bluuebunny/crossref_metadata_2025 huggingface dataset:
Anti-Inflammatory Drugs
Authors: Li Jie Jack
Published: November 2020

Inflammation and immunity, like all other normal reactions of the body, are meant to preserve or restore health. They can nonetheless cause a range of uncomfortable symptoms. Inflammation is such a complicated process that one would have a hard time reaching a consensus on its definition. Historically, inflammation was one of the earliest recognized and defined diseases. Two thousand years ago, Roman physician and encyclopedist Aulus Cornelius Celsus (25 B.C.–50 A.D., not to be confused with Celsius, the unit for temperature) described the four cardinal signs of inflammation: calor (warmth), dolor (pain), tumor (swelling), and rubor (redness). The fifth element of inflammation, functio laesi (loss of function or movement), was noted later. Classic inflammatory diseases include rheumatoid arthritis and Crohn’s disease, an inflammatory bowel disease. However, evidence is mounting that inflammation is implicated in many diseases that are not normally considered inflammatory. For instance, when arterial plaques become inflamed they can burst open, prompting a myriad of heart diseases. Inflammatory bowel conditions greatly increase the risk of colon tumors. Even diabetes has been associated with a number of inflammatory compounds. It was hard to define what inflammation was, but finding a remedy was even more challenging. Aspirin, available in 1880, represented possibly the first really effective treatment for inflammation, whereas cortisone and other corticosteroids were not available for the treatment of rheumatoid arthritis until the early 1950s. Louis Pasteur stated, “Dans les champs de l’observation, le hazard ne favorise que les esprit préparés” [In the field of experimentation, chance favors the prepared mind]. Like numerous cases in drug discovery, Philip S. Hench’s discovery of cortisone for the treatment of rheumatoid arthritis illustrates Pasteur’s point. Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by pain, swelling, and subsequent destruction of joints. Until the late 1940s, there was no viable treatment, and, understandably, pessimism prevailed in medical society about its prognosis. Even William Osler, one of the greatest physicians, said “When an arthritic patient walks in the front door, I want to run out the back door!” The situation did not change much until Hench discovered a “miracle drug” in 1949.
Bioinorganic Systems
Authors: Jordan Robert B.
Published: November 2020

The field of bioinorganic chemistry has grown tremendously in the past 25 years. Much of the work is concerned with establishing the coordination site, ligand geometry and metal oxidation state in biologically active systems. The field also extends to the preparation and characterization of simpler model complexes that mimic the spectroscopic properties and perhaps some of the reactivity of the biological system. Much of this characterization work must precede meaningful mechanistic studies. Williams has provided an interesting overview of metal ions in biology from an inorganic perspective. There are several early review series and specialized journals devoted to the subject, and a recent issue of Chemical Reviews is devoted to the area. There also are several books covering general aspects of the subject. The field is so large and the systems are so individualistic that it is necessary, for the purposes of a text such as this, to choose a few sample systems as illustrative of the mechanistic achievements and problems. Studies of bioinorganic systems inevitably use some terminology from biochemistry which may be unfamiliar to an inorganic chemist. The examples in this Chapter are all metalloenzymes which catalyze some process. Clearly they contain a metal, but there are other components of an enzyme, and terms used to describe these are summarized as follows: An apoenzyme is a polypeptide whose composition, peptide sequence and structure depend on the biological source of the metalloenzyme. Typically, the molar mass of the polypeptide is in the range of 1.5-5xl05 daltons. The polypeptide is folded into coils and sheets whose shape is determined by electrostatics and hydrogen bonding. These terms designate the same type of component, but one or the other is used more commonly for a particular system. This is a nonprotein component which binds to the apoenzyme to produce the active catalyst. It is not covalently bonded to the apoenzyme and can be removed by relatively mild denaturation of the polypeptide. Common bioinorganic examples are coenzyme B12, discussed in Section 8.3, and Zn(II) in carbonic anhydrase, discussed in Section 8.4. A prosthetic group is analogous to a coenzyme except that a prosthetic group is believed to be covalently bonded to the apoenzyme.
Offshoring the War on Terror
Authors: Raustiala Kal
Published: November 2020

