bluuebunny/crossref_metadata_2025 huggingface dataset:
Gene trap strategies in ES cells
Authors: Wurst Wolfgang , Gossler Achim
Published: November 2020

Gene trap (GT) strategies in mouse embryonic stem (ES) cells are increasingly being used for detecting patterns of gene expression (1-4, isolating and mutating endogenous genes (5-7), and identifying targets of signalling molecules and transcription factors (3, 8-10). The general term gene trap refers to the random integration of a reporter gene construct (called entrapment vector) (11, 12) into the genome such that ‘productive’ integration events bring the reporter gene under the transcriptional regulation of an endogenous gene. In some cases this also simultaneously generates an insertional mutation. Entrapment vectors were originally developed in bacteria (13), and applied in Drosophila to identify novel developmental genes and/or regulatory sequences (14-17). Subsequently, a modified strategy was developed for mouse in which the reporter gene mRNA becomes fused to an endogenous transcript. Such ‘gene trap’ vectors were initially used primarily as a tool to discover genes involved in development (1, 2,18). In the last five years there has been a significant shift of GT approaches in mouse to much broader, large scale applications in the context of the analysis of mammalian genomes and ‘functional genomics’. Sequencing and physical mapping of both the human and mouse genomes is expected to be completed within the next five years. Already, a large number of mouse and human genes have been identified as expressed sequence tags (ESTs), and very likely the majority of genes will be discovered as ESTs shortly. This vast sequence information contrasts with a rather limited understanding of the in vivo functions of these genes. Whereas DNA sequence can provide some indication of the potential functions of these genes and their products, their physiological roles in the organism have to be determined by mutational analysis. Thus, the sequencing effort of the human genome project has to be complemented by efficient functional analyses of the identified genes. One potentially powerful complementation to the efforts of the human genome project would be a strategy whereby large scale random mutagenesis in mouse is combined with the rapid identification of the mutated genes (6,7,19, and German gene trap consortium, W. W. unpublished data).
Steady-state kinetics
Authors: Cornish-Bowden Athel
Published: November 2020

All of chemical kinetics is based on rate equations, but this is especially true of steady-state enzyme kinetics: in other applications a rate equation can be regarded as a differential equation that has to be integrated to give the function of real interest, whereas in steady-state enzyme kinetics it is used as it stands. Although the early enzymologists tried to follow the usual chemical practice of deriving equations that describe the state of reaction as a function of time there were too many complications, such as loss of enzyme activity, effects of accumulating product etc., for this to be a fruitful approach. Rapid progress only became possible when Michaelis and Menten (1) realized that most of the complications could be removed by extrapolating back to zero time and regarding the measured initial rate as the primary observation. Since then, of course, accumulating knowledge has made it possible to study time courses directly, and this has led to two additional subdisciplines of enzyme kinetics, transient-state kinetics, which deals with the time regime before a steady state is established, and progress-curve analysis, which deals with the slow approach to equilibrium during the steady-state phase. The former of these has achieved great importance but is regarded as more specialized. It is dealt with in later chapters of this book. Progress-curve analysis has never recovered the importance that it had at the beginning of the twentieth century. Nearly all steps that form parts of the mechanisms of enzyme-catalysed reactions involve reactions of a single molecule, in which case they typically follow first-order kinetics: . . . v = ka . . . . . . 1 . . . or they involve two molecules (usually but not necessarily different from one another) and typically follow second-order kinetics: . . . v = kab . . . . . . 2 . . . In both cases v represents the rate of reaction, and a and b are the concentrations of the molecules involved, and k is a rate constant. Because we shall be regarding the rate as a quantity in its own right it is not usual in steady-state kinetics to represent it as a derivative such as -da/dt.
Spectrophotometric assays
Authors: Mantle T. J. , Harris D. A.
Published: November 2020

Chapter 1 describes the principles and practice of spectrophotometry, and in this chapter we will consider how this technique can be used to measure the amount of analyte in solution, when the product of a reaction between the analyte and a ‘very useful reagent’ produces a measurable change in absorbance. Some good examples of this type of reaction are given together with various protocols for routine applications such as the measurement of protein concentration. If there are no contaminating species absorbing at the wavelength of interest, it may be possible to measure the analyte directly simply by taking absorbance measurements. Spectrophotometry has also proved to be fundamental for rate measurements using a wide variety of enzyme-catalysed and non-catalysed reactions. We will also see that it is often the case that we will use an enzyme reaction that has gone to completion to measure the amount of an analyte that is limiting in the reaction. Furthermore, in some cases we can get the reaction to cycle so that the amplified rates can provide a highly sensitive assay, see, for example, the Tietze method (1) for measuring glutathione (Section 3.3). We will also briefly cover the use of so-called ‘plate readers’ as these are being used increasingly as ‘multi-cuvette spectrophotometers’. Finally, ‘plate readers’ will be compared with ‘centrifugal analysers’, much beloved in clinical chemistry labs. The reader should note that some methods are dealt with in detail here to allow selected protocols to be used directly. Also, a number of useful reference works for enzyme assays are given, including (2-4), which should be consulted. With a little thought novel assays can often be developed based on the various ‘coupling’ methodologies described below. The design of standard spectrophotometers has been covered in Chapter 1 and we should simply mention that most modern ‘plate readers’ work in essentially the same way. The major difference is in their beam geometry. In spectrophotometers, samples are read through cuvettes with a horizontal light path which is normally 1 cm in length allowing the Beer-Lambert Law (see Section 1.2) to be applied in its simplest form (constant light path).
Stopped-flow fluorescence spectroscopy
Authors: Gore Michael G. , Bottomley Stephen P.
Published: November 2020

