bluuebunny/crossref_metadata_2025 huggingface dataset:
Legislation and Standards
Authors: Brack Graham , Franklin Penny , Caldwell Jill
Published: November 2020

Handling medicines is only part of the nurse’s role, but it is a very important part. Handled properly, medicines can make a great contribution to improving the health of your patients. Handled badly, they can do a lot of harm. It is therefore not surprising that there is a lot of legislation relating to medicines, and that the Nursing and Midwifery Council has laid down important standards for the way in which nurses conduct the management of medicines. The legislation is complex, but it has to be learned. Nurses do not need to become lawyers, but they do need a working knowledge of the law relating to medicines so that they can keep within it. This chapter will set out some of the key legislation that will affect your practice as a student or qualified nurse. It will also look at the rights that patients have and give you the opportunity to reflect on the practice you see around you. Most of us will be patients ourselves at some time and we will have a good idea of the way in which we would want to be treated by nurses. It is too easy for people who care for others to fall into the trap of doing what they think is best for the patient, or for their own good, and ignoring the patient’s legitimate wishes. After reading this chapter, you should know how this can be avoided. You cannot register as a nurse without demonstrating knowledge of medicines management. Understanding the laws and regulations that are relevant is the first step in building that knowledge. The law on medicines is primarily designed to keep patients safe, so a nurse who does not know it is unlikely to be able to practise safely. As was remarked in the foreword, the main aim of this book is to help you do that. The concepts of accountability and responsibility are fundamental to any practice related to the administration of medicines. They are inter-related but distinct. Accountability involves being called to explain (account for) your actions or omissions by someone to whom you owe a duty. This might be a legal duty, a professional duty, a contractual duty, or a civil duty arising from a duty of care. Nurses are therefore accountable to a range of others.
Patient Safety and Error Reduction
Authors: Brack Graham , Franklin Penny , Caldwell Jill
Published: November 2020

Most healthcare professionals take up their career because they want to make people better. It is rare—but not unknown—to find nurses deliberately harming patients. It is not always possible to cure a patient’s condition, and readers may be surprised to hear the view of Lord Justice Stuart-Smith that our ‘only duty as a matter of law is not to make the victim’s condition worse’ (Capital and Counties plc v Hampshire CC (1997) 2 All ER 865 at 883). Despite our best intentions, healthcare professionals do sometimes make the patient’s condition worse. There are too many instances of harm caused to patients. Not only does the patient suffer harm, staff will be upset (some may even give up their careers) and large compensation claims may be made which deplete NHS resources. According to the NHS Litigation Authority, in 2010–11 it received 8655 claims of clinical negligence and 4346 claims of non-clinical negligence against NHS bodies, and paid £863 million in connection with clinical negligence claims (NHSLA Annual Report and Accounts, 2011). To put that into perspective, NHS Warwickshire had a budget of £827m for that year, so this amount would fund a mediumsized PCT. For all these reasons, therefore, our first concern must be to do no harm to our patient. If we can improve their condition, so much the better, but at the very least we must leave them no worse off for having put themselves in our care. Patient safety must be everyone’s concern. It is monitored by the NHS Commissioning Board Special Health Authority. Until June 2012 there was a separate agency, the National Patient Safety Agency (NPSA), which produced a report in 2009 entitled Safety in doses: improving the use of medicines in the NHS . There were 811 746 reports to the NPSA in 2007, of which 86 085 were related to medication. The figures for July 2010– June 2011 show an increase to 1.27 million incidents, of which 133 727 were related to medication.
Blood Thinners: From Heparin to Plavix
Authors: Li Jie Jack
Published: November 2020

Three types of blood cells exist in the human body: red blood cells, white blood cells, and platelets, in addition to plasma, which takes up 55 percent of the blood’s volume. Red blood cells take up approximately 45 percent of the blood’s volume. They transport oxygen from the lungs to other body parts. White cells defend us against bacterial and viral invasions. Platelets (less than 1 percent of the blood), the third type of blood cells, are sticky little cell fragments that are involved in helping the blood clot, a process known as coagulation. Without platelets (even though they constitute less than 1 percent of blood), our blood would not be able to clot, and we would have uncontrolled bleeding. However, formation of blood clots is a double-edged sword. Clots are beneficial because they heal cuts and wounds; blood clots in the bloodstream are harmful because they block coronary arteries, constrict vital oxygen supplies, and cause heart attacks and strokes, more and more frequent modern maladies as the baby boomers get older. Whenever the body is cut or injured and blood comes into contact with cells outside the bloodstream, a tissue factor on these cells encounters a particular protein within the blood, which triggers the clotting process. In the same vein, a series of other blood factors then come into action and amplify one another to quickly form a jelly-like blood clot. Blood clots form when an enzyme called thrombin marshals fibrin (a blood protein) and platelets (tiny cells that circulate in the blood) to coagulate at the site of an injury. Individuals with no ability to clot have a genetic condition called hemophilia; such people are also known as “bleeders.” Queen Victoria was hemophilic, and she passed on her genes to her many heirs who ruled Europe for over a century. This is why hemophilia is sometimes known as the royal disease. Symptoms of hemophilia manifest only in male offspring. People with hemophilia must periodically administer a clotting factor to their blood to prevent constant bleeding.
The Reason for This Book and Why These Women Were Chosen
Authors: Brown Jeannette
Published: November 2020

