bluuebunny/crossref_metadata_2025 huggingface dataset:
Site-specific recombination in cells and mice
Authors: Dymecki Susan M.
Published: November 2020

The use of site-specific recombinase systems has revolutionized our ability to genetically manipulate embryonic stem (ES) cells and mice. Recent advances using the Cre-loxP and Flp-FRT systems have now made it possible to generate ‘clean’ germline mutations following a single gene targeting event, as well as to (in)activate genes in a conditional manner in the living mouse. Not only can target gene mutations be induced in a spatially and temporally restricted fashion, but lineage tracers can be activated in specific progenitor populations to chart cell fate directly in the wild-type or mutant mouse. This chapter introduces site-specific recombination and details a variety of applications, many of which are extensions of the gene targeting vectors and manipulations presented by Hasty et al. in Chapter 1. Many of the mutagenesis techniques which exploit the Cre-loxP system have been compiled earlier in an excellent book by Torres and Kühn (1). In this chapter, I present the Flp-FRT system in addition to the Cre-loxP system, for individual or combined uses. Together, these surveys and protocols should provide a basis for a wide variety of studies on gene function in vivo. As novel recombinase based applications continue to be developed, the possibilities for genome engineering appear without limit. The simplest site-specific recombination systems are comprised of two elements: the recombinase enzyme and a small stretch of DNA specifically recognized by the particular recombinase. These two elements work together to either delete, insert, invert, or translocate associated DNA. Two such recombinase systems have been established in mice (2-5) providing the basic tools for in vivo genetic engineering: the Cre-loxP system from the bacteriophage P1 and the Flp-FRT system from the budding yeast Saccharomyces cerevisiae. Both Cre and Flp are members of the λ integrase superfamily of site-specific recombinases (6) that cleave DNA at a distinct target sequence and then ligate it to the cleaved DNA of a second identical site to generate a contiguous strand. This recombination reaction is carried out with absolute fidelity, such that not a single nucleotide is gained or lost overall, and with no other requirements than the recombinase, the specific target DNA sequence, and some mono- or divalent cations (7).
Introduction to light absorption: visible and ultraviolet spectra
Authors: Poole Robert K. , Kalnenieks Uldis
Published: November 2020

Light is a form of electromagnetic radiation, usually a mixture of waves having different wavelengths. The wavelength of light, expressed by the symbol λ, is defined as the distance between two crests (or troughs) of a wave, measured in the direction of its progression. The unit used is the nanometre (nm, 10-9 m). Light that the human eye can sense is called visible light. Each colour that we perceive corresponds to a certain wavelength band in the 400-700 nm region. Spectrophotometry in its biochemical applications is generally concerned with the ultraviolet (UV, 185-400 nm), visible (400-700 nm) and infrared (700-15 000 nm) regions of the electromagnetic radiation spectrum, the former two being most common in laboratory practice. The wavelength of light is inversely related to its energy (E), according to the equation: . . . E = ch/ λ . . . where c denotes the speed of light, and h is Planck’s constant. UV radiation, therefore, has greater energy than the visible, and visible radiation has greater energy than the infrared. Light of certain wavelengths can be selectively absorbed by a substance according to its molecular structure. Absorption of light energy occurs when the incident photon carries energy equal to the difference in energy between two allowed states of the valency electrons, the photon promoting the transition of an electron from the lower to the higher energy state. Thus biochemical spectrophotometry may be referred to as electronic absorption spectroscopy. The excited electrons afterwards lose energy by the process of heat radiation, and return to the initial ground state. An absorption spectrum is obtained by successively changing the wavelength of monochromatic light falling on the substance, and recording the change of light absorption. Spectra are presented by plotting the wavelengths (generally nm or μm) on the abscissa and the degree of absorption (transmittance or absorbance) on the ordinate. For more information on the theory of light absorption, see Brown (1) and Chapters 2, 3 and 4. The most widespread use of UV and visible spectroscopy in biochemistry is in the quantitative determination of absorbing species (chromophores), known as spectrophotometry.
Time-resolved fluorescence and phosphorescence spectroscopy
Authors: Bradrick Thomas D. , Churchich Jorge E.
Published: November 2020