Biochemical reactions, such as substrate or coenzyme binding to enzymes are usually completed in no more than 50-100 ms and thus require rapid reaction techniques such as stopped-flow instrumentation for their study. Fortunately, many such reactions can be followed by changes in the absorption properties of the substrate, product or coenzyme, and examples of these have been described in Chapters 1, 7 and 8. An alternative possibility is that during the reaction there is a change in the fluorescence properties of the substrate, coenzyme or the protein itself. Some reactions, particularly those involving the oxidation/ reduction of coenzymes, involve both changes in absorption and changes in fluorescence emission intensity. In many cases, the fluorescence properties of the ligand or protein itself may change when a complex is formed, even in the absence of a full catalytic reaction occurring, e.g. the protein fluorescence emission of most pyridine or flavin nucleotide-dependent dehydrogenases is quenched when NAD(P)H or FADH (respectively) binds to them, due to resonance energy transfer from the aromatic amino acids of the protein to the coenzyme. Conversely, the fluorescence emission from the reduced-coenzymes is usually enhanced on formation of the complex with these enzymes (1-3). The principles behind both fluorescence and stopped-flow techniques have been described in preceding chapters (2 and 8, respectively) and therefore readers should familiarize themselves with these chapters for some of the background information. In this chapter, we discuss the use of stopped-flow fluorescence spectroscopy and its application to a number of biochemical problems. A typical stopped-flow system is assembled from modular components of a conventional spectrophotometer/fluorimeter, a device permitting rapid mixing of the components of a reaction and a data recording system with a fast response. Commercially available instruments offer facilities for the observation of changes in absorption and/or fluorescence emission after rapid mixing of the reagents. These measurements can often be made simultaneously due to the different optical requirements of the two spectroscopic techniques. Figure 1 gives a generalized diagram of the geometry of a stopped-flow system able to simultaneously measure changes in absorption and fluorescence intensity of a reaction.
Decision Making for Transition to Registration and Preceptorship
Authors: Ratcliffe Sarah , Smith Joyce
Published: November 2020

This chapter will explore and discuss issues that may impact on your transition from third-year student nurse to newly qualified nurse (registrant). The issues that will be explored include delegation skills, challenging others, accountability, and prioritizing skills. Case studies will be included that will help you to consider how to respond in some situations that you may encounter. There are no right or wrong answers, but it is important to reflect on the many ways in which decision making occurs in terms of how you might act in certain circumstances. (See Chapters 9, 10, 11, and 12 for illustrations from actual practice situations.) Based on the case studies described in the chapter and on the experience of the authors, top tips will be offered to help you to consider a range of options to deal with the identified problems. It is hoped that the chapter will help you to plan key goals to achieve in your final placement, and to identify specific developmental goals to facilitate your transition to registered nurse and during your preceptorship experience. ‘Transition’ can be described as a challenging process that involves moving through a period of uncertainty from a familiar to an unfamiliar role. It is defined by Kralik et al. (2006: 323) as ‘a passage from one life phase, condition, or status to another’, often linked with a life-changing event. However, Meleis et al. (2000) state that change does not necessarily result in a transition and in fact change, according to Bridges (2003), is situational, whereas transition is psychological. Transition is a natural progression throughout life and, even though it can be actively sought and positive, it may be stressful as a result of psycho-social alterations (Brown and Olshansky 1997). Bridges (2004: 4) describes transition as being ‘composed of three stages: an ending, a neutral zone and a new beginning’. The first step is letting go, or ending, a past or former self; the next step, the neutral zone, is identified as a critical point for psychological readjustment; the final step is a new beginning. Bridges (2003) discusses fear of the unknown within the neutral zone, a stage of being in-between the end of the old and the beginning of the new.
EMQs for the MRCS Part A
Authors: Thrumurthy Sri G. , De Silva Tania S. , Moinuddin Zia M. , Enoch Stuart
Published: November 2020

