Books on the topic 'Active bonnet'

This chapter examines continuity and change in representations of women Friends by non-Quakers in the first 150 years of Quakerism’s existence. Unsurprisingly, given their active role, including the unusual position of female travelling preachers, a large amount of attention, often negative, was paid to Quaker women by male non-Quakers. Analysis of such depictions reveals that stereotyping of female Friends served a number of different ends: it sought to titillate non-Quaker men with depictions of young Quaker women, and to reinforce non-Quaker men’s self-appointed role as moral guardians with religious, moral, and gendered superiority over Quaker women. The chapter considers how such responses were likely driven by anxious hegemonic masculinity, identified by several scholars as central to mainstream male identity, which led Quaker women to initially be viewed as a potent threat and later as stock figures, created to belittle female Friends’ growing moral and political influence.

Bone is metabolically active throughout life and metabolic disturbances may have wide-ranging consequences that are not restricted to altering its mechanics. The study of some genetic bone diseases has already provided remarkable insights into the normal regulation of bone metabolism. Skeletal dysplasias are developmental disorders of the chondro-osseous tissues commonly resulting in short stature, which is often disproportionate. The underlying mutations are often in the structural genes encoding components of the matrix but may also involve growth factors or cell signalling. In contrast, the dysostoses tend to affect single bones or groups of bones, reflecting the transient nature of the many different signalling factors to which they are responsive during development. Abnormalities of bone density (high or low) may be due to primary deficiency of bone matrix synthesis (e.g. osteogenesis imperfecta and hypophosphatasia) but may also reflect an imbalance between bone formation and resorption. This may be caused by abnormalities of bone formation (e.g. hyperostosis/sclerosteosis and osteoporosis pseudoglioma syndrome) or bone resorption (e.g. classic osteopetrosis and fibrous dysplasia).

Osteomalacia is a disorder of bone mineralization and is due to a lack of vitamin D. Vitamin D is a prohormone formed by the action of UV radiation on the vitamin’s precursor (7-dehydrocholesterol) in the skin. It undergoes two hydroxylation steps to become an active hormone. The commonest cause of osteomalacia is vitamin D deficiency due to a lack of UVB skin exposure. Other causes include malabsorption (coeliac disease and pancreatic insufficiency), obesity, and chronic kidney disease. The typical symptoms of osteomalacia are non-specific bone pain, proximal myopathy, fatigue, and polyarthralgia. This chapter addresses the causes, diagnosis, and management of osteomalacia.