In this chapter, we outline the basic theory and methodology for making time resolved fluorescence and phosphorescence measurements. We begin with a brief discussion of the intrinsic time dependence of fluorescence and phosphorescence decays, and also introduce several important photophysical concepts. Energy transfer measurements, which are important for determining molecular distances, are then addressed, followed by the convolution integral (which describes the luminescence decay that is actually observed in pulsed excitation experiments) and the relationships that are used to determine fluorescence lifetimes from phase/modulation data. Polarized fluorescence measurements, which are an important tool for following molecular motions, are then discussed, and the fluorescence portion of the chapter concludes with an overview of data analysis and brief descriptions of the instrumentation that is used in making time-resolved fluorescence measurements. The remainder of the chapter is then devoted to a discussion of phosphorescence spectroscopy. The intrinsic time dependence of fluorescence decays is derived in Section 3.3 of Chapter 2. There it is shown that if a population of excited singlet-state molecules is generated instantaneously, its size decreases exponentially with time, as does the intensity of the emitted photons. The fluorescence lifetime τS is typically used to describe the rate of decay, where τs-1 = kR + kNR + kISC + kPR and kR, kNR, kISC and kpR are the rate constants for the various parallel unimolecular de-excitation processes. If there are several non-interacting fluorophore species in solution, their excited states will decay independently and a sum of exponentials will be needed to describe how the sample’s fluorescence intensity decreases with time.
Nursing Practice and Decision Making
Authors: Gawthorpe Dawn
Published: November 2020

You have already seen in earlier chapters that decision making is the cognitive process of reaching a decision—of considering a number of options from which only one can be chosen. Student nurses need to develop knowledge not only of generic nursing skills, but those related specifically to their chosen field of practice (NMC 2010). So how much knowledge do you need to be a nurse and how do you know when you have acquired it? It is often said that ‘a little knowledge is a dangerous thing’—a saying attributed to Alexander Pope (1688–1744). In nursing terms, this could mean that this small amount of knowledge can potentially mislead you into thinking that you are more competent than you actually are. How much knowledge is required to ensure competency as a qualified nurse is not easily determined, however, because we all learn in different ways and over time. Lifelong learning is advocated for all nurses and, indeed, is a requirement of continued registration (NMC 2011); as a qualified nurse, you will be making decisions on a daily basis for the rest of your working life, which will require you to be aware of best evidence for practice and patient care. The nature of these decisions forms an important part of this chapter and there will be a number of case studies related to all fields of practice for you to consider. It is important that you do not consider and answer only those related to your own field of practice, because you might encounter a situation in which you might have to care for a child or young person on an adult ward in hospital, or during a home visit in the community: for example, a grandparent might suddenly complain of feeling unwell and collapse whilst visiting his or her grandchild on a children’s ward. The Nursing and Midwifery Council (NMC) reminds us that nurses’ decision making must also be shared with service users, carers, and families—that is, that we must work with people to ensure the best and most appropriate decision for their needs at that time (NMC 2010).
Decision Making in Learning Disability Nursing
Authors: Hart Sue , Scarlett Eva
Published: November 2020

This chapter focuses on exploring decision making in the learning disability nursing field of practice. Previous chapters have covered the background about decision making, the principles, tools, and the use of evidence, as well as the way in which decision making fits in with the Nursing and Midwifery Council (NMC) Standards for Pre-Registration Nursing Education (NMC 2010) and competencies. The content of these early chapters and learning will help you to build your understanding of the issues when applied particularly to learning disability nursing skills in practice. This chapter also follows those addressing decision making in mental health nursing, children and young people’s nursing, and adult nursing. This ‘separating out’ of the fields of practice is helpful to give particular clarity and focus to issues relevant within them. It is, however, equally important to remind you that these apparently clear-cut distinctions between the disciplines are not necessarily reflected in practice, and that clients and patients do not always fit neatly into these artificial ‘boxes’. People with a learning disability have a right to equal treatment from registered nurses in adult and mental health settings, and children and young people with learning disabilities should expect the same standard of care as their typically developing peers. The NMC’s The Code: Standards of Conduct, Performance and Ethics for Nurses and Midwives (NMC 2008: 3) reminds us that ‘You must not discriminate in any way against those in your care’ and that ‘You must treat people as individuals and respect their dignity’. So, whatever your chosen future field of practice, please read on, because when people with learning disabilities require nursing, they are—and always will be—your responsibility too. Case study 12.1 has been chosen intentionally to highlight the partnership working and decision making that can go on between adult nurse specialists and learning disability nurses. The underpinning value base of decision making in learning disability nursing today is best understood with brief reference to the past. It is in recent memory for many service users that ‘home’ was a long-stay hospital ward or villa, which, despite the best efforts of nursing staff, would invariably be managed along quite regimented lines.
Frozen Rivers and Fault Lines
Authors: Searle Mike
Published: November 2020

