bluuebunny/crossref_metadata_2025 huggingface dataset:
Enhanced pinning in superconducting thin films with graded pinning landscapes
Authors: Motta M. , Colauto F. , Ortiz W. A. , Fritzsche J. , Cuppens J. , Gillijns W. , Moshchalkov V. V. , Johansen T. H. , Sanchez A. , Silhanek A. V.
Published: May 2013

A graded distribution of antidots in superconducting a-Mo79Ge21 thin films has been investigated by magnetization and magneto-optical imaging measurements. The pinning landscape has maximum density at the sample border, decreasing linearly towards the center. Its overall performance is noticeably superior than that for a sample with uniformly distributed antidots: For high temperatures and low fields, the critical current is enhanced, whereas the region of thermomagnetic instabilities in the field-temperature diagram is significantly suppressed. These findings confirm the relevance of graded landscapes on the enhancement of pinning efficiency, as recently predicted by Misko and Nori [Phys. Rev. B 85, 184506 (2012)].
Development of a compact combined plasma sensor for plasma surface engineering processes
Authors: Welzel T. , Kellermeier M. , Harbauer K. , Ellmer K.
Published: May 2013

A combined sensor for the investigation of plasma-based surface engineering processes has been developed, which basically consists of a quartz crystal microbalance that is simultaneously used as a heat flux sensor and a planar Langmuir probe in one active element. The sensor can thus measure deposition flux, heat flux, and charged particle flux laterally resolved at the same time and position. The setup and working principle of the sensor are shown, and the suitability for process investigations is demonstrated exemplarily for a dc magnetron sputtering discharge for Ti thin film deposition.
Environmental sensitivity of n-i-n and undoped single GaN nanowire photodetectors
Authors: González-Posada F. , Songmuang R. , Den Hertog M. , Monroy E.
Published: May 2013

In this work, we compare the photodetector performance of single nearly defect-free undoped and n-i-n GaN nanowires (NWs). Undoped NWs present a dark current three orders of magnitude lower than n-i-n structures, about ten times lower gain, and a strong dependence of the measurement environment. In vacuum, undoped NWs react with an increase of their responsivity, accompanied by stronger nonlinearities and persistent photoconductivity effects. This behavior is attributed to the unpinned Fermi level at the m-plane NW sidewalls, which enhances the role of surface states in the photodetection dynamics. In the air, adsorbed oxygen accelerates the carrier dynamics at the price of reducing the photoresponse. In contrast, in n-i-n NWs, the Fermi level pinning at the contact regions limits the photoinduced sweep of the surface band bending, hence reducing the environment sensitivity and preventing persistent effects even in vacuum.
Optimal power dispatch in wind farm with life extension of wind turbine blades as target
Authors: Zhang Jinhua , Liu Yongqian , Tian De , Chen Gouhong
Published: May 2013

The importance of optimal dispatch in wind farm has been increasingly prominent for large-scale wind farms. The blades are integral parts of wind turbines, which have much influence on the wind turbine life. This paper analyzes the force on the wind turbine blades in different conditions and determines the relationship between the wind turbine blades damage value and different operating conditions and the relationship between the wind turbine blades damage value and life of wind turbine blades. With life extension of wind turbine blades as the optimization objective, the optimal dispatch model is established by Dijkstra's algorithm. It is verified that this optimal dispatch model is reliable in the wind farm operation.
Local Mn structure and room temperature ferromagnetism in Mn-doped In2O3 films
Authors: An Yukai , Wang Shiqi , Duan Lingshen , Liu Jiwen , Wu Zhonghua
Published: May 2013

Local Mn structure, magnetic, and transport properties in Mn-doped In2O3 films were investigated systematically. The detailed structural analysis and multiple-scattering calculations reveal that Mn2+ ions substitute for In3+ sites of the In2O3 lattice and form MnIn2+ + VO complex with the O vacancy in the nearest coordination shell. All films show clear room temperature ferromagnetism and Mott variable range hopping transport behavior. The saturation magnetization of films increases first, and then decreases with Mn doping, while carrier concentration nc decreases monotonically, implying that the ferromagnetism is not mediated by the charge carriers. These results provide strong evidence that oxygen vacancies play an important role in activating the ferromagnetic interactions in Mn-doped In2O3 films.
On-chip intra- and inter-layer grating couplers for three-dimensional integration of silicon photonics
Authors: Zhang Yang , Kwong David , Xu Xiaochuan , Hosseini Amir , Yang Sang Y. , Rogers John A. , Chen Ray T.
Published: May 2013