Specifically designed to help candidates revise for the MRCS exam, this book features 250 extended matching questions divided into 96 themes, covering the whole syllabus. Containing everything candidates need to pass the MRCS Part A EMQ section of the exam, the book focuses intensively on topics relating to principles of surgery-in-general, including peri-operative care, post-operative management and critical care, surgical technique and technology, management and legal issues in surgery, clinical microbiology, emergency medicine and trauma management, and principles of surgical oncology. The high level of detail included within the questions and their explanations allows effective self-assessment of knowledge and quick identification of key areas requiring further attention. Varying approaches to extended matching questions are used, giving effective exam practice and guidance through revision and exam technique. This includes clinical case questions, positively-worded questions, requiring selection of the most appropriate of relatively correct answers; 'two-step' or 'double-jump' questions, requiring several cognitive steps to arrive at the correct answer; as well as factual recall questions, prompting basic recall of facts.
The Intelligent Web
Authors: Shroff Gautam
Published: November 2020

As we use the Web for social networking, shopping, and news, we leave a personal trail. These days, linger over a Web page selling lamps, and they will turn up at the advertising margins as you move around the Internet, reminding you, tempting you to make that purchase. Search engines such as Google can now look deep into the data on the Web to pull out instances of the words you are looking for. And there are pages that collect and assess information to give you a snapshot of changing political opinion. These are just basic examples of the growth of "Web intelligence", as increasingly sophisticated algorithms operate on the vast and growing amount of data on the Web, sifting, selecting, comparing, aggregating, correcting; following simple but powerful rules to decide what matters. While original optimism for Artificial Intelligence declined, this new kind of machine intelligence is emerging as the Web grows ever larger and more interconnected. Gautam Shroff takes us on a journey through the computer science of search, natural language, text mining, machine learning, swarm computing, and semantic reasoning, from Watson to self-driving cars. This machine intelligence may even mimic at a basic level what happens in the brain.
Goblins and Demons
Authors: Wothers Peter
Published: November 2020

The belief that there were no more than seven metals persisted for hundreds of years, and it was not until the seventeenth century that the inconvenient, inescapable realization came that there were probably many more. I’ve already mentioned Barba’s report from 1640 about the new metal bismuth; it was one of a number of metals or metal-like species that began to be noticed in the sixteenth and seventeenth centuries. In his History of Metals from 1671, Webster begins Chapter 27: ‘Having now ended our Collections and Discourse of the seven Metals, vulgarly accounted so; we now come to some others, that many do also repute for Metals; and if they be not so, at least they are semi-Metals, and some of them accounted new Metals or Minerals, of that sort that were not known to the Ancients.’ In the chapter Webster speaks of antimony, arsenic, bismuth, cobalt, and zinc. While we now understand these as distinct elements, earlier on there was great confusion, with the names being used for compounds rather than the elements themselves—and, furthermore, the different compounds and elements often being mistaken for each other. This makes unravelling their history all the more complicated. We’ll start with Barba’s ‘Mettal between Tin and Lead, and yet distinct from them both’: bismuth. The first mention of bismuth predates Barba’s reference by more than one hundred years. The name appears in its variant spelling, ‘wissmad’, in what is probably the very first book on mining geology. This was published around the turn of the sixteenth century and attributed to one Ulrich Rülein von Calw, the son of a miller who entered the University of Leipzig in 1485. Ulrich mentions in passing that bismuth ore can be an aid to finding silver, since the latter is often found beneath it. Consequently, miners called bismuth ‘the roof of silver’. As Webster later put it in his History of Metals, ‘The ore from whence it is drawn . . . is also more black, and of a leaden colour, which sometimes containeth Silver in it, from whence in the places where it is digged up, they gather that Silver is underneath, and the Miners call it the Cooping, or Covering of Silver.’
Oceans and Continents
Authors: Searle Mike
Published: November 2020

Sitting atop a rickety Indian bus trundling up the Beas Valley to the delightful hill station of Manali in the Kulu Valley of Himachal Pradesh, peering between swaying bodies and piles of luggage, I caught my first glimpse of the snowy peaks of the Himalaya. Yes, those white streaks way up in the sky were not, after all, clouds: they were glints of sunlight on impossibly high and steep ice-fields plastered onto the sides of mountains that tore up into the sky. It was a sight to take one’s breath away and I knew instantly that this was going to be the start of a great adventure. We were a typical shoestring British student expedition of five friends who could fit easily into two overloaded rickshaws, heading for the mountains around the Tos Glacier. Mountaineers dream about climbing in the Himalaya. Since my earliest days of climbing the hills and crags of Snowdonia and northern Scotland, I had yearned to see and climb those magical Himalayan Mountains. Now here I was, and the reality of the Himalaya was even better than I imagined. I had taken three months off from my PhD studies on the geology of the Oman Mountains to go on this expedition. We had driven a Land Rover out from England to Muscat through a snowy Europe and across the Empty Quarter of Arabia from Syria and Jordan to the United Arab Emirates and Oman. After three months’ fieldwork in Oman I caught a passenger ship, the MV Dwarka, last of the British East India Company merchant vessels that plied the Gulf route from Basra via Kuwait, Bahrain, Dubai, and Muscat to Karachi, and then travelled through Pakistan by train into India. That first expedition to Kulu was a revelation. We camped on the Tos Glacier, four days’ walk above the village of Manikarin in the Parbati Valley of eastern Kulu, for about four weeks. During that time the weather was perfect almost every day.
Continents in Collision: Kashmir, Ladakh, Zanskar
Authors: Searle Mike
Published: November 2020