Many people have studied the history of African American women chemists, but the information is scattered in many references, articles, and trade books. Until now, there was no one place where one could access extensive information about these women. This book is a compilation of all the references to date about the lives of these women; the chapters include a brief biography of each woman, with citations to the published information. The back matter provides a list of references. Not all of the women that I have written about are primarily researchers; some of them chose to be educators or businesspeople. My selection includes women pioneers—women who were the first to enter the field and receive a degree in chemistry, biochemistry, or chemical engineering. Some of these women were able to work as chemists before obtaining an advanced degree in chemistry. They later chose to pursue the PhD degree when major colleges and university allowed all students, regardless of race, to study. Some of the women chose not to pursue PhD degrees, ending their education with an MS degree. I extended my research to try to find the earliest women to pursue chemistry after the Civil War. It was difficult to find such early documents; however, I have not stopped searching. The first woman in this book, Josephine Silone Yates, was born into a family of free blacks in the north in 1852, before the Civil War. The next woman, Bebee Steven Lynk, was born in Mason, Tennessee in 1872 but not much is known about her early life. Alice Ball was born in 1896 into a family of free blacks in Seattle. These women, who were born in the nineteenth century, studied chemistry. Only one obtained an advanced degree: a PhC, which may have been a two-year degree. Josephine Silone Yates is reputed to have obtained a master’s degree. Most of the women in this book were, as the expression is used today, “nerds.” They were outstanding students in school.
Genes and Hormones
Authors: White Perrin C .
Published: November 2020

Much of the knowledge presented in the following chapters has been gained using molecular genetic techniques to analyze the structure, synthesis, regulation, and effects of hormones. This chapter provides an overview of some of the relevant techniques and associated concepts. To allow the reader to understand older experiments, we have tried to include techniques that are now of mainly historical interest as well as current concepts. Deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) consist of nucleotides . A nucleotide consists of a base , a sugar moiety (either deoxyribose or ribose), and a phosphate group. The sugars and phosphates alternate in the backbone of a nucleic acid strand. In general, there are four possible bases. In DNA, these are adenine ( A ), cytosine ( C ), guanine ( G ), and thymine ( T ). Adenine and guanine are purines , whereas cytosine and thymine are pyrimidines . The corresponding nucleotides are adenosine , cytidine , guanosine , and thymidine. In RNA, uracil (uridine) is substituted for thymine (thymidine). DNA is double stranded. Each strand has a direction because the deoxyribose molecules forming the backbone are asymmetrical, with the phosphate bonds linking each two sugar molecules going from the 3’ position of one to the 5’ position of the next. Thus, the 5’ position of a sugar molecule is free at one end (the 5’ end) of the strand, and the 3’ position is free at the other. The two strands of a DNA molecule run in opposite directions, so that the 5’ end of one strand is opposed to the 3’ end of the complementary strand. The DNA strands interact with each other through complementary (Watson-Crick) base pairing , in which A and T, or C and G, are paired through hydrogen bonds. Thus, the sequence of one DNA strand unambiguously determines the sequence of the complementary strand during DNA replication. The length of a DNA segment is typically given in bases or nucleotides (nt) or, if double stranded, base pairs (bp).
Female Reproductive Function
Authors: Ojeda Sergio R.
Published: November 2020

The production of germ cells is essential for the continuation of a species. In the female this function is accomplished by the ovaries. In addition, the ovaries secrete steroids and nonsteroidal hormones that not only regulate the secretion of anterior pituitary hormones but also act on various target organs, including the ovaries themselves, the uterus, fallopian tubes, vagina, mammary gland, and bone. Morphologically, the ovary has three regions: an outer cortex that contains the oocytes and represents most of the mass of the ovary; the inner medulla, formed by stromal cells and cells with steroid-producing characteristics; and the hilum, which, in addition to serving as the point of entry of the nerves and blood vessels, represents the attachment region of the gland to the mesovarium. The cortex, which is enveloped by the germinal epithelium, contains the follicles, which are the functional units of the ovary. They are present in different states of development or degeneration (atresia), each enclosing an oocyte. In addition to the oocyte, ovarian follicles have two other cellular components: granulosa cells, which surround the oocyte, and thecal cells, which are separated from the granulosa cells by a basal membrane and are arranged in concentric layers around this membrane. The follicles are embedded in the stroma, which is composed of supportive connective cells similar to that of other tissues, interstitial secretory cells, and neurovascular elements. The medulla has a heterogeneous population of cells, some of which are morphologically similar to the Leydig cells in the testes. These cells predominate in the ovarian hilum; their neoplastic transformation results in excess androgen production. The ovary produces both steroids and peptidergic hormones. Whereas the steroids are synthesized in both interstitial and follicular cells, peptidergic hormones are primarily produced in follicular cells and, after ovulation, by cells of the corpus luteum. The initial precursor for steroid biosynthesis is cholesterol, which derives from animal fats of the diet or from local synthesis.
Calcium Homeostasis
Authors: Maalouf Naim M
Published: November 2020