A few days before New Year’s Day, 2002 John Yoo and Patrick Philbin, two lawyers in the Department of Justice, drafted a memorandum for the Department of Defense. The memo was entitled Possible Habeas Jurisdiction over Aliens Held in Guantanamo Bay, Cuba. Shortly after the attacks on September 11, 2001, the Bush administration had announced plans to try suspected terrorists by military commission, a kind of military court. As the memo was being completed, the war in Afghanistan was still ongoing. But coalition forces had taken Kabul and other major cities and had already captured many suspected Al Qaeda members. The Bush administration feared detaining these individuals within the United States and generally rejected the criminal justice model of counterterrorism championed by previous presidents. The United States naval base at Guantanamo, the subject of the lawyers’ memo, was appealing as a long-term site for detention and trial. It was distant from the Middle East, very secure, and, as the Justice Department noted, probably free of the influence of American courts due to its location outside the territory of the United States. In time the detention camp at Guantanamo would become a source of sustained criticism around the world and a major political liability for the United States. But in late 2001, with the World Trade Center site still a smoking ruin, Guantanamo appeared to be a very attractive option to those formulating the legal response to the 9/11 attacks. Two years after the Guantanamo memo was written the New York Times reported that the CIA and the Pentagon were operating a network of offshore prisons in various foreign locations. In these overseas prisons, so reported the Times, were some of the most high-value detainees in the war on terror. Successive stories in the Washington Post revealed that a number of these “black site” prisons were in Europe, and that the CIA had flown individuals there for extensive and coercive interrogation. As the Times reported, the “suggestion that the United States might be operating secret prisons in Europe and the idea that American intelligence officers might be torturing terrorism suspects incarcerated on foreign soil have been incendiary issues across Europe in recent weeks.”
The Role of the Recovery Guide
Authors: Davidson Larry , Rowe Michael , Tondora Janis , O'Connell Maria J. , Lawless Martha Staeheli
Published: November 2020

We have defined and discussed the nature of various notions of recovery, grappled with the implications of a recovery vision for mental health system transformation, and begun to draw the outlines of a transformed system. Now we can turn to the question of how such services and supports can actually be offered to people who need them. Here we propose what we call the recovery guide model. Analogous to the role currently played by case management, the recovery guide model is an organizing vehicle by which practitioners can offer a range of services and supports to people, either directly or through others. As with case management, the intensity, scope, focus, and duration of a recovery guide’s work with a person will depend on that person’s needs, preferences, life circumstances, and goals at a given point in his or her unique recovery journey. In this chapter we describe the basic aims, tenets, and tools of this approach. First, though, we offer a brief review of advances in mental health case management that preceded and led up to the concept of recovery guides, including the present recognition that, in a recovery-oriented system of care, people with serious mental illness can no longer be considered “cases” that others manage (Everett & Nelson, 1992). With the failure of a combination of Thorazine and psychotherapy to achieve the aims of deinstitutionalization (Johnson, 1992), case management became the predominant service that mental health systems offered their clients with serious mental illness (Sledge, Astrachan, Thompson, Rakfeldt, & Leaf, 1995). In addition to being inadequately funded, community-based systems of care that were developed to enable people with serious mental illness to leave state hospitals were fragmented and uncoordinated “non-systems” of care (Hoge, Davidson, Griffith, & Jacobs, 1998). As it was practically impossible for people seeking care to navigate these complex and unintegrated health and social service systems on their own, the case manager role was created to identify and coordinate the provision of services to meet their multiple needs in the community (Hoge, Davidson, Griffith, Sledge, & Howenstine, 1994; Sledge et al., 1995). Case managers’ primary responsibility was to assess people’s needs, link them to services, and monitor their service use and outcomes.
Parkinson’s Disease
Authors: Marsh Laura
Published: November 2020

Parkinson’s disease (PD), the second most common neurodegenerative disorder after Alzheimer’s disease (AD), causes a progressive neurologic syndrome characterized by bradykinesia, tremor, rigidity, and, in its later stages, postural instability. The motor signs of PD correspond to loss of dopaminergic neurons in the substantia nigra pars compacta within the ventral midbrain. Neuronal inclusions, called Lewy bodies, are also present in the same region, but they can also be present in limbic and cortical regions and, along with other neurotransmitter deficits, are associated with nonmotor aspects of the disease. PD is to be distinguished from parkinsonism, a general term that refers to clinical conditions with the same motor phenomena, but without reference to a specific etiology. Prevalence rates of PD vary. Epidemiologic studies show ageadjusted prevalence rates (per 100,000 individuals) range from 104.7 in Japan, 114.6 in the United States, 168.8 in Taiwan, and 258.8 in Sicily (Korell and Tanner, 2005). The disease affects about 1 million individuals in North America—approximately 0.5% to 1% of the population older than age 65 years of age. The average age of onset is about 60 years, but 5% to 10% of patients have young-onset PD, beginning before age 40 (Tanner and Ben-Shlomo, 1999). The disease affects all races, and there is a slightly higher prevalence of PD among men. The diagnosis of PD relies on the clinical history and motor examination, which usually distinguish it from other parkinsonian disorders. However, because there is no biological marker that verifies the diagnosis of PD, neuropathologic findings remain the gold standard for confirmation of the clinical diagnosis. Even at specialized movement disorder centers, autopsy studies reveal that 10% to 20% of patients with clinical diagnoses of PD have other neuropathologic diagnoses (Hughes, Daniel, and Lees, 2001). Two of the three cardinal motor signs (tremor, akinesia/bradykinesia, and rigidity) are required to establish the diagnosis of PD, but these motor features overlap with other parkinsonian disorders. However, in patients without an overt tremor, early signs of PD such as decreased arm swing, limb stiffness, and diminished facial expression can be subtle, and the diagnosis of PD maybe delayed for several years.
Electroconvulsive Therapy
Authors: Lipsey John R.
Published: November 2020

