bluuebunny/crossref_metadata_2025 huggingface dataset:
From the depths of the Earth
Authors: Zalasiewicz Jan
Published: November 2020

The planet Theia had, like the Earth, formed early, from the mass of dust and rock-melt droplets of the accretionary disc. Theia is calculated to have been about the size of Mars, yet it was to have nothing like that planet’s longevity. Its orbit was close enough to that of Earth for collision to be certain, sooner or later. The two planets came together at something of the order of 40,000 kilometres per hour. Theia lost its separate identity over a few tumultuous minutes, and the Earth was smashed, like a grapefruit hit hard with a hammer. In that conflagration the material of the two planets, having instantly converted into boiling magma and vapour, simply merged. Theia’s core sank to join the Earth’s. Some of the outer layer of both planets splashed out into a cloud of plasma that encircled the suddenly re-formed Earth, and that cloud condensed to form a new companion to our planet—the Moon. It is a fine story, this, of the Moon’s creation through a spectacular planetary collision. It is likely true, too: though it is not certainly so, simply being the hypothesis that now best explains the character of our Earth and its satellite. Like many such stories in science, it is currently the one that best fits the evidence. It has been calculated, on the basis of these two bodies’ mass, momentum and orbit, that it would have been extraordinarily difficult for the Earth to have captured intact a stray planetary body of this size. However, holding onto a mass of ejecta flung out by impact, kept in balance by the twin, opposing forces of gravity and centrifugal force, is a more plausible means of having formed the Moon. More, this concept explains the remarkable isotopic similarity of these two bodies, generated by the intense mixing associated with impact. Mars, by contrast, has very different proportions of, say, the different isotopes of oxygen, because it formed in a different part of the Solar System, where the atoms of the original accretionary disk had been shuffled into different combinations.
The theatre team
Authors: Tan Suyin GM , McWilliam Andy
Published: November 2020

A core attribute of the anaesthetist is the ability to communicate effectively in a variety of difficult situations and contexts. During the course of a theatre list the anaesthetist may interact with literally dozens of people—surgeons, patients, nurses, wardspeople, radiographers, trainees, and so on. Many will be complete strangers while others may be old friends, or enemies! Virtually all of them will have some part, be it big or small, to play in achieving a safe and successful outcome for patients. Operating theatres are often busy, stressful places. Events can unfold quickly and in unpredictable ways. Tension is frequently an integral part of the process of undertaking surgical procedures. Observational studies demonstrate that communication errors are common, and result in tension, delay, and wastage— as borne out by everyday experience. There is a tendency to view communication breakdowns as an inevitable fact of theatre life. However, evidence shows that behaviours and attitudes can be altered. Improving teamwork and communication improves morale and has the potential to improve patient outcomes. Most anaesthetists view themselves as good communicators, able to deal with virtually all communication problems, yet breakdown in communication is commonly cited as a root cause of medical error. Interestingly most anaesthetists feel that their training in communication has been adequate and do not seek further education in communication skills despite the evidence that poor communication leads to adverse events. Much of what follows is generic to all interactions with co-workers, and some aspects are of particular significance to particular disciplines. The evidence would indicate that everyone needs to improve their communication skills for the benefit of patients, and this chapter is written with the intention of providing tools to do this. The relationship between anaesthetist and surgeon is unique in medicine. In no other context, except possibly in the resuscitation room, do two or more specialists, from different disciplines, spend extended periods of time simultaneously treating a single patient. The quality of this relationship has important repercussions for patient safety and outcome, professional job satisfaction and the maintenance of good team-work in the theatre environment.
Examination of the cardiovascular system
Authors: Zengeya Stanley Tamuka , Serane Tiroumourougane V
Published: November 2020

All candidates taking the MRCPCH clinical examination will be expected to show competency in carrying out the cardiovascular examination. It is important to listen carefully to the examiner’s instructions and follow them. You may be asked only to auscultate the heart. If the examiner gives such an instruction, simply follow it! … You are advised to buy a good paediatric stethoscope, as it can reduce the difficulty in identifying cardiac sounds. The diaphragm of the stethoscope is designed to amplify high-pitched sounds; the bell does not amplify sound but transmits low-pitched sounds better than the diaphragm. The bell should be placed lightly against the skin, while the diaphragm should be placed firmly on the skin for ideal sound amplification and transmission. It is possible to make the bell act like a diaphragm by placing it firmly against the skin…. Examination of the cardiovascular system is best done in correlation with the available medical history, as this often gives major clues. It is helpful to have a systematic approach to presenting the findings, which of course should be practised thoroughly. However, the examination itself can be performed in a different sequence depending on the age of the child and their degree of cooperation. Key competence skills required in the cardiovascular examination are given in table 5.1. Cardiovascular cases commonly encountered in the MRCPCH Clinical Exam are listed in table 5.2. These steps are repeated in every system to reiterate their importance and to help you recollect the initial approach for any clinical exam. Also, refer to chapter 4. • On entering the examination room, demonstrate strict adherence to infection control measures by washing your hands or using alcohol rub. • Introduce yourself both to the parents and the child. • Talk slowly and clearly with a smile on your face. • Establish rapport with the child and parents. • Undress the child to the waist to allow proper examination. Expose adequately while ensuring their privacy. • Positioning: it is easier to examine older children while they sit on the edge of the bed, or on a chair when they are not acutely ill.
Examination of the child with short stature
Authors: Zengeya Stanley Tamuka , Serane Tiroumourougane V
Published: November 2020