Ionized calcium plays a pivotal role in many physiological and biochemical processes, including the contraction of muscles, the clotting of blood, and impulse conduction in the heart and nervous system. Moreover, it acts as a secondary messenger within the cell to initiate other cascades important for cell signaling and both exocrine and endocrine secretion. The major storage sites for calcium in the body are the teeth and skeleton. These hard tissues, which contain 99 % of the body’s calcium (approximately 1 kg), provide the structure necessary for mastication, locomotion, and protection of internal organs. In the blood, calcium is found in three forms — ionized (50%), protein-bound (40 %), and soluble complexes (10 %). Unlike the other two forms of calcium, the protein-bound fraction, which is primarily bound to albumin, is not filtered by the kidney. In normal individuals, the range of serum total calcium is 8.5 to 10.3 mg/dl. In a given individual, however, the diurnal variation of serum calcium is limited to 0.3 mg/dl. This chapter reviews calcium homeostasis in the extracellular fluid, the integrated response to calcium stressors, and disorders of calcium metabolism. The bone, kidneys, and intestines are the most important calcium-transporting tissues and play an important role in calcium homeostasis. These three corners of the calcium homeostasis triangle are discussed individuallyin the sections that follow. The bone is a dynamic tissue that is constantly changing. From birth until the completion of puberty, bone lengthens and changes shape by a process called modeling. In the adult skeleton, remodeling is the process used to repair damaged areas, to strengthen sites of stress or injury, and to remove unnecessary bone from sparsely used skeletal sites. The entire skeleton is demolished and refabricated by this process within 10 years. There are two main types of bone that remodel at different rates. Cortical bone, which makes up 80 % of the bone mass, is highly calcified, dense tissue found mainly in the appendicular skeleton such as the arms and legs.
Orbital Connective Tissue
Authors: Jordan David , Mawn Louise , Anderson Richard L.
Published: November 2020

A diffuse connective tissue framework exists within the orbital space that supports various orbital structures, maximizing their function and maintaining anatomic relationships between them. Some connective tissue septa are aligned with directions of force and serve to resist displacement of the extraocular muscles during contraction. Other fascial septa suspend and support delicate orbital vascular and neural elements. All orbital structures, including the periorbita, globe, optic nerve, and extraocular muscles, are involved in the organization and suspension of these extensive connective tissue septal systems. This intricate framework has several important components that are oft en difficult to see clinically and during orbital surgery but which must always be kept in mind as playing a role in the clinical presentation of a particular orbital problem. For example, a blowout fracture of the orbital floor with restricted motility in upgaze might be due to entrapment of the inferior rectus muscle within the fracture, but more commonly it is due to entrapment of the connective tissue framework + / − fat in the inferior orbit. Enophthalmos, a deep superior sulcus, ptosis, and lower eyelid malposition are commonly seen following enucleation surgery. Loss of volume (of the globe) certainly plays a role, but other contributing factors, including a disruption of the connective tissue framework (which helps support the globe), might be playing a role. Trauma to Tenon’s capsule, Whitnall’s ligament, Lockwood’s ligament, or check ligaments associated with the recti muscles, as well as the intermuscular fascial connections, might also contribute to the postenucleation socket abnormalities mentioned above, as their disruption allows the shifting of orbital tissues to occur. Evisceration surgery is associated with less disruption to the connective tissue framework, and as a result features of postenucleation socket syndrome other than loss of volume are not as common. Historically, four major connective tissue components in the orbit have been described: 1. the bulbar fascia, or Tenon’s capsule, which surrounds the globe; 2. the fascial sheaths of the extraocular muscles; 3. the intermuscular septum (the common muscle sheath connecting the four rectus muscles); and 4. the medial and lateral check ligaments.
Causal Thinking in Psychiatry: A Genetic and Manipulationist Perspective
Authors: Kindler Kenneth S.
Published: November 2020

A large and daunting philosophical literature exists on the nature and meaning of causality. Add to that the extensive discussions in the statistical literature about what it means to claim that C causes E, and it can be overwhelming for the scientists, who, after all, are typically just seeking guidelines about how to conduct and analyze their research. Add to this mix the inherent problems in psychiatry—which examines an extraordinarily wide array of potential causal processes from molecules to minds and societies, some of which permit experimental manipulation but many of which do not—and you can readily see the sense of frustration and, indeed, futility with which this issue might be addressed. In the first section of this chapter, I reflect on two rather practical aspects of causal inference that I have confronted in my research career in psychiatric genetics. The first of these is what philosophers call a ‘‘brute fact’’ of our world—the unidirectional causal relationship between variation in genomic DNA and phenotype. The second is the co-twin–control method—a nice example of trying to use twins as a ‘‘natural experiment’’ to clarify causal processes when controlled trials are infeasible. In the second section, I briefly outline and advocate for a particular approach to causal inference developed by Jim Woodward (2003) that I term ‘‘interventionism.’’ I argue that this approach is especially well suited to the needs of our unusual field of psychiatry. I often teach students that it is almost too easy in psychiatric research to show that putative risk factors correlate with outcomes. It is much harder to determine if that relationship is a causal one. Indeed, assuming that for practical or ethical reasons a randomized trial of exposure to the risk factor is not feasible, one must rely on observational data. In these instances, it can be ‘‘damn near impossible’’ to confidently infer causation. However, in this mire of casual uncertainty, it is interesting to note that one relationship stands out in its causal clarity: the relationship between variation in germline DNA (gDNA) and phenotypes.
Obtaining Robust Causal Evidence from Observational Studies: Can Genetic Epidemiology Help?
Authors: Smith George Davey
Published: November 2020

