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1

Broadbent, Stefana. L'intimité au travail: La vie privée et les communications personnelles dans l'entreprise. [France]: éditions Fyp, 2011.

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2

1943-, Okada Yasunobu, ed. Cell volume regulation: The molecular mechanism and volume sensing machinery : proceedings of the 23rd Taniguichi Foundation Biophysics Symposium held in Okazaki, Japan, 17-21 November 1997. Amsterdam: Elsevier, 1998.

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3

Population balances in biomedical engineering: Segregation through the distribution of cell states. New York: McGraw-Hill, 2006.

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4

Hjortsø, Martin A. Population balances in biomedical engineering: Segregation through the distribution of cell states. New York: McGraw-Hill, 2006.

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5

Skrzeszewska-Paczek, Elżbieta. Cele i przesłanki programów stabilizacyjno-wyrównawczych międzynarodowego funduszu walutowego. Warszawa: Instytut Finansów, 1988.

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6

Ulrike, Beisiegel, Joost Hans-Georg, and SpringerLink (Online service), eds. Sensory and Metabolic Control of Energy Balance. Berlin, Heidelberg: Springer-Verlag Berlin Heidelberg, 2010.

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7

W, Beyenbach Klaus, ed. Cell volume regulation. Basel: Karger, 1990.

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8

Aoyagi, Yuki, and Richard A. Zuckerman. Fuzzy Vision and Balance Problems. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780199938568.003.0027.

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These case studies illustrate infections encountered in hospitals among patients with compromised immune systems. As a result of immunocompromise, the patients are vulnerable to common and uncommon infections. These cases are carefully chosen to reflect the most frequently encountered infections in the patient population, with an emphasis on illustrations and lucid presentations to explain the state-of-the-art approaches in diagnosis and treatment. Common and uncommon presentations of infections are presented while the rare ones are not emphasized. The cases are written and edited by clinicians and experts in the field. Each of these cases highlight the immune dysfunction that uniquely predisposed the patient to the specific infection, and the cases deal with infections in the cancer patient, infections in the solid organ transplant recipient, infections in the stem cell recipient, infections in patients receiving immunosuppressive drugs, and infections in patients with immunocompromise that is caused by miscellaneous conditions.
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9

Eljaafari, Assia, and Pierre Miossec. Cellular side of acquired immunity (T cells). Oxford University Press, 2013. http://dx.doi.org/10.1093/med/9780199642489.003.0049.

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The adaptive T-cell response represents the most sophisticated component of the immune response. Foreign invaders are recognized first by cells of the innate immune system. This leads to a rapid and non-specific inflammatory response, followed by induction of the adaptive and specific immune response. Different adaptive responses can be promoted, depending on the predominant effector cells that are involved, which themselves depend on the microbial/antigen stimuli. As examples, Th1 cells contribute to cell-mediated immunity against intracellular pathogens, Th2 cells protect against parasites, and Th17 cells act against extracellular bacteria and fungi that are not cleared by Th1 and Th2 cells. Among the new subsets, Th22 cells protect against disruption of epithelial layers secondary to invading pathogens. Finally these effector subsets are regulated by regulatory T cells. These T helper subsets counteract each other to maintain the homeostasis of the immune system, but this balance can be easily disrupted, leading to chronic inflammation or autoimmune diseases. The challenge is to detect early changes in this balance, prior to its clinical expression. New molecular tools such as microarrays could be used to determine the predominant profile of the immune effector cells involved in a disease process. Such understanding should provide better therapeutic tools to counteract deregulated effector cells.
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10

Doucet, Alain, and Gilles Crambert. Potassium homeostasis. Edited by Robert Unwin. Oxford University Press, 2015. http://dx.doi.org/10.1093/med/9780199592548.003.0023.

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The equilibrium between the concentration of K+ in the extracellular space (low) and the intracellular compartment (high) is crucial for maintaining the electrical properties of excitable and non-excitable cells, because it determines the membrane resting potential. The high intracellular concentration of K+ (120–140 mmol/L) also contributes to the intracellular osmolarity, a determinant of cell volume. It is therefore crucial to finely tune both extracellular and intracellular K+ concentrations. There is a coordinated regulation between processes/mechanisms that store/release K+ from internal stores (internal balance) and those that retain/excrete K+ (external balance).
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11

Cook, PG, and AL Herczeg. Groundwater Chemical Methods for Recharge Studies - Part 2. CSIRO Publishing, 1998. http://dx.doi.org/10.1071/9780643105348.