Assessment of a child with short stature is one of the commonest endocrinology cases seen in the exam. It is important to remember that short stature is not a disease by itself and is an impairment of linear growth. The term ‘short stature’ is restricted to height-related issues above 2 years of age, in contrast to ‘faltering growth’ which focuses on weight-related issues in those less than 2 years. Short stature is a height which is less than the third percentile for age on the growth chart derived from local data. Other definitions of impaired linear growth are height significantly below genetic potentials (−2 standard deviations below midparental height), abnormally slow growth velocity, and downwardly crossing percentile channels in a child older than 18 months. To determine the normalcy of stature, one needs a relevant history and serial height measurements over time documented on a growth chart. In the exam, the examiner may provide the context of the case and the child’s growth chart. In the United Kingdom, the most widely used charts include the one published by the Child Growth Foundation 1996/1, and the UK–WHO growth charts published by the Royal College of Paediatrics and Child Health using the World Health Organization standards (figure 13.1). Be familiar with the use of the different charts and remember to use growth charts appropriate for sex and underlying disease (Down’s syndrome, Turner’s syndrome). The causes of short stature are given in table 13.1 and features of common conditions causing short stature in table 13.2. Possible conditions seen in a child with short stature commonly encountered in the MRCPCH Clinical Exam are listed in table 13.3. You may be asked to assess the child’s growth or assess the child with short stature. Such an assessment is appropriate only after taking into account the history and physical examination findings. However, in the clinical exam, you will not be allowed to take a history and have to evaluate the child based on the clues available at the bedside and examination findings.
Environment in Soviet and Post-Soviet Archaeology
Authors: Smyntyna Olena V.
Published: November 2020

Soviet archaeology, based on a revized Marxist paradigm of historical process, traditionally emphasized the primacy of social and economic processes, while at the same time empirically creating a foundation for palaeoenvironmental studies based on the interdisciplinary reconstruction of a subsistence economy. The collapse of the Soviet Union caused the break-up of the well-composed strict Soviet methodology of historical reconstruction, provoking intensive searches for new theoretical frameworks for both field and interpretative investigations. This paradigmatic and in some aspects epistemological crisis has created a unique background for the critical revision of a series of approaches and scientific schools which functioned during the second half of the twentieth century. As a result of this difficult, long-lasting, and often ambiguous process of self-reflection only a few concepts applied in Soviet archaeology have demonstrated a vital, cognitive capacity in the post-Soviet period; however, environment is one of these. The history of environmental thought in Soviet archaeology (as in Soviet social sciences in general) represents a unique genre: officially neglected and even theoretically non-existent, it was nevertheless broadly applied in practical research, and many important theories, concepts, and reconstructions have been developed on the basis of palaeoenvironmental data. This ambiguity of lack of official status mixed with practical application of an environmental approach in Soviet archaeology explains why a detailed history of Soviet theoretical approaches to the environment is as yet unwritten. However, this contribution tries to begin this process by briefly summing up the history of environmental approach implementation in Soviet and post-Soviet archaeology, outlining the basic stages of this process and examining the main concepts and notions explored in this context. The specificity of the material remains of hunter-gatherer daily life and subsistence as well as features of their archaeological investigation techniques (including studies of the geological characteristics of cultural layers alongside detailed examination of faunal remains) caused Stone Age archaeology to emerge within the framework of the natural sciences—geology and palaeontology. From the very beginning of Stone Age archaeology the Early Prehistoric population was viewed as an integral part of the natural environment.
Effects of Ocean Acidification on Sediment Fauna
Authors: Widdicombe Stephen , Spicer John I.
Published: November 2020