Bones are multifunctional passive organs of movement that supports soft tissue and directly attached muscles. They also protect internal organs and are a reserve of calcium, phosphorus and magnesium. Each bone is covered with periosteum, and the adjacent bone surfaces are covered by articular cartilage. Histologically, the bone is an organ composed of many different tissues. The main component is bone tissue (cortical and spongy) composed of a set of bone cells and intercellular substance (mineral and organic), it also contains fat, hematopoietic (bone marrow) and cartilaginous tissue. Bones are a tissue that even in adult life retains the ability to change shape and structure depending on changes in their mechanical and hormonal environment, as well as self-renewal and repair capabilities. This process is called bone turnover. The basic processes of bone turnover are: • bone modeling (incessantly changes in bone shape during individual growth) following resorption and tissue formation at various locations (e.g. bone marrow formation) to increase mass and skeletal morphology. This process occurs in the bones of growing individuals and stops after reaching puberty • bone remodeling (processes involve in maintaining bone tissue by resorbing and replacing old bone tissue with new tissue in the same place, e.g. repairing micro fractures). It is a process involving the removal and internal remodeling of existing bone and is responsible for maintaining tissue mass and architecture of mature bones. Bone turnover is regulated by two types of transformation: • osteoclastogenesis, i.e. formation of cells responsible for bone resorption • osteoblastogenesis, i.e. formation of cells responsible for bone formation (bone matrix synthesis and mineralization) Bone maturity can be defined as the completion of basic structural development and mineralization leading to maximum mass and optimal mechanical strength. The highest rate of increase in pig bone mass is observed in the first twelve weeks after birth. This period of growth is considered crucial for optimizing the growth of the skeleton of pigs, because the degree of bone mineralization in later life stages (adulthood) depends largely on the amount of bone minerals accumulated in the early stages of their growth. The development of the technique allows to determine the condition of the skeletal system (or individual bones) in living animals by methods used in human medicine, or after their slaughter. For in vivo determination of bone properties, Abstract 10 double energy X-ray absorptiometry or computed tomography scanning techniques are used. Both methods allow the quantification of mineral content and bone mineral density. The most important property from a practical point of view is the bone’s bending strength, which is directly determined by the maximum bending force. The most important factors affecting bone strength are: • age (growth period), • gender and the associated hormonal balance, • genotype and modification of genes responsible for bone growth • chemical composition of the body (protein and fat content, and the proportion between these components), • physical activity and related bone load, • nutritional factors: – protein intake influencing synthesis of organic matrix of bone, – content of minerals in the feed (CA, P, Zn, Ca/P, Mg, Mn, Na, Cl, K, Cu ratio) influencing synthesis of the inorganic matrix of bone, – mineral/protein ratio in the diet (Ca/protein, P/protein, Zn/protein) – feed energy concentration, – energy source (content of saturated fatty acids - SFA, content of polyun saturated fatty acids - PUFA, in particular ALA, EPA, DPA, DHA), – feed additives, in particular: enzymes (e.g. phytase releasing of minerals bounded in phytin complexes), probiotics and prebiotics (e.g. inulin improving the function of the digestive tract by increasing absorption of nutrients), – vitamin content that regulate metabolism and biochemical changes occurring in bone tissue (e.g. vitamin D3, B6, C and K). This study was based on the results of research experiments from available literature, and studies on growing pigs carried out at the Kielanowski Institute of Animal Physiology and Nutrition, Polish Academy of Sciences. The tests were performed in total on 300 pigs of Duroc, Pietrain, Puławska breeds, line 990 and hybrids (Great White × Duroc, Great White × Landrace), PIC pigs, slaughtered at different body weight during the growth period from 15 to 130 kg. Bones for biomechanical tests were collected after slaughter from each pig. Their length, mass and volume were determined. Based on these measurements, the specific weight (density, g/cm3) was calculated. Then each bone was cut in the middle of the shaft and the outer and inner diameters were measured both horizontally and vertically. Based on these measurements, the following indicators were calculated: • cortical thickness, • cortical surface, • cortical index. Abstract 11 Bone strength was tested by a three-point bending test. The obtained data enabled the determination of: • bending force (the magnitude of the maximum force at which disintegration and disruption of bone structure occurs), • strength (the amount of maximum force needed to break/crack of bone), • stiffness (quotient of the force acting on the bone and the amount of displacement occurring under the influence of this force). Investigation of changes in physical and biomechanical features of bones during growth was performed on pigs of the synthetic 990 line growing from 15 to 130 kg body weight. The animals were slaughtered successively at a body weight of 15, 30, 40, 50, 70, 90, 110 and 130 kg. After slaughter, the following bones were separated from the right half-carcass: humerus, 3rd and 4th metatarsal bone, femur, tibia and fibula as well as 3rd and 4th metatarsal bone. The features of bones were determined using methods described in the methodology. Describing bone growth with the Gompertz equation, it was found that the earliest slowdown of bone growth curve was observed for metacarpal and metatarsal bones. This means that these bones matured the most quickly. The established data also indicate that the rib is the slowest maturing bone. The femur, humerus, tibia and fibula were between the values of these features for the metatarsal, metacarpal and rib bones. The rate of increase in bone mass and length differed significantly between the examined bones, but in all cases it was lower (coefficient b <1) than the growth rate of the whole body of the animal. The fastest growth rate was estimated for the rib mass (coefficient b = 0.93). Among the long bones, the humerus (coefficient b = 0.81) was characterized by the fastest rate of weight gain, however femur the smallest (coefficient b = 0.71). The lowest rate of bone mass increase was observed in the foot bones, with the metacarpal bones having a slightly higher value of coefficient b than the metatarsal bones (0.67 vs 0.62). The third bone had a lower growth rate than the fourth bone, regardless of whether they were metatarsal or metacarpal. The value of the bending force increased as the animals grew. Regardless of the growth point tested, the highest values were observed for the humerus, tibia and femur, smaller for the metatarsal and metacarpal bone, and the lowest for the fibula and rib. The rate of change in the value of this indicator increased at a similar rate as the body weight changes of the animals in the case of the fibula and the fourth metacarpal bone (b value = 0.98), and more slowly in the case of the metatarsal bone, the third metacarpal bone, and the tibia bone (values of the b ratio 0.81–0.85), and the slowest femur, humerus and rib (value of b = 0.60–0.66). Bone stiffness increased as animals grew. Regardless of the growth point tested, the highest values were observed for the humerus, tibia and femur, smaller for the metatarsal and metacarpal bone, and the lowest for the fibula and rib. Abstract 12 The rate of change in the value of this indicator changed at a faster rate than the increase in weight of pigs in the case of metacarpal and metatarsal bones (coefficient b = 1.01–1.22), slightly slower in the case of fibula (coefficient b = 0.92), definitely slower in the case of the tibia (b = 0.73), ribs (b = 0.66), femur (b = 0.59) and humerus (b = 0.50). Bone strength increased as animals grew. Regardless of the growth point tested, bone strength was as follows femur > tibia > humerus > 4 metacarpal> 3 metacarpal> 3 metatarsal > 4 metatarsal > rib> fibula. The rate of increase in strength of all examined bones was greater than the rate of weight gain of pigs (value of the coefficient b = 2.04–3.26). As the animals grew, the bone density increased. However, the growth rate of this indicator for the majority of bones was slower than the rate of weight gain (the value of the coefficient b ranged from 0.37 – humerus to 0.84 – fibula). The exception was the rib, whose density increased at a similar pace increasing the body weight of animals (value of the coefficient b = 0.97). The study on the influence of the breed and the feeding intensity on bone characteristics (physical and biomechanical) was performed on pigs of the breeds Duroc, Pietrain, and synthetic 990 during a growth period of 15 to 70 kg body weight. Animals were fed ad libitum or dosed system. After slaughter at a body weight of 70 kg, three bones were taken from the right half-carcass: femur, three metatarsal, and three metacarpal and subjected to the determinations described in the methodology. The weight of bones of animals fed aa libitum was significantly lower than in pigs fed restrictively All bones of Duroc breed were significantly heavier and longer than Pietrain and 990 pig bones. The average values of bending force for the examined bones took the following order: III metatarsal bone (63.5 kg) <III metacarpal bone (77.9 kg) <femur (271.5 kg). The feeding system and breed of pigs had no significant effect on the value of this indicator. The average values of the bones strength took the following order: III metatarsal bone (92.6 kg) <III metacarpal (107.2 kg) <femur (353.1 kg). Feeding intensity and breed of animals had no significant effect on the value of this feature of the bones tested. The average bone density took the following order: femur (1.23 g/cm3) <III metatarsal bone (1.26 g/cm3) <III metacarpal bone (1.34 g / cm3). The density of bones of animals fed aa libitum was higher (P<0.01) than in animals fed with a dosing system. The density of examined bones within the breeds took the following order: Pietrain race> line 990> Duroc race. The differences between the “extreme” breeds were: 7.2% (III metatarsal bone), 8.3% (III metacarpal bone), 8.4% (femur). Abstract 13 The average bone stiffness took the following order: III metatarsal bone (35.1 kg/mm) <III metacarpus (41.5 kg/mm) <femur (60.5 kg/mm). This indicator did not differ between the groups of pigs fed at different intensity, except for the metacarpal bone, which was more stiffer in pigs fed aa libitum (P<0.05). The femur of animals fed ad libitum showed a tendency (P<0.09) to be more stiffer and a force of 4.5 kg required for its displacement by 1 mm. Breed differences in stiffness were found for the femur (P <0.05) and III metacarpal bone (P <0.05). For femur, the highest value of this indicator was found in Pietrain pigs (64.5 kg/mm), lower in pigs of 990 line (61.6 kg/mm) and the lowest in Duroc pigs (55.3 kg/mm). In turn, the 3rd metacarpal bone of Duroc and Pietrain pigs had similar stiffness (39.0 and 40.0 kg/mm respectively) and was smaller than that of line 990 pigs (45.4 kg/mm). The thickness of the cortical bone layer took the following order: III metatarsal bone (2.25 mm) <III metacarpal bone (2.41 mm) <femur (5.12 mm). The feeding system did not affect this indicator. Breed differences (P <0.05) for this trait were found only for the femur bone: Duroc (5.42 mm)> line 990 (5.13 mm)> Pietrain (4.81 mm). The cross sectional area of the examined bones was arranged in the following order: III metatarsal bone (84 mm2) <III metacarpal bone (90 mm2) <femur (286 mm2). The feeding system had no effect on the value of this bone trait, with the exception of the femur, which in animals fed the dosing system was 4.7% higher (P<0.05) than in pigs fed ad libitum. Breed differences (P<0.01) in the coross sectional area were found only in femur and III metatarsal bone. The value of this indicator was the highest in Duroc pigs, lower in 990 animals and the lowest in Pietrain pigs. The cortical index of individual bones was in the following order: III metatarsal bone (31.86) <III metacarpal bone (33.86) <femur (44.75). However, its value did not significantly depend on the intensity of feeding or the breed of pigs.