Observational epidemiological studies have clearly made important contributions to understanding the determinants of population health. However, there have been high-profile problems with this approach, highlighted by apparently contradictory findings emerging from observational studies and from randomized controlled trials (RCTs) of the same issue. These situations, of which the best known probably relates to the use of hormone-replacement therapy (HRT) in coronary heart disease (CHD) prevention, have been discussed elsewhere (Davey Smith & Ebrahim, 2002) . The HRT controversy is covered elsewhere in this volume (see Chapter 5). Here, I will discuss two examples. First, consider the use of vitamin E supplements and CHD risk. Several observational studies have suggested that the use of vitamin E supplements is associated with a reduced risk of CHD, two of the most influential being the Health Professionals Follow-Up Study (Rimm et al., 1993) and the Nurses’ Health Study (Stampfer et al., 1993), both published in the New England Journal of Medicine in 1993. Findings from one of these studies are presented in Figure 9.1, where it can be seen that even short-term use of vitamin E supplements was associated with reduced CHD risk, which persisted after adjustment for confounding factors. demonstrates that nearly half of U.S. adults are taking either vitamin E supplements or multivitamin/multimineral supplements that generally contain vitamin E (Radimer et al., 2004). presents data from three available time points, where there appears to have been a particular increase in vitamin E use following 1993 (Millen, Dodd, & Subar, 2004), possibly consequent upon the publication of the two observational studies already mentioned, which have received nearly 3,000 citations between them since publication. The apparently strong observational evidence with respect to vitamin E and reduced CHD risk, which may have influenced the very high current use of vitamin E supplements in developed countries, was unfortunately not realized in RCTs, in which no benefit from vitamin E supplementation use is seen.
Why Buy That Theory?
Authors: Hoffmann Roald
Published: November 2020

The theory of theories goes like this: A theory will be accepted by a scientific community if it explains better (or more of) what is known, fits at its fringes with what is known in other parts of our universe, and makes verifiable, preferably risky, predictions. Sometimes it does go like that. So the theory that made my name (and added to the already recognized greatness of the man with whom I collaborated, the synthetic chemist of the 20th century, R. B. Woodward) did make sense of many disparate and puzzling observations in organic chemistry. And “orbital symmetry control,” as our complex of ideas came to be called, made some risky predictions. I remember well the day that Jerry Berson sent us his remarkable experimental results on the stereochemistry of the so- called 1,3-sigmatropic shift . It should proceed in a certain way, he reasoned from our theory—a non-intuitive way. And it did. But much that goes into the acceptance of theories has little to do with rationalization and prediction. Instead, I will claim, what matters is a heady mix of factors in which psychological attitudes figure prominently. A simple equation describing a physical phenomenon (better still, many), the molecule shaped like a Platonic solid with regular geometry, the simple mechanism (A→B, in one step)—these have tremendous aesthetic appeal, a direct beeline into our soul. They are beautifully simple, and simply beautiful. Theories of this type are awesome in the original sense of the word—who would deny this of the theory of evolution, the Dirac equation or general relativity? A little caution might be suggested from pondering the fact that political ads patently cater to our psychobiological predilection for simplicity. Is the world simple? Or do we just want it to be such? In the dreams of some, the beauty and simplicity of equations becomes a criterion for their truth. Simple theories seem to validate that idol of science, Ockham’s Razor. In preaching the poetic conciseness and generality of orbital explanations, I have succumbed to this, too.
Nearly Circular Reasoning
Authors: Hoffmann Roald
Published: November 2020