The vast majority of the seafloor is covered not in rocky or biogenic reefs but in unconsolidated sediments and, consequently, the majority of marine biodiversity consists of invertebrates either residing in (infauna) or on (epifauna) sediments (Snelgrove 1999). The biodiversity within these sediments is a result of complex interactions between the underlying environmental conditions (e.g. depth, temperature, organic supply, and granulometry) and the biological interactions operating between organisms (e.g. predation and competition). Not only are sediments important depositories of biodiversity but they are also critical components in many key ecosystem functions. Nowhere is this more apparent than in shallow coastal seas and oceans which, despite covering less than 10% of the earth’s surface, deliver up to 30% of marine production and 90% of marine fisheries (Gattuso et al. 1998). These areas are also the site for 80% of organic matter burial and 90% of sedimentary mineralization and nutrient–sediment biogeochemical processes. They also act as the sink for up to 90% of the suspended load in the world’s rivers and the many associated contaminants this material contains (Gattuso et al. 1998). Human beings depend heavily on the goods and services provided, for free, by the marine realm (Hassan et al. 2005 ) and it is no coincidence that nearly 70% of all humans live within 60 km of the sea or that 75% of all cities with more than 10 million inhabitants are in the coastal zone (Small and Nicholls 2003; McGranahan et al. 2007) Given these facts, it is clear that any broad-scale environmental impact that affects the diversity, structure, and function of sediment ecosystems could have a considerable impact on human health and well-being. It is therefore essential that the impacts of ocean acidification on sediment fauna, and the ecosystem functions they support, are adequately considered. This chapter will first describe the geochemical environment within which sediment organisms live. It will then explore the role that sediment organisms play as ecosystem engineers and how they alter the environment in which they live and the overall biodiversity of sediment communities.
Interview Candidates
Authors: Watkin Sara , Vincent Andrew
Published: November 2020

In this chapter, we focus on the dynamic brought by different combinations of candidate, looking at three specific scenarios. Firstly, we look at the implications of there being an internal candidate, from the perspective of being both the internal candidate and the competing external candidate. We then examine the implications of being either the only candidate or a head-hunted candidate, two scenarios where it is easy to ‘undo’ being offered the job. There is no doubt that being an internal candidate can put you at a considerable advantage. Some of the interview committee may well: • Know your past, your good points and bad points and will be better able to judge your likely future contribution • Have already developed a relationship with you, including a sense of whether they feel comfortable working with you for the next 30 years However, this familiarity or perceived familiarity can also be the internal candidate’s downfall. It is not infrequent that we come across internal candidates who believe the job is in the bag and so fail to prepare or engage in the activity that ensures they are likely to be offered the job, e.g. undertaking pre-interview visits. Sometimes it is because they think it is embarrassing to do something like a pre-interview visit if they are already employed in the Trust and know the staff well. We also find internal candidates who are reluctant to really sell themselves at interview when already known, again out of embarrassment. The advice is clear—prepare as though you were an external candidate whilst making best use or advantage of your internal status. Take nothing for granted and ensure you do your homework as thoroughly as any good external candidate. When experiencing your efforts to prepare, your colleagues, far from thinking it is weird, are likely to view this as the sort of commitment they would want from a future colleague. Box 7.1 explores the internal candidate’s ‘must do’ list if you are to be successful.
Behaviour of Fluids (Liquids and Gases, Flow and Pressure)
Authors: Magee Patrick , Tooley Mark
Published: November 2020

A fluid can be either a liquid or a gas. Fluids exhibit different flow behaviours depending on their physical properties, in particular viscosity and density. Flow characteristics also depend on the geometry of the pipes or channels through which they flow, and on the driving pressure regimes. These principles can be applied to any fluid, and the complexity of the analysis depends on the flow regimes described in this section [Massey 1970]. Fluid flow is generally described as laminar or turbulent. Laminar flow, demonstrated by Osborne Reynolds in 1867, is flow in which laminae or layers of fluid run parallel to each other. In a circular pipe, such as a blood vessel or a bronchus, velocity within the layers nearest the wall of the pipe is least; in the layer immediately adjacent to the wall it is probably actually zero. In fully developed laminar flow, the velocity profile across the pipe is parabolic, as shown in Figure 7.1, and as discussed in Chapter 1. Peak velocity of the fluid occurs in the mid line of the pipe, and is twice the average velocity across the pipe at equilibrium, and layers equidistant from the wall have equal velocity. The importance of laminar flow is that there is minimum energy loss in the flow, i.e. it is an efficient transport mode. This is in contrast to turbulent flow, where eddies and vortices (flow in directions other than the predominant one) mean that energy in fluid transport is wasted in production of heat, additional friction and noise. The result is that the pressure drop required to drive a given flow from one end of the pipe to the other is greater in turbulent than in laminar flow. The shear stress τ, which is the mechanical stress between layers of fluid and between the fluid and the tube wall, is proportional to the velocity gradient across the tube (dv/dr) of the fluid layers. The constant of proportionality between these two variables is the dynamic viscosity, η.
Electrophysiology and Stimulation
Authors: Magee Patrick , Tooley Mark
Published: November 2020

