bluuebunny/crossref_metadata_2025 huggingface dataset:
The Geopolitics of Postwar Recovery
Authors: Soennecken Brendan
Published: November 2020

Postwar recovery is an elusive term. Often it is identified with words like reconstruction or nation and peace building and may be related to historical events such as the American Civil War or the Marshall Plan. Perhaps, however, the term is elusive because its distinct parts offer it a host of meanings. Post is a prefix that means after or later, war is the exertion of violence or hostility, and recovery is a restoration or return. As such, postwar recovery might be read as “after exerting violence, return later and restore hostility.” While this may be a word game, the semantics of postwar recovery, at face value, provoke some very difficult questions. At least, what is war, what is peace, and in the absence of both, what is to be recovered? In the past, recovery has encompassed almost every level of society, from institutions and government to economies, industry, infrastructure, and housing. At its best, recovery has embodied aspirations for future peace; at its worst, it has remained the harsh reality of sifting through ashes to find what is left. As part of the geographic study of war and peace, this introduction to the field of postwar recovery presents a brief history of its modern development by emphasizing the intersections of territorial sovereignty, international intervention, and subnational spaces. The chapter concludes by discussing its application in the field from the perspective of international practitioners. Part of the analysis reflects calls for further study on issues relevant to both geography and postwar recovery such as the impact of Non-Governmental Organizations on the “front lines” of geopolitics or issues of migration, a major propellant of which is violent conflict. Suggesting potentials for synthesis of postwar recovery and geography, the analysis alludes to different scales of recovery and through a case study of northern Afghanistan presents regional elements of postwar environments and their impact on field level recovery. The history of postwar recovery parallels that of political geography and has seen the task of civilians to restore, with limited assistance, what was lost in war become a multibillion-dollar industry infused with state responsibilities, international intervention, and structured civilian participation.
Discrete Event Abstraction: An Emerging Paradigm for Modeling Complex Adaptive Systems
Authors: Zeigler Bernard P.
Published: November 2020

John Holland's views on modeling and simulation and why these activities are needed to make progress in understanding complex adaptive systems (CAS) are well summarized in his article in Daedalus [10]. With examples such as economies, ecologies, immune systems, developing embryos, and brains, he characterizes CAS as distributed many-ruled organizations with little or nothing in the way of central control. The aggregate behavior that emerges is too hard to predict with thought experiments or conventional mathematics, with the consequence that computer simulation is an indispensable tool for the study of CAS. Because many rules can be active simultaneously, massively parallel computers hold the promise of providing fast enough execution so that humans can interact with a simulated CAS much in the same way that pilots interact with flight training simulations. Mathematics and theory are not to be thrown to the wind however, since relevant pieces of mathematics can provide insight and put some bounds on what can be expected to emerge from a simulation. Indeed, the classical theoryexperiment cycle, well established for physical science, is the ideal to be sought, with the computer taking the role of Mother Nature in providing the outcomes of experiments. Modeling and simulation enter in yet another way in CAS study. Holland asserts that the fundamental attribute of CAS is their use of internal models to anticipate the future, basing current actions on expected outcomes. It is important to understand how such systems use internal models, since so much of their behavior stems from anticipations based on them. So how can CAS build and use internal models? Some anticipatory models are no more than rules (follow the chemical gradient to food). Some are clearly more sophisticated such as CAS models that researchers (themselves CAS) build. What determines the type of model that a CAS can build and use? Are there some better ways to build and use CAS models than others? As a student of Holland's, who has spent the past 30 years of his professional life studying modeling and simulation, I am writing this tribute to him, with the belief that there are indeed some insights to be offered to the study of CAS and the next generations of CAS investigators.
Moore's Law, Artificial Evolution, and the Fate of Humanity
Authors: Hofstadter Douglas R.
Published: November 2020

More or less simultaneously in the closing year of the twentieth century, there appeared a curious coterie of books whose central, sensational-sounding claim was that humanity was on the verge of producing its own successors, thereby rendering itself both obsolete and superfluous. Chief among these books were The Age of Spiritual Machines by computer engineer and industrialist Ray Kurzweil, Robot by Carnegie-Mellon computer science professor Hans Moravec, and The Spike by technology writer Damien Broderick. There were several others that at least treated this theme seriously, such as Out of Control by Kevin Kelly, an editor at Wired magazine. The science-fiction tone of these books is clearly revealed by their subtitles: When Computers Exceed Human Intelligence (Kurzweil), Mere Machine to Transcendent Mind (Moravec), Accelerating into the Unimaginable Future (Broderick), and The Rise of Neobiological Civilization (Kelly). There would have been little reason for a serious reader to pay any attention to these books and their wild-sounding claims, had their authors not had the most respectable of credentials and had the books not been reviewed in the most serious of venues, often favorably. Thus, Kurzweil's and Moravec's books were reviewed together in the New York Times Sunday Book Review in January 1999, and although the reviewer, Rutgers University philosophy professor Colin McGinn, had some skeptical words to say about their views of consciousness, he essentially accepted all of their technical claims, which are extraordinary, at face value. Scientific American gave Moravec's book its glowing "Editors' Choice." On almost the same spring day of 2000 as Ray Kurzweil was receiving from the hands of President Clinton the National Medal of Technology for his pioneering efforts to help the handicapped through the use of computers, an apocalyptic reaction to the Kurzweil and Moravec books, written by the well-known computer scientist Bill Joy (a co-founder of Sun Microsystems), appeared as a cover article in Wired under the title "Why the Future Doesn't Need Us."
Supercontinents Older than Gondwana
Authors: Rogers John J. W. , Santosh M.
Published: November 2020

