bluuebunny/crossref_metadata_2025 huggingface dataset:
Encouragement to Others, 1650–1780
Authors: Abulafia David
Published: November 2020

In the course of the seventeenth century the character of the relationship between the European states changed dramatically, with important repercussions in the Mediterranean. Until the end of the Thirty Years’ War in 1648, Catholic confronted Protestant, and confessional identity was an issue of surpassing significance for the competing powers in Europe. After 1648, a greater degree of political realism, or cynical calculation, began to intrude. Within a few years, it was possible for the English arch-Protestant Oliver Cromwell to cooperate with the Spanish king, while English suspicion of the Dutch led to conflict in the North Sea. The character of English involvement in the Mediterranean changed: royal fleets began to intervene and the English (after union with Scotland in 1707, the British) sought out permanent bases in the western Mediterranean: first Tangier, then Gibraltar, Minorca and, in 1800, Malta. The period from 1648 to the Napoleonic Wars was marked, therefore, by frequent about-turns as the English switched from Spanish to French alliances, and as the whole question of the Spanish royal succession divided Europe and opened up the prospect of spoils from a declining Spanish empire in the Mediterranean. While Spain’s difficulties were obvious, it was less clear that the Ottomans had passed their peak: the Ottoman siege of Vienna in 1683 was unsuccessful, but in the Mediterranean Turkish galleys still posed a serious threat, and their Barbary allies could be relied upon to give support when naval conflict broke out. Even so, the Venetians managed to gain control of the Morea or Peloponnese for several years, and, interestingly, it was they who were the aggressors. Bolder than they had been for some time, the Venetians ambitiously aimed to crack Turkish power in the regions closest to their navigation routes. In 1685 and 1686 they captured and demolished a number of Turkish fortresses on either side of the Morea, culminating in the capture of Nafplion on 30 August 1686. This was only the prelude to an attempt to clean up the Dalmatian coast, starting with the Turkish base at Herceg Novi, which they captured in September 1687.
Ottoman Exit, 1900–1918
Authors: Abulafia David
Published: November 2020

The history of the Mediterranean has been presented in this book as a series of phases in which the sea was, to a greater or lesser degree, integrated into a single economic and even political area. With the coming of the Fifth Mediterranean the whole character of this process changed. The Mediterranean became the great artery through which goods, warships, migrants and other travellers reached the Indian Ocean from the Atlantic. The falling productivity of the lands surrounding the Mediterranean, and the opening of high-volume trade in grain from Canada or tobacco from the United States (to cite two examples), rendered the Mediterranean less interesting to businessmen. Even the revived cotton trade of Egypt faced competition from India and the southern United States. Steamship lines out of Genoa headed across the western Mediterranean and out into the Atlantic, bearing to the New World hundreds of thousands of migrants, who settled in New York, Chicago, Buenos Aires, São Paulo and other booming cities of North and South America in the years around 1900. Italian emigration was dominated by southerners, for the inhabitants of the southern villages saw none of the improvement in the standard of living that was beginning to transform Milan and other northern centres. For the French, on the other hand, opportunities to create a new life elsewhere could be found within the Mediterranean: Algeria became the focus of French emigration, for the ideal was to create a new France on the shores of North Africa, while keeping the wilder interior under colonial rule. Two manifestations of this policy were the rebuilding of large areas of Algiers as a European city, and the collective extension of French citizenship to 35,000 Algerian Jews, in 1870. The Algerian Jews were seen as évolé, ‘civilized’, for they had embraced the opportunities provided by French rule, opening modern schools under the auspices of the Alliance Israélite Universelle, founded to promote Jewish education on the European model, and transforming themselves into a new professional class.
Discovery of Lipitor
Authors: Li Jie Jack
Published: November 2020

Parke-Davis was not the first drug company to put a statin on the market (Merck was), but it was the one to do it the best, with Lipitor (atorva statin). When Parke-Davis Pharmaceuticals in Ann Arbor, Michigan, began to look for its own statin in 1982, it was late in the game. Parke-Davis’s Lipitor was discovered in the mid- to late 1980s and brought to market in 1997. Already ahead of it were four statins: Merck’s Mevacor was released in September 1987 and Zocor in December 1991, Bristol-Myers Squibb’s Pravachol in October 1991, and Sandoz’s Lescol in March 1994. Despite the competition, by 2006 Lipitor had become the best-selling drug in history, with one-year sales totaling $12.9 billion, more than the net worth of the 10th biggest drug company in the world. Although the drug firm Parke-Davis had in recent times been relegated to history books, half a century ago, Parke, Davis and Company once enjoyed the status of the largest pharmaceutical manufacturer in the world. In 1866, 38-year-old Hervey C. Parke, a businessman, and Samuel P. Duffield, a chemist and physician, founded Duffield, Parke & Company— Manufacturing Chemists in Detroit, Michigan. Duffield originally studied under the father of organic chemistry, Justus von Liebig, at the University of Giessen in Germany. He continued to pursue his academic interests even after the founding of the company and published several articles in the American Journal of Pharmacy. In 1867, 22-year-old George S. Davis joined the company as the firm’s first salesman. Four years later, Parke and Davis bought out Duffield’s shares of the company. In November 1871, Parke, Davis & Company was born, with Parke as the president and Davis as the general manager. The company’s inventory was typical of the time: aconite, belladonna, ergot, spirit of ammonia, arsenic, and ether. Davis, a Napoleonic, small-statured man, was clearly responsible for building the company’s sales and its enterprise in many directions. He pioneered product promotion by publishing books and magazines, a practice later followed by many other companies. When vaccines were first invented in Europe, Parke-Davis was one of the first pharmaceutical companies to move into this new field.
Ocular Motor Disorders Caused by Lesions in the Brainstem
Authors: Wong Agnes
Published: November 2020