This chapter covers the processing and application of electrical signals from the body, in particularly the electroencephalogram (EEG), the electrocardiogram (ECG), and the electromyogram (EMG). The EEG and ECG will be considered in their monitoring capacity. The EMG will be discussed along with simulation and neuromuscular blockade and monitoring. The electrocardiogram (ECG) is a surface reflection of the propagation of electrical depolarisation and repolarisation over the various contractile chambers of the heart. Depolarisation is the trigger for releasing the stored contractile energy in the cardiac muscle. Each chamber also produces electrical action and polarising recovery potentials associated with the mechanical contribution of the recovery. The ECG can be divided into two major components: one associated with the propagation of excitation and recovery of the atria; the other with these events occurring in the ventricles. Excitation of the atria gives rise to the P wave, after which the atrial contractions propel blood into the ventricles. An atrial recovery wave exists, but it is rarely seen, as it is obscured by ventricular excitation, which is signalled by the QRS wave. During the later part of the QRS wave, ventricular contraction commences. Recovery of the ventricles is preceded by the T wave. The ECG labels, i.e. PQRST, are shown in Figure 18.1. To localise the direction of excitation and recovery of the heart chambers (and also to estimate the extent of cardiac injury), a variety of electrode arrangements can be used. The electrodes (which are normally disposable silver–silver chloride as described in Chapter 5) are positioned on easily located anatomical landmarks such as the right arm (RA), the left arm (LA), and the left leg (LL), with the right leg usually providing the reference or common. The standard (1, II, III), augmented (aVR, aVL, aVF) and precordial (V) leads are routinely recorded by electrocardiographers. It is possible to locate the direction of excitation and recovery by considering that the direction of the event (excitation or recovery) is at right angles to the isoelectric lead (i.e. the lead with equal forces in the positive and negative). This can be demonstrated by forming an equilateral triangle (Einthoven’s triangle) such as in Figure 18.2(a).
Medical Training using Simulators
Authors: Magee Patrick , Tooley Mark
Published: November 2020

Training and education using simulation has been used extensively in many high risk industries including aviation, nuclear power, military and rail. Repeated exposure to simulated crises and events has meant that, for example, airline crews are well prepared to face a rare disaster when it happens in real life. The use of simulation and simulators in medicine, to train and educate healthcare professionals has gained increasing attention in recent years and many simulation centres have now been set up in the UK. The Bristol Medical Simulation Centre, which opened in 1997, was the first training centre of its kind in the UK. There are now over 70 similar centres in the UK and many more with manikins in simpler settings, and hundreds of centres throughout the world [Department of Health 2010]. These offer a similar concept to that which the high risk industries use, where training for medical emergencies using sophisticated manikins are used in realistic medical settings, and task trainers are used to teach, for example, practical surgical skills. Many potential accidents in medicine are due to human error and communication problems [(Kohn et al. 1999, Department of Health 2009)]. Simulators can help train teams to function optimally using human factors style teaching. Simulation could also be a practical solution to several current educational issues. These include the challenges faced by educational institutions in securing clinical placements, the decrease in social acceptance of trainees learning on patients, the drive to maximise patient safety, and the dramatic decrease in training time being available to junior doctors due to the reduction in hours through the European Working Time Directive. The simulations centres consist of a number of different designated rooms. Simulated operations and team training can be carried out in the operating room. This room is made as close as possible to the modern operating room. It contains real equipment such as ventilators, defibrillators, patient monitors, trolleys and drip stands. A control room is next to the operating room, with a one way viewing window. This is where the manikin is controlled and where the simulation training is viewed and video recorded.
General Approach
Authors: Gupta Pawan
Published: November 2020