The configurations of Gondwana and Pangea are well known because the histories of oceans that opened to disperse Pangea can be reconstructed from their patterns of magnetic stripes (chapters 1 and 9). The configurations of older supercontinents cannot be easily determined because the oceanic lithosphere formed when they dispersed is so old that it has been completely subducted and destroyed. Thus the histories, and even existence, of these older continents must be inferred from indirect evidence. The four most widely used techniques for reconstructing old supercontinents are: paleomagnetic data; correlation of orogenic belts that developed during accretion of the supercontinent: correlation of extensional features that developed when the supercontinent fragmented; and recognition that sediment in one present continent was derived from a source now in another continent. Paleomagnetic information can be used in two ways. One is to compare APW curves for different continental blocks to determine whether there were periods of time when two or more blocks seem to have been joined (appendix C). If similar movements are found for several continental blocks that are now separated, then we can infer that they formed a single block, perhaps a supercontinent, during the period when they had identical APW paths. Another method of using paleomagnetic data is simply to compare the apparent latitudes of numerous continental blocks. Even though longitudes cannot be specified, latitudes can be used to infer proximity of different blocks, thus supporting other information that suggests the configuration of a supercontinent. Correlation of orogenic belts starts with identification of belts of different ages in present continents. Belts of the same age are now scattered all over the earth’s land surface because of fragmentation of supercontinents and movement of modern continents to their present positions. The configurations of older supercontinents can be inferred by placing modern continents into positions in which these orogenic belts line up to form a pattern that would be expected to develop during accretion of a supercontinent. We demonstrate this technique below in our discussion of the configurations of Rodinia and Columbia.
History of Continents after Rifting from Pangea
Authors: Rogers John J. W. , Santosh M.
Published: November 2020

As continents moved from Pangea to their present positions, they experienced more than 100 million years of geologic history. Compressive and extensional stresses generated by collision with continental and oceanic plates formed mountain belts, zones of rifting and strike-slip faulting, and magmatism in all of these environments. In this chapter we can only provide capsule summaries of this history for each of the various continents, but many of their salient features have been discussed as examples of tectonic processes in earlier chapters. The final section analyzes the breakup of Pangea as part of the latest cycle of accretion and dispersal of supercontinents. Because it involves continuation of this cycle into the future, it is necessarily very speculative. Figure 10.1 shows approximate patterns of movement of each continent from its position in Pangea to the present. The dominant feature of this pattern is northward movement of all continents except Antarctica, which has remained over the South Pole for more than 250 million years. Shortly after geologists recognized the concept of continental drift, this movement was referred to by the German word “Polflucht” (flight from the pole) because all of the continents were seen to be fleeing from the South Pole. The only continent that did not simply move northward was Eurasia, which essentially rotated clockwise and changed its orientation from north–south to east–west. Comparison of fig. 10.1 with fig. 8.12a (locations of continents shortly before the assembly of Gondwana) shows that the net effect of the last 580 million years of earth history has been a transfer of most continental crust from the southern hemisphere to the northern hemisphere. Accretion and compression against the southern margin of Eurasia constructed a series of mountain belts from the Pyrenees in the west to the numerous ranges of Southeast Asia in the east. This collision generated extensional and transtensional forces that opened rifts and pull-apart basins. Tectonic loading created foreland basins with sediment thicknesses of several kilometers. Opposite the area where the collision of India caused the most intense compression, the extensional basins are interspersed with mountain ranges that were lifted up intracontinentally. We divide the discussion of Eurasia into a section where compression dominates to the south (present orientation) of the former margin of Pangea and a section that describes processes within the landmass to the north.
Psychosocial and Behavioral Issues in Stem Cell Transplantation
Authors: Phipps Sean
Published: November 2020