Scientific argument is supposed to be logical. But do scientists study logic? Probably not. Were they asked about the advisability of learning formal or applied logic, most would likely say, “Logic, as studied by philosophers, is just a systemization or description of what we, as scientists, do naturally. So we don’t need to study it.” The chain of reasoning that I’ve ascribed here to a straw-man scientist is, on analysis, full of the fallacies described by Aristotle in Sophistical Refutations (De sophisticis elenchis) more than 2,300 years ago. The argument suffers from circular reasoning, the fallacy of false cause, the argument ad populum (the populus here being scientists, as opposed to philosophers), and more. But actually I do not want to berate here the logically unsophisticated scientist (myself), nor to urge that scientists need study philosophy. Rather, I’d like to examine the curious role of logic in science. Good logical thinking is absolutely necessary to both everyday and revolutionary science. But I will argue that at the same time, reasoning in all science, paradigmatic or ground-breaking, on close scrutiny often turns out to be in part illogical. There is nothing new in this—we see readily the fallacies in the work of others, especially when they disagree with us, don’t we? I will try to make a case, however, that there may be a real advantage implicit in occasionally faulty reasoning, especially a mode which I will call nearly circular reasoning. Science is a curious mixture of the real and the ideal, the material and the spiritual, held together by discourse or argument. The latter is sometimes mathematical, but more often it transpires in the words of some language. The real is the material, say, a vial of a chemical, or its measured spectrum, the relative amount of light a solution of that chemical absorbs. The ideal may be a proposal on the mechanism of formation of the molecule, or a theory that interprets that spectrum as necessarily indicating the molecule contains a carbon-hydrogen bond. The discourse consists of the exposition of several arguments, several alternative models explaining the observable, and a choice between them.
Learning from Molecules in Distress
Authors: Hoffmann Roald , Hopf Henning
Published: November 2020

From the time we first got an inkling of the geometries and metrics of molecules, the literature of organic chemistry has contained characterizations of molecules as unstable, strained, distorted, sterically hindered, bent and battered. Such molecules are hardly seen as dull; on the contrary, they are perceived as worthwhile synthetic goals, and their synthesis, or evidence of their fleeting existence, acclaimed. What is going on here? Why this obsession with abnormal molecules? Is this molecular science sadistic at its core? Let’s approach these questions, first describing what is normal for molecules, so we can define the deviance chemists perceive. After a digression into the anthropomorphic language chemists generally use, and the psychology of creation in science, we will turn to the underlying, more serious concern: “What is the value of contemplating (or creating) deviance within science?” As many as 366,319 different eicosanes (C20H42) are conceivable, not counting optical isomers. And an enumeration of the components of a reasonably constrained universe of all compounds with up to 11 C, N, O, F atoms comes to >26 million compounds. An important feature of the chemical universe is that the tree of possible structures is denumerable. At the same time, the playground of chemical structures is subject to systematic elaboration, through the decoration of an underlying skeleton by functional groups of some stability. Very quickly a multitude turns into a universe. Of structure, and of function. Thinking of these molecules as fixed, rigid structures is natural—don’t they look like olive and toothpick assemblages, prettied up by computer rendering? And one can certainly get a long way in organic chemistry in the classical, mechanical mode. But the atoms in a molecule move continually, deviating, oscillating, as if held by springs, around an average position. The honey-comb structure of the benzene ring (a molecular tile, seemingly ever so flat and rigid as the one on your bathroom floor) has become an icon of chemistry just as the angled water molecule. Yet that tile is not rigid, it moves—and one can see the deformations/deviations by looking at its vibrational (what a telling name!) spectrum.
Under the Surface of the Chemical Article
Authors: Hoffmann Roald
Published: November 2020

You open an issue of a modem chemical periodical, say the important German Angewandte Chemie or the Journal of the American Chemical Society, and what do you see? Riches upon riches: reports of new discoveries, marvelous molecules, unmakeable, unthinkable yesterday—made today, reproducibly, with ease. The chemist reads of the incredible properties of novel high-temperature superconductors, organic ferromagnets, and supercritical solvents. New techniques of measurement, quickly equipped with acronyms—EXAFS, INEPT, COCONOESY—allow you to puzzle out more expeditiously the structure of what you make. Information just flows. No matter if it’s in German, if it’s in English. It’s chemistry—communicated, exciting, alive. Let’s, however, take another perspective. To the pages of the same journal turns a humanist, a perceptive, intelligent observer who has grappled with Shakespeare, Pushkin, Joyce, and Paul Celan. I have in mind a person who is interested in what is being written, and also in how and why it is written. My observer notes in the journal short articles, a page to ten pages in length. She notes an abundance of references, trappings familiar to literary scholars, but perhaps in greater density (number of references per line of text) than in scholarly texts in the humanities. She sees a large proportion of the printed page devoted to drawings. Often these seem to be pictures of molecules, yet they are curiously iconic, lacking complete atom designations. The chemist’s representations are not isometric projections, nor real perspective drawings, yet they are partially three-dimensional. My curious observer reads the text, perhaps defocusing from the jargon, perhaps penetrating it with the help of a chemist friend. She notes a ritual form. The first sentences often begin: “The structure, bonding and spectroscopy of molecules of type X have been subjects of intense interest.a-z” There is general use of the third person and a passive voice. She finds few overtly expressed personal motivations, and few accounts of historical development. Here and there in the neutered language she glimpses stated claims of achievement or priority—“a novel metabolite,” “the first synthesis,” “a general strategy,” “parameter-free calculations.”
Art in Science?
Authors: Hoffmann Roald
Published: November 2020