Oculopalatal tremor usually occurs many months after an initial insult, due to neural deafferentation. It rarely resolves spontaneously. Treatment is with gabapentin, ceruletide, or anticolinergic agents. The y-group is a small group of cells that lies rostral to the inferior cerebellar peduncle. It receives inputs from the saccule (part of the otolith) and from Purkinje cells of the flocculus, and it projects to the oculomotor and trochlear nuclei via the superior cerebellar peduncle and a crossing ventral tegmental tract. 1. Discharge during upward smooth pursuit, optokinetic, and combined eye-head tracking (VOR cancellation), but not during VOR in darkness (see sections 3.14 and 5.2) 2. Together with the flocculus and ventral paraflocculus, may contribute to vertical VOR adaptation (see section 3.12) No known documented clinical correlate Collections of neurons scattered along the midline fiber tracts in the pons and medulla, including: 1. The nucleus pararaphales in the medulla, which receives vertical eye position signals from the INC, and projects to the flocculus and ventral paraflocculus 2. The nucleus incertus in the pons, which contains burst-tonic neurons that mainly discharge in relation to horizontal eye movements, and projects to the flocculus Function: may send an “efference copy” of eye movement commands to the flocculus for gaze holding or longer term adaptation No known documented clinical correlate The abducens nucleus contains: 1. Abducens motoneurons that innervate the ipsilateral lateral rectus 2. Abducens internuclear neurons, the axons of which cross the midline and ascend via the MLF to innervate the contralateral medial rectus motoneurons in the oculomotor nucleus. 3. Neurons that project to the cerebeller flocculus The abducens nucleus is the final common motor pathway for horizontal conjugate eye movements, as it receives input for horizontal saccades, VOR, and smooth pursuit. The paramedian pontine reticular formation (PPRF) contains: Excitatory burst neurons (EBN) in the dorsomedial nucleus reticularis pontis caudalis (NRPC) that ■ Project to the ipsilateral abducens nucleus to generate ipsilateral, conjugate, horizontal saccades ■ Project to inhibitory burst neurons in the nucleus paragigantocellularis dorsalis (PGD) and receive inhibitory inputs from omnipause neurons in nucleus raphe interpositus (rip)
Dr. Jekyll’s Mysterious Transformative Formula
Authors: Griep Mark A. , Mikasen Marjorie L.
Published: November 2020

“Jekyll and Hyde” is a phrase known to many, though few have read the short novella published in 1886. It is far more likely that people have encountered the phrase during conversation or in one of its numerous adaptations. In fact, the Strange Case of Dr. Jekyll and Mr. Hyde by Robert Louis Stevenson is the most adapted story of all time, even exceeding such texts as Mary Shelley’s Frankenstein, Charles Dickens’s A Christmas Carol, and Shakespeare’s The Tempest (Rose 1996). The idiom “Jekyll and Hyde” usually refers to someone or something that manifests its opposite tendency in different contexts. Colloquially, it does not always carry an explicit chemical connotation. But, in the more than 100 stage, movie, television, and cartoon adaptations (for a continually updated list, see Dury 2006), Jekyll is nearly always transformed into Hyde after ingesting or injecting a chemical formula of his own manufacture. For this reason, it is the single most important example of chemical self-experimentation in the movies. Nearly all of the dramatic Jekyll and Hyde adaptations have important scenes in which the mirror is used as a research tool. After Jekyll transforms into Hyde for the first time, he determines that the experiment was a success by looking into a mirror. He sees the monstrous Hyde in the reflection and knows that he, Jekyll, no longer looks like himself. It is very likely he no longer even feels viscerally like himself. The transformation scene, preceding the mirror scene, often shows Jekyll painfully grimacing, shaking, or groaning. The mirror scene is the point of full realization. We can conclude that Jekyll’s mind, though now contained in the persona of Hyde for the first time, is still able to internalize this realization with a scientist’s thinking process. As the story progresses, however, Hyde becomes increasingly more powerful and uses the mirror for self-satisfied confirmation that he has trumped Jekyll yet again. The mirror is the axis on which the status of the Jekyll and Hyde character flips. The mirror scene initiates an understanding that Jekyll and Hyde function as a paired unit.
Isomorphs of Paranoia: Chemical Arsenals
Authors: Griep Mark A. , Mikasen Marjorie L.
Published: November 2020