Stem cell transplantation (SCT) or bone marrow transplantation (BMT) has evolved from a heroic, experimental therapy of last resort to a standard therapy for many high-risk leukemias and the preferred first option after leukemic relapse (Sanders, 1997; Santos, 2000; Treleaven & Barrett, 1998; Wingard, 1997). The indications for SCT have widened to include a number of other malignant disorders, including lymphomas, solid tumors, and even brain tumors, as well as to a growing number of nonmalignant disorders (Meller & Pinkerton, 1998; Santos, 2000; Treleaven & Barrett, 1998). The growth of bone marrow registries that allow for wider use of unrelated donor transplants and developments in stem cell selection techniques that allow for haplotype transplants using mismatched family donors, including parents, have greatly increased the availability of SCT as a viable treatment option for seriously ill children (Mehta & Powles, 2000). At the same time, advances in supportive care have led to improved survival outcomes and thus to a rapidly growing number of long-term survivors of SCT (Santos, 2000; Treleaven & Barrett, 1998). Yet, despite the extraordinary medical and technical advances that have saved the lives of many children, SCT remains a high-risk medical procedure involving a prolonged and physically demanding treatment regimen that can challenge the coping capacities of patients and their families. Psychosocial research in pediatric SCT has progressed more slowly, but available studies indicate that SCT is a stressful experience that can have a negative impact on the social functioning, self-esteem, and general emotional well-being of survivors (Barrera, Pringle, Sumbler, & Saunders, 2000; McConville et al., 1990; Parsons, Barlow, Levy, Supran, & Kaplan, 1999; Phipps, Brenner, et al., 1995; Phipps & Barclay, 1996; Rodrigue, Graham-Pole, Kury, Kubar, & Hoffman, 1995; Stuber, Nader, Yasuda, Pynoos, & Cohen, 1991; Vannatta, Zeller, Noll, & Koontz, 1998). A number of studies have also focused on parental response to SCT (Barrera et al., 2000; Kronenberger et al., 1998; Manne et al., 2001, 2002; Phipps, Dunavant, Lensing, & Rai, 2004; Rodrigue et al., 1996; Streisand, Rodrigue, Houck, Graham-Pole, & Berlant, 2000). Much of the literature to date has focused on long-term outcomes in survivors, particularly neurocognitive and academic outcomes.
Power in the East
Authors: Thomson Peter
Published: November 2020

On the western coast of Honshu, Japan’s main island, there’s a tiny town called Fushiki. It doesn’t appear on many maps. Its dusty, somewhat unkempt streets make it feel more like the Philippines than sleek, modern Japan. Maybe there’s a boat that sails from there to Russia, and maybe there isn’t. After six days in Japan, we’ll find out. Our travel agent, who specializes in getting to and from Russia, had never heard of this boat. And the guidebooks I’d consulted had said the ferries from Japan to Russia had gone out of business years ago, when they lost their subsidy from the Russian government. But a couple of hours on the Web had turned up a lead, and a fax to a number in Vladivostok had brought a cryptic response. Perhaps the ship was still running after all. I gave our travel agent the coordinates, and she went to work. A few days later, she reported in the affirmative—it seemed that there was a boat, and she’d made the arrangements. But we would have to pick up our tickets on the dock. We had no confirmation of the sailing, no receipt from the company, no physical evidence that the boat really did exist. The overnight journey from Tokyo to Fushiki is more like traveling through time than through space. A Shinkansen bullet train whisks you at 175 miles per hour from the pulsating megalopolis of year 2000 Tokyo to a transfer station in Yuzawa, where you catch an only slightly less astonishing express train to the spotless but eerily empty western city of Toyama, where you spend the night. The next morning, you board a still-more ordinary train for a twelve-minute ride to the even smaller city of Takaoka, with a decidedly older and shabbier downtown—the Japan, perhaps, of 1960. And finally, you find your way onto an unkempt two-car shuttle train, perhaps the only remaining diesel train in all of Japan, which clatters and chugs off through a maze of power lines, rusting cranes, and decrepit warehouses and creaks to a halt at a dusty little station, from which you emerge onto the forlorn streets of Fushiki.
Affirmative Action and Racial Fortuity in Action
Authors: Bell Derrick
Published: November 2020

The Conclusions Of Legal Commentators about the less than crit­ical role of Brown in post–World War II racial reform are not well known and would probably not be accepted by much of the public. It thus should not be surprising that the mostly unrecognized racial fortuity that so influenced the outcomes in school desegregation campaigns are also central to the decades-long controversy over the legality and fundamental fairness of affirmative action in general, and minority admissions to colleges and professional schools in particular. Once again, the rhetoric obscures the issues, allowing the argument to focus on the cost to whites of racial remedies rather than their necessity or appropriateness. As a result, few persons have recognized why, without the pressure of law, white-dominated institutions began opening schooling and employment areas to minorities long excluded both by outright bias and by discrimination’s debilitating effect on their qualifi­cations. The major cases I will review in this chapter reflect the pressures of interest-convergence and the resistance to any reform that threatened alteration of the racial status quo. As we have seen, an implicit stumbling block impedes society’s approach to racial remedies. The issues of cost and cost assessment crucial to earlier racial remedies, though, were not closely examined during the tumult of the late 1960s. Then, urban rebellions, sparked by the 1968murder of Dr. Martin Luther King, Jr., served as scary reminders that, more than a dozen years after Brown and a half-dozen years after enactment of federal civil rights laws, most corporations, government tagencies, and institutions of higher learning remained virtually all-white and mostly male. At these organizations, managers chose toestablish “racial and gender preferences” to accomplish the admission, hiring, and upgrading of a moderate number of white women and people of color. They did so rather than overhaul the policies and practices that, beyond blatant racial and sexual discrimination, were responsible for their institutions’ all-white and all-male culture. The affirmative action approach served the immediate need of breaking down this culture, and as a bonus it brought in competent individualsable and willing to advance the institutions’ goals. This was certainly the case with minority admissions programs. Faced with social and political pressures to increase the minuscule number of minority students, colleges and professional schools typically opted to use minority racial status as a positive admissions factor.
Broadcast Science Journalism
Authors: Palca Joe
Published: November 2020