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These notes are restricted to those geochemical methods which have been used to quantify rates of groundwater recharge. There have been two main approaches. The first involves the use of mass balances and mixing cell models, mainly using conservative (non-reacting) dissolved species. The methods range in complexity from simple back-of-the-envelope calculations (zero-dimensional chloride mass balance), to complex three-dimensional computer models. The second approach seeks to estimate the age or residence time of the groundwater by measuring compounds which are radioactive, or whose input to the aquifer has been changing over time (chlorofluorocarbons). In this report, the methodology and case examples are described. References to further information on the techniques are also provided.
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12

Bertolaso, Marta, and John Dupré. A Processual Perspective on Cancer. Oxford University Press, 2018. http://dx.doi.org/10.1093/oso/9780198779636.003.0016.

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This chapter attempts to illuminate the dynamic stability of the organism and the robustness of its developmental pathway by considering the biology of cancer. Healthy development and stable functioning of a multicellular organism require an exquisitely regulated balance between processes of cell division, differentiation, and death (apoptosis). Cancer involves a disruption of this balance, which results in unregulated cell proliferation. The thesis defended in this chapter is that the coupling between proliferation and differentiation, whether normal or pathological (as in cancer), is best understood within a process-ontological framework. This framework emphasizes the interactions and mutual stabilizations between processes at different levels and this, in turn, explains the difficulty in allocating the neoplastic process to any particular level (genetic, epigenetic, cellular, or histological). Understanding these interactions is likely to be a precondition of a proper understanding of how these mutual regulations are disrupted in the processes we call cancerous.
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13

Giangrande, Paul L. F. Haemoglobinopathies. Oxford University Press, 2011. http://dx.doi.org/10.1093/med/9780199550647.003.0005.

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♦ Haemoglobinopathies are commonly inherited disorders of haemoglobin synthesis♦ Thalassaemia is commonest around the Mediterranean countries and has skeletal manifestations due to massive marrow expansion with thinning of the cortex♦ Sickle cell crises occur in homozygotes and are a result of venous occlusion causing avascular necrosis. Infection and exposure to cold can sometimes precipitate these painful events♦ If surgery is needed blood cross-match must be carefully performed in advance, the theatre should be kept warm, and the hydration and acid/base balance of the patient monitored carefully.
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14

Güell, Oriol. A Network-Based Approach to Cell Metabolism: From Structure to Flux Balances. Springer, 2018.

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15

Güell, Oriol. A Network-Based Approach to Cell Metabolism: From Structure to Flux Balances. Springer, 2017.

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16

Baloh, Robert W. Breuer Discovers How the Balance Portion of the Inner Ear Works. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780190600129.003.0004.

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Josef Breuer presented his initial work on the inner ear to the Imperial Society of Physicians in 1873. His basic premise was that the semicircular canals sense angular movement of the head by movement of the fluid (endolymph) within them. The endolymph moves relative to the walls of the canals because of its inertia. In dissecting the semicircular canals of pigeons, he noted nerve endings contacting cells at the base of the ampulla and microscopic hairs extending from the top of the cells into a gelatinous bulb (the cupula). He hypothesized that movement of the endolymph fluid triggered by angular head movements bent the tiny hairs, activating the nerve endings at the base of the hair cells. The nerves in turn passed on signals reflecting the direction and magnitude of hair deflection to the central nervous system. At approximately the same time, Ernst Mach came to a similar conclusion.
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17

Dineen, Kelly K. Opioid Prescribing in Stigmatized and Special Populations. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780199981830.003.0009.