Electroconvulsive therapy (ECT) is a highly effective intervention for severe major depression (American Psychiatric Association Committee on Electroconvulsive Therapy, 2001). ECT is most often used because pharmacotherapy has failed. In certain clinical situations, however, ECT is the initial treatment of choice. Ten to fifteen percent of patients with major depression fail to respond to antidepressants. Such outcomes may persist despite adequate treatment with multiple classes of antidepressant drugs (Rush et al., 2006) and other pharmacologic augmentation strategies (eg, the addition of lithium to an antidepressant). Eventually, social relationships and work performance decline as patients lose hope and other depressive symptoms worsen in intensity. ECT should be strongly considered for such patients because many may fully recover with it. Those with an episodic, rather than chronic, course of depressive disorder are most likely to respond. Patients with persistent suicidal intention or actions are often given ECT as primary treatment because it would be dangerous to undergo a potentially prolonged series of medication trials while the patient remained at risk of self-injury. Similarly, those with severe inanition, psychomotor retardation, and depressionrelated immobility are usually treated with ECT first, to avoid medical complications such as aspiration, atelectasis, pneumonia, other infections, decubitus ulcers, and venous thrombosis. In both of these classes of patients, ECT is much more likely than antidepressants to rapidly improve depressive symptoms. Although delusionally depressed patients may respond to a combination of an antidepressant and neuroleptic, they are more likely to respond to ECT and to do so rapidly. The mental suffering associated with depressive delusions (eg, of hopelessness, criminality, bodily decay, or self-loathing) is often unbearable, and the patient’s response to such beliefs may make behavior impulsive and unpredictable. ECT is the treatment of choice to accelerate recovery and enhance patient safety. Catatonic patients almost always respond quickly to ECT and should be treated with it early. Although a minority of catatonics have a sustained positive response to benzodiazepines, this improvement is usually transient, and ECT is then required. Other medications are rarely effective. Retarded and agitated forms of catatonia are dangerous for the patient, and effective treatment with ECT should not be delayed.
Language Development and Deaf Children
Authors: Marschark Marc , Lang Harry G. , Albertini John A.
Published: November 2020

To understand the complex relations between language and learning, we have to look at both how children learn language and what it is that they learn that allows them to communicate with others. To accomplish this, we need to distinguish between apparent differences in language that are related to the modality of communication and actual differences in language fluencies observed among deaf children. It also will help to examine some relevant differences between deaf children and hearing children. We have already pointed out that the distinction between spoken language and sign language, while a theoretically important one for researchers, is an oversimplification for most practical purposes. It is rare that deaf children are exposed only to spoken language or sign language, even if that is the intention of their parents or teachers. According to 1999 data, approximately 55 percent of deaf children in the United States are formally educated in programs that report either using sign language exclusively (just over 5 percent) or signed and spoken language together (just over 49 percent) (Gallaudet University, Center for Applied Demographic Statistics). Because almost half of all deaf children in the United States are missed in such surveys, however, these numbers only should be taken as approximate. Comparisons of the language abilities of deaf children who primarily use sign language with those who primarily use spoken language represent one of the most popular and potentially informative areas in research relating to language development and academic success. Unfortunately, this area is also one of the most complex. Educational programs emphasizing spoken or sign language often have different educational philosophies and curricula as well as different communication philosophies. Programs may only admit children with particular histories of early intervention, and parents will be drawn to different programs for a variety of reasons. Differences observed between children from any two programs thus might be the result of a number of variables rather than, or in addition to, language modality per se. Even when deaf children are educated in spoken language environments, they often develop systems of gestural communication with their parents (Greenberg et al., 1984).
Tectonism, Climate, and Landscape Change
Authors: Orme Antony R.
Published: November 2020