This chapter will focus on the day-to-day issues encountered in the ED for an overall understanding of the scenarios new doctors are expected to face on the very first day of their exciting career. The first issue dealt with in this chapter is triage. Triage is the hub of clinical practice and used on a regular basis in one form or another. Although some departments have gradually developed the service of ‘see and treat’ and escaping triage, it is still applied formally or informally by a practising clinician. It is vital to prioritize patients attending with a wide range of clinical presentations. A few questions on this topic are included to give a flavour of what to expect when you join the ED. The other issue discussed in this chapter is legal medicine, which again a newly qualified doctor may encounter on their first entry to the ED. But, it must be emphasized that plenty of support is provided to newcomers to put them at ease so that they may use their initial few days for settling into the department. To overcome the dilemma of ethical and legal issues, doctors can also contact medical defence organizations (the Medical Defence Union, the Medical Protection Society, etc.) and almost every doctor subscribes to one of the unions for this kind of support. It is increasingly recognized that an appropriate level of communication is of the utmost importance for the safer and effective care of patients attending the ED. There is always the issue of when to refer a borderline case to a specialty peer for possible admission and further care. I am sure there are innumerable examples of a junior doctor feeling pressured to send a patient home inappropriately. Therefore the system of SBAR has been included in this chapter to remind every junior doctor as to how best to make effective referrals, no matter at what stage of their career they are or the clinical setting in which they work. Lastly, dealing with a situation involving a major incident or disaster is always at the heart of every ED.
Poisoning
Authors: Gupta Pawan
Published: November 2020

EDs in the UK see a significant number of patients (347 per 100 000/year and ever-increasing) with acute overdose of drugs. Most of them are ingested orally, but other modes of intake can be used, such as IV and nasal. Sometimes it is not uncommon to see a patient presenting themselves to the ED feeling unwell after having ingested packets of Class I drugs to transport across continents. Another group of patients include those who present themselves after self-harming with a knife or blade on their wrists, arms, abdomen, or other parts of the body. These patients may have a previous history of drug overdose. Management of situations such as those described above requires both a generalized approach and specific actions against each drug involved. The common antidotes are covered in this chapter and advice is available in all EDs through the NPIS (www.toxbase.org) to deal with such emergencies, particularly with the treatments of unusual poisons. I encourage all the junior doctors to use the website for all the poison cases presenting to the ED to help build up confidence while treating them. Readers should note though that the URLs provided in this chapter can be accessed only by foundation and more senior doctors as the NPIS does not provide usernames and passwords to medical students. The priorities in the management of poisoned patients are similar to other ED presentations (ABCDE). Most of these patients require supportive therapy for recovery. Some poisons have specific antidotes which could be life-saving and are to be administered straightway. The initial assessment should be able to indicate whether or not the patient has been exposed to a specific poison for which an antidote is available. Hypoglycaemia must be excluded in every patient who presents with a low GCS score or convulsions by performing a capillary blood glucose by the bedside. A patient with respiratory depression, low GCS, and constricted pupils should be given naloxone while preparations are made to secure the airway. The recognition of such a pattern sometimes may direct the treating clinician towards a specific poison immediately, so that treatment with a definitive antidote can be given without delay.
The development of ultrasound in radiology in Sweden
Authors: Andersson Torbjörn
Published: November 2020

Diagnostic ultrasound in radiology started up in Sweden in the 1970s. And, as elsewhere in the world, it was a couple of enthusiasts who found out that a new and interesting technology was used in other departments and thought it could be used in radiology as well. The main inspiration came from the departments of obstetrics and gynaecology where ultrasound had been shown to be of great use in different obstetrical problem situations. Obstetrical ultrasound was initially used only in the larger university hospitals, which is why the first attempts to use ultrasound in radiology also started there. In southern Sweden, ultrasound was used extensively both for cardiac and obstetrical diagnosis, thus its use in radiology came on early at Lund and Malmö University Hospitals. In Lund, the radiologist wilhelm Karp introduced static ultrasound scanning in radiology. He and his co-worker Lillemor Forsberg published several papers with reference to the use of ultrasound technology in various fields and he also defended the first Swedish thesis in radiology dealing with ultrasound. Their publications showed that this new technology was not just a flash in the pan but here to stay. In Malmö, static ultrasound within the radiology department was introduced by a group lead by Jan Hildell and Peter Aspelin. Simultaneously ultrasound became more and more popular in the larger Swedish hospitals such as Karolinska Hospital in Stockholm and Uppsala Academic Hospital. In Stockholm, several of the radiology departments were pioneering ultrasound in obstetrics and this became the incentive to also use the technology for abdominal and genitourinary diagnosis. Some of the most active radiologists in this work were Ingmar Fernström, who was responsible for both obstetric and radiological ultrasound at Karolinska Hospital for several years, and Anders Törngren and Gunnar westberg who had similar positions at Danderyd and Serafimer Hospitals. Commercial ultrasound equipment at that time were rather complicated to use and to calibrate. The first scanners also utilized so-called bi-stable displays, which lacking in grey-scale made it rather complicated to interpret the images. Therefore ultrasound did not have the same rapid breakthrough as other later introduced radiological imaging modalities.
Technology and Work Practices
Authors: O'Brien William
Published: November 2020