Buoyancy largely supports fish, reducing the role of the skeleton, which functions as an attachment for muscle involved in movement and in protection, as exoskeleton (scales, scutes, bony plates) and as endoskeleton (vertebral column, skull). The general organization of fish skeletons and their component parts are described, as well as bone and cartilage. The interesting occurrence of acellular bone, additional to cellular bone, in teleosts is considered. Fish show metameric segmentation with myotomes on either side of the vertebral column, the latter acting as a compression strut, preventing shortening. Myotome muscle is organized into linear units named sarcomeres which contract by means of protein fibres, myosin and actin, sliding past each other. Usually fish body wall muscles occur as a thin outer layer of aerobic red muscle, with an inner thick region of anaerobic white muscle. Interspecific variability in the relative roles of myotomes and fin musculature in swimming is discussed.

Under physiological conditions, the subchondral bone of diarthrodial joints such as the hip, knee, and phalanges forms an integrated biocomposite with the overlying calcified and hyaline articular cartilage that is optimally organized to transfer mechanical load. During the evolution of the osteoarthritic process both the periarticular bone and cartilage undergo marked changes in their structural and functional properties in response to adverse biomechanical and biological signals. These changes are mediated by bone cells that modify the architecture and properties of the bone through active cellular processes of modelling and remodelling. These same biomechanical and biological factors also affect chondrocytes in the cartilage matrix altering the composition and structure of the cartilage and further disrupting the homeostatic relationship between the cartilage and bone. This chapter reviews the structural alterations and cellular mechanisms involved in the pathogenesis of osteoarthritis bone pathology and discusses potential approaches for targeting bone remodelling to attenuate the progression of the osteoarthritic process.

This chapter deals with Riemann surfaces, coverings, and hypergeometric functions. It first considers the genus and Euler number of a Riemann surface before discussing Möbius transformations and notes that an automorphism of a Riemann surface is a biholomorphic map of the Riemann surface onto itself. It then describes a Riemannian metric and the Gauss-Bonnet theorem, which can be interpreted as a relation between the Gaussian curvature of a compact Riemann surface X and its Euler characteristic. It also examines the behavior of the Euler number under finite covering, along with finite subgroups of the group of fractional linear transformations PSL(2, C). Finally, it presents some basic facts about the classical Gauss hypergeometric functions of one complex variable, triangle groups acting discontinuously on one of the simply connected Riemann surfaces, and the hypergeometric monodromy group.

Sickle cell anemia is a disease that combines molecular biology, clinical features, biochemistry, pathology, natural selection, population genetics, gene expression, and genomics and is the world’s most common life-threatening monogenic disorder. Clinical features include anemia; painful crisis especially in fingers, chest, and long bones; hemolysis; splenic infarction resulting in functional asplenia; and microinfarction leading to neurologic and renal impairment. The maintenance of adequate body temperature with active warming devices and warmed intravenous fluids, monitoring hydration and urine output, providing supplemental oxygen, and limiting surgical and anesthesia times to reduce pulmonary complications constitute the best management for patients with sickle cell disease.

Ca2+ homeostasis is achieved through a fine balance among three main organs: the intestine, the kidney, and bone. Blood levels of Ca2+ are accurately tuned through the Ca2+ sensing receptors and regulated by several hormones, including parathyroid hormone (PTH), active vitamin D, and calcitonin. The most recent findings in Ca2+ handling are described. The role of the Ca2+ sensing receptor, as well as Klotho, a new player participating in Ca2+ homeostasis, are described. Finally, the effects of diuretics, calcineurin inhibitors, and the link between hypertension and Ca2+ metabolism are reviewed.