To understand how the Himalaya were formed it seemed logical to start at the actual zone of plate collision, the Indus suture zone. Most of this collision zone runs across southern Tibet, which in the 1970s was almost impossible to travel through. Following Mao Tse-tung’s Red Army’s invasion and occupation of Tibet in October 1950, that region had remained firmly closed to all foreigners. In the western Himalaya the Indus suture zone runs right across the northernmost province of Ladakh. Ladakh used to be a part of southwestern Tibet before the British annexed it during the Raj. Leh, the ancient capital of Ladakh at 3,500 metres in the Indus Valley, was the final outpost of British India before the great trans-Himalayan barrier of the Karakoram Range. Only the Nubra Valley and the Tangtse Valley north of Leh were beyond the Indus, and these valleys led directly up to the desolate high plateau of Tibet. Leh was a major caravan route and a crossroads of high Asia, with double-humped dromedary camel caravans coming south from the Silk Route towns of Yarkhand and Khotan; Kashmiris and Baltis came from the west and Indian traders from the Hindu regions of Himachal and Chamba to the south. Ladakh, Zanskar, and Zangla were three ancient Himalayan kingdoms ruled by a Giapo, or King, each from a palace that resembled a small version of the Potala Palace in Lhasa. In 1978, when we were climbing in the mountains of Kulu, I had looked from our high summits across to the desert mountains of Lahoul and Zanskar, north of the main Himalayan watershed. Here, in the ancient Buddhist kingdoms of Zanskar and Ladakh lay wave upon wave of unexplored and unclimbed mountains. They lay north of the monsoon limits and in the rain shadow of the main Himalaya, so the vegetation was sparse, and the geology was laid bare. Flying north from Delhi, or east from Kashmir into Leh, the views were simply mesmerizing.
Changes in the Pattern of Settlement (1600–1100 BC)
Authors: Bradley Richard , Haselgrove Colin , Vander Linden Marc , Webley Leo
Published: November 2020

The Three Age Model has outlived its usefulness, but even now it is difficult to see how it can be replaced. The beginning of the Bronze Age is sometimes termed the Chalcolithic, and the transition to the Iron Age has also been treated as distinct phase, but a still greater problem is how to acknowledge the changes that came about during the later second millennium BC. Some of those developments are considered here. When Coles and Harding wrote The Bronze Age in Europe over thirty years ago, there seemed to be a solution to the problem. They divided this phase into an ‘earlier’ and a ‘later’ Bronze Age (Coles and Harding 1979), acknowledging the important developments that happened part way through the period. These concerned settlements, houses, food production, mortuary rituals, and metalwork, although the significance of these elements differed from place to place. In their view the important division happened at about 1300 BC. They may have been influenced by Eogan’s review of Irish Bronze Age metalwork, which adopted a similar terminology, although he dated the transition to 1200 BC (Eogan 1964). In 1990 a similar division was proposed for the British Bronze Age, but that was based on developments in the pattern of settlement that began around 1500 BC (Barrett and Bradley 1980). It is revealing that subsequent accounts of Irish prehistory have reverted to a more complex chronological scheme based on successive styles of metalwork, whilst British researchers who used the terms favoured by Coles and Harding were unable to agree when a change from an ‘earlier’ to a ‘later’ phase occurred. Different versions favour starting dates of 1500 BC (or a little before) or 1100 BC (Bradley 2007, 178–81). Anthony Harding published a more recent account of the European Bronze Age in 2000 and it is revealing that the two-fold division of this period no longer plays a part. The chronology is based on the typological schemes worked out by Montelius, Reinecke, and their successors, and on radiocarbon and tree-ring dating (Harding 2000).
The Anthropocene
Authors: Dryzek John S. , Norgaard Richard B. , Schlosberg David
Published: November 2020