In the United States after the September 2001 attacks, citizens were advised to protect themselves from toxic dusts by covering their windows with plastic sheeting and duct tape that could be purchased from any hardware store. One hundred years ago, terrorists would not have had ready access to today’s common chemicals to create makeshift explosives, and citizens would not have had access to plastic sheeting or duct tape to protect themselves from aerosols or gases. Chemical weapons have engendered a cloud of fear since their introduction into warfare during World War I. Recently, the large-scale use of chemicals as lethal weapons has drifted from warfare to terrorism. Chemical weapons are often equated with poison gases (either asphyxiation or nerve agents), but as can be seen in the list of movies for this chapter, they are actually the most diverse type of weapon. Some of these weapons are discussed elsewhere in the book (psychedelic agents, chapter 5; explosives, chapter 9). The chemistry in nuclear weapons movies is discussed in the commentary sections for those movies that use them. The movies in this chapter are closely linked to spy movies, which lie at the nexus of the action and thriller genres. Spy movies are appealing in part because these charming, good-looking government employees live by their wits and gut reactions to make split-second decisions that are best for the spy and the government. But a spy is only as good as the villain; otherwise, it wouldn’t be challenging or fun. So, the final ingredient for the movie choices in this chapter is that many of them refer to actual chemical weapons, which grounds them in the real world. The audience knows these weapons are dangerous and can be misused by the wrong person. Only about 70 chemical compounds have been put to use during military conflicts over the past century, and they are classified based on their effects. Asphyxiating and blistering agents were created for WWI (1914–1918); nerve agents were developed for WWII (1940–1945) but never used in that war; napalm was also created for WWII but it generated public comment only when used in the Vietnam War; nonlethal psychedelics were tested extensively during the 1950s but haven’t been documented as having been used yet; herbicides and tear gas were used tactically during the Vietnam War.
Hard Science = Hard Evidence: Forensic Chemistry and Chemical Detectives
Authors: Griep Mark A. , Mikasen Marjorie L.
Published: November 2020

Someone killed the mayor of Chatsberg using a makeshift pipe bomb in Kid Glove Killer (1942). It was connected with a wire to the electrical system of the mayor’s automobile and exploded when he turned the ignition key. The two members of the Chatsberg police forensic team, supervisor Gordon McKay (Van Heflin) and his assistant Jane “Mitchell” Mitchell (Marsha Hunt), visit the crime scene to collect clues such as a coat fiber caught in the garage door, the exploded bomb fragments with attached wire, and the burlap bag beneath the automobile. Their hypothesis is never stated, but it is clear from their actions they are using Locard’s exchange principle: “Every contact leaves a trace.” McKay and Mitchell focus their subsequent efforts on finding physical evidence on suspects that connects them with the material collected at the crime scene. In forensic science, crime scene reconstruction is the “thought experiment,” the documented crime scene is the “effect,” and the evidence is used to establish “cause.” In the case of murder, “cause” equates to who did what to whom. An examination of the chemistry in detective and spy movies shows they fall into the two main categories of elemental analysis or qualitative analysis. Most qualitative analyses fall under the category of forensic toxicology, the identification and quantification of drugs and poisons. Toxicology also happens to be one of the oldest branches of forensic chemistry. None of the movies shows the creation or even improvement of a chemical procedure. Instead, chemistry plays an infallible supporting role in solving a crime or mystery. For instance, in Kid Glove Killer, elemental analysis determines that vanadium was present as a tracer in the gunpowder but is not under the fingernails of the prime suspect, thereby decisively eliminating him as a suspect in the eyes of the forensic experts. The actual proof linking the killer to the crime scene does not involve chemistry but, rather, repetitive routine testing coupled with good guesswork. Even though the ability to detect arsenic in body tissues in 1815 gave chemical forensics its start (see “Limits of Detection,” below), the next advances in forensics were philosophical.
First, Do No Harm: (but Before That, Self-Experiment)
Authors: Griep Mark A. , Mikasen Marjorie L.
Published: November 2020

“The physician must . . . have two special objects in view with regard to disease, namely, to do good or to do no harm.” Hippocrates (Of the Epidemics, 400 B.C.E.) (Adams 1891). This phrase from Hippocrates is more often quoted in its shortened version: “First, do no harm.” In the movies, this sentiment lies at the heart of the bioethical dilemmas in the drug discovery and development process. In horror movies, any step in the drug discovery process can go terribly wrong. This reveals public fears about human fallibility, or even malice, subverting even the best protocols. In the dramatic movies, each new drug or medical protocol is one more step into the bright light of a better future. The goal for these noble scientists is to reduce human suffering. The most common first phase of drug discovery for compounds in this book has been the result of happy accidents and ethnobiological ventures. In chapter 5, the properties of LSD and Thorazine were both discovered while searching for other effects, although the discovery of these drugs has not been dramatized cinematically. Ethnobiology entered the picture in chapter 9 in the form of two movies from about 1990. Dr. Dennis Alan in The Serpent and the Rainbow searches for the zombie powder and discovers that it requires both puffer fish toxin and a cultural belief in zombies. Dr. Robert Campbell in Medicine Man searches for botanical pharmaceuticals and finds a cure for lymphoma. An ethical dilemma is presented in that movie with regard to who should benefit from the compound he discovers. Within the movie, we have to believe that no chemist would be able to synthesize the compound called “Mother Nature’s kitchen” and that Campbell is unable to replicate its isolation from the Amazonian flower. When one vial of the compound remains, a local boy gets cancer and Dr. Crane asks who is more important: one boy, or the rest of the world. Later, she chooses the boy. The movie does not give voice to the interesting question of the pharmaceutical company’s compensation to the locals’ discovery of the anticancer extract.
Vitrectomy for Retinal Detachment
Authors: Brinton Daniel A. , Wilkinson Charles P.
Published: November 2020