After seven summer field seasons working in the north-western Himalaya in India, I had heard of a winter trade route that must rank as one of the most outlandish journeys in the Himalaya. The largely Buddhist Kingdoms of Ladakh and Zanskar are high, arid, mountainous lands to the north of the Greater Himalayan Range and in the rain shadow of the summer monsoon. Whereas the southern slopes of the Himalaya range from dense sub-tropical jungles and bamboo forests to rhododendron woods and magnificent alpine pastures carpeted in spring flowers, the barren icy lands to the north are the realm of the snow leopard, the yak, and the golden eagles and lammergeier vultures that soar overhead. The Zanskar Valley lies immediately north-east of the 6–7,000-metre-high peaks of the Himalayan crest and has about thirty permanent settlements, including about ten Buddhist monasteries. I had seen the Zanskar Ranges from the summit of White Sail in Kulu and later spent four summer seasons mapping the geology along the main trekking routes. In summer, trekking routes cross the Himalaya westwards to Kashmir, southwards to Himachal Pradesh, and northwards to Leh, the ancient capital of Ladakh. Winter snows close the Zanskar Valley from the outside world for up to six months a year when temperatures plummet to minus 38oC. Central Zanskar is a large blank on the map, virtually inaccessible, with steepsided jagged limestone mountains and deep canyons. The Zanskar River carves a fantastic gorge through this mountain range and for only a few weeks in the middle of winter the river freezes. The Chaddur, the walk along the frozen Zanskar River, takes about ten to twelve days from Zanskar to the Indus Valley and, in winter time, was the only way in or out before the road to Kargil was constructed. I mentioned this winter trek to Ben Stephenson during our summer fieldwork in Kishtwar and he stopped suddenly, turned around, and said ‘Mike we just have to do this trek!’ So the idea of a winter journey into Zanskar was born, and four of us set off from Oxford in January 1995.
Higher education—triumph of the knowledge-intensive society?
Authors: Alvesson Mats
Published: November 2020

‘Be something great’ and ‘fast track to top jobs’ were two headlines in advertisements for education that caught my eye some time ago. The specific message was that a specific school was offering a route to success and a brilliant career. In other words, education paves the way for success in life. With the passing of time, this has become a well-established truth. There are no other options—unless you have exceptional talents in the arts, sports, or the entertainment context. Fantasies and hopes for an outstanding career are encouraged on a broad front. The higher education sector has developed rapidly, even exploded, in recent decades and so have promises of a fantastic career resulting from a degree of the right kind and at the right place. In one UK university, the business school building is plastered with large posters claiming that ‘We create world-class minds’. And a Swedish university, located in a remote part of the country and with difficulties in recruiting faculty members and students, advertises heavily, claiming ‘research and education in world class’. If an institution is not ‘world class’ it is often described in terms of ‘excellence’. At my own university a few years ago, I saw a poster headed ‘Do you want to be President or Group CEO?’ for a course in commercial law specially designed for people who expect to reach the top in the near future. Since the target group consists of students, and most of them will probably have to bide their time for a decade or two before they can put ‘President’ or ‘Group CEO’ on their business cards, we may conclude that the department in question has realized the value of a long-term approach, and is assuming that many students have a high estimation of their potential. Perhaps education institutions support such more or less realistic self-images and career aspirations. If the department in question succeeds in recruiting a large number of students, it is perhaps primarily the less realistic self-images that will be reinforced. At a more collective level, education is now also considered to pave the way for national greatness.
Rendezvous on the High Plateau
Authors: Öhrström Lars
Published: November 2020

The two men in white anoraks were slowly approaching, skiing in the bitter cold over the Hardangervidda mountain plateau in the winter of 1943. Were they friends or foes? This was a matter of life and death for the six young men watching the only other living beings in sight for miles of snow-clad wilderness. Their pace was slow, the men were thin and didn’t look too well, just as if they might well have spent 130 days of the winter of 1942–43 hidden in a rudimentary hut on the mountain, surviving on moss and poached reindeer. It had to be them. The group’s leader, Joachim Rønneberg, decided to make contact. This story is first a tragedy and then a success, and it does not begin on the Hardangervidda but in Scotland where Britain’s ski capital, the small town of Aviemore in the Cairngorms National Park, is going to be our starting point for several dangerous journeys across the North Sea. A few years ago we drove up the main mountain road, eventually leading to the Cairn Gorm peak itself, 4,084 feet (1,245 metres) above sea level, and passed the park’s visitors’ centre located in pretty surroundings by a small lake. We glimpsed something flapping in the wind that did look a bit like the Union Jack, an unlikely occurrence in the highlands. We turned around and took the path up the hill, and soon discovered that what we first mistook for the British ensign, because of its colours, was in fact the Norwegian national flag. In 1468, when the Norwegians gave away their last Scottish possessions to King James III in Edinburgh, the Norwegian flag had not even been invented, so we were a wee bit curious as to why it was flying here, in the heart of the Cairngorms. But of course, mountains, snow, and skiing—what could be more Norwegian? And this simplistic reasoning is actually closer to the answer than we might have thought, as a commemorative sign told us that on this spot were the lodgings of the famous Kompani Linge during World War II.
When State Security was a Stinking Business
Authors: Öhrström Lars
Published: November 2020

