bluuebunny/crossref_metadata_2025 huggingface dataset:
Maternal and offspring mental health: From bench to bedside
Authors: Pawlby Susan , Sharp Deborah
Published: November 2020

Translational research has become one of the key concepts of medical science in the 21st century, with academics and clinicians coming together in a joint effort to bring findings from basic research into the clinical setting so that they can benefit patients. Channi Kumar may not have recognized this phrase, but his work was truly translational. Indeed his perinatal research programme was bi-directional in its translation. As a clinician and an academic, Channi’s research was informed by his clinical work with mothers suffering from severe mental illness (SMI) following childbirth. He recognized the importance of treating a mother’s mental illness, while at the same supporting her in the care of her baby. His clinical work on the Mother and Baby Unit at the Bethlem Royal Hospital gave rise to research into the understanding of antenatal and postnatal mental illness and its effects on the child as well as into improving services and treatment for women and their babies. In this chapter we will show how two of Channi’s flagship studies, the South London Child Development Study (SLCDS) and a video feedback intervention programme on the Mother and Baby Unit, continue to gather evidence and to inform perinatal guidelines in the 21st century. The SLCDS is unique in that it is one of the first longitudinal studies of women’s mental health and its impact on the children to begin during pregnancy. Specifically, families from two inner-city London General Practice sites were initially recruited into a longitudinal prospective study of emotional disorders related to childbirth when the women were pregnant between 1 January and 31 December 1986. It has followed the lives of 151 families through pregnancy and the index child’s first year, with 86% participating when the index child was 4 years, 89% at 11 years, and 83% at 16 years. At the outset of the study, the mean age of the women was 25.9 years (range 16–43 years); 60% were married, 32% had a regular partner, and 8% were single; 78% were of white British origin; 86% were working class; 30% had no educational qualifications.
Neurobiological outcomes in the offspring of postnatally depressed mothers: Causes and consequences
Authors: Halligan Sarah L.
Published: November 2020

Postnatal depression (PND) is the most common psychological disorder to affect women in the postpartum period, with an estimated prevalence of 13% in high-income countries (Gavin et al. 2005; O’Hara and Swain 1996). In low and middle income countries, the available evidence suggests that rates of PND may be substantially higher, with prevalence estimates ranging from 15 to 57% (Wachs et al. 2009). In terms of clinical presentation, depression occurring in the postnatal period appears to be indistinguishable from depression occurring at other times (Cooper et al., 2007), with persistent low mood and/or a profound loss of interest and enjoyment being defining characteristics. Other symptoms are mood-related disturbances in sleep, altered appetite, concentration impairment, retardation, agitation, feelings of guilt and hopelessness, and suicidal thoughts or impulses. The duration of episodes varies, but the majority of postpartum depressive episodes resolve spontaneously within 6 months to a year (Cooper and Murray 1995; Cox et al. 1993). Although PND may not be unique in terms of the symptom profile, the fact that this disorder occurs in the postpartum period is a particular concern. Specifically, PND affects the mother–infant dyad at a time when the infant is particularly reliant on his or her caregiver to meet their physical, social, and cognitive needs. The postpartum period is also a time when the family unit as a whole is likely to experience additional stress, and is therefore particularly vulnerable. Given these considerations, and the relatively high prevalence of PND, the potential for adverse impact is significant. One area of research focus, reviewed here, has examined the possibility the disturbances in the mother–child relationship occurring in the context of maternal PND result in fundamental alterations in key psychobiological systems in the infant, with persistent consequences. Notably, as PND typically resolves within the first year postpartum, and therefore is particularly relevant to early development, observations deriving from the study of PND in this area offer potentially broad insights into the relevance of early environmental factors to child neurobiological functioning. Given that depressive disorder is characterized by profound impairments in mood, energy levels, motivation, and feelings of self-worth, and has established detrimental effects on interpersonal functioning, it is perhaps unsurprising that mothers with PND have been found to show disturbances in the quality of care that they provide for their infant (for a review, see Murray et al. 2010a).
Psychiatric causes of maternal deaths: Lessons from the Confidential Enquiries into Maternal Deaths
Authors: Oates Margaret R.
Published: November 2020