Following the introduction of closed vitrectomy techniques by Robert Machemer in the early 1970s, complicated retinal detachments became one of the important indications for vitreous surgery. Most of these were due to proliferative diabetic retinopathy (PDR) or to proliferative vitreoretinopathy (PVR), frequently following failure of routine scleral buckling procedures. As experience in vitreoretinal surgery expanded, the advantages of these techniques in the management of more routine types of retinal detachment became apparent. The popularity of vitrectomy for primary retinal detachments continues to grow, particularly with regard to pseudophakic cases. Indications for performing a vitrectomy rather than a scleral buckle or a pneumatic retinopexy are summarized in Chapter 10. Virtually all authorities note that a vitrectomy is required (along with a broad scleral buckle) in eyes with severe PVR, and the technique is also clearly indicated for cases due to PDR, detachments associated with major vitreous hemorrhage or scarring from penetrating trauma, and those with giant retinal tears. On the other hand, few would suggest a vitrectomy to repair a very shallow and small retinal detachment due to a single break that could be easily closed with a scleral buckle or pneumatic procedure. Between these two extremes, indications remain a matter of personal choice of the surgeon, and they are influenced by his or her training and experiences with a variety of techniques. Most surveys demonstrate a growing popularity of vitrectomy for an increasing percentage of cases. The goals of vitrectomy for retinal detachment are to… 1. Remove axial opacities such a 1. s vitreous hemorrhage or debris. 2. Eliminate vitreoretinal, epiretinal, or subretinal traction. 3. Identify and treat all retinal breaks. 4. Internally reattach the retina. 5. Facilitate placement of a large intraocular tamponade. 6. Avoid complications associated with scleral buckling surgery…. The usual sequence of events includes removal of vitreous gel and epiretinal membranes, identification of retinal breaks, internal removal of subretinal fluid, laser therapy to all responsible breaks and areas of significant vitreoretinal degeneration, and placement of an internal tamponade with gas or silicone oil. Vitrectomy is frequently combined with placement of a scleral buckle.
Fundamentals of Fourier Analysis
Authors: Marks II Robert J
Published: November 2020

This chapter contains foundational material for modelling of signals and systems. Section 2.2 introduces classes of functions useful in signal processing and analysis. The Fourier transform, in Section 2.3, begins with the Fourier integral and develops the Fourier series, the discrete time Fourier transform and the discrete Fourier transform as special cases. The following material in this chapter can be skipped on a first reading. † denotes material relevant to multidimensional signals in Chapters 8 and 11. ‡ denotes material relevant to probability and stochastic processes in Chapter 4. ¶ denotes material used in continuous sampling in Chapter 10. There are a number of signal classes to which we will make common reference. Continuous time signals are denoted with their arguments in parentheses, e.g., x(t). Discrete time signals will be bracketed, e.g., x[n]. A continuous time signal, x(t), is periodic if there exists a T such that x(t) = x(t − T) for all t. The function x(t) = constant is periodic. A discrete time signal, x[n], is periodic if there exists a positive integer N such that x[n] = x[n − N] for all n. The function x[n] = constant is periodic.
Reconstruction of Canthal Defects
Authors: Bernardino C. Robert
Published: November 2020

Reconstruction of the medial and lateral canthal region can be quite challenging because in these two regions, soft tissue (canthal tendons) interacts directly with bony tissue to determine the location and function of the eyelids. Poor knowledge of the anatomy in these regions or poor surgical technique and planning can lead to poorly functioning eyelids in both opening and closing as well as associated lacrimal drainage and pump deficiency and aesthetic asymmetry. Tissue loss in these regions can be from many causes, including trauma, inflammation, and neoplasia. When dealing with malignant neoplasia, it is particularly important to ensure that surgical margins are free of tumor prior to reconstruction. Particularly in the medial canthus, incompletely excised lesions can spread deep into the orbit, into the periocular sinuses (ethmoid and maxillary), and down the nasolacrimal system. Therefore, excision with margin control (Mohs, frozen, or permanent sections) is warranted. When a tumor is heading toward the orbit, this author recommends margin control with permanent fixed tissue to ensure proper diagnosis. When tumor cannot be cleared with this technique an exenteration is offered. Repair of the canthal regions involves first repairing deep structures and any bony defects with autologous or synthetic materials, followed by resuspending eyelid structures to a location analogous to their native location. If remnants of the canthal tendon are present, it can be sutured to periosteum, or sutured or wired to bone through drilled pilot holes. Other techniques may involve using titanium miniplates to fixate the soft tissue to bone. If canthal tendon is not present, periosteum of the orbital rim can be fashioned into a flap simulating a canthal tendon, or the tarsus of the eyelid can be split with one arm forming a new canthal tendon. No matter what technique is used, care must be taken to ensure the tendon or tendon substitute is fixed into the orbit, deeper than the orbital rim; failure to do so will cause the eyelids to function poorly. Once deeper structures are restored, repair of the soft tissue must be undertaken.
Surgical Exploration of the Orbit
Authors: Dolman Peter J.
Published: November 2020