Climate change will challenge the human community in many ways for centuries to come. Human influence on the climate is now the primary driver of the shift to a less stable and more dynamic global environmental system—the Anthropocene. In this chapter we explore some profound implications of this new age. First, what we mean by “the environment” is now itself ever-changing, with human actions affecting the very makeup, functioning, and evolution of global and local ecosystems, pushing them in new directions that can be difficult to predict. Second, this new reality has consequences for the founding principles of environmental management, conservation, ecosystem restoration, and action on the environment in general. The use of the past as a baseline natural world to be restored or mimicked is no longer possible, and so the era of preservation as the basis of environmental management is over. Climate change is pushing ecological systems out of their Holocene comfort zone (the last 10,000 years of unusual climatic stability). Our conceptions of a “natural” world and how people relate to it will have to change as well. Scientific controversies, environmental politics, and ecological management begin to look very different as a result. While most environmental scientists warn of the profound difficulties of navigating the Anthropocene, some technological optimists envisage a brave new future where humanity progresses through continued advances in biotechnology, information technology, and nanotechnology (Silver, 1997; Kurzweil, 2005). In this light, climate change and the transition to the Anthropocene are just a bump in the path of human progress. This kind of thinking extends to geo-engineering the planet to both avoid the worst of climate change and even push human development in new directions. While some climate scientists are beginning to explore the possibilities and consequences of geo-engineering, others are concerned that such bold action will exacerbate environmental uncertainties. These tensions among scientists represent competing visions of the degree to which governance informed by science can really understand and constructively guide Earth processes. If humanity survives into the long run, there may be ways that the Anthropocene can be organized to provide for both ecosystem and human functioning.
Drugs and Travel
Authors: Colbert Dom
Published: November 2020

Travel medicine is unique in that drugs and vaccines are given to perfectly healthy people either to prevent an illness that they have only a remote chance of acquiring, e.g. Japanese encephalitis, or to treat an illness that they do not already have, e.g. travellers’ diarrhoea. It is therefore incumbent on travel health advisors to be fully familiar with the nature of the drugs/vaccines they use, the indications and contraindications and the individual cost/benefit ratios. It is useful to give travellers a printout about any drugs prescribed so that they can refer to it when overseas, where medical help may not be always available. It is also useful to know the cost of medicines because this may play a part in choosing a generic versus a proprietary brand. In the opinion of many, buying drugs on the internet is not to be encouraged because of doubts about quality and effectiveness. Purchasing drugs abroad may be easy but beware of the profusion of illicit and counterfeit drugs which are for sale at deceptively cheap prices. There are electronic methods being developed so that any drug purchased anywhere has an identifiable secure ID. However, such methods are not available in the places where they are most needed. Some drugs deteriorate over time, especially in warm climates, so that if the patient is given a large supply before travel, e.g doxycycline, there may be difficulty in storing it correctly. Finally, carriage of drugs across borders is fraught with danger, even if the drugs are accompanied by a doctor’s letter. All medications, including codeine, should be declared at Customs if problems are to be avoided.
Personal reflections on the early development of the EPDS
Authors: Cox John
Published: November 2020

Shortly after returning to the London Hospital from Uganda in 1974, and still jet-lagged and culture-shocked, I had an unexpected call from a Dr Kumar at the Maudsley Hospital whose name was then unfamiliar to me. Stephen Wolkind (Child Psychiatrist at the London Hospital working with Professor Pond) had informed him that I had completed a study of postnatal depression in East Africa and had used Goldberg’s Standardised Psychiatric Interview (SPI) translated into Luganda. Could we meet, and could I advise him on the use of the SPI? I was surprised, flattered and motivated by this request. We met in Turner St, London E1. This was the beginning of a friendly and mutually respectful collaboration, which facilitated the later development of the Edinburgh Postnatal Depression Scale (EPDS) (Cox et al. 1987), helped launch the 1980 meeting in Manchester, when the Marcé Society was founded, and motivated Phase One of the International Transcultural Postnatal Depression Study. Channi Kumar was a fine team player, and as a leader had that knack of making you feel respected and at ease. His greeting ‘Come in dear boy and have a seat’ when he ushered you to a chair piled high with research papers, was characteristic of his style and productivity. We would then talk, not only about screening scales, but about College matters and the Perinatal Special Interest Group (which later became a Specialty Section), as well as our ‘Blue Skies’ research programmes. My interest in perinatal psychiatry began when, as an impressionable medical student, I first met Brice Pitt at Claybury Hospital. He was carrying out a study of ‘atypical’ postnatal depression and was devising a self-report questionnaire to detect increases in depression scores after birth. This early experience, together with a postgraduate seminar some years later, must surely have been on my mind when I was asked by Allen German on my arrival in Uganda, what research I was planning to do. I replied that I wished to replicate Assael’s finding (1972) that a quarter of pregnant women at Kasangati had mental health problems, and I was curious to know whether African women experienced depression as described by Pitt (1968)—and if not, what were the differences.
Specificity of effects in the association between maternal postnatal depression and child development: evidence from the Cambridge longitudinal study
Authors: Murray Lynne
Published: November 2020