The UK Confidential Enquiries into Maternal Deaths, published triennially, are over 50 years old. Its forebears are even older; enquiries into maternal deaths began early in the 19th century in Scotland. In the 20th century the numbers of women dying from childbirth has steadily declined, influenced by many factors, including improved public health and maternity care, smaller family size, blood transfusions, and antibiotics, to name but a few. The introduction of the Abortion Act in 1967 was followed by a marked reduction of deaths in pregnancy from the consequences of illegal abortion. The rate and causes of maternal death have always been influenced by changes in reproductive epidemiology and technology, and continue to be so. Maternal deaths in pregnancy and in the 6 weeks following delivery are required to be reported to the Coroner, if directly related to childbirth. However, there are other causes of maternal death due to conditions exacerbated by pregnancy: for example, diabetes, cardiac disease, epilepsy. These are referred to as indirect deaths. Women who die from conditions unrelated to pregnancy or childbirth are counted and described as coincidental deaths. Over the years as the direct causes of maternal death have fallen, the indirect causes of maternal death have achieved more prominence and case ascertainment has improved. Improvements in medical care and in particular intensive care have resulted in some women developing their fatal condition within 6 weeks of childbirth, only to die beyond it. For this reason, the UK Enquiry extended their period of surveillance beyond 6 weeks to include late maternal deaths, both a small number of late direct deaths and a larger number of late indirect deaths. Suicide in pregnancy and following delivery has always been included in the Enquiries. However, prior to 1994 the cases were not separately analysed and were included in the group of late Coincidental Deaths (i.e. not thought to be related to pregnancy or childbirth). The 1994–1996 Enquiry, under the Directorship and Editorship of Dr Gwyneth Lewis and Professor James O’Drife, heralded a change in presentation of the Enquiry.
Public health approaches to prevention
Authors: Daly Blánaid , Batchelor Paul , Treasure Elizabeth , Watt Richard
Published: November 2020

Oral diseases are largely preventable but are still highly prevalent. What is going wrong? Why have oral diseases not been eradicated? The answer to these questions is not straightforward. As highlighted in Chapter 2, a complex array of factors influence the health status of individuals and populations. Many of these factors are outside the control of health professionals and the health service. If oral diseases are to be prevented, it is necessary to have a strategy or a plan to tackle the determinants. This chapter discusses the principles of strategy design with reference to prevention. First, it considers the basic principles that need to be addressed when preparing any strategy. Second, it examines the various approaches that can be taken when considering prevention and discusses the advantages and disadvantages of each. It looks at issues concerning selection of population groups and individuals through screening, and considerations involved in designing a strategy to tackle a major oral health problem. The existence of a strategy implies that there is an organized plan to reach a goal. In this sense, designing preventive strategies is similar to other health care planning. The same essential elements must be present (Box 4.1). It is important to have a clear vision of what you are trying to achieve and how it is planned to get there, otherwise it is unlikely that the goal will ever be realized. The first stage is to identify the aim of the project. What is to be achieved? The second stage is to identify the objectives of the project. What are the various steps that will eventually mean that the aim is reached? To formulate the aims and objectives of a programme it is necessary to collect data to provide information. Asking a series of questions can facilitate this. These data will include the following. What is the problem that is to be addressed? Is it, for example, caries in pre-school children or early identification of oral cancer? What is the natural history of the disease? What are its aetiology, risk factors, and predisposing factors? What is its epidemiology? Is the incidence increasing, decreasing, or stable? How important is the disease within the population? It may be important in two ways: it may affect many people within the population or it may affect few people but be of major impact.
Sugars and caries prevention
Authors: Daly Blánaid , Batchelor Paul , Treasure Elizabeth , Watt Richard
Published: November 2020

Dental caries remains the single most important oral condition treated by the dental profession on a daily basis. From a public health perspective, the prevention of caries is still therefore a major challenge. As outlined in Chapter 4 , before effective prevention can be delivered the cause of the condition needs to be fully understood. In addition, the disease process should be clear. This chapter will review the evidence on the aetiology of dental caries and present an overview of preventive measures that can be adopted at an individual clinical level, as well as community wide.
Dental caries occurs because of demineralization of enamel and dentine structure by organic acids formed by oral bacteria present in dental plaque through the anaerobic metabolism of dietary sugars. The caries process is influenced by the susceptibility of the tooth surface, the bacterial profile, the quantity and quality of saliva, and the presence of fluoride which promotes remineralization and inhibits the demineralization of the tooth structure. Caries is a dynamic process involving alternating periods of demineralization and remineralization. However, the majority of lesions in permanent teeth advance relatively slowly, with an average lesion taking at least 3 years to progress through enamel to dentine (Mejare et al. 1998). In populations with low DMF/dmf levels, the majority of carious lesions are confined to the occlusal surfaces of the molar teeth. At higher DMF/dmf levels, smooth surfaces may also be affected by caries (Sheiham and Sabbah 2010). Many different terms have been used to name and classify sugars. This has caused a degree of confusion amongst both the general public and health professionals. In recognition of this, an expert UK government committee—Committee on Medical Aspects of Food Policy (COMA)—has recommended a revised naming system, which has now become the standard classification of sugars in the UK (Department of Health 1989). The COMA classification is based upon where the sugar molecules are located within the food or drink structure. Intrinsic sugars are found inside the cell structure of certain unprocessed foodstuffs, the most important being whole fruits and vegetables (containing mainly fructose, glucose, and sucrose).
Overview of health care systems
Authors: Daly Blánaid , Batchelor Paul , Treasure Elizabeth , Watt Richard
Published: November 2020