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There is no question that a lack of careful decision-making around opioid prescribing in the past contributed to the current opioid-related harms. Yet opioids—usually in combination with other treatments—are sometimes the only effective therapies for certain chronic pain patients, in whom the benefits of opioids outweigh the risks of a substance use disorder. This chapter examines special populations such as those with sickle cell disease or those experiencing pain in end-of-life care. Caring for chronic pain patients can be challenging, especially now that the use of opioids for long-term pain control has been called into question. This chapter draws attention to attitudes and biases that may contribute to decision-making errors on the part of providers who are trying to balance the benefits and harms of opioids when treating these particularly vulnerable groups.
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18

Tuschl, Karin, Peter T. Clayton, and Philippa B. Mills. Disorders of Manganese Metabolism. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780199972135.003.0045.

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Manganese is an essential trace metal for numerous metalloenzymes. Manganese homeostasis requires tight regulation in vivo and disruption of this balance can lead to manganese overload and subsequent accumulation of manganese in brain, liver, and blood. Mutations in SLC30A10, a cell surface-localized manganese efflux transporter, cause an autosomal recessive hypermanganesemia syndrome with two distinct phenotypes: childhood onset dystonia and adult onset Parkinsonism, associated with chronic liver disease, polycythemia and features of iron depletion. MRI brain appearances are characteristic of Mn deposition with hyperintense basal ganglia on T1-weighted images. Chelation therapy with disodium calcium edetate and iron supplementation effectively lower blood manganese levels, halt liver disease progression and improve neurological symptoms.The inherited form of hypermanganesemia can be distinguished from acquired causes of manganese overload including environmental overexposure and acquired hepatocerebral degeneration in cases of end stage liver disease.
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19

Neumann, Peter J., Joshua T. Cohen, and Daniel A. Ollendorf. The Right Price. Oxford University Press, 2021. http://dx.doi.org/10.1093/oso/9780197512883.001.0001.

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New medications can provide substantial benefits, but high prescription drug prices have led to calls to contain costs. Even after accounting for discounts and rebates, average prices of leading brand-name drugs in the United States are two to four times higher than in other wealthy countries, raising questions about what these higher prices are buying us. With the advent of ever more targeted and powerful treatments, including cell- and gene-based therapies with multimillion dollar price tags, the need for sensible drug pricing policies will intensify. Price controls, common in other countries, seem appealing, but these measures can discourage innovation. Moreover, on what basis should policymakers develop such controls? This book argues that pricing prescription drugs to reflect the value they bring to patients, families, and society achieves the right balance. The book reviews the distinguishing features of the prescription drug market and explains why simple solutions like price controls and importing drugs from countries with lower drug prices are problematic without explicit assessments of value. It then describes how economists measure value, how value assessment for drugs is now being used in the United States, and what must happen going forward to overcome challenges.
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20

Broadbent, Stefana. Intimacy at Work: How Digital Media Bring Private Life to the Workplace. Taylor & Francis Group, 2015.

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21

Intimacy at Work: How Digital Media Bring Private Life to the Workplace. Taylor & Francis Group, 2015.

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22

Hendriks, Herman G. D., and Joost T. M. de Wolf. Haematological and coagulation disorders and anaesthesia. Edited by Philip M. Hopkins. Oxford University Press, 2017. http://dx.doi.org/10.1093/med/9780199642045.003.0084.

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This chapter covers the principal haematological disorders and their implications for anaesthesia. Haemoglobin concentration is the main determinant of oxygen delivery to the tissues making anaemia a potential concern for the anaesthetist. In deciding whether to correct anaemia with a red blood cell transfusion, the anaesthetist must consider the nature of the surgery and the underling cause of the anaemia as well as the haemoglobin concentration. Techniques to limit the need for blood transfusion and the complications of transfusion are discussed. Perfect haemostasis means control of bleeding without the occurrence of thrombotic events. Coagulation management requires an understanding of this balance and the knowledge that altered coagulation activity may result in clinically relevant bleeding or, in contrast, thrombosis. Therefore, the key in haemostasis is an understanding that every anticoagulant action enhances the risk of bleeding and every procoagulant action enhances the risk of thrombosis. If a specific defect in the haemostatic system is known, treatment is tailored to restore this defect. However, tests to predict surgical bleeding do not exist, as it is for test to predict thrombotic events. The strengths and limitations of coagulation tests should be appreciated before they are used to assist clinical decision-making in the perioperative period. An excellent coagulation test is the clinical field (i.e. the surgical wound). If there are abnormalities in the coagulation tests without clinical bleeding, a correction is hardly necessary. In patients taking anticoagulant medication, consideration must be given on an individual patient basis, to the relative risks of continuing (bleeding) or stopping (thrombotic events) the medication.
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23

Zietse, Robert, and Ewout Hoorn. Approach to the patient with hypernatraemia. Edited by Robert Unwin. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780199592548.003.0029_update_001.

