefficients (ICCs).

Results

The composite IMU score correlated closely (r = 0.88) with the BASMI. Conventional Cx rotation and lateral flexion tests correlated closely with IMU equivalents (r = 0.85, 0.84). All IMU movement tests correlated strongly with BASFI, while this was true for only some of the BASMI tests. The reliability of both conventional and IMU tests (except for chest expansion) ranged from good to excellent. Test–retest ICCs for individual conventional tests varied between 0.57 and 0.91, in comparison to a range from 0.74 to 0.98 for each of the IMU tests. Each of the composite regional IMU scores had excellent test–retest reliability (ICCs=0.94–0.97), comparable to the reliability of the BASMI (ICC=0.96).

Conclusion

Cx and Lu spinal mobility measured using wearable IMU sensors is a valid and reliable assessment in multiple planes (including rotation), in patients with a wide range of axSpA severity.
Forecasting the Equity Premium: Mind the News!*
Authors: Adämmer Philipp , Schüssler Rainer A
Published: March 2020

We introduce a novel strategy to predict monthly equity premia that is based on extracted news from more than 700,000 newspaper articles, which were published in The New York Times and Washington Post between 1980 and 2018. We propose a flexible data-adaptive switching approach to map a large set of different news-topics into forecasts of aggregate stock returns. The information that is embedded in our extracted news is not captured by established economic predictors. Compared with the prevailing historical mean between 1999 and 2018, we find large out-of-sample (OOS) gains with an ROOS2 of 6.52% and sizeable utility gains for a mean–variance investor. The empirical results indicate that geopolitical news are at times more valuable than economic news to predict the equity premium and we also find that forecasting gains arise in down markets.
Real-time quantification of damage in structural materials during mechanical testing
Authors: Christian W. J. R. , Dvurecenska K. , Amjad K. , Pierce J. , Przybyla C. , Patterson E. A.
Published: March 2020

A novel methodology is introduced for quantifying the severity of damage created during testing in composite components. The method uses digital image correlation combined with image processing techniques to monitor the rate at which the strain field changes during mechanical tests. The methodology is demonstrated using two distinct experimental datasets, a ceramic matrix composite specimen loaded in tension at high temperature and nine polymer matrix composite specimens containing fibre-waviness defects loaded in bending. The changes in the strain field owing to damage creation are shown to be a more effective indicator that the specimen has reached its proportional limit than using load-extension diagrams. The technique also introduces a new approach to using experimental data for creating maps indicating the spatio-temporal distribution of damage in a component. These maps indicate where damage occurs in a component, and provide information about its morphology and its time of occurrence. This presentation format is both easier and faster to interpret than the raw data which, for some tests, can consist of tens of thousands of images. This methodology has the potential to reduce the time taken to interpret large material test datasets while increasing the amount of knowledge that can be extracted from each test.
Roseimaritima sediminicola sp. nov., a new member of Planctomycetaceae isolated from Chilika lagoon
Authors: Kumar Dhanesh , Gaurav Kumar , U Jagadeeshwari , G Deepshikha , Ch. Sasikala , Ch.V. Ramana
Published: March 2020

Strain JC651T was isolated from a sediment sample collected from Chilika lagoon, which is one of the world’s most important brackish water lakes with estuarine characteristics. Colonies of this strain are light pink and cells are Gram-stain negative, spherical to pear shaped and form rosettes. Strain JC651T grows well up to pH 9.0 and tolerates up to 5 % NaCl (w/v). The respiratory quinone is MK6. The detected major fatty acids are C18 : 1 ω9c and C16 : 0. Its polar lipids are diphosphatidylglycerol, an unidentified phospholipid, phosphatidylglycerol and phosphatidylcholine. Strain JC651T shows highest 16S rRNA gene sequence similarity (97.8%) to the type species of the genus

Roseimaritima

,

Roseimaritima ulvae

UC8T. The genome size of strain JC651T is 6.2 Mb with a G+C content of 62.4 mol%. For the resolution of the phylogenetic congruence of the novel strain, the phylogeny was also reconstructed with the sequences of 92 core genes. Based on the phylogenetic analyses, low digital DNA–DNA hybridization values (19.5%), low (74.9%) genome average nucleotide identity results, chemotaxonomic characteristics and differential physiological properties, strain JC651T is recognized as a new species of the genus

Roseimaritima

for which we propose the name Roseimaritima sediminicola sp. nov. The type strain is JC651T (=KCTC 72178T=NBRC 113926T).
Estimate the incubation period of coronavirus 2019 (COVID-19)
Authors: Men Ke , Wang Xia , Yihao Li , Zhang Guangwei , Hu Jingjing , Gao Yanyan , Han Henry
Published: March 2020

Motivation

Wuhan pneumonia is an acute infectious disease caused by the 2019 novel coronavirus (COVID-19). It is being treated as a Class A infectious disease though it was classified as Class B according to the Infectious Disease Prevention Act of China. Accurate estimation of the incubation period of the coronavirus is essential to the prevention and control. However, it remains unclear about its exact incubation period though it is believed that symptoms of COVID-19 can appear in as few as 2 days or as long as 14 or even more after exposure. The accurate incubation period calculation requires original chain-of-infection data that may not be fully available in the Wuhan regions. In this study, we aim to accurately calculate the incubation period of COVID-19 by taking advantage of the chain-of-infection data, which is well-documented and epidemiologically informative, outside the Wuhan regions.