The World Health Organization defines a health care system as: . . . all organizations, people and actions whose primary intent is to promote, restore or maintain health. This includes efforts to influence determinants of health as well as more direct health-improving activities. . . . . . . (WHO 2007) . . . Such a definition covers a myriad of potential elements and factors, of which the dental element is but one. A health care system is not static: it evolves as part of the more general social and welfare arrangements in a society. As a member of a health care profession, all dental care providers need to have an appreciation of the wider aspects of any arrangements of health, its determinants, and care delivery, if only to understand how the pressures on a system may impact on their current and future activities. This chapter provides an overview of health care systems and provides the framework for Chapters 18–23. Health care systems are complex organizations that are in a constant process of change and evolution. Dentistry is one very small component of the wider health care system, which is itself part of the overall social welfare system within society. Dentists, as health professionals, need to understand the basic elements of the health care system within which they are working. The development of health care systems is an ongoing process in which all societies try to meet the health needs of its citizens. There is no society that has yet designed a system that meets the needs of all its citizens. Indeed, historically in many countries it was only the wealthy that were able to access health care in a society. As societies evolved, the pressures to make the health care system accessible to all its members grew. Mays (1991) has highlighted the political importance of health care, showing that many health care systems reforms were designed to prevent political instability and improve the fitness of army recruits. Indeed, the development of the then School Dental Service in the UK was brought about following questions in Parliament about the poor state of soldiers’ teeth in the Boer War.
The structure of dental services in the UK
Authors: Daly Blánaid , Batchelor Paul , Treasure Elizabeth , Watt Richard
Published: November 2020

This chapter will briefly describe how oral health care may be managed and organized and how health workers may be remunerated. This will be followed by a short outline of the ways in which oral health care is provided in the UK. A separate overview of dental care professionals (DCPs) is presented in this chapter. The reform of the NHS is ongoing, so this chapter discusses principles rather than detail. Since the devolution of health care to governments in Scotland, Wales, and Northern Ireland, variations in provision are occurring across the UK and some of these differences are highlighted. If oral health care is to be provided it has to be funded. The money has to be derived from the public and this can be either from individuals or from taxation. Within the UK there are a variety of ways in which oral health care is funded. Figure 19.1 shows the possible flows of money. The model that exists in the UK is in the main centred on routes 1 and 3, based on taxation, either direct or through national insurance contributions, and its subsequent allocation to various public-funded services, including dentistry. In Germany, the arrangement is slightly different in that third-party insurance groups are involved and a proportion of an individual’s annual salary is allocated to health care. A third model operates in the USA under the guise of managed care. Individuals buy into a care plan that is organized by a health care company, which subsequently contracts with dentists to provide a level of care. In route 2, the public pays the dentist directly for his or her services; this is a private arrangement. A third party may intervene to control pricing. For example, Dutch and Swedish adult dental care is now mostly in the private sector, but each year the profession negotiates the scale of fees with their government. The subsequent distribution process for paying oral care workers is illustrated in Figure 19.2. There are again three mechanisms: . . . 1 A purely private arrangement. . . . . . . 2 The state pays the total cost. . . .
The method of joint probability distribution functions, neighbourhoods, and representations
Authors: Giacovazzo Carmelo
Published: November 2020

Wilson statistics, described in Chapter 2, aims at calculating the distribution of the structure factor P(F) ≡ P(|F|, φ) when nothing is known about the structure; the positivity and atomicity of the electron density (both promoted by the positive nature of the atomic scattering factors fj) are the only necessary assumptions. Wilson results may be synthesized as follows: . . . the modulus R = |E| is distributed according to equations (2.7) or (2.8), while no prevision is possible about φ, which is distributed with constant probability 1/(2π). . . . In other words, knowledge of the R moduli does not provide information about a phase; this agrees well with Section 3.3, according to which experimental data only allow an estimate of s.i. (and also s.s. if the algebraic form of the symmetry operators has been fixed). Let us now consider P(Fh1 , Fh2 ) ≡ P(|Fh1 |, |Fh2 |, φh1 , φh2 ), the joint probability distribution function of two structure factors. If the two structure factors are uncorrelated (i.e. no relation is expected between their moduli and between their phases), P will coincide with the product of two Wilson distributions (2.7) or (2.8), say, . . . P(Fh1 , Fh2 ) ≡ P(|Fh1 |, φh1 ) · P(|Fh2 |, φh2 ) = 1/4π2 P(|Fh1 |)P(|Fh2 |), . . . which is useless (because the two Wilson distributions are useless) for solving the phase problem; indeed, the relation does not provide any phase information. The question is now: if two structure factors are correlated, may their joint probability distribution function be used for solving the phase problem? Let us first use a simple example to show how much additional information (i.e. that is not present in the two elementary distributions) may be stored in a joint probability distribution function; then we will answer the question. Let us suppose that the human population of a village has been submitted to statistical analysis to define how weight and height are distributed.
Patterson methods and direct space properties
Authors: Giacovazzo Carmelo
Published: November 2020