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Hypernatraemia is much less common than hyponatraemia, and its prevalence is higher in certain populations, including children, the elderly, and critically ill patients. A common feature is that patients affected have been unable to drink water to correct the disorder. Hyponatraemia and hypernatraemia are both primarily disorders of water balance. Hypernatraemia is caused by a relative deficit of total body water in comparison to total body sodium. Both disorders are often associated with disturbances in the hormone governing water balance, arginine vasopressin (antidiuretic hormone). Hypernatraemia may be due to an inability to secrete vasopressin or a resistance to its actions in the kidney. The diagnostic approach relies on the assessment of the time of development, symptoms, and volume status, along with laboratory parameters such as urine sodium and urine osmolality. If hypernatraemia develop acutely, treatment should be directed towards counteracting the water shift to or from brain cells. In more chronic cases, treatment should be directed to the underlying cause while avoiding overcorrection.
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24

Weyker, Paul David, Christopher Allen-John Webb, and Tricia E. Brentjens. Hypovolemic Shock. Edited by Matthew D. McEvoy and Cory M. Furse. Oxford University Press, 2017. http://dx.doi.org/10.1093/med/9780190226459.003.0097.

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Broadly defined, hypovolemia represents inadequate circulating plasma volume leading to decreased cardiac preload and thus decreased cardiac output and blood pressure. Many classification schemes have been proposed to categorize hypovolemia based on relative levels of decreased plasma volume. Common causes of hypovolemic shock during the perioperative period include hemorrhage and diuretic use. In general, studies support a conservative hemoglobin goal of about 7 g/dL as compared with a liberal goal of 10 g/dL in hemodynamically stable patients without active cardiac ischemia or risk factors. In patients with large volume blood loss, institutionally approved massive transfusion protocols can help provide blood products quickly. The trauma literature supports a balanced massive transfusion protocol using a 1:1:1 (plasma:platelet:red blood cell) strategy of transfusion.
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25

Beattie, R. Mark, Anil Dhawan, and John W.L. Puntis. Cystic fibrosis. Oxford University Press, 2011. http://dx.doi.org/10.1093/med/9780198569862.003.0021.

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Gastrointestinal manifestations 156Management of gastrointestinal symptoms in children with CF 158Nutrition in CF 158Nutritional management 159Vitamins 160The incidence of cystic fibrosis (CF) is around 1 in 2500. Cases are diagnosed as a consequence of population screening or high-risk screening, or following presentation with clinical symptoms typical of the disorder. The basic defect is in the CFTR (cystic fibrosis transmembrane conductance regulator) protein which codes for a cyclic adenosine monophosphate-regulated chloride transporter in epithelial cells of exocrine organs. This is involved in salt and water balance across epithelial surfaces. The gene is on chromosome 7. There are multiple known mutations, the most common being ...
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26

Ellam, Rob. 5. Physics heal thyself. Oxford University Press, 2016. http://dx.doi.org/10.1093/actrade/9780198723622.003.0005.

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Stable and radioactive isotopes are used extensively in diagnostic and therapeutic medical applications including studies of human body composition, energy balance, protein turnover, and metabolism. ‘Physics heal thyself: isotopes in medicine’ shows how ionizing radiation is key to a host of medical imaging techniques with radioactive isotopes widely used to target and kill cancer cells. Enriched isotopes are used as biological tracers; doubly labelled water in the diagnosis of type 2 diabetes; and 13C-labelled urea in diagnosing stomach and duodenal ulcers. Medical uses of ionizing radiation are manifold including X-ray imaging, radiotherapy with external X-ray beams, brachytherapy, targeted radionuclide therapy, single photon emission computed tomography, and positron emission tomography.
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27

Hoorn, Ewout J., and Robert Zietse. Approach to the patient with hyponatraemia. Edited by Robert Unwin. Oxford University Press, 2015. http://dx.doi.org/10.1093/med/9780199592548.003.0028.