The production of copper in prehistory was a complex undertaking, involving a sequence of inter-related activities that required specialist knowledge and informed organization. The operation of early copper mines demanded a long-term commitment that had important implications for the societies in question. There are obvious parallels with modern mining in terms of the multi-stage nature of the process, from the initial search for copper ores to their extraction, treatment, and eventual conversion to metal. This explains why early mining is often characterized as an ‘industry’, with its own specialists and techniques. Given their professional background, it is not surprising that the earliest researchers in this field focused on the geological setting, technology, and engineering aspects of prehistoric copper mines. Modern research also deals with these aspects, but is more concerned with understanding the wider societal context of this activity. It is now recognized that any reconstruction of the chaîne opératoire of early copper mining cannot be based solely on technique and process, but needs to incorporate the dynamic social context of this activity. It also needs to recognize that human choice played a significant role in determining the process of mining. While some areas are not amenable to archaeological enquiry, a reconstruction of task structure and work routines should capture many aspects of decision making in these mines. This will be revisited in the next chapter to explore the distinctive nature of prehistoric mining communities and how they interacted with the external world. Before doing so, it is necessary to examine the process of mining in terms of the techniques employed and the work environment of these miners. The opening chapter of this book considered the concept of ore, as it would have applied in prehistory. The modern definition is essentially an economic one that relates the cost of mining a mineral deposit to perceived financial returns or strategic interests. The effort of extraction must be set against the concentration or ‘grade’ of metal present in the rock, which will determine whether it can be profitably extracted.
The Enormous Room
Authors: Bradley Richard
Published: November 2020

It is ironic that anyone studying the domestic architecture of Copper Age Sardinia must turn to underground tombs as a source of information, whilst the monumental ‘houses’ of the Bronze Age are among the most conspicuous structures anywhere in Europe. The contrast between these two periods introduces a new theme. The first part of this chapter will study stone towers and related structures in the West Mediterranean. In every case they were associated with settlement sites and some may have been domestic buildings in their own right. Over time, they came to favour a circular plan. This section considers monuments in Sardinia, Corsica, and the Balearics and compares them with sites in Spain. It also asks whether they represent a single phenomenon. The second part considers three groups of timber buildings in Britain and Ireland and the enclosures with which they are associated. In this case they date from different periods. Although they resemble one another on the ground, there were few direct connections between them and, in at least two instances, they are thought to have been ceremonial centres. These sites in the Mediterranean and the North Atlantic are considered together in the light of a recent analysis of monumental architecture in the eastern USA. Both sections are designed to complement one another. The first considers the development of Great Houses in a series of well-populated landscapes. The second works at a larger geographical scale and studies the ways in which such buildings, and the earthworks associated with them, were related to a still more extensive area, until the most elaborate of all could be considered as microcosms of the wider world. Chapter Four discussed the domus de janas of Sardinia, the surprisingly realistic copies of domestic interiors provided for the dead during the Ozieri Culture. They were lavishly decorated and have produced radiocarbon dates which suggest that they were contemporary with the later phases of megalithic art in Western Europe. At the same time, most of the Sardinian structures were roughly square or rectangular and only a minority were designed as depictions of roundhouses. That reflects the results of excavation at the comparatively few surviving settlements of the same date.
The Attraction of Opposites
Authors: Bradley Richard
Published: November 2020

One of the best known accounts of the psychology of perception is Richard Gregory’s book Eye and Brain (Gregory 1998). It is relevant to this chapter because it uses an example from archaeology to illustrate the way in which the mind creates visual patterns. The author considers the methods by which excavators distinguish between the remains of rectangular and circular buildings. He considers the Middle Bronze Age settlement of Thorny Down in southern England, where different scholars have inferred the existence of different types of buildings on the basis of the same field evidence. The original excavator was uncertain of the precise form of the settlement (Stone 1941), but, in later years, Piggott identified the site of a large rectangular house there (1965: Figure 87) and Musson recognized circular structures (1970: 267; Figure 57). Gregory’s summary of their method is as follows:… Science and perception work by knowledge and rules, and by analogy . . . [In the case of Thorny Down] some of the holes in the ground might be ancient post holes; others might be rabbit holes, to be ignored. One group of archaeologists accepted close-together large holes as evidence of a grand entrance. They were altogether rejected by other archaeologists. One group constructed a large rectangular hut; the other, a small rectangular hut, and a circular building. ‘Bottomup’ rules—holes being close together and forming straight lines or smooth curves, and ‘top-down’ knowledge or assumptions of which kinds of buildings were likely—affected the ‘perceptions’. Both could have been wrong (1998: 11–12)…. The identification of a rectangular building at Thorny Down took place at a time when it was believed that the Netherlands had been settled from England during the Bronze Age. The argument was based on pottery styles and the distribution of metalwork (Theunissen 2009). Most likely there were contacts in both directions. As the Low Countries were characterized by a tradition of rectilinear architecture, what could be more natural than the construction of a longhouse at a site on the Wessex chalk? Dutch prehistorians attempted to find similar links between domestic architecture on both sides of the North Sea and soon they identified roundhouses of British type in their excavations.
Purification strategy
Authors: Roe Simon D.
Published: November 2020