We present on-chip intra- and inter-layer grating couplers fabricated on double-layer, single crystalline silicon nanomembranes. The silicon nanomembranes were fabricated using an adhesive bonding process. The grating couplers are based on subwavelength nanostructures operating at the transverse-electric polarization. Such nanostructures can be patterned in a single lithography/etching process. Simultaneous intra-layer coupling to separate silicon photonic layers is demonstrated through grating couplers with peak efficiencies of 18% and 44% per grating coupler for bottom and top layer, respectively, at 1550 nm wavelength. The inter-layer grating coupler has an efficiency of 25% at 1560 nm wavelength with a 3 dB bandwidth of 41 nm.
Technical impacts of grid-connected photovoltaic systems on electrical networks—A review
Authors: ElNozahy M. S. , Salama M. M. A.
Published: May 2013

This paper addresses the potential impacts of grid-connected photovoltaic (PV) systems on electrical networks. The paper starts by emphasizing the increased importance of generating electricity from PV arrays. The growth in PV installed capacity worldwide is elaborated; futuristic expansion plans for several countries as well as existing PV projects worldwide are highlighted. The paper continues by evaluating the most important impacts of PV electricity on electrical networks. Finally, the authors summarize the literature's findings regarding the maximum allowable PV penetration that can be safely integrated into existing networks.
Magnetic properties of MnBi based alloys: First-principles calculations for MnBi-Co and MnBi-Co-Fe cases
Authors: Hong Yang-Ki , Park Jihoon , Mryasov Oleg N. , Kim Seong-Gon , Kim Sungho , Lee Jaejin , Abo Gavin S. , Choi Chul-Jin , Lee Junggoo
Published: May 2013

First-principles calculations of fundamental magnetic properties were performed for ordered MnBi, MnBi-Co, and MnBi-Co-Fe alloys to evaluate maximum energy product (BH)max. Full potential linear-augmented plane wave (FLAPW) and linear-muffin-tin-orbital (LMTO) calculations using density functional theory (DFT) within the local spin density approximation (LSDA) were used and found to give a reasonable description of saturation magnetization (Ms), effective anisotropy constant (Keff), and Curie temperature (Tc) for NiAs-structured MnBi crystal. We found that upon addition of Co, the Ms and Keff increased, while Tc reduced. The magnetic anisotropy changed from weak anisotropy easy plane for MnBi to the strong easy axis anisotropy for MnBi-Co and MnBi-Co-Fe.
Effects of Retinal Position on the Visuo-Motor Adaptation of Visual Stability in a Virtual Environment
Authors: Kitazaki Michiteru
Published: May 2013

Although the retinal image changes a great deal with the movement of our head or eyes, we perceive a stable world (a phenomenon known as visual stability or position constancy). Visual stability adaptively changes for each new combination of vision and head motion, or to compensate for manipulated visuo-motor gain. This study aims to investigate the effects of retinal positions on visuo-motor adaptation and to discuss the neural mechanisms involved. I found that visuo-motor adaptation occurred, and was transferable from right to left visual fields (Experiment 1), between the upper and lower visual fields (Experiment 2), and between the central and peripheral visual fields (Experiment 4), and that for the left visual field (Experiment 1) and the large visual field (Experiment 3) visuo-motor adaptations were effective. The dominance of the central vision was found in Experiment 3 but not found in Experiment 4. These results suggest that the visuo-motor adaptation of visual stability was not specific to the retinal location, but is processed by a relatively high level of the perceptual system.
Zograscopic Viewing
Authors: Koenderink Jan , Wijntjes Maarten , van Doorn Andrea
Published: May 2013