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Hyponatraemia is the most common electrolyte disorder in hospitalized patients and is primarily a water balance disorder. Therefore, hyponatraemia is due to a relative excess of water in comparison with sodium in the extracellular fluid volume. Hyponatraemia is usually due to the release of vasopressin despite hypo-osmolality; this secretion is either ‘appropriate’ (i.e. due to a low intravascular volume) or ‘inappropriate’. The diagnostic approach to hyponatraemia relies on the assessment of the time of development, symptoms, and volume status, along with laboratory parameters such as urine sodium and urine osmolality. Complications are mainly neurological and usually depend on the rate of development and correction. If hyponatraemia develops acutely, treatment should be directed towards counteracting the water shift to or brain cells. Conversely, in more chronic cases of hyponatraemia, treatment should be directed at the underlying cause, while avoiding over-correction.
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28

Winyard, Paul. Human kidney development. Edited by Adrian Woolf. Oxford University Press, 2015. http://dx.doi.org/10.1093/med/9780199592548.003.0343.

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The kidneys perform diverse functions including excretion of nitrogenous waste products, homeostasis of water, electrolytes and acid–base balance, and hormone secretion. The simplest functional unit within the kidneys is the nephron, which consists of specialized segments from glomerulus, through proximal tubule, loop of Henle, and distal tubule. Human nephrogenesis starts with two stages of transient kidneys, termed the pronephros and mesonephros, and ends with development of a permanent organ from the metanephros on each side. The latter consists of just a few hundred cells when it is formed in the fifth week of pregnancy but progresses to a nephron endowment of between 0.6 to 1.3 million by the time nephrogenesis is completed at 32–36 weeks of gestation. Key events during this process include outgrowth of the epithelial ureteric bud from the mesonephric duct, interactions between the bud and the metanephric blastema (a specific region of mesenchyme) that cause the bud to branch and mesenchyme to condense, epithelialization of the mesenchyme to form proximal parts of the nephron, and differentiation of segment specific cells. Molecular control of these events is being unpicked with data from human genetic syndromes and animal models, and this chapter highlights several of the most important factors/systems involved. Increased understanding of development is not just relevant to congenital kidney malformations, but may also be important in designing rational therapies for diseases of the mature kidney where recapitulation of developmental pathways is common.
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29

Senecal, Kelly, and Felix Leach. Racing Toward Zero: The Untold Story of Driving Green. SAE International, 2021. http://dx.doi.org/10.4271/9781468601473.

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In Racing Toward Zero, the authors explore the issues inherent in developing sustainable transportation. They review the types of propulsion systems and vehicle options, discuss low-carbon fuels and alternative energy sources, and examine the role of regulation in curbing emissions. All technologies have an impact on the environment, from internal combustion engine vehicles to battery electric vehicles, fuel cell electric vehicles, and hybrids-there is no silver bullet. The battery electric vehicle may seem the obvious path to a sustainable, carbon-free transportation future, but it's not the only, nor necessarily the best, path forward. The vast majority of vehicles today use the internal combustion engine (ICE), and this is unlikely to change anytime soon. Improving the ICE and its fuels-entering a new ICE age-must be a main route on the road to zero emissions. How do we go green? The future requires a balanced approach to transportation. It's not a matter of choosing between combustion or electrification; it's combustion and electrification. As the authors say, "The future is eclectic." By harnessing the best qualities of both technologies, we will be in the best position to address our transportation future as quickly as possible.
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30

Chakera, Aron, William G. Herrington, and Christopher A. O’Callaghan. Polyuria. Edited by Patrick Davey and David Sprigings. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780199568741.003.0057.