The orbit comprises the globe and optic nerve surrounded by a complex tangle of muscles, nerves, and vessels, all cushioned in pockets of fat. While surgery in the anterior orbit is readily performed, the challenge increases significantly for deeper orbital pathology because the bony walls on four sides and the eyeball and lid structures anteriorly limit both access and visibility. The apex is a particularly difficult area because so many vital structures converge in its narrow confines. The history and physical examination help narrow the differential diagnosis so that appropriate imaging and special investigations may be arranged. The urgency of these diagnostic tests to allow appropriate medical or surgical intervention is partly determined by the speed of symptom onset and by the presence of significant pain or progressive functional impairment such as vision loss or diplopia. Computed tomography (CT) scans are usually readily available and help define the tissue characteristics and location of an orbital lesion. Reformatting allows coronal, sagittal, and 3-D views without repositioning the patient, although a true coronal CT scan may be requested if a distensible varix is suspected. Contrast CT scans may be useful for assessing the vascularity of the lesion but require an evaluation of renal function. Magnetic resonance (MR) scans may characterize certain soft tissue features better, identifying fluid levels and determining whether a lesion involves normal anatomic structures such as the optic nerve, muscle, or lacrimal gland. They are particularly useful in evaluating lesions of the optic nerve and chiasm. Ultrasounds may help to define certain superficial orbital lesions (distinguishing a lymphoma from a pleomorphic adenoma in the lacrimal gland, for example) and are very useful in assessing intraocular pathology. Positron emission tomography (PET) scans may help determine the presence of recurrent malignancy or lymphoma in a previously operated or treated site and whole body evaluation may be helpful for staging lymphomas. A trained neuroradiologist can help interpret a complex image. In general, well-circumscribed, accessible lesions are excised in toto. Poorly defined, infiltrative lesions and those causing tissue destruction (suggestive of malignancy or aggressive inflammation) usually are biopsied, either by needle or with surgery.
Face-Lifting Techniques
Authors: Holck David E.E. , Kopelman Joel
Published: November 2020

Facial rhytidectomy is a rejuvenative surgical procedure designed to improve the aging changes in the lower third of the face and neck. It can significantly improve jowling, the jaw line, and the portion of the neck from the hyoid bone to the jaw line (the cervicomental angle). It is less successful at improving the midface or nasolabial folds. Rhytidectomy optimizes the age-appropriate aesthetic but does not stop the normal aging progression after surgery. While a wellperformed rhytidectomy is extremely gratifying for both patient and surgeon, it is elective and invasive, with prolonged rehabilitation and potential morbidity. Complications are poorly tolerated, and therefore pitfalls should be meticulously avoided. Fundamental steps in facial rhytidectomy include incision planning, skin flap dissection, addressing the superficial musculo-aponeurotic system (SMAS) and platysma, liposuction or direct lipectomy, skin redraping, and wound closure. These are standard in lower-third facial and neck rejuvenation. Face lifting is an imperfect procedure: the surgeon takes advantage of camouflaged incisions and healing patterns to obtain optimal rejuvenation. The facial anatomy of the lower third of the face and neck is complex but may be best viewed in a layered approach. Facial skin varies in thickness, with eyelid skin being the thinnest and cheek skin the thickest. The skin of the face is nourished via a dermal plexus, which must be maintained in rhytidectomy surgery. Beneath the skin lies facial subcutaneous fat. This fat is lobulated and enclosed by fibrous septa, which connect the superficial fascia to the dermis. The thickest portion of subcutaneous fat is the malar fat pad, bounded by the infraorbital rim above, the nasolabial fold medially, and the zygomaticus major muscle laterally. Minimal subcutaneous fat is located in the lower eyelid region and in the perioral region. Below the level of the subcutaneous fat is the SMAS. This fibromuscular sheet is continuous with the superficial temporalis fascia and galea cranially and the platysma muscle caudally. The SMAS envelops and connects the superficial mimetic muscles to the dermis, expanding the range of facial expression to the skin via distribution of force.
Psychological Effects of Precocious and Delayed Puberty
Authors: Derose Laura M. , Graber Julia A.
Published: November 2020