It is spring 1708, and Sweden has been at war for eight years. Charles XII camps out with the army in Lithuania, still a year from the fatal battle of Poltava in Ukraine, and it is a busy time for seasonal workers Per Larsson Gässaboda and Esbjörn Persson Bölsö. In the southern province of Småland (The Small Lands), the former border region with Denmark now just north of the new Swedish province of the recently occupied Skåne, the cows are out of the barns in which they have spent the cold winter, and it is time for Per and Esbjörn to take out their shovels, load their wagon, and set out on their mission for the King to the farmers of the region. They are part of the army, enrolled men, but not for combat because they are petermen, or ‘sjudare’ (simmers) as they were called in Swedish. The farmers do not look forward to their visits as these men can command their chariots and their horses at will, take the firewood (and they need huge quantities), and wreak havoc to barns, stables, and houses in their quest for the manure and urine-rich soils that form the valuable raw material for their trade. These men make nitrate—or to be specific, potassium nitrate (KNO3), also known as saltpetre—for delivery to the King’s gunpowder factories. More than 100 years ago Henry VIII’s contemporary, the equally shrewd and ruthless King Gustav Wasa, had realized Sweden’s precarious situation when it came to gunpowder, and with a simple stroke of his pen ruled that the soil underneath barns, stables, and cowsheds belonged to the King. In an additional law, perhaps more illustrating his fear of being cheated by innovative farmers than his well-known attention to detail, he also banned any building housing livestock from being paved with a stone floor. In a country in which buildings of stone were virtually unheard of, except for housing the very rich, this was hardly likely anyway, but the King didn’t like to take chances with money and the saltpetre was a valuable commodity that otherwise would have had to be imported.
Selected Arthropods
Authors: Colbert Dom
Published: November 2020

It is important that the travel health provider has some knowledge of medically important arthropods. While visual identification of some of the most common arthropods, e.g. Culex pipiens, is difficult, identification of others is easy, e.g. a resting female Anopheles spp. or an Aedes albopictus (tiger mosquito). There is hardly a more neglected field in the undergraduate curriculum of nurses, doctors, and pharmacists than medical entomology. Many well-qualified professional healthcare workers do not know that a spider has eight legs (class arachnida) or that an insect (class insecta) has six legs. Although it may seem that this information borders on trivia sometimes it may be extremely important.
Pre-Travel Consultation
Authors: Colbert Dom
Published: November 2020

The importance of a comprehensive pre-travel consultation cannot be overemphasized. Each clinic should have a detailed questionnaire that the traveller can fill out while waiting. Details of past history, a list of past vaccinations, known allergies, current medications, the planned itinerary, the length of stay, the time of year, and proposed activities are all important as well as age, sex, pregnancy, medical travel insurance, and contact numbers. Such a review is extremely helpful and cuts down on the time required when the traveller is admitted to see you.
Fish Hazards
Authors: Colbert Dom
Published: November 2020

Most people know that, apart from choking on a fish bone, eating fish overseas can cause a variety of gastrointestinal upsets. Most travellers would not wish to eat raw fish. However, raw fish dressed up in spices or marinated or undercooked may well be acceptable to them, especially in a foreign land. There are also occasional dangers in eating some fish that are salted or even wellcooked, and which look, smell, and taste normal.
Air Travel
Authors: Colbert Dom
Published: November 2020

Most travel overseas is by air, although more and more people today, especially the elderly, are taking cruises. Passenger comfort has declined over the past 40 years despite the advances in aeronautics. This is due to the huge increase in the numbers travelling, the existence of cheaper flights, and the lack of staff to cope with the numbers of passengers both in airports and during flights. There is severe stress associated not only with air travel per se but also with all its accompaniments, such as getting through security, checking passports, tickets, and luggage, fear of overweight bags, finding the right gate, delays and cancellation of flights, missing connections, losing baggage, unexpected strikes, queueing interminably on arrival, and paying airport taxes. This list is seemingly endless.
Psychopharmacology
Authors: Iwata Kazuya
Published: November 2020