Earth’s physical landscapes are framed initially by tectonism, reshaped by climate, garnished by plants and animals, and modified by human activity. Tectonism constructs the physical framework of the continents and ocean floors. Climate, the synthesis of weather, generates the surface processes that reshape this framework through erosion and sedimentation, and also provides the conditions necessary to support life. In various guises, tectonism and climate have played these roles from early in Earth history, although 90% of Earth time had passed before the continents began to acquire vascular plants and land animals. However, because Earth’s crust is ponderously mobile and climate depends ultimately on the variable receipt of solar radiation, tectonic and climatic forcing vary across time and space. Consequently, continents come to acquire distinctive suites of landscapes that reflect changing locational, tectonic, climatic, and biotic influences over time. South America exemplifies this concept—a continent whose distinctive qualities owe much to the roles played by tectonism and climate over time, including their impacts on landforms and biota. Tectonism and climate are interactive forces. By determining the distribution and shape of land masses and ocean basins, tectonism influences the relative importance of continentality and oceanicity to climate. Over time, tectonism also influences climate change by promoting uplift favorable to prolonged cooling and perhaps glaciation, by opening and closing seaways to ocean circulation, and by influencing atmospheric composition by the generation and consumption of crustal rocks. Though more subtle, climate may in turn affect tectonism by redistributing continental mass through erosion and deposition, thereby generating isostatic adjustments to crustal loading and unloading. Tectonism also influences plant and animal distributions directly, for example by providing linkages or barriers to migration, while climate and biota are intimately linked in the biome concept and the feedback effect of biomes on climatic processes. This chapter examines the interactive roles of tectonism and climate in changing the South American landscape over the 200 million years that have passed since the initial breakup of Pangea. It then discusses the implications of these changes for geomorphology and biogeography, and concludes with a brief evaluation of the pace of landscape change.
Late Quaternary Glaciation of the Tropical Andes
Authors: Seltzer Geoffrey O.
Published: November 2020

The effects of climate change are intrinsic features of Earth’s landscapes, and South America is no exception. Abundant evidence bears witness to the changes that have shaped the continent over time—from the glacial tillites inherited from late Paleozoic Gondwana to recent terrigenous sediments and life forms trapped in alluvial, lacustrine, and nearby marine deposits. Preeminent among this evidence are the landforms and sediments derived from the late Cenozoic glaciations of the Andes, which have been the focus of so much recent and ongoing research. Because South America has long been a mainly tropical and subtropical continent, most of it escaped the direct effects of these glaciations. Nevertheless, portions of the continent extend sufficiently far poleward and rise high enough to attract snowfall and promote glaciers today. Glaciers were more emphatically present during Pliocene and Pleistocene cold stages, and it is their legacies that provide information about the changing environments of those times, and more especially of the past 30,000 years. There is evidence for glaciation in the tropical and extratropical Andes as early as Pliocene time (Clapperton, 1993). In southern South America, along the eastern side of the Patagonian Andes, Mercer (1976) dated a series of basalts interbedded with glacial tills that suggest multiple glacial advances after ~3.6 Ma (million years before present). In the La Paz Valley, Bolivia, volcanic ashes dated by K/Ar (potassium/argon) methods are interbedded with glacial tills indicative of at least two phases of glaciation in the late Pliocene, at 3.27 and 2.20 Ma (Clapperton, 1979, 1993). This evidence for early glaciation in disparate parts of the Andes indicates that portions of the cordillera were high enough and climatic variations were great enough in the Pliocene for glaciers to form long before the cold episodes of the Pleistocene. Glacial deposits in Ecuador, Perú, and Bolivia provide evidence for climate variability in tropical South America in the recent geological past. In the late Pleistocene, glacier equilibrium-line altitudes were as much as 1,200 m lower than they are today on the eastern slopes of the Andes, indicative of a significant depression in mean annual temperature in the tropics at maximum glaciation (e.g., Klein et al., 1999).
Soils
Authors: Buol Stanley W.
Published: November 2020

Soil is a physical, chemical, and biological medium at the upper surface of Earth’s land areas capable of accepting plant roots and thereby enabling plants to extend their photosynthetic tissues upward and intercept radiant energy from the sun. Each day, chemical and biological activities in soil change in response to temperature and moisture dynamics. Each soil has a range of physical, chemical, and biological properties determined by inherited mineral composition and biogeochemical processes existing in a quasi-steady state of flux. Most primary minerals in soil formed in geologic environments of high temperature and pressure. When exposed to lower temperatures and pressures, meteoric water, and organic compounds near Earth’s surface, primary minerals slowly decompose in response to weathering processes. As primary minerals weather, some elements necessary for plant growth are released as inorganic ions, some reassemble to form secondary silicate and oxide clay minerals, and some elements are lost via dissolution and leaching. After prolonged or intense weathering, few minerals containing elements necessary for plant growth remain. Weathering most often occurs in or slightly below the soil but may not be entirely related to the present soil. Material from which a present soil is formed may have been weathered in a soil environment, and eroded and deposited many times before coming to rest in its present location. Such materials are often almost devoid of nutrient- bearing minerals, and the soils formed provide scant amounts of the elements essential for plant growth. In contrast, minerals exposed to a soil environment for the first time on rapidly eroding slopes, fluvial deposits, or as volcanic ejecta succumb more rapidly to weathering and release essential elements in forms needed by plants. Plants ingest inorganic ions and water from the soil through their roots and combine them with carbon secured as carbon dioxide from the air, and with hydrogen and oxygen from water to form organic tissues. Organic residues are added to the soil as various plant parts, insects, and animals die. Microorganisms in and above the soil then decompose the organic residues, carbon returns to the air as carbon dioxide, and essential elements contained in the organic compounds are released as inorganic ions within the soil.
Isolation and Insulation, 22000 BC–3000 BC
Authors: Abulafia David
Published: November 2020