When I first made the jump from print to broadcast, people kept asking me if I missed writing. The question was funny, but also vexing. I hadn't stopped writing, I was just writing in a different way. And not really all that different, just shorter. But after a time my vexation went away, and I decided the question was a form of flattery. Good radio stories are intimate and personal, where the listener gets a sense of being talked with, not talked at. It's not supposed to sound scripted, or like someone reading from a book. It's supposed to sound like a dinner conversation. Susan Stamberg once described good radio as akin to the guilty pleasure of listening in on a really interesting conversation at the next table in a restaurant. Radio also gives people a chance to use their imaginations. Take the interview I did with Harold Varmus when he took over as director of the National Institutes of Health in 1993.1 wanted to present Varmus as the academic scientist who didn't give a damn about the norms of Washington bureaucracy. So I interviewed him on his way to work, not in the government car that most agency heads used, but the way he always commuted: on his bicycle. You didn't have to see Varmus pedaling through traffic; all you needed for the mental picture was the up-close sound of traffic and a bicycle chain gliding through a derailleur. Writing for broadcast comes in various flavors. I've written stories as short as 30 seconds, and as long as 30 minutes. Although it's rarer these days, the one-hour radio documentary is not unheard of. But in all broadcast formats, long or short, there's one crucial rule: Keep it moving forward. Your viewers or listeners can't flip back to the start to remind themselves what happened five minutes ago. If too much time has passed since you last introduced a character, introduce him again. The best writing for broadcast, both radio and television, involves telling a story. Stories are engaging. They give you a structure. They have a beginning, a middle, and an end. They have characters. They set up a conflict, which helps you see a scientific issue in a more exciting way.
Molecular Paleontology and Biochemical Evolution
Authors: Gaines Susan M. , Eglinton Geoffrey , Rullkötter Jürgen
Published: November 2020

Carl Woese’s drive for a unified system of biological classification didn’t just open the microbial world to exploration: it reshuffled the entire taxonomic system and revolutionized the way that biologists study evolution, reigniting interest in preanimal evolution. Studies of evolution from the mid-nineteenth through most of the twentieth century relied on the comparison of forms in living and fossil organisms and were limited to the complex multicellular organisms that developed over the past 550 million years. In other words, much was known about the evolution of animals and land plants that left distinctive hard fossils, and very little was known about the unicellular algae and microorganisms that occupied the seas for most of the earth’s history. Woese’s Tree of Life, derived from nucleic acid sequences in ribosomal RNA, has revealed ancestral relationships that form and function don’t even hint at, allowing biologists to look beyond the rise of multicellular life and link it with less differentiated, more primal forms—which was precisely Woese’s intention. But evolution is a history, not just a family tree of relationships. If the information stored in the genes of extant organisms is to provide true insight into that history, it needs to be anchored in time, linked to extinct organisms and to past environments. Ultimately, we must look to the record in the rocks and sediments, just as paleontologists and biologists have been doing for the past two centuries. In Darwin’s time, that record comprised rocks from the past 550 million years, a span of time that geologists now call the Phanerozoic eon, based on Greek words meaning visible or evident life. The eon began with the rocks of the Cambrian period, in which nineteenth- and early-twentieth-century paleontologists discovered a fabulous assortment of fossils—traces of trilobites, anemones, shrimp, and other multicellular animals that were completely missing from any of the earlier strata. Thousands of new animals and plants, including representatives of almost all contemporary groups, as well as hundreds of now-extinct ones, appeared so suddenly between 542 and 530 million years ago that paleontologists refer to the phenomenon as the Cambrian “explosion.”
Origins, Changing Concepts, and Legal Safeguards
Authors: Harris James C.
Published: November 2020