According to the basic principles of structural crystallography, stated in Section 1.6: (i) it is logically possible to recover the structure from experimental diffraction moduli; (ii) the necessary information lies in the diffraction amplitudes themselves, because they depend on interatomic vectors. The first systematic approach to structure determination based on the above principle was developed by Patterson (1934a,b). In the small molecule field related techniques, even if computerized (Mighell and Jacobson, 1963; Nordman and Nakatsu, 1963), were relegated to niche by the advent of direct methods. Conversely, in macromolecular crystallography, they survived and are still widely used today. Nowadays, Patterson techniques have been reborn as a general phasing approach, valid for small-, medium-, and large-sized molecules. The bases of Patterson methods are described in Section 10.2; in Section 10.3 some methods for Patterson deconvolution (i.e. for passing from the Patterson map to the correct electron density map) are described, and in Section 10.4 some applications to ab initio phasing are summarized. The use of Patterson methods in non-ab initio approaches like MR, SAD-MAD, or SIR-MIR are deferred to Chapters 13 to 15. We do not want to leave this chapter without mentioning some fundamental relations between direct space properties and reciprocal space phase relationships. Patterson, unlike direct methods, seek their phasing way in direct space; conversely, DM are the counterpart, in reciprocal space, of some direct space properties (positivity, atomicity, etc.). One may wonder if, by Fourier transform, it is possible to immediately derive phase information from such properties, without the heavy probabilistic machinery. In Appendix 10.A, we show some of many relations between electron density properties and phase relationships, and in Appendix 10.B, we summarize some relations between Patterson space and phase relationships. Patterson (1949) defined a second synthesis, known as the Patterson synthesis of the second kind. Even if theoretically interesting, it is of limited use in practice. We provide information on this in Appendix 10.C.
Animal burials and animal symbolism
Authors: Harding Dennis
Published: November 2020

Animal remains may be deposited archaeologically in a great variety of circumstances, many of which must reflect their role in the domestic and agricultural economy of Iron Age communities, and result from normal disposal of the residues of butchery or consumption. In some circumstances the reason for disposal will have been death through disease or misadventure. The case of the cow in pit 61 of the phase 3 settlement at Gussage All Saints (Wainwright, 1979) that apparently died in calving is a case in point, though it is not clear why this animal was not processed for consumption, and we may suspect that an inauspicious omen was inferred that may have resulted in some special act of deposition. Ritual killing of animals, nevertheless, has been attested throughout Europe from earliest prehistory to the medieval period (Pluskowski, 2011). In reviewing animal sacrifices among the Gauls, Méniel (1992) divided the evidence into three principal categories of deposits found in habitation sites, in cemeteries, and in sanctuaires. The special character of those found on sanctuary sites, or accompanying human burials, individually or in cemeteries, is implicit from context, but animal burials that may have been deposited ritually on habitation sites are more difficult to distinguish from other forms of domestic or agricultural discard. The key problem, of course, is distinguishing ‘special deposits’ from normal butchery waste, which itself may have been disposed of in a systematic but not ritually significant fashion, a notion that was first advanced by Maltby (1985b) in the context of the Winnall Down animal remains. Despite interest generated by the Danebury project in special treatment of animal remains, the majority of faunal material from the 1985–6 excavations at Maiden Castle (Sharples, 1991a) was interpreted as the product of animal husbandry for domestic consumption or secondary products. Even in the few instances in which a possible ritual dimension was conceded, the animal remains showed evidence of butchery, involving removal of skins and flesh and disarticulation of the skeletons. Special treatment in particular may have been accorded to dogs (Smith, 2006).
Disposable Computing
Authors: Bentley Peter J.
Published: November 2020

A billion times improved, what once filled large halls and cost millions are now so small and cheap that we throw them away like empty sweet wrappers. Their universal design and common language enables them to talk to each other and control our world. They follow their own law, a Law of Moore, which guarantees their ubiquity. But how fast and how small can they go? When the laws of physics are challenged by their hunger and size, what then? Will they transform into something radical and different? And will we be able to cope with their future needs? . . . A high-pitched voice cut through the general murmur of the Bell Telephone Laboratories Cafeteria. ‘No, I’m not interested in developing a powerful brain. All I’m after is a mediocre brain, something like the President of American Telephone & Telegraph Company.’ Alan Turing was in town. Turing was visiting the Bell Labs towards the end of his American visit, in early 1943. He was there to help with their speech encipherment work for transatlantic communication (coding the transmission of speech so that the enemy could not understand it). But the visit soon became beneficial for a different reason. Every day at teatime Turing and a Bell Labs researcher called Claude Shannon had long discussions in the cafeteria. It seemed they were both fascinated by the idea of computers. But while Turing approached the subject from a very mathematical perspective, Shannon had approached the topic from a different angle. Claude Shannon was four years younger than Turing. Born in a small town called Petoskey, MI, USA, on the shores of Lake Michigan, his father was a businessman, and his mother was the principal of GayLord High School. Claude grew up in the nearby town of GayLord and attended his mother’s school. He showed a great interest in engineering and mathematics from an early age. Even as a child he was building erector sets, model planes, a radio controlled boat, and a telegraph system to his friend’s house half a mile away (making use of two barbed wires around a nearby pasture).
Your Life in Binary Digits
Authors: Bentley Peter J.
Published: November 2020