Psychotropic drugs are the main form of physical treatment in psychiatry and they exert their action by mainly acting on dopamine, noradrenaline, serotonin, and muscarinic receptors. Antipsychotics, which are the mainline treatment for psychotic ill­nesses, usually act by blocking dopamine receptors in the dopamine pathways of the brain, usually the mesolimbic system. The D2 receptors are the usual target of the antipsychotics, although clozapine, which is considered the gold standard antipsychotic, has a strong affinity for the D4 receptors. The underlying principle of antipsychotic treatment builds on the dopamine theory of schizophrenia, whereby an excess of dopa­mine is linked to the development of psychotic symptoms. Overactive dopamine receptors are thought to be involved in this, and thus block­age of the dopamine receptors through antipsychotics can provide relief from psychotic symptoms. Antipsychotics are divided into typical and atypical, and the defining feature of typicals is their propensity to cause EPSEs. This is thought to be due to the fact that typical antipsychotics are not specific for dopa­mine receptors in the mesolimbic pathways, but can also block those in mesocortical, tuberoinfundibular, and nigrostriatal pathways. Atypical antipsychotics can impact on a variety of receptor types, such as serotonin, and thus they are usually subclassified according to their pharmacological properties. Their heterogeneous pharmacodynamics in part explains their variable side-effect profile. One common side-effect of atypical antipsychotics is their tendency to trigger metabolic syndrome, which is a cluster of cardiovascular risk factors including dyslipidaemia, hypertension, central obesity, and impaired glucose tolerance. They also cause endocrine-related side-effects, such as hyperprolactinaemia. An important adverse effect seen with any antipsychotic is neuroleptic malignant syndrome (NMS), which is an idiosyncratic reaction to antipsy­chotics taken even at therapeutic doses. Patients can present with hyper­thermia, rigidity, autonomic disturbances, and altered mental state over 24–48 hours. It can be potentially life threatening, and thus, if suspected, urgent referral to a general hospital is required. Antidepressants also vary greatly with regards to their pharmacologi­cal properties, but the majority increase the concentration of neuro­transmitters in the synaptic cleft to alleviate depressive symptoms.
Liaison Psychiatry and Organic Illness
Authors: Horton Andrew , Broadhurst Mark
Published: November 2020

Liaison psychiatry is a subspecialty of psychiatry which involves the diag­nosis, treatment, and management of psychiatric illness in patients who have physical illnesses or present with physical symptoms. There is considerable overlap between psychiatric and medical condi­tions which requires close working relationships with medical colleagues. Liaison psychiatry is a fascinating area where the range of psychiatric presentations is wide, every case is different, and there is opportunity to keep up to date with medicine as it evolves. Within the UK there are different models practiced in different areas, ranging from assessment and signposting services to services with provi­sion for long-term outpatient follow-up. There is increasing interest in the provision of liaison services in primary care because of the challenges faced by GPs in treating patients with medically unexplained symptoms. Another driver is the hugely increased morbidity and mortality rates seen in patients with co-morbid physical and mental illnesses who receive the majority of their treatment in secondary care.
Soil and the Distant Past
Authors: Bardgett Richard
Published: November 2020

Rainbow Beach is a small town on the coastal dunes of eastern Australia, near Brisbane. I had travelled there to meet with some colleagues to sample soils from the vast coastal sand dunes that surround the area. It might seem an unusual place to visit to collect soil, but a unique sequence of soils has formed in the sand dunes, which differ greatly in age. As you move inland from the sea, the soils get progressively older and deeper, and more weathered and nutrient-poor. The youngest soils are shallow, having only just started to form in recent sand dunes, whereas the oldest soils are around half a million years old and can reach 25 metres deep. These are among the oldest, deepest, and most weathered soils that I have sampled, and what I recall most vividly is how stunted and sparse the vegetation was that grew there, reflecting their struggle to grow in such ancient, weathered soil. The soils of Rainbow Beach are by no means the oldest on Earth. Hidden beneath ice sheets in Greenland, scientists recently discovered a soil that was 2.7 million years old, a remnant of the fertile tundra that covered the area before the ice sheets came. And scientists working in South Africa recently discovered a soil, now compacted in rock, that is 3 billion years old. One of the most fascinating things about soil is that it is incredibly diverse; soils vary enormously across continents, countries, and from valley to valley and field to field. Even within a small patch of land, such as a field, forest, or vegetable garden, the underlying soil can vary considerably. Over distances of metres, it might differ in its texture and depth, and in its pH, being acid in one patch of a field and neutral in another. Soils also vary greatly in the diversity of living organisms that live within them. I will go into more detail about the diversity of soil life later in this book; but for now suffice to say that it is vast. Soils also change with time.
Soil and the Future
Authors: Bardgett Richard
Published: November 2020