The timing of pubertal onset is marked by substantial variability within the range of normative development. Pubertal onset has mainly been measured by appearance of secondary sex characteristics—pubic hair development across sexes, and breast development in girls and testicular development in boys. This chapter provides statistics for the average age of pubertal onset, including findings for how average age differs by race. The two major types of pubertal disorders, precocious puberty and delayed puberty, are described, with a brief synopsis of the possible causes (for a comprehensive review of medical causes, see Grumbach and Styne 2003). The major focus of the chapter is on the psychological and behavioral consequences of precocious and delayed puberty. Although the majority of research on this topic has included nonclinical samples (onset or delay of puberty nearing 2 standard deviations [SD] from the mean), findings would be applicable to children who exhibit clinical precocious or delayed puberty (onset or delay of puberty >2 SDs from the mean). Finally, the chapter reviews the clinical practices for “treating” puberty that is normative by pediatric standards. Breast budding is generally the first sexual characteristic to appear in females, and is most commonly classified by Marshall and Tanner’s (1969) five stages of development. Breast development begins in the United States between ages 8 and 13, with a mean age of 9.96 for Caucasian girls and a mean age of 8.87 for African American girls (Herman-Giddens et al. 1997). Pubic hair development typically begins shortly after breast budding; however approximately 20 percent of girls experience pubic hair development prior to breast budding (Brooks-Gunn and Reiter 1990). Pubic hair development also begins between the ages of 8 and 13 years, with a mean age 10.5 years in Caucasian girls and 8.8 years for African American girls (Herman-Giddens et al. 1997). Menarche is a late sign of pubertal development in girls and occurs following the peak in height velocity and during the rapid increase in weight and body fat (Tanner 1978). The mean age of menarche in North America is 12.88 years for Caucasian girls and 12.16 years for African American girls (Herman-Giddens et al. 1997).
Prader-Willi Syndrome
Authors: Zarcone Jennifer , Welsh Sarah Spencer
Published: November 2020

Prader-Willi syndrome (PWS) is the most common genetic cause of obesity and the first identified genetic imprinting syndrome. Prader-Willi syndrome is caused by the lack of paternally expressed genes in the q11–q13 region of chromosome 15, while the nonexpression of maternally derived genes in the same region leads to Angelman syndrome (a neurologically distinct disorder causing severe mental impairment, seizures, and excessive laughter) (Oliver et al. 2007). Prader-Willi syndrome was first described in 1956 by Prader, Labhart, and Willi (in Butler, Lee, and Whitman 2006) and occurs in approximately 1 in 15,000 births. There is no racial or gender predilection for PWS (however, the syndrome is reported more frequently in Caucasians; Butler, Hanchett and Thompson 2006). Dysmorphic facial features are common in patients with PWS, although these are less specific than the clinical features. Findings may include almond-shaped eyes, strabismus, a narrow temple and nasal bridge, and a down-turned mouth with thin upper lip (Wattendorf and Muenke 2005). Initially, the syndrome was diagnosed via the frequency of key clinical features; however, diagnosis is currently made on the evaluation of gene expression. Prader-Willi syndrome has two distinct clinical phases: the neonatal phase and the hyperphagic (excessive eating) phase, which begins in early childhood. The primary characteristics of the neonatal phase include severe hypotonia, hyporeflexia, poor sucking ability, and decreased weight gain/failure to thrive due to inadequate oral intake, although birth weight is typically normal (McCandless 2005). Thus, feeding is a key concern in infants with PWS. Often, nasogastric tube feedings are employed, and infants are then weaned to breast- or bottle-feeding as they are able. While such difficulties may lead to the suggestion for feeding gastrostomy, this is best avoided due to the scarring effect, magnified by the excess truncal fat that will accumulate in later years (McCandless 2005). Developmental progress during infancy and early childhood is delayed, with most children sitting independently at 1 year and walking at about 2 years. Speech is also slow to advance, and language processing difficulties often continue into adulthood (Lewis 2006).
Urea Cycle Disorders
Authors: Lanpher Brendan
Published: November 2020

The urea cycle is a series of steps required to generate urea from nitrogen produced by protein catabolism. The cycle was first described in 1932 by Krebs and Henseleit (Krebs and Henseleit 1932). Six enzymes and two transporters are necessary for urea cycle activity. Specific deficiencies have been described with each of these. The process converts nitrogen from ammonia and aspartate into urea, which is freely excreted by the kidney (Brusilow 1995). Embedded within the urea cycle is the nitric oxide cycle. Nitric oxide is generated from arginine by nitric oxide synthase (NOS), producing citrulline (Scaglia et al. 2004). The entire urea cycle is present only in the liver. The proximal cycle (N-acetylglutamate synthase [NAGS], carbamyl phosphate synthetase [CPS], ornithine transcarbamylase [OTC]) is also present in the intestinal tract, whereas the distal cycle (argininosuccinic acid synthase [ASS], argininosuccinic acid lyase [ASL], arginase [ARG]) is active in the kidney. The most common of the urea cycle disorders (UCDs) is ornithine transcarbamylase deficiency, which is inherited in an X-linked manner. All of the others are autosomal recessive. The overall incidence of all urea cycle disorders is estimated at between 1/10,000 to 1/25,000, although patients with incomplete deficiency are likely significantly more common (Nagata, Matsuda et al. 1991). When the urea cycle function is absent or diminished, either by direct enzymatic deficiency or by secondary inhibition of the proximal four steps, nitrogen accumulates in the form of toxic ammonium. In null activity patients, this typically presents in the first days of life with hyperammonemia, resulting in central nervous system (CNS) dysfunction with overwhelming encephalopathy and coma, brain edema, seizures, and potentially death, with severe long-term neurodevelopmental sequelae if not rapidly reversed. The differential diagnosis of severe hyperammonemia includes organic acidemias, herpes-related hepatitis, and other disorders of liver function. Respiratory alkalosis and hyperventilation is classically seen in UCDs, although if encephalopathy progresses, apneas and acidosis may be seen (Burton 1998). If not recognized and reversed immediately, this may progress to fatal cerebral edema and herniation. There are multiple postulated mechanisms for ammonia-related neurotoxicity.
Neurofibromatosis Type 1: Cognitive and Behavioral Phenotype: Diagnosis and Treatment
Authors: Acosta Maria T.
Published: November 2020