Human movement is brought about by the musculoskeletal system under the control of the nervous system. By coordinated activity between the various muscle groups, forces generated by the muscles are transmitted by the bones and joints to enable the individual to maintain an upright or partially upright posture and bring about voluntary controlled movements. Biomechanics of human movement is the study of the relationship between the external forces (due to body weight and physical contact with the external environment) and internal forces (active forces generated by muscles and passive forces exerted on other structures) that act on the body and the eff ect of these forces on the movement of the body. This chapter specifically addresses developmental biomechanics as it relates to the development of coordination in children.

The aim of this chapter is to review nutrition, hormones, natural substances, and integrative aspects to men’s health specific to the geriatric population. This segment of the population is growing, and they are more active and want to remain so for as long as possible. Older men therefore are entitled to and demand healthy options and lifestyle education and interventions to meet their future goals. This chapter covers exercise, nutrition, and food recommendation for the healthy aging male. Topics include prostate health, sexuality, erectile dysfunction, and hormone deficiencies, specifically testosterone and DHEA. Recommendations are provided on bone health, sleep, balance, and mind–body intervention. A global approach to healthy aging is suggested when providing care for aging men.

Mechanical devices that include home appliances, automobiles, and airplanes are typically driven by electric motors or combustion engines through gearboxes and other linkages. Airplane wings, for example, have hinged control surfaces such as ailerons. Now imagine a wing that has no hinged control surfaces or linkages but that instead bends or warps to assume an appropriate shape, like the wing of a bird. Such a device could be enabled using an electro-active polymer technology based on electronic artificial muscles. Artificial muscles act directly on a structure, like our leg muscles that are attached by tendon to our bones and that through phased contraction enable us to walk. Sensory feedback from our muscles enables proprioceptive control. So, for artificial muscles to be used appropriately we need to pay attention not only to mechanisms for muscle actuation but also to how we can incorporate self-sensing feedback for the control of position.

In this chapter, patients with adverse tumour characteristics and a high risk of tumour progression are discussed. In the current era of PSA testing, the proportion of patients presenting with high-risk prostate cancer (PCa) is estimated between 10% and 20% with a 10-year cancer specific survival approaching 40% for those not receiving active local treatment. The prevalence of high-risk disease varies with community PSA use, and is higher in countries (e.g. 30% in the United Kingdom) with little PSA testing. Adequate staging with magnetic resonance imaging for tumour extension, computer tomography for visceral metastases, and bone scan for skeletal metastasis is advocated in this group. The treatment of locally advanced or high-risk prostate cancer is a contemporary challenge.

Macrophage activation syndrome (MAS) is a life-threatening condition caused by excessive activation and proliferation of T lymphocytes and haemophagocytic macrophages. Although MAS has been reported in association with almost any rheumatic disease, it is by far most common in systemic juvenile idiopathic arthritis. Flares of the underlying disease or infection are most common triggers of MAS. The pathognomonic feature of MAS is typically found in bone marrow: numerous, well-differentiated macrophagic histiocytes phagocytosing normal haematopoietic elements. The expansion of these histiocytes leads to a massive systemic inflammatory reaction associated with three cardinal clinical features: severe cytopenias, liver dysfunction, and coagulopathy consistent with disseminated intravascular coagulation. Clinically, MAS is strikingly similar to the autosomal recessive disorders collectively known as familial haemophagocytic lymphohistiocytosis (FHLH). FHLH has been associated with various genetic defects affecting the cytolytic pathway. Cytolytic function is profoundly depressed in MAS patients as well, and this abnormality is caused by both genetic and acquired factors. Studies in animals suggest that uncontrolled expansion of activated CD8+ T lymphocytes secreting cytokines that activate macrophages is central to the pathophysiology of haemophagocytic syndromes. Consistent with this view, the combination of steroids and ciclosporin, an immunosuppressant that preferentially inhibits T lymphocytes, is an effective treatment for the majority of MAS patients. Patients in whom MAS remains active despite this treatment present a serious challenge and require more aggressive immunosuppression. However, in MAS triggered by infection, the optimal level of immunosuppression is difficult to determine. As a result, reported mortality rates reach 20%.

Renal osteodystrophy (ROD) is a term that encompasses the various consequences of chronic kidney disease (CKD) for the bone. It has been divided into several entities based on bone histomorphometry observations. ROD is accompanied by several abnormalities of mineral metabolism: abnormal levels of serum calcium, phosphorus, parathyroid hormone (PTH), vitamin D metabolites, alkaline phosphatases, fibroblast growth factor-23 (FGF-23) and klotho, which all have been identified as cardiovascular risk factors in patients with CKD. ROD can presently be schematically divided into three main types by histology: (1) osteitis fibrosa as the bony expression of secondary hyperparathyroidism (sHP), which is a high bone turnover disease developing early in CKD; (2) adynamic bone disease (ABD), the most frequent type of ROD in dialysis patients, which is at present most often observed in the absence of aluminium intoxication and develops mainly as a result of excessive PTH suppression; and (3) mixed ROD, a combination of osteitis fibrosa and osteomalacia whose prevalence has decreased in the last decade. Laboratory features include increased serum levels of PTH and bone turnover markers such as total and bone alkaline phosphatases, osteocalcin, and several products of type I collagen metabolism products. Serum phosphorus is increased only in CKD stages 4-5. Serum calcium levels are variable. They may be low initially, but hypercalcaemia develops in case of severe sHP. Serum 25-OH-vitamin D (25OHD) levels are generally below 30 ng/mL, indicating vitamin D insufficiency or deficiency. The international KDIGO guideline recommends serum PTH levels to be maintained in the range of approximately 2-9 times the upper normal normal limit of the assay and to intervene only in case of significant changes in PTH levels. It is generally recommended that calcium intake should be up to 2 g per day including intake with food and administration of calcium supplements or calcium-containing phosphate binders. Reduction of serum phosphorus towards the normal range in patients with endstage kidney failure is a major objective. Once sHP has developed, active vitamin D derivatives such as alfacalcidol or calcitriol are indicated in order to halt its progression.