If the importance of soil for human lives hasn’t leapt out of the previous pages, this book has failed in its goal. Soil touches so many aspects of human life, often in ways of which we are not even aware. There are the obvious, such as when we dig up the soil to grow vegetables and flowers, or when a farmer takes a plough to a field. But there are also the less obvious, such as the role of soil in dampening climate change, filtering the water we drink, and breaking down and recycling the billions of tonnes of dead plant remains that annually fall to the ground. Soils have also played their role in warfare, thwarting military advances and providing underground shelter to those under attack. I could go on, but I think the message is clear: earth matters. Looking to the future, a major challenge for humans will be how to deal with rapid soil change. I emphasized at the start of this book that the natural rate of soil formation is spectacularly slow; it takes literally thousands of years for a mature soil to develop. But within just a few years, or decades, humans can completely transform the structure, chemistry, and biology of soils, often leading to their degradation. This degradation of soil can be catastrophic, for example when soils are over-cultivated or overgrazed, or when unstable hill slopes are deforested and left exposed to the erosive forces of wind and rain. Or it can be progressive, such as that caused by climate warming which, in some places, such as the Arctic, is gradually speeding up organic-matter decay and carbon dioxide release from soils. It can also be abrupt, such as when land is sealed by asphalt and concrete during the construction of expanding cities, or during war when major offensives obliterate the fabric of soil. As I stressed earlier in this book, the causes of soil degradation are complex: population growth, poverty, poor delivery of information to farmers, conflict, shortage of land, and climate change all play a role.
Pregnancy prescribing of psychotropic drugs: Keeping pace in a contemporary landscape
Authors: Abel Kathryn M.
Published: November 2020

Pregnant women and their fetuses are more likely than ever to be exposed to antipsychotic medications; perhaps to the newer agents in particular. Drugs like clozapine, olanzapine, risperidone, and quetiapine are increasingly used in women of reproductive age for a range of psychiatric and behavioural disorders other than schizophrenia (Buchanan et al. 2009). Reproductive safety data remain surprisingly incomplete and guideline recommendations lend limited support to clinical risk-benefit analyses (Howard 2005; McKenna et al. 2005; NICE 2007). This is a problem not least because the gold standard randomized controlled trial is considered unethical for assessing psychotropic medication use during pregnancy, while other available observational studies are generally underpowered, with biased samples and therefore remain unfit for purpose in a rapidly changing prescribing landscape (NICE 2007). In a UK population approaching 66 million, –3,000–4,000 births per year may be exposed to antipsychotics or other psychotropic medications. This chapter provides a critical summary of current knowledge about potential risks of fetal antipsychotic and antiepileptic drug exposure and proposes how future observational studies might fill crucial gaps in the evidence. Most incident cases of severe mental illness (schizophrenia, related disorders, and bipolar disorder) occur during the reproductive years and most are treated with continuous psychotropic pharmacotherapy (Buchanan et al. 2009). Better care, deinstitutionalization and the use of newer agents with fewer effects on fertility means that women with psychotic disorders maybe increasingly likely to become pregnant (Howard 2005; NICE 2007), while the use of newer ‘atypical’ antipsychotics for other mental disorders common among women of childbearing age is also expanding (McKenna et al. 2005). For these reasons, psychotropic medications is increasingly likely to be prescribed to mothers during pregnancy (Newport et al. 2007). It is surprising then that reproductive safety data for psychotropic agents remains so incomplete (Barnes 2008; Webb et al. 2004) and guideline recommendations lend limited support to women, their partners and their treating clinicians in difficult clinical risk-benefit analyses (NICE 2007). Recent reports conclude that prospective studies are needed which can access unbiased, reliable (large enough) samples of ill mothers exposed to psychotropic medication and take account of key maternal characteristics (e.g. psychiatric diagnosis, smoking, pregnancy weight) in the estimation of risk (Barnes 2008; NICE 2007).
Introduction to the principles of public health
Authors: Daly Blánaid , Batchelor Paul , Treasure Elizabeth , Watt Richard
Published: November 2020

Public health is now recognized as being a core component of the undergraduate medical and dental curricula in many parts of the world (Association for Dental Education in Europe 2010; General Dental Council 2011; General Medical Council 2009). This recognition acknowledges that public health is an important subject relevant to the practice of medicine and dentistry. This chapter will outline what is meant by public health and, in particular, its relevance to clinical dental practice. The philosophical and historical background of public health will be reviewed and the limitations of the traditional system of health care highlighted. Finally, a dental public health framework will be outlined to highlight the central importance of public health to the future development of dentistry. Dental public health can be defined as the science and practice of preventing oral diseases, promoting oral health, and improving quality of life through the organized efforts of society. The science of dental public health is concerned with making a diagnosis of a population’s oral health problems, establishing the causes and effects of those problems, and planning effective interventions. The practice of dental public health is to create and use opportunities to implement effective solutions to population oral health and health care problems (Chappel et al. 1996). Dental public health is concerned with promoting the health of the population and therefore focuses action at a community level. This is in contrast to clinical practice which operates at an individual level. However, the different stages of clinical and public health practice are broadly similar. Dental public health is a broad subject that seeks to expand the focus and understanding of the dental profession on the range of factors that influence oral health and the most effective means of preventing and treating oral health problems. Dental public health is underpinned by a range of related disciplines and sciences that collectively enrich the value and relevance of the subject (Box 1.1) The practice of dentistry is undergoing a period of rapid change due to a wide range of factors in society ( Box 1.2 ).
Determinants of health
Authors: Daly Blánaid , Batchelor Paul , Treasure Elizabeth , Watt Richard
Published: November 2020