Practical approaches to protein purification contains detailed practical information on separations techniques and the chapters of Protein purification techniques cover the unit operations and analytical techniques involved in some detail while Protein purification applications provides details of how to approach purification from a selected number of typical sources. However a key element of every purification, whether in University research or as part of scaling-up an industrial process, is planning. Time spent at the outset in establishing the key goals of the process prior to going into the laboratory will invariably save much time and effort. Key points to consider from the outset are: (a) Why are you doing the work—what is the reason for the purification? (b) What are the key considerations in selecting how to purify? (c) What implications does this have on how you will approach the purification? At the start of a purification, the target protein may be a minor component among millions of other proteins and other contaminants. This presents boundless opportunities for miscalculations, blind-alleys, and wasted effort. Years of practical work by separation scientists have derived certain rules which will help to minimize such problems and ensure protein purifications are successful. Here are ten purification rules to consider: 1. Keep the purification simple—minimize the number of steps and avoid difficult manipulations which will not reproduce. 2. Keep it cheap—avoid expensive techniques where a cheaper one will do. 3. Adopt a step approach—and optimize each step as you go. 4. Speed is important—avoid delays and slow equipment. 5. Use reliable techniques and apparatus. 6. Spend money on simple bits and pieces—e.g. test-tubes, pipettes. 7. Write out your methods before you start and record what you have done accurately. 8. Ensure your assays are developed to monitor the purification. 9. Keep notes on yields and activity throughout. 10. Bear in mind your objectives—be it high yield, high purity, final scale of operation, reproducibility, economical use of reagents/apparatus, convenience, throughput. Protein purification uses time, money, effort, and valuable equipment. Therefore, it is always advisable to pause for some moments to consider the reasons for purification in the first place.
Chromatography on the basis of size
Authors: Cutler P.
Published: November 2020

Chromatography has been employed for the separation of proteins and other biological macromolecules on the basis of molecular size since the mid 1950s when Lathe and Rutheven employed modified starch as a media for separation. Porath and Flodin developed the technique further using cross-linked dextran and coined the term gel filtration. Some confusion over nomenclature has been created by the term gel permeation, used to describe separation by the same principle in organic mobile phases using synthetic matrices. It is now generally agreed that the terms gel filtration and gel permeation do not accurately reflect the nature of the separation. Size exclusion Chromatography (SEC) has been widely accepted as a universal description of the technique and in line with the IUPAC nomenclature this term will be adopted. The historical development of SEC for protein separation has been reviewed. SEC is a commonly used technique due to the diversity of the molecular sizes of proteins in biological tissues and extracts. In addition to isolating proteins from crude mixtures, SEC has been employed for many roles including buffer exchange (desalting), removal of non-protein contaminants (DNA, viruses), protein aggregate removal, the study of biological interactions, and protein folding. The principle of size exclusion is based on a solid phase matrix consisting of beads of defined porosity which are packed into a column through which a mobile liquid phase flows. The mobile phase has access to both the volume inside the pores and the volume external to the beads. Unlike many other chromatographic procedures size exclusion is not an adsorption technique. Separation can be visualized as reversible partitioning into the two liquid volumes. The elution time is dependent upon an individual protein’s ability to access the pores of the matrix. Large molecules remain in the volume external to the beads as they are unable to enter the pores. The resulting shorter flow path means that they pass through the column relatively rapidly, emerging early. Proteins that are excluded from the pores completely, elute in the void volume, V0. This is often determined experimentally by the use of a high molecular weight component such as blue dextran or calf thymus DNA.
Scale-up considerations
Authors: Noble John B.
Published: November 2020