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Polyuria describes the passage of more than 3 l of urine a day. This is an arbitrary definition, and the term is commonly applied to patients who are complaining of passing larger than normal volumes of urine. As water excretion is tightly regulated by the body to maintain normal osmolality, water excretion varies greatly depending on intake. Polyuria may be physiological or pathological. A patient with polyuria often presents with nocturia, urination overnight that disturbs sleep. It is usually accompanied by polydipsia (to maintain normal fluid balance). In hospital the commonest causes of polyuria are diuretic therapy and recovery from an acute renal injury (e.g. acute tubular necrosis or obstruction). This polyuric phase can result in an impressive diuresis (8–10 l/day) before tubular cells recover their ability to concentrate urine. During this period, patients are vulnerable to dehydration and may require intravenous fluid replacement. Following pituitary surgery, the urine output should be closely monitored for evidence of new diabetes insipidus. This chapter covers the approach to diagnosis, diagnostic tests, therapy, and prognosis.
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31

Keshav, Satish, and Alexandra Kent. Immunology and genetics in gastrointestinal and hepatic medicine. Edited by Patrick Davey and David Sprigings. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780199568741.003.0196.

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The gut has a pivotal role in immune homeostasis. It is constantly exposed to a wide array of antigens in food, and resident and consumed microorganisms. It is estimated that the number of bacterial cells in the gastrointestinal tract is tenfold greater than the number of cells in the human body. The gut needs to recognize harmful bacteria, and consequently contains the largest number of immune cells in the body. However, it must remain tolerant to commensal bacteria. Bacteria express antigens that stimulate an immunological response via the gut-associated lymphoid tissue (GALT). The GALT includes the appendix, tonsils, Peyer’s patches, and mesenteric lymph nodes. Therefore, the intestinal immune system is finely balanced between tolerance and reactivity. An example of an abnormal response that generally the individual should be tolerant to is gliadin peptides in coeliac disease. An example of excessive tolerance to an otherwise controllable infection is cryptosporidiosis, which causes diarrhoea in patients with HIV infection. The understanding of genetics in disease has progressed rapidly with the introduction of genome-wide association studies. The Welcome Trust Case Control Consortium has performed extensive research on the genetics of many illnesses, including Crohn’s disease, ulcerative colitis, Barrett’s oesophagus, oesophageal adenocarcinoma, and primary biliary cholangitis. Although these studies have increased our understanding of the molecular basis of disease, they have had little impact on clinical management. This may change as studies associate genotype and phenotype. Several gastrointestinal diseases have an etiology based on immunological or genetic aberrations, and these immunological mechanisms and genetic mutations can be utilized for diagnostic purposes. However, there is no genetic or immunological marker that is 100% specific to a disease and, consequently, the markers are used to support clinical, histological, and/or radiological findings.
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32

Barsoum, Rashad S. Schistosomiasis. Edited by Neil Sheerin. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780199592548.003.0181_update_001.

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AbstractSchistosomes are blood flukes that parasitize humans, apes, cattle, and other animals. In these definitive hosts they are bisexual, and lay eggs which are shed to fresh water where they complete an asexual cycle in different snails, ending in the release of cercariae which infect the definitive hosts to complete the life cycle.Seven of over 100 species of schistosomes are human pathogens, causing disease in different organs depending on the parasite species. Racial and genetic factors are involved in susceptibility, severity, and sequelae of infection.Morbidity is induced by the host’s immune response to schistosomal antigens. The latter include tegument, microsomal, gut, and oval antigens. The former are important in the process of invasion and establishment of infection, oval antigens in formation of granulomata which lead to fibrosis in different sites, and the gut antigens constitute the main circulating antigens in established infection, leading to immune-complex disease, particularly in the kidneys. The host immunological response includes innate and adaptive mechanisms, the former being the front line responsible for removing 90% of the infecting cercarial load. Adaptive immunity includes a Th1 phase, dominated by activation of an acute inflammatory response, followed by a prolonged Th2 phase which is responsible for immunity to re-infection as well as progression of tissue injury. Switching from Th1 to Th2 phases is controlled by functional and morphological change in the antigen-presenting cells, which is achieved by molecules of host as well as parasitic origin.Many cells participate in parasite killing, but also in the induction of tissue injury. The most potent of these is the eosinophil, which by binding antibodies to the parasite, particularly immunoglobulin E, facilitates parasite elimination. However, this process is complex, including agonist as well as antagonist pathways, which provide escape mechanisms for the parasite to survive, thereby achieving a delicate balance that permits schistosomes to live for decades in the infected host.
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33

Grant, Robert. Tumours of the brain and skull. Oxford University Press, 2011. http://dx.doi.org/10.1093/med/9780198569381.003.0624.