When a health care professional becomes engaged in diagnosing and treating or supporting a person with intellectual disability, the complexities of the disorder become apparent. To provide the best care and the best support, knowledge about neurogenetic syndromes, management of biomedical and behavior features, psychosocial interventions, and the natural history of the disorder are critical. Background knowledge and sensitivity to the needs and life challenges of the affected person are especially important. With new knowledge in genetics, the neurosciences, and social sciences, and the utilization of the richness of family, school, and community resources for these individuals as they develop, the historical stigma of the diagnosis can be reduced and hopefully eliminated. Professionals, families, and community support personnel must join forces so that all available resources are fully utilized, thus allowing the person with intellectual disability to be appropriately treated for his condition and to begin to make choices and become a self-advocate to the extent possible. This chapter will review changing concepts of intellectual disability over the centuries to provide a context for current diagnostic and treatment approaches. An awareness of this history provides perspective on the centuries-long struggle to recognize the needs of and to provide support to persons with intellectual disability. Legal safeguards are now in effect and are continuing to emerge as services are established that use a developmental model and emphasize a developmental perspective. This model emphasizes how comprehensive evaluation and positive supports at home and in the community can make a difference in the lives of persons with disabilities. The starting point is a definition of the term “intellectual disability.” This will be followed by a brief historical survey of origins and attitudes that are changing after centuries of stigmatization and separation. National and international efforts, which began in the 1970s, are continuing to encourage community placement of and self-determination by persons with intellectual disability. Although “mental retardation” is the term used in both the International Classification of Diseases (lCD-10) (World Health Organization, 1992) and the Diagnostic and Statistical Manual (DSM-IV, DSM-IVTR) (American Psychiatric Association, 1994, 2000) systems that describe an intellectual and adaptive cognitive disability that begins in early life during the developmental period, the preferred term is “intellectual disability” internationally, especially in English-speaking countries.
Epidemiology: Who Is Affected?
Authors: Harris James C.
Published: November 2020

Intellectual disability is the most common developmental disorder and the most handicapping of the disorders beginning in childhood. It ranks as first among chronic conditions that limit full participation in society. Epidemiologic approaches provide a basis for understanding the distribution and dynamics of health, disease, and disorder for persons with intellectual disability; epidemiology is the foundation of public health practice. Because it relies largely on statistical methods, accurate data and clear definitions are essential. The interpretation of epidemiologic information requires background knowledge of demography, social sciences, environmental science, and the clinical sciences. Although epidemiologic studies are essential in establishing prevalence, and in describing the demography of a disorder, the role of epidemiology is far more extensive than this. Epidemiology can teach us about the nature and scope of intellectual disability and associated general medical, behavioral, emotional, and psychiatric problems. In so doing, epidemiologic approaches may be combined with neurobiologic and psychosocial measures. Moreover, epidemiologic studies can disclose individual developmental trajectories and the influences that shape those trajectories. Some of these influences promote risk; others provide protection and promote resiliency in the individual. Finally, experimental approaches in epidemiology allow the study of causative processes, factors that influence the course of the disorder, and service needs. It is these more extensive uses of epidemiology that are called for in future research. Chapter 3 outlines the classification of intellectual disability. This chapter will discuss the use of definitions of intellectual disability in establishing its prevalence, factors affecting prevalence, variability in rates in the various states, demographic features including the impact of increasing life expectancy, associated physical, behavioral, and emotional impairments, and new research directions. Accurate estimates of the number of intellectually disabled individuals are required for planning purposes and to gain better knowledge of the impact of interventions. Studies of the prevalence and incidence of intellectual disability date back to at least 1811, when Napoleon ordered a census of “cretins” to be made in one of the Swiss cantons (Kanner, 1964). Although little information is available about how this census was used, many surveys have been carried out since that time.
A Life Span Developmental Approach
Authors: Harris James C.
Published: November 2020

Intellectual disability is a neurodevelopmental disorder that continues throughout the life span of the affected person. It is essential to understand how persons with intellectual disability progress throughout their life span from infancy to old age. The maturation of the brain, their environmental experiences, and the mastery of developmental challenges and tasks must all be considered. A focus on brain development is in keeping with neuroscience research indicating that progressive brain maturation is accompanied by successive synaptic reorganization as one moves from one developmental stage to the next. Anatomical Magnetic Resonance Imaging Studies are playing a major role in understanding the developmental trajectories of normal brain development (Durston et al., 2001; Giedd et al., 1999). Understanding the developmental trajectories of normal brain development is crucial to the interpretation of brain development in neurodevelopmental disabilities. During normal development, white matter volume increases with age, and although gray matter volumes increase during childhood, they decrease before adulthood. These changes in the brain are accompanied by changes in cognitive processing; for example, executive functioning shows a progressive emergence from the preschool years (Espy et al., 1999) into the adolescent years. Working memory and inhibitory processes may be measured during the preschool years. By adolescence, abstract reasoning, anticipatory planning, and mental judgment have emerged and may be measured. Cognitive abilities in adolescence are qualitatively different from those of young children as a result of the reorganization of the prefrontal cortex during maturation. How genetic background and environment interact in producing these changes is the object of ongoing study, yet investigators are beginning to understand how physiological processes of synaptic development, circuits, and neuronal network formation relate to processes of cognitive development (Fossella et al., 2003). The development of persons with intellectual disability is now being evaluated systematically, and developmental trajectories are being established for known neurogenetic syndromes. These studies are making up for a surprising lack of application of a developmental perspective to persons with intellectual disability. Developmental theorists have, for the most part, monitored and measured development in normally intelligent persons in establishing developmental landmarks.
Ethics and Spirituality
Authors: Harris James C.
Published: November 2020