Your ideas, money, memories, and entertainment are dreams in the minds of computers. But the thoughts of each computer are not simple, they are layered like our own minds. Their lowest, most primitive layers are the instincts of the machine. Middle layers perform more general functions of its silicon mind. Higher layers think about overall concepts. Unlike us, the computer has languages for every layer. We can teach it new ideas by changing any one or all of its layers of thought. We can tell it to consider vast and convoluted concepts. But if we make a single mistake in our instructions, the mind of our digital slave may crash in a virtual epileptic fit. When our silicon students are so pedantic, how can we engineer their thoughts to make them reliable and trustworthy assistants? And if their thoughts become more complicated than anything we can imagine, how can we guarantee they will do what we want them to? . . . Light poured in through the large windows of the lecture room. The sound of scratching pens from nearly thirty distinguished engineers and scientists accompanied every word spoken by John Mauchly. One fellow by the name of Gard from the Wright Field’s Armament Laboratory seemed to be especially diligent, writing hundreds of pages of notes. It was Monday morning, a warm mid-summer day of 1946, some three years after his stimulating tea-time discussions with Turing. Claude Shannon was three weeks into the eight-week course at the Moore School of Electrical Engineering, in the University of Pennsylvania. It had been an honour to be one of the select few invited to hear lectures on designing electronic digital computers. This was the first ever course to be taught on computer science, and Shannon was finding many of the ideas highly stimulating. He’d recently learned a new word from Mauchly: ‘program’ used as a verb. To program an electronic computer was an interesting concept. He was also hearing about some of the politics: apparently two of the lecturers, Mauchly and his colleague Eckert, had resigned from the university just four months ago because of some form of disagreement.
Building Bionic Brains
Authors: Bentley Peter J.
Published: November 2020

Since the birth of computer science, researchers have secretly thought of themselves as brain-builders. After all, our thoughts are made from billions of little electrical impulses fired by neurons. Why can’t computers be made to think in similar ways to us, using the electrical impulses in their electronic circuits? Why can’t we make intelligent computers that can perform tasks that require intelligence? We could have learning, predicting, walking, talking, seeing, speaking computers. We might also have computers that can diagnose our illnesses, drive our cars, or explore distant planets for us. But how do you make intelligence? Through logic and reasoning? Or through lessons learned in life? How do intelligent minds think about their environments and themselves? Could we ever create a conscious artificial brain? . . . Cheerful music plays in the background. The grainy colour film shows a tall, slightly gaunt American man wearing a dark suit. As he speaks, he holds up something in his right hand. ‘This is Theseus.’ The film switches to a close-up of a little white mouse in a maze, moving forwards, flicking right, left, and forwards again. ‘Theseus is an electrically controlled mouse. He has the ability to solve a certain class of problems by trial and error, and then remember the solution. In other words, he can learn from experience.’ Once again, the work of Claude Shannon was attracting the attention of the public and academics alike. When he demonstrated his amazing machine at the Eighth Cybernetics Conference it created nothing but fascination and admiration from the other scientists. Perhaps to sound a little more serious, he usually called the mouse a ‘finger’ at the scientific conference. ‘You see the finger now exploring the maze, hunting for the goal,’ says Shannon, as he demonstrates the device live at the conference. ‘When it reaches the centre of a square the machine makes a new decision as to the direction to try. If the finger hits a partition, the motors reverse, taking the finger back to the center of the square, where a new direction is chosen.
Cardiovascular medicine
Authors: Emmett Stevan R. , Hill Nicola , Dajas-Bailador Federico
Published: November 2020