Carved out millions of years before mankind reached its coasts, the Mediterranean Sea became a ‘sea between the lands’ linking opposite shores once human beings traversed its surface in search of habitation, food or other vital resources. Early types of humans inhabited the lands bordering the Mediterranean 435,000 years before the present, to judge from evidence for a hunters’ camp set up near modern Rome; others built a simple hut out of branches at Terra Amata near Nice, and created a hearth in the middle of their dwelling – their diet included rhinoceros and elephant meat as well as deer, rabbits and wild pigs. When early man first ventured out across the sea’s waters is uncertain. In 2010, the American School of Classical Studies at Athens announced the discovery in Crete of quartz hand-axes dated to before 130,000 BC, indicating that early types of humans found some means to cross the sea, though these people may have been swept there unintentionally on storm debris. Discoveries in caves on Gibraltar prove that 24,000 years ago another species of human looked across the sea towards the mountain of Jebel Musa, clearly visible on the facing shore of Africa: the first Neanderthal bones ever discovered, in 1848, were those of a woman who lived in a cave on the side of the Rock of Gibraltar. Since the original finds were not immediately identified as the remains of a different human species, it was only when, eight years later, similar bones were unearthed in the Neander Valley in Germany that this species gained a name: Neanderthal Man should carry the name Gibraltar Woman. The Gibraltar Neanderthals made use of the sea that lapped the shores of their territory, for their diet included shellfish and crustaceans, even turtles and seals, though at this time a flat plain separated their rock caves from the sea. But there is no evidence for a Neanderthal population in Morocco, which was colonized by homo sapiens sapiens, our own branch of humanity. The Straits apparently kept the two populations apart.
Crossing the Boundaries between Christendom and Islam, 900–1050
Authors: Abulafia David
Published: November 2020

The enlargement of Muslim domination to include Morocco, Spain and eventually Sicily meant that the southern half of the Mediterranean became a Muslim-ruled lake, offering splendid new opportunities for trade. Jewish merchants emerge most prominently from the records. Whether this is an accident of survival, or whether they were more successful than Coptic and Syriac Christians or Muslim townsmen of North Africa, Spain and Egypt is uncertain. There are grounds for thinking that non-Muslim merchants had a distinct advantage. Muslims were constrained by legal rulings that forbade them from living or even trading in infidel lands. Over the centuries this meant that the rulers of Muslim cities in the Mediterranean opened their doors to Christian and Jewish traders, but their Muslim inhabitants were wary of venturing to Italy, Catalonia or Provence. The reason so much is known about the Jewish traders is that hundreds of their letters and business documents have survived in the collection known as the Cairo Genizah. In the mid-seventh century, the Arab invaders of Egypt established their base at Fustat (meaning ‘the Ditch’) on the edge of modern Cairo, and only later moved their capital to the surroundings of the great citadel of New Cairo. Old Cairo, or Fustat, became the base for the city’s Jewish and Coptic population; in the eleventh century one group of Jews rebuilt the Ben Ezra synagogue, incorporating on the upper floor a storeroom, or Genizah, accessible only by ladder, into which they threw and stuffed their discarded papers and manuscripts. They wished to avoid destroying anything that carried the name of God; by extension they did not destroy anything written in Hebrew characters. It has been well said that the Genizah collection is ‘the very opposite of an archive’, because the aim was to throw away documents without destroying them, in effect burying them above ground, rather than to create an accessible room that could be used for systematic reference.
Ways across the Sea, 1160–1185
Authors: Abulafia David
Published: November 2020

There are no diaries or log-books of sea captains from the twelfth century, but there are vivid accounts of crossing the Mediterranean written by Jewish and Muslim pilgrims journeying from Spain to the East. Benjamin of Tudela was a rabbi from a town in Navarre, and he set out on his travels around 1160. The aim of his diary was to describe the lands of the Mediterranean, large areas of Europe, and Asia as far as China, in Hebrew for a Jewish audience, and he carefully noted the number of Jews in each town he visited. His book reports genuine travels across the Mediterranean, through Constantinople and down the coast of Syria, though his descriptions of more remote areas beyond the Mediterranean are clearly based on report and rumour, which became more fantastic the further his imagination ventured. He evidently did go to Jerusalem, though, and expressed his wonderment at the supposed tomb of King David on Mount Zion. As Christian passions about the Holy Land became more intense, the attention of Jewish pilgrims was also directed there, under the influence of the crusaders whom they scorned. Benjamin’s route took him down from Navarre through the kingdom of Aragon and along the river Ebro to Tarragona, where the massive ancient fortifications built by ‘giants and Greeks’ impressed him. From there he moved to Barcelona, ‘a small city and beautiful’, full of wise rabbis and of merchants from every land, including Greece, Pisa, Genoa, Sicily, Alexandria, the Holy Land and Africa. Benjamin provides precious and precocious evidence that Barcelona was beginning to develop contacts across the Mediterranean. Another place that attracted merchants from all over the world, even, he says, from England, was Montpellier; ‘people of all nations are found there doing business through the medium of the Genoese and Pisans’. It took four days to reach Genoa by sea from Marseilles. Genoa, he wrote, ‘is surrounded by a wall, and the inhabitants are not governed by any king, but by judges whom they appoint at their pleasure’. He also insisted that ‘they have command of the sea’.
Interlopers in the Mediterranean, 1571–1650
Authors: Abulafia David
Published: November 2020