Calcium homeostasis is maintained through a fine balance between calcium absorption, parathyroid hormone secretion and action, vitamin D production and action, cellular compartmentalization of calcium ions, and renal function. Although the extracellular calcium level does not vary with age, the maintenance of calcium faces the significant mineral requirement of skeletal growth and bone mass acquisition during childhood. Acquired or genetic defects in any determinants of blood calcium (i.e. vitamin D, parathyroid hormone, calcium absorption, etc.) may manifest as hypocalcaemia, especially during childhood/adolescence. The discovery of hypocalcaemia in a patient should trigger two clinical responses: (1) therapy to restore the calcium level to normal and (2) investigations to determine the cause of hypo/hypercalcaemia.

This is the first book to comprehensively and critically examine the nature and background of the Chinese phenomenon of guanxi. It does this by reviewing and taking account of the major theoretical frameworks that relate to these closely bonded long-term relationships that are developed in order to pursue instrumental advantage in a society marked by relatively weak legal and regulatory institutions. The book locates such theorizing in the major features of the rapidly evolving Chinese market society, whilst paying attention to the historical origins and cultural sources of this highly particularistic approach to the acquisition of social and material resources, an approach which relies on obligatory relations of favour exchange between persons who self-consciously and strategically select their associates and goals. The book goes on to develop an improved way of understanding this extremely significant and distinct feature of social, political and economic relations that are characteristic of mainland China’s relentlessly active population. The book uniquely proposes an inclusive approach to guanxi based on comprehensive theorizing which both challenges many conventions and at the same time introduces a research orientation which captures the pertinent psychological dispositions, cultural expressions, and institutional frameworks that underpin guanxi.

Axial spondyloarthritis (axSpA) is a potentially disabling chronic inflammatory disease affecting the spine and sacroiliac (SI) joints. Lead symptoms are chronic back pain and stiffness. The disease is called radiographic axSpA or ankylosing spondylitis (AS) when, on plain radiographs, bone changes consistent with sacroiliitis are present. When no evidence of sacroiliitis is seen on radiographs, it is called non-radiographic axSpA. In such cases, diagnosis is made based on evidence of active inflammation of SI joints on magnetic resonance imaging (MRI) and clinical and laboratory features, or a combination of clinical and laboratory features only. Apart from affecting the spine and SI joints, axSpA may involve peripheral joints (e.g. knee, ankle) and manifest in extra-articular manifestations, for example uveitis, psoriasis, and inflammatory bowel disease. In this chapter, diagnosis and classification of axSpA is discussed, including use of MRI in detecting sacroiliitis and the difference between clinical diagnosis and disease classification.

Highly active antiretroviral therapy remains the mainstay of treatment for patients chronically infected with HIV. Novel drugs, both within existing classes and new ones, are in various stages of development and testing. New medications within existing classes of antiretroviral agents are in clinical trials and will likely offer activity against resistant HIV-1 strains and provide alternatives for combination pill therapy. Novel therapeutics including oral attachment inhibitors and monoclonal antibody treatments continue to show efficacy against HIV-1 and progress in clinical trials. Tenofovir alafenamide is a prodrug that produces higher intracellular levels of tenofovir diphosphate with likely less renal and bone toxicity. Among traditional classes of HIV treatment, both doravirine (a non-nucleoside reverse transcriptase inhibitor) and cabotegravir (an integrase strand inhibitor) are newer agents with activity against resistant virus. Maturation inhibitors are a new class of treatment that block protease cleavage, leading to the release of an immature virion.

♦ Stress fractures are fractures occurring as the result of repetitive, submaximal loads, in the absence of a specific precipitating traumatic event.♦ These fractures can be subdivided into two groups on the basis of aetiology. Whereas ‘fatigue fractures’ result from the excessive repetitive (i.e. abnormal) loading of normal bone, ‘insufficiency fractures’ are fractures resulting from normal forces acting on abnormal bone.♦ Early diagnosis allows the initiation of effective treatment that can prevent prolonged pain and disability, as well as avoiding the progression to displacement or a non-union.♦ While management decisions are generally focused on activity modification, protection of weight bearing, and immobilization, there is a subset of fractures at high risk for progression to complete fracture, non-union, or delayed union. These high-risk stress fractures, including tension-side femoral neck fractures and anterior tibial cortex fractures, require aggressive treatment to prevent the sequelae of poor healing.