From 1985, when I first met Channi Kumar, he played a seminal role in the research I have conducted with my colleagues on the effects of postnatal depression on child development. At the time I was a very junior researcher, struggling to get my work underway, and his enthusiasm and encouragement were invaluable. Channi played a particularly important role from 1989 when, with the support of the Tedworth Charitable Trust and the Winnicott Trust, the Winnicott Research Unit was established in Cambridge, under the joint Directorship of myself and Peter Cooper, together with Alan Stein. Channi became a key member of the Unit’s advisory committee and, right up until the time of his death, he regularly, and very kindly, provided the wisest counsel and support, and he is still very sorely missed. He was an inspiring friend and colleague, with the deepest compassion and humanity for the plight of the families he helped, and boundless enthusiasm for new perspectives and ideas that could advance understanding and clinical treatment, and I am greatly indebted to him for all his support. This chapter describes research on a prospective longitudinal study of the development of children of depressed and well mothers conducted in the Winnicott Research Unit; much of it took place under Channi’s watch. The work has involved a large number of colleagues, aside from the contributions of Peter Cooper and Alan Stein, and I am particularly grateful to Alison Hipwell, Matt Woolgar, Sheelah Seeley, Janet Edwards, Sarah Halligan, Adriane Arteche, Ian Goodyer, and Joe Herbert for their involvement and support. A diagnosis of ‘postnatal depression’ includes a wide range of possible symptoms, and therefore this unitary term can mask considerable variation in the nature of its presentation. For example, one mother could be slowed down, sleeping excessively, and barely eating, while in another, the episode may manifest itself in restlessness and agitation, with the mother being hardly able to concentrate and feeling constantly irritable. Not surprisingly, then, studies of the effects of postnatal depression on mother-infant interactions have also identified striking variability.
Postpartum psychosis—important clues to the aetiology of mood disorders
Authors: Jones Ian
Published: November 2020

It is of great regret that although corresponding with him at the start of my research career, I never met Channi Kumar face to face. His work, however, as evidenced by this book, remains an important influence on our field. I share his belief in the ‘maternal brain as a model for investigating mental illness’ (Kumar 2001), and this conviction has underlined much of my research. In this chapter I will discuss the concept of postpartum psychosis (PP), explore what we know about the relationship of these episodes to other mood and psychotic disorders, and consider research strategies aimed at understanding the nature of the postpartum trigger. I will argue that the nosological confusion surrounding this condition has been unhelpful and that it is time, perhaps, to consider whether we should revive postpartum psychosis as a diagnostic concept. Episodes of mood disorder in relation to pregnancy and childbirth are very common. In our group we have recently examined the history of perinatal episodes in over 1,500 women with mood disorder who have participated in our genetic studies and find that approximately two thirds of parous women, with both bipolar and unipolar disorder, have experienced a significant mood episode in the perinatal period (Di Florio et al. 2013). PP refers to some of the most severe forms of postpartum psychiatric disorder. Although the boundaries of this condition are not easy to define, the core concept is the acute onset of a manic or affective psychosis in the immediate postpartum period. Depending on the definition employed, the incidence is approximately 1 in 1,000 deliveries (Jones et al. 2010). Women may go from being very well to severely ill within hours. Affective (mood) symptoms, both elation and depression, are prominent, as is a disturbance of consciousness marked by an apparent confusion, bewilderment, or perplexity. As the name suggests, psychotic phenomena occur, with delusions and hallucinations prominent. Some women with severe manic episodes, but who do not show psychotic symptoms, may receive the diagnosis, although it is also possible to reserve the label for those women with frank psychotic presentations.
Not a native son
Authors: Kapo Remi
Published: November 2020

In the summer of 1953, aged 7, I arrived with my father at the port of Southampton from the colony of Nigeria. We were making for Ledsham Court School, a boarding school in St Leonards-on-Sea, Sussex. It was a stately building sitting among many green acres. After about an hour with the headmistress, Mrs Redfarn, my father said goodbye, turned and returned to Nigeria. I did not know then that I would not see or hear from him for 10 years, by which time I had forgotten what he looked like. Ledsham’s only black pupil began his academic life speaking no English. I was duly placed in the kindergarten with daily lessons in the native tongue. After catching up with my age group, in addition to the core subjects I was thereafter given instruction in Latin, ancient Greek, poetry, and nature study. To eradicate ‘that funny African accent’ I was solely accorded a daily class of elocution for a year—one hour a day with a speech therapist, held in a long, oak-panelled gallery with a book on my head to improve my deportment. Although in receipt of the beginnings of a good classical education, I was also given what I came to understand was a prototypical quantity of punishment for a ‘darkie’—for most of that first year I was caned daily and frequently ‘sent to Coventry’ for the slightest indiscretion, usually for not understanding the customs and traditions of an alien white culture. Thus, for refusing to eat salad on my first day, I received ‘three of the best’. The staff were undoubtedly ignorant of the eggs that parasites can lay on raw vegetables in a tropical climate like Nigeria, where all vegetables were cooked and salad was unheard of. Perhaps, I thought with a child’s naivety, that with all the mosquitoes and eating of salad, no wonder West Africa was called the white man’s grave in my books and comics. I woke up—for I had clearly landed in the mother country in the wrong skin colour. It hurt. I had arrived knowing myself to be Yoruba. Suddenly, I was called ‘coloured’ and ‘darkie’.
Problems with health care delivery
Authors: Daly Blánaid , Batchelor Paul , Treasure Elizabeth , Watt Richard
Published: November 2020