The period between the battle of Lepanto and the middle of the seventeenth century has a certain unity. Barbary pirates did not go away – indeed, they became more piratical, in the sense that the Ottomans allowed them a freer hand, for the Sublime Porte no longer expected to extend its direct authority deep into the western Mediterranean. The western Mediterranean was also exposed to vicious raids by Christian corsairs – to the Knights of Malta could now be added the Knights of Santo Stefano, Tuscan pirates and holy warriors whose order was founded in 1562 by the Medici duke of Tuscany. Like the Venetians, they brought some of the Ottoman banners back in victory from Lepanto; they still hang incongruously in their church in Pisa, daily proclaiming the faith of Islam amid the incense of Catholic ritual. It would be otiose to repeat the endless saga of attacks and reprisals as Christian Knights of Malta or Santo Stefano scored points against Barbary corsairs; the most unfortunate victims were always those who were carried away into slavery from the decks of captured merchant ships, or from the shores of Italy, Spain and Africa (the French were relatively immune to Muslim raiders as a result of their ties to the Ottoman court). Galleys out of Sicily continued to patrol the seas in the hope of defending the Spanish king’s Italian possessions from sea-raiders, but large-scale galley warfare had come to an end, not just because new ship-types were seen as more efficient but because the cost of building and maintaining galleys was prohibitive. Even so, the Ottomans reconstructed their war fleet in the immediate aftermath of Lepanto. There were alarums in the West: it was confidently assumed that the Ottomans would launch a second great assault on a Christian target. Yet the Sublime Porte had lost its taste for naval warfare, and was content to leave the Spaniards alone, while pursuing its traditional rivalry with the Shi’ite emperors of Persia. This was extremely convenient, since Spanish preoccupations also now turned away from the Mediterranean; Philip II’s great ambition was to defeat the new type of Infidel who was crawling all over northern Europe: the Protestants.
The Last Mediterranean, 1950–2010
Authors: Abulafia David
Published: November 2020

The late twentieth century was one of the great periods of Mediterranean migration. Migrations out of North Africa and into and out of Israel have been discussed in the previous chapter. The history of migration out of Sicily and southern Italy began as far back as the late nineteenth century, and it was largely directed towards North and South America. In the 1950s and 60s it was redirected towards the towns of northern Italy. Southern Italian agriculture, already suffering from neglect and lack of investment, declined still further as villages were abandoned. Elsewhere, colonial connections were important; for example, British rule over Cyprus brought substantial Greek and Turkish communities to north London. Along with these migrants, their cuisines arrived: pizza became familiar in London in the 1970s, while Greek restaurants in Britain had a Cypriot flavour. Not surprisingly, the food of the south of Italy took a strong lead among Italian émigrés: the sublime creation of Genoese cooks, trenette al pesto, was little known outside Italy, or indeed Liguria, before the 1970s. But the first stirrings of north European fascination with Mediterranean food could be felt in 1950, when Elizabeth David’s Book of Mediterranean Food appeared. It drew on her often hair-raising travels around the Mediterranean, keeping just ahead of the enemy during the Second World War. Initially, the book evoked aspirations rather than achievements: Great Britain was still subject to post-war food rationing, and even olive oil was hard to find. With increasing prosperity in northern Europe, the market for unfamiliar, Mediterranean produce expanded and finally, in 1965, Mrs David found the confidence to open her own food shop. By 1970 it was not too difficult to find aubergines and avocados in the groceries of Britain, Germany or Holland; and by 2000 the idea that a Mediterranean diet rich in fish, olive oil and vegetables is far healthier than traditional north European diets often based on pork and lard took hold. Interest in regional Mediterranean cuisines expanded all over Europe and North America – not just Italian food but Roman food, not just Roman food but the food of the Roman Jews, and so on.
Triumph of the Heart
Authors: Li Jie Jack
Published: November 2020

Over 25 million people in the U.S. alone have benefited from statins--such drugs as Lipitor, Zocor, Crestor, Pravachol, and other cholesterol-lowering medicines--in preventing stroke, heart attack, and other forms of coronary heart disease. But how did these remarkable, life-saving drugs come into being? In Triumph of the Heart, Dr. Jie Jack Li, a medicinal chemist and expert on drug discovery, tells for the first time the fascinating story of statins. Drawn from discussions with many scientists involved in the discovery and development of these drugs, the book illuminates the human side of science by revealing the role played by persistence, luck, and sudden insight that characterize major discoveries. For scientists in the drug industry, health care professionals, students of medicine, and all those intrigued by the basic human drive to explore and discover, Triumph of the Heart offers a compelling view of one of the most important drug discoveries of our time.
To Market, to Market
Authors: Li Jie Jack
Published: November 2020