Neurofibromatosis type 1 (Nf1) is a neurocutaneous disorder with a prevalence of approximately 1 in 2,500–3,500 individuals (Ferner et al. 2007). The physical manifestations of Nf1, such as café au lait spots, axillary freckling, iris hamartomas (Lisch nodules), osseous lesions (sphenoid wing dysplasia, pseudoarthrosis), and benign as well as malignant neural tumors (neurofibromas, optic gliomas), are well recognized (Castle et al. 2003; Ferner et al. 2007). National Institutes of Health (NIH) criteria are currently used for clinical diagnosis (1988) (Table 31.1). The clinical severity of this disorder is quite variable, and approximately 20% of children with Nf1 will later have considerable physical complications (Castle et al. 2003; Ferner et al. 2007; Williams et al. 2009). Other clinical manifestations are abnormalities of the cardiovascular, gastrointestinal, renal, and endocrine systems, facial and body disfigurement, cognitive deficit, and malignancies of the peripheral nerve sheath and central nervous system. The tumors that occur in Nf1 are dermal and plexiform neurofibromas, optic gliomas, malignant peripheral nerve sheath tumors (MPNSTs), pheochromocytomas, and rhabdomyosarcomas (Castle et al. 2003). Children with Nf1 have an increased risk of developing myeloid disease, particularly juvenile chronic myeloid leukemia. Some 30%–40% of Nf1 patients develop plexiform neurofibromas (Szudek, Evans, and Friedman 2003). Malignant peripheral nerve sheath tumors are present in 5%–10% of cases (Evans et al. 2002), often in preexisting plexiform neurofibromas (Castle et al. 2003). Although many see the predisposition to cancer as the major concern regarding Nf1, some of the more prevalent features are not directly related to tumors (Acosta, Gioia, and Silva 2006). Cognitive dysfunction, academic difficulties, and school failure, occur in 40%–80% (Hyman, Arthur, and North 2006; Krab et al. 2008; North et al. 1997). These complications affect the day-to-day life of these children, and are the largest cause of lifetime morbidity in the pediatric Nf1 population (Acosta et al. 2006). These deficits impact on long-term adaptation to society (Acosta et al. 2006; Barton and North 2007; Krab et al. 2008; Krab et al. 2009).
Overview of the Journal Article
Authors: Robinson Marin S , Stoller Fredricka L , Constanza-Robinson Molly , Jones James K
Published: November 2020

This chapter introduces the journal article module. The chapter describes some of the defining characteristics of a journal article while emphasizing concise writing and organization. By the end of this chapter, you should be able to do the following: Recognize the importance ■ of concise writing ■ Identify the broad organizational structure of journal articles ■ Explain what is meant by targeted reading and keywords As you move through the chapter, you will begin to plan your own journal- quality paper. The Writing on Your Own tasks throughout the chapter will guide you in this process: 2A Get started 2B Select your topic 2C Conduct a literature search 2D Find additional resources 2E Decide on the broad organization of your paper Module 1 focuses entirely on writing a journal-quality paper, a paper suitable for submission to a refereed chemistry journal. Refereed journals include only articles that have made it through a rigorous peer-review process. In this process, a submitted manuscript is critically reviewed by two or more anonymous reviewers. The reviewers are asked to judge both the scientific merit and writing quality of the manuscript. Authors are often required to revise their work before it can be accepted for publication. The entire review process can take six months or longer. An account of the review process typically appears in the published article, for example, Received for review March 9, 2008. Revised manuscript received August 3, 2008. Accepted August 5, 2008. Once published, the journal article becomes part of the primary literature of chemistry. The primary literature is a permanent and public record of all scientific works, many of which are refereed journal articles.
Formatting Figures, Tables, and Schemes
Authors: Robinson Marin S , Stoller Fredricka L , Constanza-Robinson Molly , Jones James K
Published: November 2020