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Over the last 10 years, there have been several important advances in cell biology, molecular genetics, and targeted therapies in neuro-oncology. Improved neurosurgical techniques such as frameless stereotaxy, awake craniotomy, and intra-operative MRI, safer methods of directing radiotherapy, new chemotherapy approaches, and novel modalities of therapy provide optimism that there will eventually be some improvements in treatment-related morbidity and survival. There has also been an increasing change from individual clinician decision making to decision making by multidisciplinary teams of neurosurgeons, neurologists, clinical oncologists, neuropathologists, neuroradiologists, and specialist nurses with the aim of improving decision making, management planning across specialties, communication, and enrolment in suitable clinical trials. In addition, Good Clinical Practice guidelines, an international ethical and scientific quality standard for designing, conducting, recording, and reporting trials, increases the onus and responsibilities on clinical investigators to perform trials to the highest standard and to have the trials externally monitored, and the trial conduct and results audited. While these obligatory and statutory responsibilities are labour intensive and time consuming, they should improve the quality of trials by limiting the possibility of unintentional bias or fraud. Improving the recording of serious adverse event reporting through trial quality assurance and quality control procedures will help ensure that a balanced view of the effects of a drug or procedure is identified earlier than in the past. It will be interesting to see how research develops over the next decade.
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34

Kuypers, Dirk R. J., and Maarten Naesens. Immunosuppression. Edited by Jeremy R. Chapman. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780199592548.003.0281_update_001.

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Combination immunosuppressive therapy produces excellent short-term results after kidney transplantation. Long-term graft survival has improved, but less dramatically. Death with a functioning graft remains the primary cause of graft loss. Dosing of current immunosuppressive therapy balances between careful clinical interpretation of time-driven immunological risk assessments and drug-related toxicity on the one hand, and the use of simple surrogate drug exposure indicators like blood/plasma concentrations on the other. The combined use of calcineurin-inhibitors (CNIs) with mycophenolic acids and corticosteroids has been fine-tuned over the last decade, based on empirically derived observations as well as on the results of large multicentre randomized clinical studies. Corticosteroid withdrawal and avoidance are feasible, at least in patients with a low immunological risk, but CNI-free protocols have had few long-term successes. Some minimization strategies have increased risk of developing acute rejection or (donor-specific) anti-HLA antibodies, with deleterious effects on the graft. Mammalian target of rapamycin inhibitors (mTORi) have shown limited benefit in early CNI replacement regimens and their long-term use as primary drug is hampered by intolerance. In the setting of particular malignant disease occurring after transplantation, such as squamous cell carcinoma of the skin and Kaposi’s sarcoma, mTORi seem promising. Induction agents (anti-interleukin 2 receptor monoclonal antibodies, antithymocyte globulins) effectively diminish the risk of early immunological graft loss in recipients with moderate to high immunological risk but at the price of more infectious or malignant complications. While personalized transplantation medicine is only in its early stages of development, attempts are made to quantitatively measure the clinical degree of immunosuppression, to tailor immunosuppressive therapy more specifically to the patient’s individual profile, and to monitor graft status by use of invasive (e.g. surveillance renal biopsies) and non-invasive biomarkers. These scientific endeavours are a necessity to further optimize the current immunosuppressive therapy which will remain for some time to come.
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35

Wójcik-Gładysz, Anna. Ghrelin – hormone with many faces. Central regulation and therapy. The Kielanowski Institute of Animal Physiology and Nutrition, Polish Academy of Sciences, 2020. http://dx.doi.org/10.22358/mono_awg_2020.