Parke-Davis submitted Lipitor’s New Drug Application to the FDA in June 1996 and received approval in December 1996, a relatively short turnaround due to its priority review status. At the time, four statins were already on the market: Merck’s lovastatin (Mevacor, 1987) and simvastatin (Zocor, 1991), Bristol-Myers Squibb’s pravastatin (Pravachol, 1991), and Sandoz’s fluvastatin (Lescol, 1994). Th e sixth statin, Bayer’s cerivastatin (trade names Baycol and Lipobay), another optically pure synthetic statin like Lipitor, was soon to be on the market. The success of the four existing statins had already educated physicians about the benefits of lowering cholesterol levels. More important, Merck’s “4S” clinical trials (the Scandinavian Simvastatin Survival Study; see chapter 3) decisively demonstrated the positive impact of lower cholesterol levels in decreasing coronary heart disease. As a consequence, not only did the FDA approve Lipitor in only six months, but it was also widely and warmly accepted by general practitioners and patients immediately after it was available. When the drug was launched at the beginning of 1997, Warner-Lambert chose Pfizer as its comarketing partner because Pfizer had the strongest sales muscle in the drug industry. Today it is hard to imagine that when Pfizer was founded in 1849, it was a modest laboratory in Brooklyn, New York. By 2008, more than 150 years later, it had grown to become the largest pharmaceutical company in the world. In the revolutionary year of 1848, thousands of Europeans immigrated to America to seek new opportunities. Among them were a chemist (the equivalent of today’s pharmacist), 20-year-old Charles Pfizer, and his brother-in-law, 22-year-old confectioner Charles Erhart, from the small town of Ludwigsburg in Wuerttemberg, Germany. Unlike many German immigrants at the time who immediately joined the Gold Rush, Pfizer and Erhart decided to stay in New York City and make a living by taking advantage of the crafts that they learned in Germany. With $2,500 borrowed from Pfizer’s father and a $1,000 mortgage, they bought a small brick factory in the Williamsburg section of Brooklyn, largely a German neighborhood. Thus, Chas. Pfizer Co., Inc., Specialists in Fine Chemicals was founded.
Energy Efficiency and Conservation
Authors: Crane Hewitt , Kinderman Edwin , Malhotra Ripudaman
Published: November 2020

Previous chapters in this book focus on the production of energy from different sources and how we might increase the supply to meet the anticipated growth in demand. In this chapter we focus on options to manage the energy demand. There are many ways—other than complete avoidance of the use of goods or services that demand energy—by which we can “save” energy; actually, we are not saving but reducing the growth in the demand of energy. It is often convenient to think of savings arising from two categories: energy efficiency and energy conservation. Energy efficiency reduces the energy necessary to perform a desired task, and energy conservation includes all actions that avoid unnecessary use of energy. To use the automobile as an example, development of techniques that reduce the fuel needed to go from one place to another is an example of improved energy efficiency. Substituting the automobile with a more efficient mode of transportation or the avoidance of the activity entirely would be examples of energy conservation. Thoughtful use of both conservation and efficiency will be necessary if we are to achieve substantial reductions in our future energy use as individuals, nations, or the world as a whole. As discussed in chapter 4, the global energy use projected for 2050 under three scenarios with three differing growth rates ranges from a high of 9.4 CMO/yr to a low of 3.9 CMO/yr. Our recent energy use of approximately 3 CMO/yr (since 2000) is on a growth curve that follows the trajectory of the high-consumption scenario. Improvements in energy efficiency have of course been made steadily over the past century and will likely continue in the future. Much of that improvement has already been taken into account in arriving at the projections for future growth. The 2.6% annual growth in energy consumption has taken place notwithstanding steady improvements in efficiency. To bring the projected 2050 consumption down from more than 9 CMO, we will need savings that would not happen without a rededicated effort.
Establishing the Diagnosis
Authors: Brinton Daniel A. , Wilkinson Charles P.
Published: November 2020