Here are two manuscript pages from articles I’ve written. And there are the ways they appeared in print, in the Journal of the Chemical Society: Dalton Transactions and Inorganic Chemistry, two magazines you are unlikely to have read recently. The context of these images is the following: I’m a theoretical chemist. What you see is the initial draft and final printed version of fragments from two of the >500 articles I’ve written. Articles are the stock-in-trade of the professional scientist. By and large we do not write books; our achievements, such as they may be, are judged by these scholarly articles. In general they’re written in English (well, really in a jargon that has some vague relationship to English), printed in journals with limited circulation (these, among the world’s best chemistry journals, have circulations near five thousand each), glanced at only by other chemists, and read carefully by a few hundred people. On the basis of these articles my work is evaluated and I make a living. That explains circumstantially Figure 19-2, the final printed pages. What about the manuscripts, Figure 19-1? Clearly these are collages. There are samples of writing in two hands on them; one is my own, the other that of the graduate student (David Hoffman) or postdoctoral fellow (Kazuyuki Tatsumi) who has worked with me on this research. In science there is much, much collaboration. My papers typically have two or three coauthors. I pose the question, my coworkers and I discuss an approach to a solution, they do most of the tough work, we talk further, a presentation of intermediate results is made, they’re off to test various unreasonable suggestions I make, they write a draft, and I revise it into a final paper. In what you see in Figures 19-1 and 19-2, each a page of the manuscript of the final paper, I’ve pasted in photocopies of a piece of my collaborator’s draft that I decided to keep. The actual drawings that the scientific journals print are reproduced from India ink originals on tracing paper. These are masterfully done by Jane Jorgensen and Elisabeth Fields, two illustrators who worked with me for many years.
Effects of Sea-Level Rise and Subsidence on Deltas
Authors: Bianchi Thomas S.
Published: November 2020

As I briefly mentioned in Chapter 3, the global mean sea level, as deduced from the accumulation of paleo-sea level, tide gauge, and satellite-altimeter data, rose by 0.19 m (range, 0.17–0.21 m) between 1901 and 2010 (see Figure 3.3). Global mean sea level represents the longer-term global changes in sea level, without the short-term variability, and is also commonly called eustatic sea-level change. On an annual basis, global mean sea-level change translates to around 1.5 to 2 mm. During the last century, global sea level rose by 10 to 25 cm. Projections of sea-level rise for the period from 2000 to 2081 indicate that global mean sea-level rise will likely be as high as 0.52 to 0.98 m, or 8 to 16 mm/ yr, depending on the greenhouse gas emission scenarios used in the models. Mean sea-level rise is primarily controlled by ocean thermal expansion. But there is also transfer of water from land to ocean via melting of land ice, primarily in Greenland and Antarctica. Model predictions indicate that thermal expansion will increase with global warming because the contribution from glaciers will decrease as their volume is lost over time. (Take a look at Figure 5.1 if you have doubts about glaciers melting.) And remember our discussion in Chapter 2 about the role of the oceans in absorbing carbon dioxide (CO2) and the resultant ocean acidification in recent years. The global ocean also absorbs about 90% of all the net energy increase from global warming as well, which is why the ocean temperature is increasing, which in turn results in thermal expansion and sea-level rise. To make things even more complicated, the expansion of water will vary with latitude because expansion of seawater is greater with increasing temperature. In any event, sea level is expected to rise by 1 to 3 m per degree of warming over the next few millennia.
Best Synthetic Methods: Functional Group Transformation
Authors: Taber Douglass
Published: November 2020

François Morvan of the Université de Montpellier, using the inexpensive dimethyl phosphite, optimized (Tetrahedron Lett. 2008, 49, 3288) the free radical reduction of 1 to 2. Pawan K. Sharma of Kurukshetra University found (Tetrahedron Lett. 2008, 48, 8704) that NaBH4 in the presence of a catalytic amount of RuCl3.xH2 O reduced monosubstituted and disubstituted alkenes, such as 3, to the corresponding alkanes. Note that benzyl ethers were stable to these conditions. Ken Suzuki of Asahi Kasei Chemicals and Shun-Ichi Murahashi of Okayama University of Science established conditions (Angew. Chem. Int. Ed. 2008, 47, 2079) for the oxidation of primary amines such as 5 to oximes. Both ketoximes such as 6 and aldoximes were prepared using this protocol. Primary and secondary alcohols were stable to these conditions. Three noteworthy procedures for the oxidation of an aldehyde to the acid oxidation state were recently reported. Jonathan M. J. Williams of the University of Bath demonstrated (Chem. Commun. 2008, 624) that crotonitrile could serve as the hydrogen acceptor in the oxidation of an aldehyde 7 to the methyl ester 8. Note that isolated alkenes were stable to these conditions. Vikas N. Telvekar the University Institute of Chemical Technology, Mumbai improved (Tetrahedron Lett . 2008, 49, 2213) the oxidative amination of an aldehyde 9 to the nitrile 10. G. Sekar of the Indian Institute of Technology Madras effected (Tetrahedron Lett. 2008, 49, 1083) oxidation of an aldehyde 11 to the acid 12, under conditions that would be expected to not oxidize a primary or secondary alcohol. J. S. Yadav of the Indian Institute of Chemical Technology, Hyderabad observed (Tetrahedron Lett. 2008, 49, 3015) that the activation of a thiophenol 14 with N-chlorosuccimide generated a species that added regioselectively to a ketone 13 to give the thioether 15. Oxidation of the sulfide 15 followed by heating of the resulting sulfoxide would give the enone 16. This appears to be an easily scalable procedure. It is well known that an acid 17 and an amine 18 will condense at elevated temperature to give the amide 20.
Organic Functional Group Interconversion: (-)- β -Conhydrine (Barua) and (+)-6'-Hydroxyarenarol (Anderson)
Authors: Taber Douglass
Published: November 2020