The “zograscope” is a “visual aid” (commonly known as “optical machine” in the 18th century) invented in the mid-18th century, and in general use until the early 20th century. It was intended to view single pictures (thus not stereographic pairs) with both eyes. The optics approximately eliminates the physiological cues (binocular disparity, vergence, accommodation, movement parallax, and image blur) that might indicate the flatness of the picture surface. The spatial structure of pictorial space is due to the remaining pictorial cues. As a consequence, many (or perhaps most) observers are aware of a heightened “plasticity” of the pictorial content for zograscopic as compared with natural viewing. We discuss the optics of the zograscope in some detail. Such an analysis is not available in the literature, whereas common “explanations” of the apparatus are evidently nonsensical. We constructed a zograscope, using modern parts, and present psychophysical data on its performance.
Sodium/hydrogen exchanger NHA2 is critical for insulin secretion in β-cells
Authors: Deisl Christine , Simonin Alexandre , Anderegg Manuel , Albano Giuseppe , Kovacs Gergely , Ackermann Daniel , Moch Holger , Dolci Wanda , Thorens Bernard , A. Hediger Matthias , Fuster Daniel G.
Published: May 2013

NHA2 is a sodium/hydrogen exchanger with unknown physiological function. Here we show that NHA2 is present in rodent and human β-cells, as well as β-cell lines. In vivo, two different strains of NHA2-deficient mice displayed a pathological glucose tolerance with impaired insulin secretion but normal peripheral insulin sensitivity. In vitro, islets of NHA2-deficient and heterozygous mice, NHA2-depleted Min6 cells, or islets treated with an NHA2 inhibitor exhibited reduced sulfonylurea- and secretagogue-induced insulin secretion. The secretory deficit could be rescued by overexpression of a wild-type, but not a functionally dead, NHA2 transporter. NHA2 deficiency did not affect insulin synthesis or maturation and had no impact on basal or glucose-induced intracellular Ca
2+
homeostasis in islets. Subcellular fractionation and imaging studies demonstrated that NHA2 resides in transferrin-positive endosomes and synaptic-like microvesicles but not in insulin-containing large dense core vesicles in β-cells. Loss of NHA2 inhibited clathrin-dependent, but not clathrin-independent, endocytosis in Min6 and primary β-cells, suggesting defective endo–exocytosis coupling as the underlying mechanism for the secretory deficit. Collectively, our in vitro and in vivo studies reveal the sodium/proton exchanger NHA2 as a critical player for insulin secretion in the β-cell. In addition, our study sheds light on the biological function of a member of this recently cloned family of transporters.
Determining scientific impact using a collaboration index
Authors: Stallings Jonathan , Vance Eric , Yang Jiansheng , Vannier Michael W. , Liang Jimin , Pang Liaojun , Dai Liang , Ye Ivan , Wang Ge
Published: May 2013

Researchers collaborate on scientific projects that are often measured by both the quantity and the quality of the resultant peer-reviewed publications. However, not all collaborators contribute to these publications equally, making metrics such as the total number of publications and the
H
-index insufficient measurements of individual scientific impact. To remedy this, we use an axiomatic approach to assign relative credits to the coauthors of a given paper, referred to as the
A
-index for its axiomatic foundation. In this paper, we use the
A
-index to compute the weighted sums of peer-reviewed publications and journal impact factors, denoted as the
C
- and
P
-indexes for collaboration and productivity, respectively. We perform an in-depth analysis of bibliometric data for 186 biomedical engineering faculty members and from extensive simulation. It is found that these axiomatically weighted indexes better capture a researcher’s scientific caliber than do the total number of publications and the
H
-index, allowing for fairer and sharper evaluation of researchers with diverse collaborative behaviors.
RNA polymerase approaches its promoter without long-range sliding along DNA
Authors: Friedman Larry J. , Mumm Jeffrey P. , Gelles Jeff
Published: May 2013