This chapter considers ethical and spiritual issues related to intellectual disability. Consideration of the meaning of life of an intellectually disabled person must take into account how society defines and responds to individual differences. There are ethical and religious concerns regarding prenatal diagnosis and questions of how to teach ethical behavior to persons with intellectual disability. Participation in religious practices in the community and in group home settings is important for families and persons with intellectual disability. This chapter reviews these issues in detail. In biblical times, there were edicts about disability that offer insight into attitudes toward disabled people. There is an Old Testament injunction: “Thou shalt not curse the deaf, put a stumbling block before the blind, nor maketh the blind wander out of a path” (Leviticus 19:14). This may be the first Western command to legislate for the protection of the deaf and handicapped. Moreover, deaf persons without speech were viewed as children and provided the same protections as children. Yet, the threat of disability was also an element in biblical injunctions: “If you do not follow his commandments and decrees . . . all these curses will become upon you and overtake you: The Lord will afflict you with madness, blindness, and confusion of mind. At midday, you will grope around like a man in the dark” (Deuteronomy 28:15). Although help for those with disabilities was seen as a charitable obligation, disability was perceived potentially as a punishment from God. Ancient people often believed that illness was inflicted by a deity or supernatural power (Rosen, 1968). In records dating back before 2000 B.C., the birth of children with congenital impairments were used to predict the future of the community. In Babylonia, those who prophesized about the future kept a list of birth deformities and the specific meaning and prophecy that these disabilities foretold. Although a disability was viewed as a portent of things to come (Braddock and Parish, 2002) or punishment for immorality, there also existed the attitude that the disabled should be treated with compassion. The New Testament provides insight into how attitudes about disability evolved.
Carbon−Carbon Bond Formation
Authors: Li Jie Jack , Limberakis Chris , Pflum Derek A.
Published: November 2020

Reviews: (a) Vicarion, J. L.; Badia, D.; Carillo, L.; Reyes, E.; Etxebarria, J. Curr. Org. Chem. 2005, 9, 219-235. (b) Mahrwald, R. Ed. In Modern Aldol Reactions; Wiley-VCH: Weinheim, 2004; Vol. 1., pp. 1-335 (c) Mahrwald, R. Ed. In Modern Aldol Reactions; Wiley-VCH: Weinheim, 2004; Vol. 2., pp. 1-345.(d) Machajewski, T. D.; Wong, C.-H. Angew. Chem. Int. Ed. 2000, 39, 1352-1375. (e) Carriera, E. M. In Modern Carbonyl Chemistry; Otera, J.; Wiley-VCH: Weinheim, 2000; Chapter 8: Aldol Reaction: Methodology and Stereochemistry, 227-248. (f) Paterson, I.; Cowden, C. J.; Wallace, D. J. In Modern Carbonyl Chemistry; Otera, J.; Wiley-VCH: Weinheim, 2000; Chapter 9: Stereoselective Aldol Reactions in the Synthesis of Polyketide Natural Products, pp. 249-298. (g) Franklin, A. S.; Paterson, I. Contemp. Org. Synth. 1994, 1 317-338. (h) Heathcock, C. H. In Asymmetric Synthesis; Morrison, J. D., Ed.; Academic Press: Orlando, Fl.; 1984; Vol. 3., Chapter 2: The Aldol Addition Reaction, pp. 111-212. (i) Mukaiyama, T. Org. React. 1982, 28, 203-331. Since the early 1980s, aldol condensations involving boron enolates have gain great importance in asymmetric synthesis, particularly the synthesis of natural products with adjacent stereogenic centers bearing hydroxyl and methyl groups. (Z)-Boron enolates tend to give a high diastereoslectivity preference for the syn-stereochemistry while (E)-boron enolates favor the anti-stereochemistry. Because the B-O and B-C bonds are shorter than other metals with oxygen and carbon, the six membered Zimmerman–Traxler transition state in the aldol condensation tends to be more compact which accentuates steric interactions, thus leading to higher diastereoselectivity. When this feature is coupled with a boron enolate bearing a chiral auxillary, high enantioselectivity is achieved. Boron enolates are generated from a ketone and boron triflate in the presence of an organic base such as triethylamine. Reviews: (a) Abiko, A. Acc. Chem. Res. 2004, 37, 387-395. (b) Cowden, C. J. Org. React. 1997, 51, 1-200.
Cancer Drugs: From Nitrogen Mustards to Gleevec
Authors: Li Jie Jack
Published: November 2020