The differential diagnosis of rhegmatogenous retinal detachment includes secondary (nonrhegmatogenous) retinal detachment and other entities that may simulate a retinal detachment. Nonrhegmatogenous detachments are categorized as exudative (serous) and tractional detachments. Conditions that may be mistaken for retinal detachment include retinoschisis, choroidal detachment or tumors, and vitreous membranes. Sometimes benign findings in the peripheral retina are mistaken for retinal breaks. The most prominent feature of the fundus is the optic nerve head or disc, the only place in the human body that affords a direct view of a tract of the central nervous system. The foveola, the functional center of the fundus, is located in the center of the fovea, which has a diameter of about 5°. The macula is centered on the fovea and has a diameter of about 17°. The multiple branches of the central retinal artery are readily identifi ed by their bright red color and relatively narrow caliber. The multiple tributaries of the central retinal vein are recognized by their dark red color and relatively wider caliber. In a darkly pigmented fundus, the choroidal vessels in the posterior pole can be obscured from view, but in an eye with minimal pigment, they are readily visible. The venous tributaries of the choroid that make up the vortex veins are usually easily seen. The most prominent features of the choroidal venous system are the vortex ampullae, of which there are usually four (but sometimes more). They are located approximately in the 1-, 5-, 7-, and 11-o’clock meridians, just posterior to the equator. The horizontal meridians are usually identifiable by their radially oriented, long posterior ciliary nerves, and infrequently the long posterior ciliary artery can be seen adjacent to the nerve. The nerve is relatively broad and has a yellow color, and the artery is identifiable by its red color. The artery is usually inferior to the nerve temporally, and superior to it nasally (Figure 5–1).
Introduction
Authors: Lee P.J.
Published: November 2020

Petroleum resource evaluations have been performed by geologists, geophysicists, geochemists, engineers, and statisticians for many decades in an attempt to estimate resource potential in a given region. Because of differences in the geological and statistical methods used for assessment, and the amount and type of data available, resource evaluations often vary. Accounts of various methods have been compiled by Haun (1975), Grenon (1979), Masters (1985), Rice (1986), and Mast et al. (1989). In addition, Lee and Gill (1999) used the Michigan reef play data to evaluate the merits of the log-geometric method of the U.S. Geological Survey (USGS); the PETRIMES method developed by the Geological Survey of Canada (GSC); the Arps and Roberts method; Bickel, Nair, and Wang’s nonparametric finite population method; Kaufman’s anchored method; and the geo-anchored method of Chen and Sinding–Larson. Information required for petroleum resource evaluation includes all available reservoir data and data derived from the drilling of exploratory and development wells. Other essential geological information comes from regional geological, geophysical, and geochemical studies, as well as from work carried out in analogous basins. Any comprehensive resource evaluation procedure must combine raw data with information acquired from regional analysis and comparative studies. The Hydrocarbon Assessment System Processor (HASP) has been used to blend available exploration data with previously gathered information (Energy, Mines and Resources Canada, 1977; Roy, 1979). HASP expresses combinations of exploration data and expert judgment as probability distributions for specific population attributes (such as pool area, net pay, porosity). Since this procedure was first implemented, demands on evaluation capability have steadily increased as evaluation results were increasingly applied to economic analyses. Traditional methods could no longer meet the new demands. A probabilistic formulation for HASP became necessary and was established by Lee and Wang (1983b). This formulation led to the development of the Petroleum Exploration and Resource Evaluation System, PETRIMES (Lee, 1993a, c, d; Lee and Tzeng, 1993; Lee and Wang, 1983a, b, 1984, 1985, 1986, 1987, 1990). Since then, new capabilities and features have been added to the evaluation system (Lee, 1997, 1998). A Windows version was also created (Lee et al., 1999).
Estimating Mature Plays
Authors: Lee P.J.
Published: November 2020

A key objective in petroleum resource evaluation is to estimate oil and gas pool size (or field size) or oil and gas joint probability distributions for a particular population or play. The pool-size distribution, together with the number-of-pools distribution in a play can then be used to predict quantities such as the total remaining potential, the individual pool sizes, and the sizes of the largest undiscovered pools. These resource estimates provide the fundamental information upon which petroleum economic analyses and the planning of exploration strategies can be based. The estimation of these types of pool-size distributions is a difficult task, however, because of the inherent sampling bias associated with exploration data. In many plays, larger pools tend to be discovered during the earlier phases of exploration. In addition, a combination of attributes, such as reservoir depth and distance to transportation center, often influences the order of discovery. Thus exploration data cannot be considered a random sample from the population. As stated by Drew et al. (1988), the form and specific parameters of the parent field-size distribution cannot be inferred with any confidence from the observed distribution. The biased nature of discovery data resulting from selective exploration decision making must be taken into account when making predictions about undiscovered oil and gas resources in a play. If this problem can be overcome, then the estimation of population mean, variance, and correlation among variables can be achieved. The objective of this chapter is to explain the characterization of the discovery process by statistical formulation. To account for sampling bias, Kaufman et al. (1975) and Barouch and Kaufman (1977) used the successive sampling process of the superpopulation probabilistic model (discovery process model) to estimate the mean and variance of a given play. Here we shall discuss how to use superpopulation probabilistic models to estimate pool-size distribution. The models to be discussed include the lognormal (LDSCV), nonparametric (NDSCV), lognormal/nonparametric–Poisson (BDSCV), and the bivariate lognormal, multivariate (MDSCV) discovery process methods. Their background, applications, and limitations will be illustrated by using play data sets from the Western Canada Sedimentary Basin as well as simulated populations.