Sequence-specific DNA binding proteins must quickly bind target sequences, despite the enormously larger amount of nontarget DNA present in cells. RNA polymerases (or associated general transcription factors) are hypothesized to reach promoter sequences by facilitated diffusion (FD). In FD, a protein first binds to nontarget DNA and then reaches the target by a 1D sliding search. We tested whether
Escherichia coli
σ
54
RNA polymerase reaches a promoter by FD using the colocalization single-molecule spectroscopy (CoSMoS) multiwavelength fluorescence microscopy technique. Experiments directly compared the rates of initial polymerase binding to and dissociation from promoter and nonpromoter DNAs measured in the same sample under identical conditions. Binding to a nonpromoter DNA was much slower than binding to a promoter-containing DNA of the same length, indicating that the detected nonspecific binding events are not on the pathway to promoter binding. Truncating one of the DNA segments flanking the promoter to a length as short as 7 bp or lengthening it to ∼3,000 bp did not alter the promoter-specific binding rate. These results exclude FD over distances corresponding to the length of the promoter or longer from playing any significant role in accelerating promoter search. Instead, the data support a direct binding mechanism, in which σ
54
RNA polymerase reaches the local vicinity of promoters by 3D diffusion through solution, and suggest that binding may be accelerated by atypical structural or dynamic features of promoter DNA. Direct binding explains how polymerase can quickly reach a promoter, despite occupancy of promoter-flanking DNA by bound proteins that would impede FD.
SCF
KMD
controls cytokinin signaling by regulating the degradation of type-B response regulators
Authors: Kim Hyo Jung , Chiang Yi-Hsuan , Kieber Joseph J. , Schaller G. Eric
Published: May 2013

Cytokinins are plant hormones that play critical roles in growth and development. In
Arabidopsis
, the transcriptional response to cytokinin is regulated by action of type-B
Arabidopsis
response regulators (ARRs). Although central elements in the cytokinin signal transduction pathway have been identified, mechanisms controlling output remain to be elucidated. Here we demonstrate that a family of F-box proteins, called the KISS ME DEADLY (KMD) family, targets type-B ARR proteins for degradation. KMD proteins form an S-PHASE KINASE-ASSOCIATED PROTEIN1 (SKP1)/Cullin/F-box protein (SCF) E3 ubiquitin ligase complex and directly interact with type-B ARR proteins. Loss-of-function
KMD
mutants stabilize type-B ARRs and exhibit an enhanced cytokinin response. In contrast, plants with elevated
KMD
expression destabilize type-B ARR proteins leading to cytokinin insensitivity. Our results support a model in which an SCF
KMD
complex negatively regulates cytokinin responses by controlling levels of a key family of transcription factors.
Aire-expressing thymic medullary epithelial cells originate from β5t-expressing progenitor cells
Authors: Ohigashi Izumi , Zuklys Saulius , Sakata Mie , Mayer Carlos E. , Zhanybekova Saule , Murata Shigeo , Tanaka Keiji , Holländer Georg A. , Takahama Yousuke
Published: May 2013

The thymus provides multiple microenvironments that are essential for the development and repertoire selection of T lymphocytes. The thymic cortex induces the generation and positive selection of T lymphocytes, whereas the thymic medulla establishes self-tolerance among the positively selected T lymphocytes. Cortical thymic epithelial cells (cTECs) and medullary TECs (mTECs) constitute the major stromal cells that structurally form and functionally characterize the cortex and the medulla, respectively. cTECs and mTECs are both derived from the endodermal epithelium of the third pharyngeal pouch. However, the molecular and cellular characteristics of the progenitor cells for the distinct TEC lineages are unclear. Here we report the preparation and characterization of mice that express the recombinase Cre instead of β5t, a proteasome subunit that is abundant in cTECs and not detected in other cell types, including mTECs. By crossing β5t-Cre knock-in mice with loxP-dependent GFP reporter mice, we found that β5t-Cre–mediated recombination occurs specifically in TECs but not in any other cell types in the mouse. Surprisingly, in addition to cTECs, β5t-Cre-loxP–mediated GFP expression was detected in almost all mTECs. These results indicate that the majority of mTECs, including autoimmune regulator-expressing mTECs, are derived from β5t-expressing progenitor cells.
New Daily Persistent Headache
Authors: Newman Lawrence C. , Levin Morris
Published: May 2013

Patients with new daily persistent headache can generally pinpoint the date their headaches started. Characteristics of the head pain tend to be relatively nondescript, but patients are distressed by the persistence of the pain. Differential diagnosis and treatment options are described in this chapter.
Hemicrania Continua
Authors: Newman Lawrence C. , Levin Morris
Published: May 2013

Hemicrania continua is an underrecognized primary headache disorder that is uniquely responsive to treatment with indomethacin. This chapter discusses the clinical features, differential diagnosis, and work-up for this disorder and reviews the treatment options including strategies to employ when indomethacin is ineffective or contraindicated.
Trigeminal Neuralgia
Authors: Newman Lawrence C. , Levin Morris
Published: May 2013