Hypertension (HTN) is the most common condition man¬aged in primary care and a major risk factor for cardio-vascular disease. Numerous randomized controlled trials have demonstrated that the use of antihypertensives to manage blood pressure (BP) helps reduce cardiovascular disease risk. Prevalence of HTN increases with age so that around 33% of men and 25% of women aged 45– 54 years have a clinical diagnosis. It is generally defined as a raised blood pressure exceeding 140/ 90 mmHg, divided into two types: ● Essential (or primary) hypertension: accounts for 95% of cases and is where no secondary cause is identified. ● Secondary hypertension: the result of an underlying disease (e.g. renal, pulmonary, endocrine, or drug/ toxin). Pre- HTN is defined as systolic BP (SBP) 120– 139 mmHg and diastolic BP (DBP) 80– 89 mmHg. BP is the product of cardiac output (heart stroke volume and heart rate) and the total peripheral resistance of ves­sels supplied by the heart. Thus, three main systems are responsible for generating BP: the heart (pumping pres­sure), vessel tone (being the systemic resistance), and the kidney (regulating intravascular volume). Three main physiological systems regulate heart, ves­sels, and kidney with respect to blood pressure: 1. The sympathetic nervous system: changes in BP are sensed by a feedback mechanism mediated by baro­receptors in the walls of the aortic arch and carotid sinuses. Increasing BP causes firing of glossopha­ryngeal and vagus nerves, inhibiting sympathetic outflow via the medulla (tractus solitarius). This, in turn, leads to parasympathetic dominance and a reduction in peripheral resistance (vasodilation through β1- adrenoceptors) and cardiac output (by reduced heart rate and reduced contractility through α1- adrenoceptors). Centrally acting antihypertensive drugs act at the nucleus tractus solitarius (e.g. clonidine/ methyldopa) or ventrolateral medulla (e.g. moxonidine). 2. The renin- angiotensin- aldosterone system: this system regulates blood volume and systemic vascular resistance, thus influencing cardiac output and arterial pressure. This feedback mechanism starts in the kidney with the release of renin into the peripheral circula­tion. Renin release, from juxtaglomerular cells (JC), is stimulated by sympathetic mechanisms (involving α1- receptors on JC themselves), decreased afferent ar­teriole pressure (from systemic hypotension or renal artery stenosis) or declining Na+ levels in the distal tu­bules of the kidney. Prostaglandins, such as PGE2 and PGI2 (prostacyclin), also cause release of renin sec­ondary to reduced NaCl transport in the macular densa (see Topic 5.2 ‘Acute kidney injury’).
Psychiatry
Authors: Emmett Stevan R. , Hill Nicola , Dajas-Bailador Federico
Published: November 2020

Anxiety disorders fall mainly into the category of neurotic, stress, or somatoform disorders, as defined by the inter­national classification of disease system (ICD- 11, WHO, 2018). They refer to several disorders that include gener­alized anxiety disorder (GAD), phobic anxiety disorders, panic disorder (± agoraphobia), obsessive compul­sive disorder (OCD) and post- traumatic stress disorder (PTSD). Collectively, anxiety disorders affect almost 30% of people in the western world during their lifetime, with PTSD and GAD amongst the most prevalent. In general, anxiety disorders are associated with neurotransmitter dysregulation and amygdala hyperactivity. Insomnia is the unsatisfactory quantity and/ or quality of sleep, which persists for sufficient time to affect quality of life. It is often associated with other mental health (e.g. depression, anxiety, alcohol dependence) and physical (e.g. pain, neoplasms) pathologies, or iatrogenic effects (e.g. diuretic, β- blockers, statins, levodopa). It may require treatment if symptoms are troublesome. Chronic insomnia can last for years, and affects almost 10% of the popula­tion. Around 30% have symptoms that are occasionally worse, with higher prevalence in older age. Many factors interplay to generate a state of anxiety, but from a biological perspective one of the key central brain pathways involved in this process is the limbic system, which regulates an array of functions, including emo­tion, fear, behaviour, and memory. One vital brain area that processes fear reactions from the thalamus and cortex is the amygdala, with connections to the hypothal­amus, which can activate sympathetic reactions and the hypothalamic– pituitary axis (HPA). Activation/ inhibition within this pathway leads to altered neurotransmitter activity. Corticotrophin- releasing factor (CRF) is known to be released from the hypothalamus in response to stress, under the regulation of the amygdala. CRF acts to drive the HPA, promoting the release of ACTH from the pituitary and then cortisol from the adrenal gland. In effect, sus­tained CRF exposure may lead to limbic system up- regu­lation and the heightening of anxiety states. Moreover, dysregulation in this system and changes in central cor­tisol sensing systems (e.g. decreased receptor expression) may cause chronic anxiety. The locus coeruleus (LC), is another brain region partly responsible for regulating the sympathetic effects of stress, again under the control of CRF.
Haemato- oncology and malignancy
Authors: Emmett Stevan R. , Hill Nicola , Dajas-Bailador Federico
Published: November 2020

Cancer is a common cause of morbidity and mortality in the United Kingdom (UK), affecting approximately two out of every five people during their lifetime. In 2015 there was an estimated 2.5 million people in the UK who had had a cancer diagnosis, an increase of almost half a million in the previous 5 years. The proportion of people living longer after cancer is increasing, and the number of people alive more than 5 years from initial diagnosis is predicted to more than double between 2010 and 2030 to 2.7 million. By the end of 2020, more than a thousand people would have been diagnosed with cancer every day in the UK. Cancer can affect all organs of the body with over 200 types identified. However, only a small number of cancer types account for most cases. Over half of all new diagnoses are due to four cancers (in order of frequency)— breast, pros­tate, lung, and bowel. In 2011 there were approximately 50 000 new diagnoses of breast cancer in the UK. The in­cidence of cancer diagnosis is increasing year on year, in part due to improving diagnostic skills, but also because of an increasing elderly population. Cancer of unknown primary origin accounts for about 3% of total cancers. Although UK statistics show a general improvement in the 5-year survival rates for the majority of common cancers, some have not shown any notable improvement. Survival is not only determined by the type of cancer, but also the age at diagnosis, stage, and co- morbidities such as heart, pulmonary, and renal disease, which can affect the treatment regimen. As well as this, certain cancers carry a significantly worse prognosis than others. For example, 10- year survival for pancreatic and lung cancer are 1% and 5%, respectively. In comparison, the 10- year survival for testicular cancer is over 98% and almost 90% in skin con­fined melanoma. Newer diagnostic strategies are expected to detect all cancers early, allowing prompt intervention, and improving both morbidity and mortality rates further. Cancer is a product of mutations in genes involved in controlling cell growth, differentiation, and death (apop­tosis).
Give and Take: Neutralization
Authors: Atkins Peter
Published: November 2020