Once a potential indication has been found for a given protein product, it is necessary to produce increasing quantities to satisfy the demands of market trial activities. In the majority of cases, this will lead to scale-up of the purification process to meet demand whilst maintaining the safety, efficacy, and quality of the product. The following chapter provides an overview of the key issues that will arise during scale-up and provides the reader with practical advice on process and equipment selection. The text examines the key issues in defining production scale, identifies critical scale-up and development issues on an overall process basis, presents practical tips on scale-up, and concludes with two industrial scale-up case studies. The final choice of purification scale must reflect the most cost-effective solution for the whole of an organization and as such there are a great many influences to be considered. As a result the development process is an iterative exercise in which the production demand and schedule are balanced against available resources. A step-by-step approach to choice of purification scale is developed below: (a) Step 1: define volume of product required and when it is needed. (b) Step 2: develop a preliminary scale-up schedule. (c) Step 3: match scale and production schedule to production resources. Each of these steps will now be developed further. From preliminary product trials it will be possible to develop a schedule of product demand against time which can be used as the building block for step 2. Typically for pharmaceutical products the schedule will included materials for pre-clinical trials, phases I-III clinical trials, and commercial manufacture. During trials a defined quantity of product will be required over a clearly defined period whilst, once a product has been approved, demand will be less well defined and generally increase gradually over time to market saturation. From the schedule developed in step 1 and a knowledge of the approximate process yields, a preliminary assessment of overall raw material throughput can be developed. This can then be broken down and combined with information on product shelf-life to assess the most appropriate production strategy for each stage of a product’s life.
Gene targeting, principles, and practice in mammalian cells
Authors: Hasty Paul , Abuin Alejandro
Published: November 2020

When a fragment of genomic DNA is introduced into a mammalian cell it can locate and recombine with the endogenous homologous sequences. This type of homologous recombination, known as gene targeting, is the subject of this chapter. Gene targeting has been widely used, particularly in mouse embryonic stem (ES) cells, to make a variety of mutations in many different loci so that the phenotypic consequences of specific genetic modifications can be assessed in the organism. The first experimental evidence for the occurrence of gene targeting in mammalian cells was made using a fibroblast cell line with a selectable artificial locus by Lin et al. (1), and was subsequently demonstrated to occur at the endogenous β-globin gene by Smithies et al. in erythroleukaemia cells (2). In general, the frequencies of gene targeting in mammalian cells are relatively low compared to yeast cells and this is probably related to, at least in part, a competing pathway: efficient integration of the transfected DNA into a random chromosomal site. The relative ratio of targeted to random integration events will determine the ease with which targeted clones are identified in a gene targeting experiment. This chapter details aspects of vector design which can determine the efficiency of recombination, the type of mutation that may be generated in the target locus, as well as the selection and screening strategies which can be used to identify clones of ES cells with the desired targeted modification. Since the most common experimental strategy is to ablate the function of a target gene (null allele) by introducing a selectable marker gene, we initially describe the vectors and the selection schemes which are helpful in the identification of recombinant clones (Sections 2-5). In Section 6, we describe the vectors and additional considerations for generating subtle mutations in a target locus devoid of any exogenous sequences. Finally, Section 7 is dedicated to the use of gene targeting as a method to express exogenous genes from specific endogenous regulatory elements in vivo, also known as ‘knock-in’ strategies. A targeting vector is designed to recombine with and mutate a specific chromosomal locus.
Communication, Interpersonal Skills, and Decision Making
Authors: Templeman Jenni , Keeling June
Published: November 2020

This chapter explores the various aspects of communication and how these relate to our own interpersonal skills in communicating with others. The effectiveness of our communication—that is, how good we are at passing on information and ensuring that another person understands what we are trying to say—has a direct effect on both our own decision-making skills and the decisions made by those around us. We have all come across health care professionals whom we have felt have a good ‘bedside manner’ and those who do not. Historically, this term has been used to describe those who can communicate effectively. It is very important that, through our use of words, the person listening is able to understand what we mean. In nursing and health care generally, there is an increasing emphasis on communication as a means of building therapeutic relationships with both patients and their relatives. Communication, in the light of new technologies and ease of access by the wider community, extends far beyond the patient’s reliance on others for information about his or her health and well-being. It now encompasses more interpersonal communication, in which patients can be viewed as ‘the expert’ in conversations with nurses and doctors, an increased awareness of cultural influences, and the use of social networking sites, as well as the numerous Internet sites now available, to offer possible diagnoses and treatment options for the general public. Making decisions about patients’ health and often whether to accept those made on their behalf by others is now a real challenge for health professionals when communicating with patients and their families. As a nurse, it is part of your role to make decisions with patients and their families not for them, and the importance of learning how to communicate effectively, as well as how to engage in communicating with people, is clearly evident in the fact that the Nursing and Midwifery Council (NMC) Standards for Pre-Registration Nursing Education (NMC 2010b) now includes a new set of competencies solely for ‘Communication and interpersonal skills’.