The agonizing pain of trigeminal neuralgia can prove resistant to simple treatment. Differential diagnosis includes glossopharyngeal neuralgia, facial pathology, and lesions in the region of the path of the trigeminal nerve or in the brainstem near the trigeminal nuclei. Both diagnostic and treatment approaches (medical and surgical) are discussed in this chapter.
Emergency Department and Inpatient Management
Authors: Newman Lawrence C. , Levin Morris
Published: May 2013

This chapter reviews the treatment of headache in the emergency department and the indications for inpatient admission. In addition, a variety of treatment strategies are discussed, and tapering methods for butalbital-containing medications and opioids are provided.
Digital Signal Processing
Authors: Lagerlund Terrence D.
Published: May 2013

This chapter reviews the principles of digitization, the design of digitally based instruments for clinical neurophysiology, and several common uses of digital processing, including averaging, digital filtering, and some types of time-domain and frequency-domain analysis. An understanding of these principles is necessary to select and use digitally based instruments appropriately and to understand their unique features.
Electrophysiologic Generators in Clinical Neurophysiology
Authors: Lagerlund Terrence D.
Published: May 2013

This chapter reviews the generators of electrophysiologic potentials in terms of basic cellular electrophysiology and the anatomical structures that generate electrophysiologic potentials of clinical interest. Knowledge of the generators of the potentials recorded in clinical neurophysiologic studies is helpful in understanding the characteristics and distribution of the recorded potentials and is the first step in correlating the alterations seen in disease states with the pathologic changes demonstrated in the underlying generators.
Waveforms and Artifacts
Authors: Daube Jasper R.
Published: May 2013

Artifacts can alter all of the variables used to describe the continuous and discrete waveforms recorded in clinical neurophysiology. Changes in amplitude, frequency, and distribution of waveforms occur in continuous waveforms. Frequency change may include the addition of new, abnormal frequencies, the loss of normal frequencies, and either an increase or a decrease in amplitude. Discrete events themselves may be abnormal. The configuration, distribution, size, and pattern of normally occurring discrete events may be changed by disease.
Prolonged Video Electroencephalography
Authors: Shin Cheolsu
Published: May 2013

PVEEG has become an essential diagnostic tool in the management of epileptic seizures, psychogenic seizures, and other paroxysmal events. Various monitoring systems are available, mostly all digital systems. PVEEG monitoring allows psychogenic seizures and other nonepileptic paroxysmal events to be differentiated from epileptic seizures. It also enables accurate classification of most seizure types and is a necessary part of the evaluation of patients being considered for surgical treatment of epilepsy. Also, this type of monitoring allows extended observation of patients and can lead to a better understanding of their medical problems and any superimposed psychosocial issues. All these factors contribute to improved quality of life for patients and their families and more efficient delivery of appropriate medical care in these often very complex situations.
Electroencephalographic Special Studies
Authors: Worrell Gregory A. , Lagerlund Terrence D.
Published: May 2013

This chapter reviews several quantitative analysis techniques that may be applied to digitized EEG data. The technique of MEG is also discussed. Many of these techniques were primarily used as research tools; but as they have become more widely available, they are having an increasing effect on EEG interpretation and diagnosis.
Movement-Related Cortical Potentials and Event-Related Potentials
Authors: Evidente Virgilio Gerald H. , Caviness John N.
Published: May 2013

Special EEG averaging techniques may be used to study the cortical processes underlying movement and cognition. Movement-related potentials and contingent negative variation are observed before a voluntary movement occurs. The P300 and other event-related potentials provide electrophysiologic correlates of perception and cognition.
Somatosensory Evoked Potentials
Authors: Carter Jonathan L. , Stevens J. Clarke
Published: May 2013

SEPs recorded with surface electrodes represent volume-conducted activity arising from myelinated peripheral and central axons, synapses in central gray matter, and changes in the size and shape of the volume conductor. They provide an objective measure of function in large-diameter myelinated sensory afferents peripherally and in proprioceptive pathways centrally. Changes in amplitude and latency can be used to localize lesions in the nervous system, to identify objectively abnormalities in patients with few sensory manifestations or none at all, and to monitor function over time.
Thermoregulatory Sweat Test
Authors: Fealey Robert D.
Published: May 2013