The almost infinite can spring from the almost infinitesimal. Two almost infinitesimally small fundamental particles are of considerable interest to chemists: the proton and the electron. As to the almost infinite that springs from them, almost the whole of the processes that constitute what we call ‘life’ can be traced to the transfer of one or other of these particles from one molecule to another in a giant network of reactions going on inside our cells. I think it quite remarkable, and rather wonderful, that a hugely complex network of extremely simple processes in which protons and electrons hop from one molecule to another, sometimes dragging groups of atoms with them, sometimes not, results in our formation, our growth, and all our activities. Even thinking about proton and electron transfer, as you are now, involves them. Here I consider the transfer of a proton in some straightforward reactions in preparation for seeing later, in the second part of the book, how the same processes result in eating, growing, reproducing, and thinking. For reactions that involve the transfer of electrons, see Reaction 5. What is a proton? For physicists, a proton is a minute, positively charged, very stable cluster of three quarks; they denote it p. For chemists, who are less concerned with ultimate things, a proton is the nucleus of a hydrogen atom; they commonly denote it H+ to signify that it is a hydrogen atom stripped of its one electron, a hydrogen ion. I shall flit between referring to this fundamental particle as a proton or a hydrogen ion as the fancy takes me: they are synonyms and the choice of name depends on convention and context. An atom is extraordinarily small, but a proton is about 100 000 times smaller than an atom. If you were to think of an atom as being the size of a football stadium, then a proton would be the size of a fly at its centre. It is nearly 2000 times as heavy as an electron. Nevertheless, a proton is still light and nimble enough to be able to slip reasonably easily out from its home at the centre of a hydrogen atom in some types of hydrogen-containing molecules.
Changing Partners: Complex Substitution
Authors: Atkins Peter
Published: November 2020

I shall now describe a special case of the Lewis acid–base reactions I introduced in Reaction 9. I showed there that a Lewis acid is a species that can accept a lone pair from another incoming species and form a bond to it, that a Lewis base is a species that provides that lone pair, and that the result of this sharing is a complex of the two species joined together by a chemical bond. The important special case I would like to share with you here is when the Lewis acid is a metal atom or ion, especially but not necessarily one drawn from the d-block of the periodic table (a ‘transition metal’). The d-block consists of the elements that make up the skinny central rectangle of the periodic table. They include important constructional metals, such as iron, nickel, and copper, and also the chemically aloof ‘noble’ metals gold, platinum, and silver. The Lewis base that I focus on will be a molecule or ion that also has an independent existence in the wild, such as water, H2O, or ammonia, NH3. In most cases the complex consists of the central metal atom or ion with up to six Lewis bases clustering around it. In this context, the Lewis bases are known as ‘ligands’ (from the Latin for ‘bound’) and I shall use that term here. I don’t want you to think that I am embarking on stratospherically esoteric material again. These metal complexes are hugely important in many aspects of the everyday world. For instance, chlorophyll is a complex of magnesium and is responsible for capturing the energy of the Sun for photosynthesis (Reaction 26). There is hardly a more important molecule. One that comes close in importance is haemoglobin, an elaborate complex of iron, which ensures that oxygen reaches all your cells and keeps you alive. Many pigments are complexes, so your life is decorated and made more colourful by them. Some pharmaceuticals are complexes based on platinum, so one day, perhaps even now, you might be kept alive by one of these artificial complexes.
Electronic Warfare: Electrophilic Substitution
Authors: Atkins Peter
Published: November 2020