V. T. Perchyonok and Kellie L. Tuck of Monash University found (Tetrahedron Lett. 2008, 49, 4777) that a concentrated solution of Bu4NCl and H3PO2 in water effected free radical reductions and cyclizations. Stéphane G. Ouellet of Merck Frosst demonstrated (Tetrahedron Lett. 2008, 49, 6707) that an oxazoline such as 3 could be converted to the alcohol 4 by acylation followed by reduction. Elizabeth R. Burkhardt of BASF developed (Tetrahedron Lett. 2008, 49, 5152) a protocol for scalable reductive amination using an easily metered liquid pyridine-borane complex. Mohammad Movassaghi of MIT devised (Angew. Chem. Int. Ed. 2008, 47, 8909) a strategy for conversion of an allylic carbonate 8 by way of the allylic diazene to the terminal alkene 9. Philippe Compain of the Université d’Orleans uncovered (J. Org. Chem. 2008, 73, 8647) a practical procedure for oxidizing an inexpensive aldose such as 10 to the amide 12, a valuable chiral pool starting material. Karl A. Scheidt of Northwestern University extended (Organic Lett. 2008, 10, 4331) activated MnO2 oxidation to saturated aldehydes such as 13, leading to the ester 15. Tohru Fukuyama of the University of Tokyo showed (Organic Lett. 2008, 10, 2259) that halides such as 16 could be oxidized to the oxime 18 with the reagent 17. The product oximes are readily dehydrated to the corresponding nitriles. Chutima Kuhakarn of Mahidol University devised (Synthesis 2008, 2045) a simple protocol for the oxidation of a primary amine such as 19 to the nitrile 20 . Nasser Iranpoor and Habib Firouzabadi of Shiraz University developed (J. Org. Chem. 2008, 73, 4882) the reagent 22 for Mitsunobu coupling. The stereochemical course of this reaction with simple acyclic secondary alcohols such as 21 was not reported. Salvatore D. Lepore of Florida Atlantic University optimized (Angew. Chem. Int. Ed. 2008, 47, 7511) the quisylate 24 for the displacement with retention to give the azide 25. Hideki Yorimitsu and Koichiro Oshima of Kyoto University optimized (J. Am. Chem. Soc. 2008, 130, 11276) a Co catalyst for the conversion of a secondary halide such as 26 to the terminal alkene 27 . Base-mediated elimination gave primarily the internal alkene.
Best Synthetic Methods: Carbon-Carbon Bond Construction
Authors: Taber Douglass
Published: November 2020

In the context of peptidyl ketone synthesis, Troels Skrydstrup of the University of Aarhus developed (J. Org. Chem. 2008, 73, 1088) the elegant SmI2-mediated conjugate addition of acyl oxazolidinones such as 1 to acceptors such as 2. Sadagopan Raghavan of the Indian Institute of Chemical Technology, Hyderabad reported (Tetrahedron Lett. 2008, 49, 1601) that the addition of a Pummerer intermediate, generated by exposure of 4 to TFAA, to the terminal alkene 5 and SnCl4 led to efﬁcient C-C bond formation, to give the sulﬁde 6 as a single (unassigned) diastereomer. Pd-catalyzed carbonylation of aryl halides and triflates is a well-established process. Stephen L. Buchwald of MIT has now (J. Am. Chem. Soc. 2008, 130, 2754) extended this transformation to much less expensive tosylates and mesylates such as 7. β-Amino acids have often been prepared from α-amino acids by Arndt-Eistert homologation. Geoffrey W. Coates of Cornell University has devised (Angew. Chem. Int. Ed. 2008, 47, 3979) a more practical alternative, the direct Co-catalyzed carbonylation of an oxazoline 9 to the 2-oxazine-6-one 10. Eiji Shirakawa and Tamio Hayashi of Kyoto University also used (Chem. Lett . 2008, 37, 654) a Co catalyst to promote the coupling of aryl and alkenyl Grignard reagents with enol trifl ates such as 11. Alois Fürstner of the Max-Planck-Institut, Mülheim optimized (Chem. Commun. 2008, 2873) promoters for the Pd-catalyzed Stille-Migata coupling of iodo alkenes such as 14 with alkenyl stannanes such as 15 to give 16. It is particularly noteworthy that their system is fluoride free. The stereocontrolled construction of trisubstituted alkenes continues to be challenging. We described (J. Org. Chem. 2008, 73, 1605) the facile preparation of the diioide 18 from the inexpensive 2-butyn-1,4-diol 17 . Sequential coupling of 18 with an aryl Grignard followed by CH3 Li delivered 19. Brian S. J. Blagg of the University of Kansas established (Tetrahedron Lett . 2008, 49, 141) that Still-Genari homologation of 20 with 21 gave (E)- 22 with high geometric control. Biao Jiang of the Shangahi Institute of Organic Chemistry reported (Organic Lett. 2008, 10, 593) a convenient alternative protocol to give ( Z )-α- bromo unsaturated esters.
Alkene Metathesis: Synthesis of Kainic Acid, Pladienolide B and Amphidinolide Y
Authors: Taber Douglass
Published: November 2020