For health services to deliver effective prevention and treatment, a detailed understanding of the factors influencing health is critical. These factors are known as the determinants of health. Failure to address the underlying causes of disease in society will mean that sustainable improvements in the health of the population and a reduction in health inequalities will never be achieved. Tackling the contemporary determinants of health across society is a core function of public health and has now become the focus of government health policy in many parts of the world (WHO 2008). Many clinicians often feel frustrated when their advice to patients on ways of staying healthy is apparently ignored. Why don’t people stop smoking when they know the serious health risks of the habit? Why do some parents continue to give their children sweets when they have been given clear advice on the harmful effects on the child’s oral health? It is important for all health professionals to understand the factors influencing their patients’ choices and actions. Clinicians equipped with this knowledge are more likely to be effective at supporting their patients and enjoying their professional work. When asked what factors determine health, many people would probably highlight the importance of modern medicine. The use of antibiotics, high-tech equipment, and surgical advances might all be given as the most important reasons for improvements in health that have been achieved in the last hundred years. Why is modern medicine credited with such achievements and is this a true reflection of reality? Professor Thomas McKeown, a pioneer in public health research, conducted a detailed historical analysis of the reasons for the steady reduction in mortality rates that occurred in westernized countries during the last century (McKeown 1979). In his classic analysis he investigated changes in mortality rates for different conditions. As can be seen in Figure 2.1, with infectious diseases such as tuberculosis, whooping cough, and measles, significant reductions in mortality rates occurred long before treatments and vaccination programmes were even introduced.
Overview of behaviour change
Authors: Daly Blánaid , Batchelor Paul , Treasure Elizabeth , Watt Richard
Published: November 2020

Many dental practitioners become very frustrated with their patients when they fail to follow advice given to improve their oral health. This failure can often be interpreted by dentists as a sign of disinterest, lack of motivation, or sometimes even stupidity! Such an approach helps no one. As has already been identified, to successfully promote oral health the dental team need to work with their patients in a number of ways. For example, to help them select a healthy diet, maintain good oral hygiene, or stop smoking, the dental team need to understand what factors influence these behaviours and how they can be altered successfully. This chapter therefore aims to review behaviour change to help you understand more fully how you as a clinician can help your patients successfully alter their behaviour to promote and maintain their oral health. Theories and models of behaviour change will be reviewed and consideration will also focus on the practical factors influencing the process of change. Before reviewing the theoretical detail of behaviour change it is important to restate a core principle of public health, that is, the importance of the underlying social determinants of health. A wealth of evidence has highlighted that individual behaviours have a relatively limited influence on health outcomes compared to economic, environmental, and social factors (Marmot and Wilkinson 2006 ; Wilkinson 1996). Indeed, oral health behaviours play a somewhat minor role in explaining oral health inequalities (Sabbah et al . 2009; Sanders et al. 2006). Any exploration of individual behaviour change therefore needs to take into account the influence of the broader factors operating at a macro level. However, for health professionals working with individual patients, helping people change their behaviour is still an important task within their clinical practice. Traditionally, health professionals have focused largely upon giving their patients information in an attempt to change their behaviour. Such an approach has, however, been mostly unsuccessful at securing long-term changes in behaviour (Sprod et al. 1996; Yevahova and Satur 2009).
Health economics
Authors: Daly Blánaid , Batchelor Paul , Treasure Elizabeth , Watt Richard
Published: November 2020