The TST assesses the integrity of central and peripheral efferent sympathetic sudomotor neural pathways. A controlled heat and humidity stimulus is given to produce a generalized sweating response in all skin areas capable of sweating. Sweating is visualized by placing an indicator powder on the skin beforehand. The entire anterior body surface can be examined and abnormalities can usually be detected at a glance.
Cerebral Function Monitoring
Authors: So Elson L. , Sharbrough Frank W.
Published: May 2013

Intraoperative electrophysiologic monitoring of cerebral function during cardiovascular surgery requires a thorough knowledge of the effect of anesthetic agents on electrophysiologic signals. Although there are variations among anesthetic agents and their effects on the EEG, most of the agents produce similar changes that can be recognized and distinguished from the effects of ischemia. Success of the monitoring also depends heavily on the technical aspects of recording, such as the timescale of the EEG display and adjustment of the anesthetic agent used.
Compressive Optic Neuropathy
Authors: Thurtell Matthew J. , Tomsak Robert L. , Daroff Robert B.
Published: May 2013

Optic nerve compression results in progressive, and often painless, monocular vision loss. In this chapter, we review the clinical signs and common causes of compressive optic neuropathy. We discuss in more detail the imaging characteristics and management of optic nerve sheath meningioma.
Pseudopapilledema
Authors: Thurtell Matthew J. , Tomsak Robert L. , Daroff Robert B.
Published: May 2013

A diagnostic dilemma often arises when a patient with headaches is found to have optic nerve head elevation. Anomalous optic nerve head elevation often mimics papilledema and is therefore known as pseudopapilledema. In this chapter, we review the features that help to distinguish pseudopapilledema from papilledema and we discuss common causes of pseudopapilledema, such as optic nerve head drusen.
Transient Visual Loss
Authors: Thurtell Matthew J. , Tomsak Robert L. , Daroff Robert B.
Published: May 2013

Transient visual loss is common and often due to a transient loss of blood supply to the afferent visual system, although there are many other potential causes. We review the approach to the patient with transient visual loss in this chapter, with special attention to vascular causes.
Internuclear Ophthalmoplegia
Authors: Thurtell Matthew J. , Tomsak Robert L. , Daroff Robert B.
Published: May 2013

Internuclear ophthalmoplegia is a classic ocular motor syndrome that is caused by a lesion affecting the medial longitudinal fasciculus in the brainstem. In this chapter, we review the signs, causes, and differential diagnosis of internuclear ophthalmoplegia.
Progressive Supranuclear Palsy
Authors: Thurtell Matthew J. , Tomsak Robert L. , Daroff Robert B.
Published: May 2013

Patients with progressive supranuclear palsy, a sporadic akinetic-rigid syndrome, often have visual complaints and abnormal eye movements. We review the neuro-ophthalmic signs of progressive supranuclear palsy and present a practical approach to the management of its common visual symptoms, such as reading difficulty.
Tonic Pupil
Authors: Thurtell Matthew J. , Tomsak Robert L. , Daroff Robert B.
Published: May 2013

A tonic pupil is caused by a lesion affecting the postganglionic parasympathetic innervation of the pupil. It can be an incidental finding on examination or associated with visual symptoms, such as photophobia or blurred vision at near. We discuss the common causes and diagnostic evaluation of a tonic pupil in this chapter.
Cultural issues in measurement and research
Authors: Patel Vikram
Published: May 2013

The study of the epidemiology of mental disorders and their treatments in different cultures and health systems provides an important opportunity for unravelling aetiological factors underlying mental disorders and for discovering new effective treatments. There is a large body of work which serves to guide future research in different cultural settings. This evidence shows that although symptoms of mental disorders can be elicited in most cultures, taxonomies may differ considerably. Instruments developed in one culture may be used in other cultures, but great emphasis needs to be placed on their translation to ensure conceptual validity. Study designs need to incorporate a range of health system variables to ensure the findings are relevant to local health policy. A variety of research methodologies have been used to achieve these goals. Research must be planned in collaboration with potential users and a range of dissemination strategies should be considered. These principles form the basis for the growth of a truly international psychiatric epidemiology.
Randomized controlled trials
Authors: Banerjee Sube
Published: May 2013