This chapter focuses on general formatting guidelines for three commonly used graphics in chemistry writing: figures, tables, and schemes. The major purposes and uses for each graphic are described, and common formatting expectations are shared. Before-correction and after-correction examples are used to identify common formatting errors and ways to correct them. Each section of the chapter ends with a table of useful guidelines. By the end of the chapter, you will be able to do the following: ■ Know when it is appropriate to include a figure, table, or scheme ■ Recognize common formatting mistakes in figures, tables, and schemes ■ Format figures, tables, and schemes in appropriate and conventional ways As you work through the chapter, you will format your own graphic, guided by the Formatting on Your Own task at the end of the chapter. Graphics, in combination with the text, allow authors to communicate complex information efficiently. When done properly, text and graphics work together, reinforcing each other without duplicating information. Like the text, graphics must follow formatting conventions. In this chapter, we call your attention to some common formatting practices. Of course, we cannot address all of the formatting practices in chemistry, nor can we anticipate how these conventions will change over time. Thus, use this chapter for basic formatting information and for insights into the many details involved in a properly formatted graphic. As always, consult The ACS Style Guide and your targeted journal’s Information for Authors for more detailed and current information. Authors use figures (e.g., graphs, illustrations, photographs) to display scientific information. Examples of figures are included throughout the textbook, for instance, an ion source (excerpt 3S), a comet assay (excerpt 4E), a chromatogram (excerpt 9F), and an illustration of hydrogel adsorption (excerpt 131). Figures are numbered consecutively throughout a paper (Figure 1, Figure 2, etc.) and mentioned by name and number in text preceding the figure. Although many figure types exist, by far the most common is the graph. Because of their frequency, we devote this section of the chapter solely to formatting graphs; however, the guidelines presented are applicable to many other figure types as well.
Formula and Molecular Mass
Authors: Oriakhi Christopher O.
Published: November 2020

Many chemists use the terms formula mass and molecular mass interchangeably when dealing with chemical compounds of known formula. But there is a slight difference between the two terms, as explained below. The formula mass of a compound is the sum of the atomic masses of all the atoms in a formula unit of the compound, whether it is ionic or molecular (covalent). The formula mass is based on the ratio of different elements in a formula, as opposed to the molecular mass, which depends on the actual number of each kind of atom (compare section 6.2, “Empirical Formula”). Formula masses are relative since they are derived from relative atomic masses. For example, the formula mass of phosphoric acid, H3PO4, is 97.98 atomic mass units (amu), which is obtained by adding the atomic masses (taken from the periodic table) of the elements in one formula unit (i.e., 3 H + 1 P + 4 O). (3×At. wt. of H)+(1×At. wt. of P)+(4×At. Wt. of O) = (3×1.00)+(1×30.97)+(4×16.00) = 97.97 Once the actual formula of a chemical substance is known, the molecular mass can be determined in a manner similar to calculating the formula mass. The molecular mass of a compound is the sum of the atomic masses of all the atoms in one molecule of the compound. The term applies only to compounds that exist as molecules, such as H2O, SO2, and glucose, C6H12O6. For example, the molecular mass of ethanol, C2H5OH, is: (2×C)+(6×H)+(1×O) (2×12.0)+(6×1.0)+(1×16.0) = 46 When ionic compounds such as NaCl, Zn(NO3)2, andNH4Cl, are in the crystalline state or in solution form, they do not contain physically distinct uncharged molecular entities. Therefore chemists often use the term formula mass to represent the total composition of such substances. Example 4.1 Calculate the formula mass (FM) of NaOH using a table of atomic masses (AM).
Chemical Formulas and Nomenclature
Authors: Oriakhi Christopher O.
Published: November 2020

• An element is a pure substance that cannot be split up into simpler substances. There are 106 known different elements. Of these, only 92 occur naturally in the earth’s crust and atmosphere. Scientists have made the other 14 elements artificially. All the elements can be arranged in a periodic table, which displays the important relationships between the elements and the structures of their atoms. • Each element has a name and a symbol. The symbol is usually derived from the name of the element by taking the capital form of the first letter of the name. For example, the symbol for nitrogen is N. In most other cases, the capital letter followed by the next letter in lowercase is used. For example, the symbol for aluminum is Al. • The symbols for some elements are derived from their Latin names. For example, the symbol for sodium is Na, from its Latin name natrium. Potassium has the symbol K, taken from its Latin name, kalium. • Most of the known elements are metals. Only 22 are nonmetallic. • All elements are made up of atoms. Atoms of the same element are identical in all respects (except for isotopic differences, see chapter 3) but are different from atoms of other elements. • Atom: the smallest particle of an element that can take part in a chemical combination. • Molecule: a collection of two or more atoms of the same or different elements held together by covalent bonds. • Atomicity of an element: the number of atoms present in one molecule of the element. 1. Monatomic elements exist as single atoms. Examples include sodium (Na), iron (Fe), and the noble gases (He, Ne, Ar, Kr, Xe, and Rn). 2. Diatomic elements contain two atoms per molecule of the element. The atomicity is written as a subscript after the symbol of the element. Examples of diatomic molecules include H2, O2, Cl2, N2, etc. 3. Triatomic elements contain three atoms per molecule. An example is ozone (O3). 4. Tetraatomic elements contain four atoms of the element per molecule. An example is yellow phosphorus (P4).