Haycox (2009) describes economics as the science of scarcity. Economics analyses how choices about scarce goods and services are structured and prioritized by individuals in order to maximize welfare (Haycox 2009). Should economic theory have any relationship to health and health care? Clinicians will often state that they make their decisions based on their clinical judgement (what is best for the patient in front of them) and that they should not be influenced by concerns over money. Is this view entirely valid? Despite the improvements in health seen in the majority of countries, costs of health care have continued to rise above the general rate of inflation. For example, in the USA, health care costs account for 15% of Gross Domestic Product (GDP), compared to 17% in the UK (Morris et al. 2007). This is due to a number of factors, such as the price of materials, personnel salaries and wages, and the ever-increasing use of more advanced technology. There is little evidence, however, that the increased spending has contributed to better health (Abel-Smith 1996). Indeed, the evidence from Chapters 2 and 4 suggests that health will not be improved just by spending more money on health care. There is a growing awareness that health care resources are finite, while the demand for health care is apparently infinite (Cohen 2008). Economic analysis provides a systematic framework for answering questions about the justification for using these finite and scarce health resources and helps identify solutions to some common problems in health care (Morris et al. 2007). Health economics is therefore the study of the application of economic theory to decision-making about health and health care (Mooney 2003 ; Morris et al. 2007). In this context, health care decision-makers must prioritize choices about interventions informed by an analysis of both the costs and the benefits (Haycox 2009). Getting value for money involves a desire to achieve a health goal at the least cost or a desire to maximize benefits to patients where there is a limited pot of resources (Haycox 2009).
The probabilistic estimation of triplet and quartet invariants
Authors: Giacovazzo Carmelo
Published: November 2020

This chapter describes how to estimate, by probabilistic approaches, triplet and quartet invariants from diffraction magnitudes. We will skip quintet (Fortier and Hauptman, 1977a,b,c; Hauptman and Fortier, 1977a,b; Van der Putten and Schenk, 1977; Giacovazzo, 1977b, 1980; Burla et al., 1977) and higher-order s.i.s, because their usefulness in modern phasing procedures is entirely marginal. For simplicity, we will also skip the mathematics necessary to obtain conclusive formulas (the general approach is described in Appendix 4.A), except for the triplet invariants, first representation, because of their prominent role. Triplet and quartet estimates will be discussed, particularly in relation to their impact on phasing procedures. For simplicity, some other specialized topics will also be skipped, even if theoretically relevant. For example: results obtained by Shmueli and Weiss (1986, 1992), who used Fourier series representations of joint probability density functions to estimate triplets; the effect of pseudotranslational symmetry on the triplet phase estimates, as described by Cascarano et al. (1985a,b, 1987b, 1988a,b); algebraic formulas obtained by Karle and Hauptman (1957), Vaughan (1958), Hauptman et al. (1969), Hauptman (1970), Fischer et al. (1970a,b), all related to (and encompassed by) the estimation of triplet phases via their second representation. Interested readers are referred to the original papers. Let us first consider the space group P1. According to Chapter 4, the simplest way to estimate the triplet s.i. . . . Φ = φh1 + φh2 + φh3 with h1 + h2 + h3 = 0 (5.1) . . . is to study the joint probability distribution . . . P(Eh1 , Eh2 , Eh3 ) ≡ P(Rh1 , Rh2 , Rh3 , φh1 , φh2 , φh3 ). (5.2) . . . According to Section 4.1 we must first calculate the characteristic function C and then, by Fourier inversion, recover the distribution (5.2). Because of the importance of the triplet invariant, we report the necessary calculations in Appendix 5.A.
Phase improvement and extension
Authors: Giacovazzo Carmelo
Published: November 2020

The descriptions of the various types of Fourier synthesis (observed, difference, hybrid) and of their properties, given in Chapter 7, suggest that electron density maps are not only a tool for depicting the distribution of the electrons in the target structure, but also a source of information which may be continuously exploited during the phasing process, no matter whether ab initio or non-ab initio methods were used for deriving the initial model. Here, we will describe two important techniques based on the properties of electron density maps. (i) The recursive approach for phase extension and refinement called EDM (electron density modification). Such techniques have dramatically improved the efficiency of phasing procedures, which usually end with a limited percentage of phased reflections and non-negligible phase errors. EDM techniques allow us to extend phase assignment and to improve phase quality. The author is firmly convinced that practical solution of the phase problem for structures with Nasym up to 200 atoms in the asymmetric unit may be jointly ascribed to direct methods and to EDM techniques. (ii) The AMB (automated model building) procedures; these may be considered to be partly EDM techniques and they are used for automatic building of molecular models from electron density maps. Essentially, we will refer to proteins; the procedures used for small to medium-sized molecules have already been described in Section 6.3.5. Two new ab initio phasing approaches, charge flipping and VLD, essentially based on the properties of the Fourier transform, belong to the EDM category, and since they require a special treatment, they will be described later in Chapter 9. Phase extension and refinement may be performed in reciprocal and in direct space. We described the former in Section 6.3.6; here, we are just interested in direct space procedures, the so-called EDM (electron density modification) techniques. Such procedures are based on the following hypothesis: a poor electron density map, ρ, may be modified by a suitable function, f , to obtain a new map, say ρmod, which better approximates the true map: . . . ρmod (r) = f [ρ(r)]. (8.1) . . . If function f is chosen properly, more accurate phases can be obtained by Fourier inversion of ρmod, which may in turn be used to calculate a new electron density map.