Thyroid hormones act on most tissues via nuclear T3 receptors. Thyroid hormones stimulate oxygen consumption and heat production, influence cell growth and maturation (central nervous system, bone), and modulate metabolism (carbohydrates, lipids, proteins, drugs). Treatment for presumed thyroid disease frequently has to be initiated before the results of diagnostic tests are available. Treatment of hyperthyroidism should result in the reduction of serum thyroid hormone levels and their action on peripheral tissues with concurrent treatment of the precipitating event. In severe hypothyroidism the choice of thyroid hormone (thyroxine or tri-iodothyronine), optimal dosing, and the route of administration remain controversial

Ankylosing spondylitis (AS) is a chronic inflammatory disease predominantly of the sacroiliac joint (SIJ) and the spine. It starts normally in the second decade of life and has a slight male predominance. The prevalence is between 0.2 and 0.8% and is strongly dependent on the prevalence of HLA B27 in a given population. For the diagnosis of AS, the presence of radiographic sacroiliitis is mandatory. However, radiographs do not detect active inflammation but only structural bony damage. Most recently new classification criteria for axial spondyloarthritis (SpA) have been developed by the Assessement of Spondylo-Arthritis international Society (ASAS) which cover AS but also the earlier form of non-radiographic axial SpA. MRI has become an important new tool for the detection of subchondral bone marrow inflammation in SIJ and spine and has become increasingly important for an early diagnosis. HLA B27 plays a central role in the pathogenesis but its exact interaction with the immune system has not yet been clarified. Besides pain and stiffness in the axial skeleton patients suffer also from periods of peripheral arthritis, enthesitis, and uveitis. New bone formation as a reaction to inflammation and subsequent ankylosis of the spine determine long-term outcome in a subgroup of patients. Currently only non-steroidal anti-inflammatory drugs (NSAIDs) and tumour necrosis factor (TNF) blockers have been proven to be effective in the medical treatment of axial SpA, and international ASAS recommendations for the structured management of axial SpA have been published based on these two types of drugs. Conventional disease-modifying anti-rheumatic drugs (DMARDs) such as methotrexate are not effective.

Axial spondyloarthritis (axSpA) is a chronic inflammatory disease predominantly of the sacroiliac joint (SIJ) and the spine. It starts normally in the second decade of life and has a slight male predominance. The prevalence is between 0.2% and 0.8% and is strongly dependent on the prevalence of HLA-B27 in a given population. AxSpA can be split in patients with radiographic axSpA (also termed ankylosing spondylitis (AS)) and in patients with non-radiographic axSpA (nr-axSpA). For the diagnosis of AS, the presence of radiographic sacroiliitis is mandatory. However, radiographs do not detect active inflammation but only structural bony damage. Most recently new classification criteria for axSpA have been developed by the Assessment of Spondylo-Arthritis International Society (ASAS) which cover AS but also the earlier form of nr-axSpA. MRI has become an important new tool for the detection of subchondral bone marrow inflammation in SIJ and spine and has become increasingly important for an early diagnosis. HLA-B27 plays a central role in the pathogenesis but its exact interaction with the immune system has not yet been clarified. Besides pain and stiffness in the axial skeleton patients suffer also from periods of peripheral arthritis, enthesitis, and uveitis. New bone formation as a reaction to inflammation and subsequent ankylosis of the spine determine long-term outcome in a subgroup of patients. Currently only non-steroidal anti-inflammatory drugs (NSAIDs) and tumour necrosis factor (TNF) blockers have been proven to be effective in the medical treatment of axial SpA, and international ASAS recommendations for the structured management of axial SpA have been published based on these two types of drugs. Conventional disease-modifying anti-rheumatic drugs (DMARDs) such as methotrexate are not effective.

Understanding pathogenic mechanism in disease is critical for development of targeted therapeutic strategies. Although there are, at this time, only a handful of experimental approaches for treating osteoarthritis (OA), until 10 years ago this disease was almost universally considered an unmodifiable condition. Emerging data during this time, largely fuelled by studies in rodent models, has completely changed the paradigm of disease pathogenesis and has for the first time, generated novel, realistic targets for this highly prevalent and disabling condition. These targets include the aggrecanases, members of the ADAMTS family, and collagenases, which together are critical for the early breakdown of the extracellular matrix of cartilage. Some recent success has also been demonstrated by targeting bone in disease. Development of pain in OA is complex and likely arises from different tissues at different stages of disease. In the following section we describe the pathological features of OA, and discuss the evolution of theories of OA pathogenesis and factors that have limited mechanistic clarity in this disease. We summarize the molecular pathways that are now known to be active in disease, and consider how these identified molecular pathways could be linked to known epidemiological risk factors. We finish by discussing possible future therapeutic strategies that will emerge from these discoveries and the current limitations in implementing new therapies in OA.

Fibroblast growth factor 23 (FGF23) and Klotho have emerged as major hormonal regulators of phosphorus (P) and vitamin D metabolism. FGF23 is secreted by bone cells and acts in the kidneys to increase urinary P excretion and inhibit the synthesis of 1,25 dihydroxyvitamin D (1,25(OH)2D) and in the parathyroid glands to inhibit the synthesis and secretion of parathyroid hormone. Phosphorus excess stimulates FGF23 secretion, likely as an appropriate physiological adaptation to maintain normal P homeostasis by enhancing urinary P excretion and diminishing intestinal P absorption via lower 1,25(OH)2D. The FGF23 concentrations are elevated early in the course of chronic kidney disease (CKD) and may be a primary initiating factor for the development of secondary hyperparathyroidism in this setting. Klotho exists in two forms: a transmembrane form and a secreted form, each with distinct functions. The transmembrane form acts as the key co-factor needed for FGF23 to bind to and activate its cognate receptor in the kidneys and the parathyroid glands. The secreted form of Klotho has FGF23-independent effects on renal P and calcium handling, insulin sensitivity, and endothelial function. Disturbances in the expression of Klotho may play a role in the development of altered bone and mineral metabolism in early CKD. In addition, abnormal circulating concentrations of both FGF23 and Klotho have been linked to excess cardiovascular disease, suggesting that both play an important role in maintaining cardiovascular health.