Benzene, 1, is a hard nut to crack. The hexagonal ring of carbon atoms each with one hydrogen atom attached has a much greater stability than its electronic structure, with an alternation of double and single carbon–carbon bonds, might suggest. But for reasons fully understood by chemists, that very alternation, corresponding to a continuous stabilizing cloud of electrons all around the ring, endows the hexagon with great stability and the ring persists unchanged through many reactions. The groups of atoms attached to the ring, though, may come and go, and the reaction type responsible for replacing them is commonly ‘electrophilic substitution’. Whereas the missiles of Reaction 15 sniff out nuclei by responding to their positive electric charge shining through depleted regions of electron clouds, electrophiles, electron lovers, are missiles that do the opposite. They sniff out the denser regions of electron clouds by responding to their negative charge. Let’s suppose you want to make, for purposes you are perhaps unwilling to reveal, some TNT; the initials denote trinitrotoluene. You could start with the common material toluene, which is a benzene ring with a methyl group (–CH3) in place of one H atom, 2. Your task is to replace three of the remaining ring H atoms with nitro groups, –NO2, to achieve 3. And not just any of the H atoms: you need the molecule to have a symmetrical array of these groups because other arrangements are less stable and therefore dangerous. It is known that a mixture of concentrated nitric and sulfuric acids contains the species called the ‘nitronium ion’, NO2+, 4, and this is the reagent you will use. Before we watch the reaction itself, it is instructive to see what happens when concentrated sulfuric acid and nitric acid are mixed. If we stand, suitably protected, in the mixture, we see a sulfuric acid molecule, H2SO4, thrust a proton onto a neighbouring nitric acid molecule, HNO3. (Funnily enough, according to the discussion in Reaction 2, nitric ‘acid’ is now acting as a base, a proton acceptor! I warned you of strange fish in deep waters.) The initial outcome of this transfer is unstable; it spits out an H2O molecule which wanders off into the crowd. We see the result: the formation of a nitronium ion, the agent of nitration and the species that carries out the reaction for you.
Dark Matter: Photochromism
Authors: Atkins Peter
Published: November 2020

Let’s start with the ‘ionization’ of an atom, the formation of an ion by the ejection of an electron when the atom is struck by a sufficiently energetic photon. This kind of process is the basis of the operation of early versions of photochromic glasses, which darken when exposed to bright sunlight, specifically in response to the high-energy ultraviolet component of sunlight that is present outdoors. That kind of photochromic glass was made by adding silver and copper nitrates to molten glass. As the glass cools, small crystallites of the salts form. The crystallites are too small to scatter or absorb visible light, so the glass appears transparent. Now we step into the solid glass and watch what happens when we step outside and ultraviolet photons rain down on us. We see a photon plunge into the glass and strike a copper ion, Cu+. The photon has enough energy to expel an electron from the ion, so forming Cu2+. We see the ejected electron wander off through the solid. Almost immediately, however, it is captured by a silver ion, Ag+, converting it to a silver atom, Ag. (Recall that Ag is the chemical symbol for silver, from the Latin argentum.) Sunlight has induced a redox reaction, an electron transfer reaction (Reaction 5). Now, as we continue to watch, several Ag atoms cluster together to give a microscopic dot of silver metal. These little clusters act like tiny shutters to block some of the light passing through the glass, and the image is dimmed. The clusters of atoms survive for a short time, but inevitably break up and release the additional electron back into the solid. It finds its way back to the strongly attracting double positive charge of a Cu2+ ion and attaches to it, so recreating the original Cu+ ion. However, if you stay outside in the sunlight, ionization and Ag atom formation continue, and your glasses stay dimmed. Only when you come back indoors and the ultraviolet radiation no longer reaches you do the ionization processes cease, and the glass reverts to being fully transparent.
Green Chemistry: Photosynthesis
Authors: Atkins Peter
Published: November 2020

Each square metre of the Earth receives up to 1 kW of solar radiation, with the exact intensity depending on latitude, season, time of day, and weather. A significant amount of this energy is harnessed by the almost magical process we know as ‘photosynthesis’ in which water and carbon dioxide are combined to form carbohydrates. Thus, from the air and driven by sunlight, vegetation plucks vegetation. That new vegetation is at the start of the food chain, for its metabolism is used to forge protein and, in our brains, drive imagination. There is probably no more important chemical reaction on Earth. A large proportion of solar radiation is absorbed by the atmosphere. Ozone and oxygen molecules absorb a lot of ultraviolet radiation, and carbon dioxide and water molecules absorb some of the infrared radiation. As a result, plants, algae, and some species of bacteria have to make do with what gets through and evolved apparatus that captures principally visible radiation. The early forms of these organisms stumbled into a way to use the energy of visible radiation, which arrives in the packets we call photons, to extract hydrogen atoms from water molecules and use them and carbon dioxide to build carbohydrate molecules, which include sugars, cellulose, and starch. The oxygen left over from splitting up water for its hydrogen went to waste. Most of the oxygen currently in the atmosphere has been generated and is maintained by photosynthesis since Nature first stumbled on the process about 2 billion years ago and thereby caused the first great pollution. That pollution, in Nature’s characteristically careless and wholly thoughtless and unplanned way, was to turn out to be to our great advantage. Photosynthesis begins in the organelle (a component of a cell) known as a ‘chloroplast’, so you need to poke around inside one if you are to understand what is going on. I shall focus on the light harvesting and the accompanying ‘light reactions’. What follows them, the so called ‘dark reactions’ in which the captured energy is put to use to string CO2 molecules together into carbohydrates, is controlled in a highly complex way by enzymes.