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Discovered in 1999, ghrelin, is one of the peptides co-creating the hypothalamicgastrointestinal axis, otherwise known as the brain-gut axis. Ghrelin participates in many physiological processes and spectrum of its activity is still being discovered. This 28 amino acid peptide ‒ a product of the ghrl gene, was found in all vertebrates and is synthesized and secreted mainly from enteroendocrine X/A cells located in the gastric mucosa of the stomach. Expression of the ghrelin receptor has been found in many nuclei of the hypothalamus involved in appetite regulation. Therefore it’s presumed that ghrelin is one of the crucial hormones deciphering the energy status required for the maintenance of organism homeostasis. Ghrelin acts as a signal of starvation or energy insufficiency and its level in plasma is reduced after the meal. Neuropeptide Y (NPY) and agouti-related peptide (AgRP; NPY/AgRP) neurons located in the arcuate nucleus (ARC) area are the main target of ghrelin in the hypothalamus. This subpopulation of neurons is indispensable for inducing orexigenic action of ghrelin. Moreover ghrelin acting as a neurohormone, mainly in the hypothalamus area, plays an important role in the regulation of growth and reproduction processes. Indeed, ghrelin action on reproductive processes has been observed in the systemic effects exerted at both hypothalamus-pituitary and gonadal levels. Similarly the GH-releasing ghrelin action was observed both on the hypothalamus level and directly on the somatotrophic cells in the pituitary and this dose-related GH releasing activity was found in in vitro as well as in in vivo experiments. In recent years, numerous studies revealed that ghrelin potentially takes part in the treatment of diseases associated with serious disturbances in the organism energy balance and/or functioning of the gastrointestinal tract. It was underlined that ghrelin may be a hormone with a broad spectrum of therapeutic effect on obesity and anorexia nervosa, as well as may also have protective effect on neurodegenerative diseases, inflammatory disorders or functional changes in the body caused by cancers. In overall, ghrelin treatment has been tested in over 100 preclinical studies with healthy volunteers as well as patients with various types of cancer, eating disorders such as anorexia nervosa and bulimia nervosa. It was observed that ghrelin has an excellent clinical safety profile and emerging side effects occurred only in 3–10% of patients and did not constitute a sufficient premise to discontinue the therapy. In general, it can be concluded that ghrelin may be sufficiently used as a prescription drug.
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36

Armstrong, Fraser, and Katherine Blundell, eds. Energy... beyond oil. Oxford University Press, 2007. http://dx.doi.org/10.1093/oso/9780199209965.001.0001.

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As the Earth's oil supply runs out, and the effects of climate change threaten nations and their populations, the search for carbon-neutral sources of energy becomes more important and increasingly urgent. This book focuses on solutions to the energy problem, and not just the problem itself. It describes the major energy-generation technologies currently under development, and provides an authoritative summary of the current status of each one. It stresses the need for a balanced portfolio of alternative energy technologies. Certain solutions will be more appropriate than others in particular locations, due to the differences in availability of natural resources such as solar, wind, wave, tidal and geothermal. In addition, nuclear options (both fission and fusion), as well as technologies such as fuel cells, photovoltaics, artificial photosynthesis and hydrogen (as an energy carrier), all have a potential role to play. A state-of-the-art critique of energy efficiency in building design is also included. Each chapter is written by an acknowledged international expert and provides a non-technical overview of the competing and complementary approaches to energy generation. Broad in scope and comprehensive in treatment, Energy..beyond Oil provides an authoritative synthesis of the scientific and technological issues which are essential to the survival of the human race in the near future. The book will be of interest and use to graduate students and researchers in all areas of energy studies, and will also be highly useful for policy-makers and professionals in the environmental sector as well as a more general readership who wish to learn more about this extremely topical subject.
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37

Skiba, Grzegorz. Fizjologiczne, żywieniowe i genetyczne uwarunkowania właściwości kości rosnących świń. The Kielanowski Institute of Animal Physiology and Nutrition, Polish Academy of Sciences, 2020. http://dx.doi.org/10.22358/mono_gs_2020.

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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.
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38

(Editor), T. Kumazawa, L. Kruger (Editor), and K. Mizumura (Editor), eds. The Polymodal Receptor - A Gateway to Pathological Pain (Progress in Brain Research). Elsevier Science, 1996.

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39

Takao, Kumazawa, Kruger Lawrence, and Mizumura Kazue, eds. The polymodal receptor: A gateway to pathological pain. Amsterdam: Elsevier, 1996.

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