Methods

We acquired and collected officially reported COVID-19 data from 10 regions in China except for Hubei province. To achieve the accurate calculation of the incubation period, we only involved the officially confirmed cases with a clear history of exposure and time of onset. We excluded those without relevant epidemiological descriptions, working or living in Wuhan for a long time, or hard to determine the possible exposure time. We proposed a Monte Caro simulation approach to estimate the incubation of COVID-19 as well as employed nonparametric ways. We also employed manifold learning and related statistical analysis to decipher the incubation relationships between different age/gender groups.

Result

The incubation period of COVID-19 did not follow general incubation distributions such as lognormal, Weibull, and Gamma distributions. We estimated that the mean and median of its incubation were 5.84 and 5.0 days via bootstrap and proposed Monte Carlo simulations. We found that the incubation periods of the groups with age>=40 years and age<40 years demonstrated a statistically significant difference. The former group had a longer incubation period and a larger variance than the latter. It further suggested that different quarantine time should be applied to the groups for their different incubation periods. Our machine learning analysis also showed that the two groups were linearly separable. incubation of COVID-19 along with previous statistical analysis. Our results further indicated that the incubation difference between males and females did not demonstrate a statistical significance.
Subtype-specific epigenomic landscape and 3D genome structure in bladder cancer
Authors: Iyyanki Tejaswi , Zhang Baozhen , Jin Qiushi , Yang Hongbo , Liu Tingting , Wang Xiaotao , Xu Jie , Song Fan , Luan Yu , Yamashita Hironobu , Wang Lu , Warrick Joshua , Raman Jay , Meeks Joshua J. , Degraff David , Yue Feng
Published: March 2020

Muscle-invasive bladder cancers have recently been characterized by their distinct expression of luminal and basal genes, which could be used to predict key clinical features such as disease progression and overall survival. For example, FOXA1, GATA3, and PPARG have been shown to be essential for luminal subtype-specific regulation and subtype switching, while TP63 and STAT3 are critical for basal subtype bladder cancer. Despite these advances, the underlying epigenetic mechanism and 3D chromatin architecture for subtype-specific regulation in bladder cancers remains largely unknown. Here, we determined the genome-wide transcriptome, enhancer landscape, TF binding profiles (FOXA1 and GATA3) in luminal and basal subtypes of bladder cancers. Furthermore, we mapped genome-wide chromatin interactions by Hi-C in both bladder cancer cell lines and primary patient tumors, for the first time in bladder cancer. We showed that subtype-specific transcription is accompanied by specific open chromatin and epigenomic marks, at least partially driven by distinct TF binding at distal-enhancers of luminal and basal bladder cancers. Finally, we identified a novel clinically relevant transcriptional factor, Neuronal PAS Domain Protein 2 (NPAS2), in luminal bladder cancers that regulates other luminal-specific genes (such as FOXA1, GATA3, and PPARG) and affects cancer cell proliferation and migration. In summary, our work shows a subtype-specific epigenomic and 3D genome structure in urinary bladder cancers and suggested a novel link between the circadian TF NPAS2 and a clinical bladder cancer subtype.
Non-Langmuir kinetics of DNA surface hybridization
Authors: Vanjur L. , Carzaniga T. , Casiraghi L. , Chiari M. , Zanchetta G. , Buscaglia M.
Published: March 2020

Hybridization of complementary single strands of DNA represents a very effective natural molecular recognition process widely exploited for diagnostic, biotechnology and nanotechnology applications. A common approach relies on the immobilization on a surface of single stranded DNA probes that bind complementary targets in solution. However, despite the deep knowledge on DNA interactions in bulk solution, the modelling of the same interactions on a surface are still challenging and perceived as strongly system-dependent. Here we show that a two dimensional analysis of the kinetics of hybridization, performed at different target concentration and probe surface density by a label-free optical biosensor, reveals peculiar features inconsistent with an ideal Langmuir-like behaviour. We propose a simple non-Langmuir kinetic model accounting for an enhanced electrostatic repulsion originating from the surface immobilization of nucleic acids and for steric hindrance close to full hybridization of the surface probes. The analysis of the kinetic data by the model enables to quantify the repulsive potential at the surface, as well as to retrieve the kinetic parameters of isolated probes. We show that the strength and the kinetics of hybridization at large probe density can be improved by a 3D immobilization strategy of probe strands with a double stranded linker.

Statement of Significance

Hybridization of nucleic acids strands with complementary sequences is a fundamental biological process and is also widely exploited for diagnostic purposes. Despite the availability of effective models for the equilibrium strength of freely diffusing strands, a general predictive model for surface hybridization is still missing. Moreover, the kinetics of hybridization is not fully understood neither in solution nor on a surface. In this work we show that the analysis of the kinetics of hybridization on a surface reveals and enables to quantify two main additional contributions: electrostatic repulsion and steric hindrance. These are general effects expected to occur not only on a surface but in any condition with large density of nucleic acids, comparable to that of the cellular nucleus.