Whereas infectious diseases are the scourge of developing countries, cancer is the most significant affliction in developed countries. At the beginning of 2005, the American Cancer Society announced that, for the first time, cancer had surpassed heart disease as the number one killer of Americans. Cancer, which is the uncontrollable multiplication of cells, has been in existence as long as animals have; evidence of cancers has been found in dinosaur bones. Cancers have also been found on mummies dating back 2,500 years. An operation to remove cancer was documented in the Ebers papyrus found in Egypt. In ancient times cancer was a relatively rare disease, because infectious diseases often made the life span so short that cancer had little chance to proliferate. Hippocrates (460–370 B.C.) coined the word cancer, which means “crab” in Greek. There are over 110 types of cancer, which can be divided into four categories depending on the tissue involved: carcinoma, lymphoma, leukemia, and sarcoma. Carcinomas are the most common, with 85–90% of all cancers falling into this category. Carcinomas are tumors that originate in epithelial tissue such as skin, breast, lung, prostate, stomach, colon, ovary, and so forth. Lymphomas are cancers of the lymphatic system. Leukemia is the cancer of the blood, bone marrow, and liver. Sarcomas, the rarest of all four types, are tumors arising from cells in connective tissue, bone, or muscle. It seems inconceivable that we had almost no clue about the origin of cancers up until the mid-1970s, despite the existence of cancer that predates human life. The debate raged on as to what caused cancer, with one camp believing that carcinogens (cancer-causing agents such as chemicals, X-ray, and ultraviolet light) were to blame, whereas the other thought that viruses were the culprits. The carcinogen theory took root first. As early as 1775, British doctor Percival Pott made the astute epidemiological observation that young English boys employed as chimney sweeps were more prone to develop scrotal skin cancers than their French counterparts. Further scrutiny revealed that the continental sweeps bathed more frequently after work, which prompted Pott to speculate that long exposure to coal tar caused skin cancer. In 1915, 140 years later, Katsusaburo Yamagiwa and Koichi Ichikawa confirmed Pott’s theory in an animal model.
Cardiovascular Drugs: From Nitroglycerin to Lipitor
Authors: Li Jie Jack
Published: November 2020

Cardiovascular diseases are the leading cause of death worldwide and are projected to remain in the lead through 2025. Heart-related diseases include angina, arrhythmia, atrial fibrillation, congestive heart failure, hypertension, atherosclerosis, myocardial infarction (heart attack), and sudden cardiac death. More than 300,000 Americans suffer sudden heart attacks each year. In addition, one of the more important recently identified drug-induced cardiac events, which has occasionally resulted in drugs being withdrawn, is drug-induced torsade des pointes. This is a rare, fatal arrhythmia that has been associated with some drugs that prolong the QT interval of the electrocardiogram (ECG). Hypertension is America’s number one chronic disease. Fifty million Americans, one in six, suffer from high blood pressure. Similarly, high blood pressure affects about one-sixth of the world’s population (1 billion people) worldwide—mostly in the developed world. If uncontrolled, it can lead to heart attack, heart failure, stroke, and other potentially fatal events. Great strides have been made during the past 50 years in conquering cardiovascular diseases. Cardiopulmonary resuscitation (CPR) was developed by a group of researchers at the Johns Hopkins University in 1961. The 1960s also saw the emergence of beta-blockers. Calcium channel blockers, angiotensin-converting enzyme (ACE) inhibitors, and statins appeared in the 1980s and the 1990s. Angiotensin II receptor blockers (ARBs) also emerged in the 1990s. The heart, about the size of a person’s fist, beats about 2.8 billion times in a lifetime, pumping blood and oxygen through the body. Although its function was shrouded in mystery for centuries, mankind has come a long way in understanding how the heart works anatomically and physiologically, although we haven’t made much progress in understanding its “emotional” nature. Greek philosopher and anatomist Aristotle (384–322 B.C.) was the founder of biology. He was very interested in human and animal anatomy, especially the cardiovascular systems in higher animals. In his books he described, for the first time, the human blood system with an emphasis on the deeper-lying vessels. He incorrectly believed that the heart was the organ in which emotions were generated, whereas the function of the brain was to cool the blood. More than 500 years later, the German-born Roman physician Galen (130–200 A.D.) made two revolutionary discoveries about the cardiovascular system.
Cerebellar Diseases
Authors: Margolis Russell L.
Published: November 2020

After nearly 200 years, the concept that the cerebellum modulates only motor systems has been laid to rest. In the past two decades, evidence derived from neuroanatomical, neuroimaging, neuropsychologic, and psychiatric investigations has conclusively demonstrated that the normal cerebellum plays an important role in cognition and emotion and that diseases of the cerebellum may lead to cognitive impairment and psychiatric syndromes. Cerebellar damage can be a consequence of many different diseases. The total prevalence of cerebellar disorders is unknown. Heavy alcohol use is probably the most common source of cerebellar abnormality. The cerebellum is affected in 1.5% to 8% of all strokes (Raco et al., 2003), so this is probably the second mostcommoncause of cerebellar damage. In children, the incidence of primary brain tumors is about 2.8/100,000 per year; posterior fossa tumors account for about 40% of this total (Kuttesch and Ater, 2004). In adults, primary tumors of the cerebellum are less common than in children, but metastases are more frequent. The prevalence of recessive, dominant, and sporadic neurodegenerative diseases that primarily affect the cerebellum is, in aggregate, about 6/100,000 (Durr, 2002; Margolis, 2003). Other causes of cerebellar lesions are rare. A key point is that many of these disorders do not affect the cerebellum in isolation. Therefore, once disease affecting the cerebellum is established, it is critical to determine whether other brain regions are also involved. Other relevant clinical factors include the age of the patient and the duration of degenerative illness or the length of time since a stroke or a tumor resection. A neuroanatomic underpinning for the role of the cerebellum in cognition and emotion has been established over the past 25 years (Middleton and Strick, 2000; Schmahmann, 2001). The pathway from the cerebral cortex to the cerebellum originates with axons in cortical layer Vb in motor; somatosensory; association; and paralimbic regions, including prefrontal areas critical for attention, working memory, planning, motivation, decision-making, and language. After synapse in the pons, the pathway projects to the cerebellar cortex. The pathways back from the cerebellum to the cerebral cortex begin with axons projecting from cerebellar Purkinje cells to the deep cerebellar nuclei.
Mood Stabilizers
Authors: Lehmann Susan W.
Published: November 2020