Earlier chapters have highlighted the influence the medical model of health has had on both the philosophy of health care and the structures devised to deliver health care including dental care. The overriding influences of the medical model are the downstream focus on treatment of disease and the communication gap caused by differing concepts of health and need held by lay people and health professionals. Problems with health care delivery operate at a macro level (i.e. overall policy for and structure of health care) and at a micro level (how health care is delivered, one-to-one communication, and interaction with the patient and members of the dental team). Chapter 18 has described some of the specific problems with health care at the macro level. In this chapter we shall also look at some of the problems with how health care is delivered and problems with health services at the level of the user and the provider of health care. What should good health care look like? Maxwell (1984) defined six characteristics of a high-quality health care. Services should to be equitable (fair), accessible, relevant to health care needs, effective, efficient, and socially acceptable. There are recognized inequities in how health care is distributed; urban areas are often better provided for compared to rural areas, and hospital-based health care consumes more resources than community-based care. Not everyone has equal access to health care; for example, people living in deprived communities with greater health need have fewer doctors and dentists compared to richer areas with fewer health care needs. This phenomenon has been described as the inverse care law (Tudor Hart 1971). Uncomfortable choices and rationing have to take place in allocating health care resources. Ideally, these decisions should be based on the greatest health need (and the capacity to benefit) rather than who has the loudest voice. The focus on treatment inherent in the medical model of health means that resources are spent on high-technology medicine and hospitals, while programmes to prevent disease are poorly supported and resourced. There is an expectation that there will be a magic bullet for every health problem, yet most chronic diseases have no cure. People learn to adapt and cope with their chronic illness rather than recover.
Wilson statistics
Authors: Giacovazzo Carmelo
Published: November 2020

In a very traditional village game, popular over the period of Lent (usually on the pigñata day, the first Sunday of Lent), a young player, suitably blindfolded and armed with a long cudgel, tries to hit a pot (the pigñata) located some distance away, in order to win the sweetmeats contained inside. To break the pot they take random steps, and at each step they try to hit the pot with the cudgel. Is it possible to guess the distance of the player from their starting position after n random steps? Is it possible to guess the direction of the vectorial resultant of the n steps? A very simple analysis of the problem suggests that the distance after n steps may be estimated but the direction of the resultant step cannot, because a preferred privileged orientation does not exist. The situation is very similar to structure factor statistics. Each of the N atoms in the unit cell provides the vectorial contribution . . . fj = fj exp(2πih · rj) = fj exp(i θj). . . to the structure factor; this is equivalent to a vectorial step of the pigñata player. The modulus of the atomic contribution, like the amplitude of the step in the pigñata game, is known (because the chemical composition of the molecules in the unit cell is supposed to be known), but the phase θj (corresponding to the direction of the step) remains unknown; indeed we do not know the position rj of the j th atom. The analogy with the pigñata game suggests that some information on the moduli of the structure factors can be obtained via a suitable statistical approach, while no phase information can be obtained using this approach. This chapter deals just with this statistical approach and owing to the relevant contributions of A. J. C. Wilson, we call this chapter Wilson statistics.
Charge flipping and VLD (vive la difference)
Authors: Giacovazzo Carmelo
Published: November 2020