As alkene metathesis has developed into one of the tools of organic synthesis, many practical questions have arisen. In the course of a synthesis (Organic Lett. 2007, 9, 1635) of the important neuropharmacological tool (-)-kainic acid 7, Tohru Fukuyama of the University of Tokyo prepared the key intermediate 1 by chiral auxiliary mediated coupling of crotonyl chloride with acetadehyde. Dibal reduction gave the hemiaminal, which underwent reductive amination with glycine methyl ester, leading to the alkene 2. Alkene metathesis of the derived ester 3 to form the unsaturated lactone 4 was then examined in detail. It was found that 0.5 mol % of the second generation Hoveyda catalyst was sufﬁcient to cyclize 3 to 4 in 92% yield. With 0.8 mol %, the yield was 99%. The key to the efﬁcacy of this cyclization was the use of 1,2-dichloroethane at reﬂux as the reaction solvent. The macrolide pladienolide D 14 induces in vivo tumor regression in several human cancer xenograft models. This activity was important enough that a team at Esai Co., Ltd in Tsukuba headed by Yoshihiko Kotake undertook the total synthesis (Angew. Chem. Int. Ed. 2007, 46, 4350). Their approach used two alkene metathesis steps. To prepare the substrate for the macrolide construction, the alcohol 8 and the acid 9, each prepared by chiral auxiliary control, were coupled to give the ester 10. An extensive investigation led to alkene metathesis conditions that were satisfactory, the use of the second generation Hoveyda catalyst in refluxing toluene. A significant competing side reaction was the migration of the monosubstituted alkene of 10 to make the alkenyl ether. The second alkene metathesis step was the coupling of 12 with 13. The most effective catalyst in this case was the second generation Grubbs. Note that the free alcohol 13 participated successfully in the cross-coupling. According to the authors, this is one of just a few examples of successful cross coupling of an alkene adjacent to a quaternary center. The stereocontrolled construction of trisubstituted alkenes by metathesis is a particular challenge.
Complex Cyclic Ethers: (+)-Conocarpan (Hashimoto), (-)-Brevisamide (Satake/ Tachibana), (+)-Bruguierol A (Fañanás/ Rodríguez), (-)-Berkelic Acid (Snider), and (-)-Aigialomycin D (Harvey)
Authors: Taber Douglass
Published: November 2020

( + )-Conocarpan 3, isolated from the wood of Conocarpus erectus , exhibits insecticidal, antifungal and antitrypanosomal activity. Shunichi Hashimoto of Hokkaido University developed (J. Org. Chem. 2009, 74 , 4418) a chiral Rh (II) carboxylate that effected the cyclization of 1 to 2, setting the absolute configuration of 3. The dinoflagellate Karenia brevis produces the brevetoxins, a family of complex polyethers. Recently, the first N-containing cyclic ether, (-)-Brevisamide 6, was isolated from K. brevis . Masayuki Satake and Kazuo Tachibana of the University of Tokyo, in their synthesis of 6 (Organic Lett. 2009, 11, 217) found it convenient to set the relative configuration around the six-membered ring by double hydroboration/oxidation of the diene 4. ( + )-Bruguierol A 9, isolated from the mangrove Bruguiera gymmorrhiza, has an unusual bridged structure. Francisco J. Fañanás and Félix Rodríguez of the Universidad de Oviedo conceived (J. Org. Chem. 2009, 74, 932) an elegant approach to the construction of 9, based on the Pt-mediated addition of the alcohol of 7 to the alkyne to give a transient enol ether. It is not clear whether the subsequent intramolecular electrophilic addition to the aromatic ring is mediated by the Pt, or by a trace of adventitious acid. The overall transformation was remarkably efficient. The Berkeley Pit in Butte, Montana, is an abandoned open-pit copper mine filled with 30 billion gallons of pH = 2.5 water heavily contaminated with, inter alia , copper, cadmium, arsenic and zinc. Remarkably, microorganisms can be cultured from that water. (-)-Berkelic Acid 13 , isolated from a Penicillium fungus, showed selective activity against OVCAR-3 ovarian cancer. Barry B. Snider of Brandeis University set (Angew. Chem. Int. Ed. 2009, 48, 1283) the absolute configuration of the central five-membered ring ether of 13 by conjugate addition of the enantiomerically-pure reagent 11 to the prochiral lactone 10. (-)-Aigialomycin D 17, isolated from the mangrove fungus Aigialus parvus , was found to be a selective inhibitor of the kinases CDK1, CDK5 and GSK3.