The term ‘‘mood stabilizers’’ refers to a heterogeneous group of medications that are effective in the treatment of bipolar disorder, an illness characterized by recurrent episodes of mania and major depression. The list of mood stabilizers includes lithium, several anticonvulsant medications, and atypical antipsychotic medications. For some of these medications, there have been randomized, placebo-controlled studies demonstrating efficacy in reducing the severity and frequency of illness episodes (Kahn et al., 2000). For other medications, the evidence supporting therapeutic use in mood disorders is more anecdotal or preliminary. Late-onset bipolar disorder beginning after 50 years of age is more likely to be associated with comorbid medical or neurologic condition, or their treatments (McDonald, 2000; Depp and Jeste, 2004). A number of medications have been known to precipitate manic episodes. These include antiparkinsonian medications, corticosteroids, anticholinergic agents, and antidepressants. In addition, manic episodes may develop in patients with Huntington’s disease, multiple sclerosis, brain tumors, seizure disorders, dementia, neurosyphilis, human immunodeficiency virus (HIV), and some poststroke syndromes. The goal of long-term psychiatric management is to minimize affective upheaval and to diminish frequency of mood cycling. Psychotic symptoms are common in bipolar disorder, and severe behavioral disturbances such as physical aggression can occur as well during manic episodes. Depressive episodes are accompanied by a risk of suicide. Given the potential for these severe complications, and the need for continual medication reassessment and adjustment, the long-term pharmacologic and psychologic treatment of bipolar disorder is best managed by a psychiatrist. Lithium, the oldest of the mood-stabilizing medications, is also considered to be the ‘‘gold standard’’ of treatment against which all other potentially mood-stabilizing medications are compared. It is still the treatment of choice for many patients with bipolar disorder, and it has been approved by the U.S. Food and Drug Administration for treatment of manic episodes and for maintenance therapy. At least eight placebo-controlled, randomized trials have shown lithium to have efficacy in maintenance treatment of bipolar disorder (Goodwin, 2002). Lithium is effective in reducing risk of recurrent episodes of both mania and depression, although studies have suggested greater superiority in reducing risk of manic episodes.
Cholinesterase Inhibitors and Memantine
Authors: Lyketsos Constantine G.
Published: November 2020

Several lines of evidence suggest that acetylcholine (ACh) neurotransmission is important to the normal functioning of memory, and loss of ACh-producing cells in the basal forebrain (nucleus basalis) is a consistent finding in patients with Alzheimer’s disease and other dementias. The most successful approach to increasing ACh in vivo has been to develop drugs that reduce its degradation by the synaptic enzyme acetylcholinesterase (AChE). Four cholinesterase inhibitors are available to treat memory and other cognitive symptoms in dementia patients. They may also stabilize or prevent the onset of milder non-cognitive neuropsychiatric or behavioral symptoms, although their use as exclusive agents for the more severe forms of the latter is not recommended. A recent Consensus Panel has articulated sound clinical principles regarding the use of these drugs in the context of the broader treatment of Alzheimer’s dementia (Lyketsos et al., 2006). Tacrine, donepezil, rivastigmine, and galantamine have been approved by the U.S. Food and Drug Administration (FDA) for the treatment of Alzheimer’s disease. Tacrine should not ordinarily be used in light of the associated high risk of hepatotoxicity, its complex titration, and the availability of bettertolerated alternatives. The other three cholinesterase inhibitors seem similar in efficacy. All appear to modestly improve cognitive symptoms in 15% to 20% of patients, sometimes quite notably. In addition, they may either improve patient function and delay the emergence of behavioral symptoms or reduce the severity of the latter. The evidence does not support their use as single agents to treat more severe neuropsychiatric symptoms such as depression or delusions, although patients with apathy and visual hallucinations may respond. Any benefit of cholinesterase inhibitors to the long-term progression of dementia has not been shown conclusively. Some studies suggest that they may attenuate the long-term slope of cognitive or functional decline, but those studies have been flawed due to high levels of dropout and the use of historical untreated comparison groups. One brain imaging study, part of a clinical trial, has suggested that they may affect the size of the hippocampus or the integrity of hippocampal neurons. In the absence of replication or a better understanding of the imaging measures involved, these data are not conclusive.