The platelet is a small (2–4 µm in diameter), discoid, anucleate cell that circulates in the blood. In health, it plays a vital role in haemostasis, and in disease it contributes to disorders of bleeding and thrombosis. Platelets are produced from the surface of megakaryocytes in the bone marrow, under tight homeostatic control regulated by the cytokine thrombopoietin. Platelets have a lifespan of approximately 7–10 days, and usually circulate in the blood stream in a quiescent state. Intact, undamaged vessel walls help to maintain platelets in this inactive state by releasing nitric oxide, which acts both to dilate the vessel wall and to inhibit platelet adhesion, activation, and aggregation. After trauma to the blood vessel wall, platelets are activated and, acting in concert with the endothelium and coagulation factors, form a stable clot. This chapter addresses platelet structure and function, and the response of platelets to vessel injury.

Despite remarkable progress in understanding the pathological processes and alleviating symptoms by TNFα‎ blocking medication, the mechanism that converts flexible tissue into bone still cannot be completely prevented or reversed. In axial spondyloarthritis, components of motion segments, such as zygoapophyseal joints, intervertebral discs, and spinal ligaments, can ossify in varying sequence, extent, and location between the ilium and occiput. Throughout this process, the spinal column is vulnerable to kyphotic deformity due to gravity, body weight, muscle action, and life’s flexion-based activities. Areas with low fusion tendency, such as atlanto-axial joints, and post-traumatically weakened spots of formerly ankylosed vertebral block (Andersson’s lesion) can endanger the spinal cord by instability, dislocation, and compression, from what is typically minor trauma or simple repetitive, but otherwise normal, stresses. Once functionally significant deformity or presence of instability and associated symptoms are established, conservative treatment options are lacking and surgical consideration is required.

In 1949, Harold Schuknecht completed his residency in John Lindsay’s Otolaryngology Department at the University of Chicago and stayed first as a clinical instructor and then as an assistant professor. Schuknecht reviewed the temporal bone specimens from the patient reported by his mentor, John Lindsay, and from patients reported by Charles Hallpike and colleagues and was struck by the similarity in the pathologic changes. He concluded that in each case damage to the labyrinth resulted from occlusion of the anterior vestibular artery. Schuknecht believed that the delayed positional vertigo that occurred in these cases must have originated from the posterior semicircular canal. He reasoned that with degeneration of the superior vestibular labyrinth, otoconia would be released from the otolithic membrane of the utricular macule and that, in certain positions of the head, the otoconia would respond to gravity and thereby activate the cupula of the posterior semicircular canal.

This book provides a sustained, formalist and theoretically-informed reading of the multiple body parts that litter the dialogue and action of Shakespeare’s history plays, including Henry V, Richard II, Richard III, King John, and the Henry IV plays. Starting with a literary critical analysis of these dislocated bodies, the book follows Shakespeare’s own relentless pursuit of a specific political question: how does human flesh, blood, and bone relate to sovereignty? Shakespeare’s treatment of the body is also read against two other bodies of work: early modern political writing, and twentieth- and twenty first-century critical theory. Like Shakespeare’s histories, these develop understandings of sovereign power through considerations of the body: from Jean Bodin’s inalienable sovereignty, located in the body of the monarch, through Hobbes’ mechanistic Leviathan, to Kantorowicz’s “two bodies” and Derrida’s “prosthstatics” in which forms of sovereign power are imagined as machine- or animal-like. Along the way, particular body parts – knees, hands, heads, and throats – come to the fore as particular objects of interest.

Vascular calcification (VC) is a common feature of patients with advanced CKD and it could be, at least in part, the cause of increased cardiovascular mortality in these patients. From a morphologic point of view, there are at least two types of pathologic calcium phosphate deposition in the arterial wall—namely, intima calcification (mostly associated with atherosclerotic plaques) and media calcification (associated with stiffening of the vasculature, resulting in significantly adverse cardiovascular outcomes). Although VC was viewed initially as a passive phenomenon, it appears to be a cell-mediated, dynamic, and actively regulated process that closely resembles the formation of normal bone tissue, as discovered recently. VC seems to be the result of the dysregulation of the equilibrium between promoters and inhibitors. The determinants are mostly represented by altered calcium and phosphorus metabolism, secondary hyperparathyroidism, vitamin D excess, high fibroblast growth factor 23, and high levels of indoxyl sulphate or leptin; meanwhile, the inhibitors are vitamin K, fetuin A, matrix G1a protein, osteoprotegerin, and pyrophosphate. A number of non-invasive imaging techniques are available to investigate cardiac and vascular calcification: plain X-rays, to identify macroscopic calcifications of the aorta and peripheral arteries; two-dimensional ultrasound for investigating the calcification of carotid arteries, femoral arteries, and aorta; echocardiography, for assessment of valvular calcification; and, of course, computed tomography technologies, which constitute the gold standard for quantification of coronary artery and aorta calcification. All these methods have a series of advantages and limitations. The treatment/ prevention of VC is currently mostly around calcium-mineral bone disease interventions, and unproven. There are interesting hypotheses around vitamin K, Magnesium, sodium thiosulphate and other potential agents.