Direct methods procedures (see Chapter 6) or Patterson techniques (see Chapter 10), primarily the former, have been methods of choice for crystal structure solution of small- to medium-sized molecules from diffraction data. Over the last 30 years, several new phasing algorithms have been proposed, not requiring the use of triplet and quartet invariants, but based only on the properties of Fourier transforms. These were not competitive with direct methods and have never became popular, but they contain a nucleus for further advances. Among these we mention: (i) Bhat (1990) proposed a Metropolis technique (Metropolis et al., 1953; Kirkpatrick et al., 1983; Press et al., 1992), also known as simulated annealing (the reader is referred to Section 12.9 for details on the algorithm). From a random set of phases, an electron density map is calculated, modified, and inverted. The corresponding phases are altered according to the simulated annealing algorithm, and then used to calculate a new electron density map. The procedure is cyclic. (ii) A strictly related simulated annealing procedure has been proposed by Su (1995). The objective function to minimize was . . . R = ∑h (S|Fh|calc − |Fh|obs)2, . . . where S is the scale factor. The scheme is as follows: random atomic positions are generated and in succession shifted; the simulated annealing algorithm is applied to accept or reject atomic shifts. At the end, a new atomic structure is generated, whose positions are shifted in succession, and so on in a cyclic way. (iii) The forced coalescence method (FCP) was proposed by Drendel et al. (1995). Hybrid electron density maps (see Section 7.3.4) were actively used with different values of τ and ω. Even if never popular, the above algorithms opened the way to two other methods which are much more efficient, charge flipping and VLD (vive la difference), to which this chapter is dedicated. Both are based on the properties of the Fourier transform; they do not require the explicit use of structure invariants and seminvariants, or a deep knowledge of their properties. The reader should not, however, conclude that the invariance and seminvariance concepts are not necessary in the handling of these approaches, on the contrary, understanding these basic concepts is essential to the appreciation of these new methods.
Phasing via electron and neutron diffraction data
Authors: Giacovazzo Carmelo
Published: November 2020

Among the statistics freely available on the webpage of the Cambridge Structural Database, there is a detail of interest for this chapter: of the 596 910 crystal structures deposited up to 1 January 2012, only 1534 were solved by neutron data (see Table 1.11). No information is provided on the number of structures solved by electron data because it is negligible (organic samples are soon damaged by the electron beams). A statistical search of the Inorganic Crystal Structure Database (ICSD, Ver. 2012–1, about 150 000 entries; by courtesy of Thomas Weirich) on structures that have been solved by means of electron diffraction, eventually in combination with other techniques, indicates a total of about 0.7%. In spite of limited impact on the databases, electron and neutron diffraction play a fundamental role in materials science and in crystallography. The main reason is that they provide alternative techniques to X-rays. Let us first consider electron diffraction (ED) techniques. The study of crystalline samples at the nanometer scale is mandatory for many industrial applications; indeed, physical properties depend on the crystal structure. Unfortunately it is not unusual for compounds to only exist in the nanocrystalline state; then, traditional X-ray diffraction techniques for atomic structure determination cannot be applied, because of the weak interactions between X-rays and matter. As a consequence, such structures remain unknown, in spite of their technological importance. This limits the contribution of X-ray crystallography to nanoscience, a growing scientific area, crucial to many fields, from semiconductors to pharmaceuticals and proteins. The result is a lack of knowledge on the underlying structure–property relationships, which often retards further research and development. Structure analysis by electron diffraction began as early as the 1930s (in particular, by Rigamonti, in 1936), but the interest of the crystallographic community in such a technique soon faded, mostly because electron diffraction intensities are not routinely transferable into kinematical |F|2. In spite of this limitation, the technique has been used for investigating the structure of many inorganic, organic, and metallo-organic crystals, biological structures, and various minerals, especially layer silicates.
Dead among the living landscape
Authors: Harding Dennis
Published: November 2020

The discovery of human remains in both hillforts and settlements has a long archaeological history, whether whole or partial skeletons or simply individual bones and fragments, though the former were often dismissed as the atypical disposal of social outcasts or malefactors, and the latter were never satisfactorily explained as casual discards. The fact that complete or near-complete skeletons were found in pits that evidently had been designed for another purpose, together with the absence of grave-goods, militated against their interpretation as formal burials, and set these apart from those grouped burials in pits that we have treated as small cemeteries. As regards fragmentary remains, the idea that the dead were exposed for excarnation, possibly over a protracted period of time, is now well established in Iron Age studies. What happened after excarnation is less clear, whether the skeleton was reassembled and buried, either in a formal cemetery or in a settlement context, or distributed as body parts or individual bones in pits, ditches, entrances, or other locations around settlements. Alternatively, in ethnographic contexts it is not unknown for the dead to be interred in a temporary burial ground for a period of months or even years, whilst the process of decomposition took place, before exhumation and re-burial following a final funerary feast. That final stage of re-interment in the British Iron Age likewise could have involved complete or near-complete re-burial, or separation of body parts and their distribution into liminal locations, as a means of incorporating the benign dead into the living community. And hillforts might well have served as the location, not only for excarnation platforms, but for temporary burial as well. We should not, however, exclude other possible interpretations. As Duday (2006: 30) warned, ‘one must not presuppose a funerary context of all such deposits because certain intentional deposits of human remains have nothing to do with burial’. Necessarily, of course, researchers are dependent upon the quantity as well as the quality of the excavated data-base, particularly in terms of statistical assessments, and for this reason Danebury has tended to dominate recent studies.