In all patients with chronic kidney disease (CKD) stages 3–5, regular monitoring of serum markers of CKD-mineral and bone disorder, including calcium (Ca), phosphorus (P), parathyroid hormone (PTH), 25-hydroxyvitamin D, and alkaline phosphatase, is recommended. Target ranges for these markers are endorsed by guidelines. The principles of therapy for secondary hyperparathyroidism include control of hyperphosphataemia, correction of hypocalcaemia, use of vitamin D sterols, use of calcimimetics, and parathyroidectomy. of hyperphosphataemia is crucial and may be achieved by means of dietary P restriction, use of P binders, and P removal by dialysis. Dietary P restriction requires caution, as it may be associated with protein malnutrition. Aluminium salts are effective P binders, but they are not recommended for long-term use, as Aluminium toxicity (though from contaminated dialysis water rather than oral intake) may cause cognitive impairment, osteomalacia, refractory microcytic anaemia, and myopathy. Ca-based P binders are also quite effective, but should be avoided in patients with hypercalcaemia, vascular calcifications, or persistently low PTH levels. Non-aluminium, non-Ca binders, like sevelamer and lanthanum carbonate, may be more adequate for such patients; however, they are expensive and may have several side effects. Furthermore, comparative trials have failed so far to provide conclusive evidence on the superiority of these newer P binders over Ca-based binders in terms of preventing vascular calcifications, bone abnormalities, and mortality. P removal is about 1800–2700 mg per week with conventional thrice-weekly haemodialysis, but may be increased by using haemodiafiltration or intensified regimens, such as short daily, extended daily or three times weekly nocturnal haemodialysis. Several vitamin D derivatives are currently used for the treatment of secondary hyperparathyroidism. In comparison with the natural form calcitriol, the vitamin D analogue paricalcitol seems to be more fast-acting and less prone to induce hypercalcaemia and hyperphosphataemia, but whether these advantages translate into better clinical outcomes is unknown. Calcimimetics such as cinacalcet can significantly reduce PTH, Ca, and P levels, but they have failed to definitively prove any benefits in terms of mortality and cardiovascular events in dialysis patients. Parathyroidectomy is often indicated in CKD patients with severe persistent hyperparathyroidism, refractory to aggressive medical treatment with vitamin D analogues and/or calcimimetics. This procedure usually leads to rapid improvements in biochemical markers (i.e. significant lowering of serum Ca, P, and PTH) and clinical manifestations (such as pruritus and bone pain); however, the long-term benefits are still unclear.

In depth molecular and cellular analysis of synovial tissue and fluid from patients with rheumatoid arthritis has provided important insights into understanding disease pathogenesis. Advances in the 1980s and 1990s included modern cloning strategies, sensitive and specific assays for inflammatory mediators, production of high-affinity neutralizing monoclonal antibodies, advances in flow cytometry, and gene targeting and transgenic strategies in rodents. In the 21st century, technological platforms offer unparalleled opportunities for systematic and unbiased interrogation of the disease process at a whole-genome level. Here we describe the key molecular and cellular characteristics of the inflamed synovium and how infiltrating cells get there. With this background, we outline current concepts of the different phases of disease, how the first phase of genetic susceptibility evolves into autoimmunity, triggered by the exposome, prior to the onset of clinically apparent inflammatory disease. We then describe the pathways that actively contribute to this early inflammatory phase and document the key effector cells and molecules of the innate and adaptive immune systems that orchestrate and maintain chronic synovial inflammatory responses. We summarize how this inflammatory milieu translates to cartilage destruction and bone resorption in synovial joints, and conclude by reviewing those factors in inflamed synovium that promote immune homeostasis.

In the Hebrew Bible/Old Testament, a good death meant burial inside the family tomb, where one would join one’s ancestors in death. This was the afterlife in biblical literature; it was a postmortem ideal that did not involve individual judgment or heaven and hell—instead it was collective. In Hebrew scriptures, a postmortem existence was rooted in mortuary practices and conceptualized through the embodiment of the dead. But this idea of the afterlife was not hopeless or fatalistic, consigned to the dreariness of the tomb. The dead were cherished and remembered, their bones were cared for, and their names lived on as ancestors. This book examines the concept of the afterlife in the Hebrew Bible by studying the treatment of the dead, as revealed both in biblical literature and in the material remains of the southern Levant. The Iron Age mortuary culture of Judah is the starting point for this study, and the practice of collective burial inside the Judahite rock-cut bench tomb is compared to biblical traditions of family tombs and of joining one’s ancestors in death. This archaeological analysis, which also incorporates funerary inscriptions, will shed important insight into biblical literature concerning such issues as the construction of the soul in death, the nature of corpse impurity, and the concept of Sheol. Death was a transition managed through ritual action. The connections that were forged through such actions, such as ancestor veneration, were socially meaningful for the living and ensured a measure of immortality for the dead.

Magnesium is critically important in the process of energy release. Although most magnesium is stored outside the extracellular fluid compartment, the regulated concentration appears in blood. Urinary magnesium excretion can decrease rapidly to low values when magnesium entry rate into the extracellular fluid volume is low, which has several important implications: cell and bone magnesium do not play a major role in the defence of blood magnesium concentration; while a major role is played by the kidney and especially the renal tubule, which adapts to match the urinary magnesium excretion and net entry of magnesium into extracellular fluid. In the kidney, magnesium is reabsorbed in the proximal tubule, the thick ascending limb of the loop of Henle (TALH), and the distal convoluted tubule (DCT). Magnesium absorption is mainly paracellular in the proximal tubule and TALH, whereas it is transcellular in the DCT. The hormone(s) regulating renal magnesium transport and blood magnesium concentration are not fully understood. Renal tubular magnesium transport is altered by a number of hormones, mainly in the TALH and DCT. Parathyroid hormone, calcitonin, arginine vasopressin, ß-adrenergic agonists, and epidermal growth factor, all increase renal tubular magnesium reabsorption; in contrast, prostaglandin E2 decreases magnesium reabsorption. Non-hormonal factors also influence magnesium reabsorption: it is decreased by high blood concentrations of calcium and magnesium, probably via the action of divalent cations on the calcium-sensing receptor; metabolic acidosis decreases, and metabolic alkalosis increases, renal magnesium reabsorption.