There are three main questions in health care: ‘what is going on?’, ‘why?’ and ‘what do we do about it?’. ‘What is going on?’ forms the basis for clinical assessment including history taking, examination, and diagnosis. The question ‘why?’ underlies all aetiological research from laboratory science to epidemiology. The cross-sectional, case–control and cohort methodologies discussed in other chapters in this book provide the methodology for addressing ‘why?’ questions. However, just as medicine is more than diagnosis it also covers treatment, medical research is more than aetiology: it also necessarily extends to the evaluation of interventions.

Aetiological research which cannot be translated into health benefits through new or improved interventions is at best sterile and at worse selfindulgent, begging another important question: ‘so what?’. Flawed evaluations of interventions can be even more problematic since these may harm rather than help. Intervention studies (of which randomized controlled trials (RCTs) are the most important type, on the basis of quality of evidence available from them) take aetiological insights into action and provide the best evidence upon which to found clinical practice.

In this chapter we will consider some of the more important factors in the design, conduct, analysis, and interpretation of RCTs.
Inference 1: chance, bias, and confounding
Authors: Stewart Robert
Published: May 2013

A fundamental process in interpreting one's own or another's research is to consider what the observations ‘mean’, that is, what can be inferred from them. This involves a series of questions and considerations (Fig. 12.1). The first step theoretically is to decide whether observations can be believed in the first place. It is the duty of the guarantor for any submitted research paper to ensure that the data and results derived from analyses are valid—and to withdraw a submission promptly if there are any concerns over this. Readers have no choice but to assume the integrity of the raw data. The first formal stage of appraisal is to decide to what extent the observations in the sample are likely to apply to the source population. The principal considerations here are chance and bias. If the reader is happy that a population-level association is likely, the next stage is to consider what can be inferred concerning cause and effect. This begins with considering whether the association between proposed exposure and outcome is a direct one and not confounded by other factors. After this point, there are a series of more complex decisions regarding causal pathways, which may not always be inferred from a single study but may require a more broad knowledge of the background literature. These are discussed in Chapter 13 and include the direction of causality (whether an association between A and B is because A causes B or vice versa), mediating factors (does A cause C because A causes B which in turn causes C, or are there other pathways by which A and C are related?), and effect modification (does A cause B to a uniform extent across the population or does the strength of association depend on other factors being present?). Finally, the implications of these inferences need to be considered with respect to developing new hypotheses and investigations, as well as for clinical practice and Public Health.
Cardiac arrest
Authors: Soar Jasmeet , Nolan Jerry P. , Gabbott David A.
Published: May 2013

Cardiovascular disease is the most common cause of sudden cardiac arrest, which causes over 60% of adult coronary heart disease deaths. In Europe, the annual incidence of out-of-hospital cardiopulmonary arrests treated by emergency medical systems is 38 per 100 000.

Survival from cardiac arrest depends on a sequence of interventions—the Chain of Survival—comprising (1) early recognition and call for help, (2) early cardiopulmonary resuscitation (CPR), (3) early defibrillation, and (4) postresuscitation care. The division between basic life support and advanced life support (ALS) is arbitrary—the resuscitation process is a continuum....
Thoracic imaging
Authors: Copley Susan J. , Hansell David M.
Published: May 2013

Radiographic findings should always be interpreted in conjunction with the clinical picture.

Chest radiography—this remains the commonest technique in the investigation of suspected thoracic disease. Advantages are cost, availability, and a significantly lower radiation dose than CT, but even with optimal technique nearly one-third of the lungs are partially obscured by the overlying mediastinum, diaphragm, and ribs....
Bronchiectasis
Authors: Bilton R.D.
Published: May 2013

Bronchiectatic lung contains permanently dilated subsegmental airways that are inflamed, tortuous, and often partially or totally obstructed with secretions. It arises as a result of the combination of an infectious insult with associated impaired clearance mechanisms: local obstruction and infection distal to the obstruction are both required. Causes include developmental defects, immune deficiency, mucociliary clearance defects and mechanical obstruction, but in many cases (40–60%) the cause is unknown....
Sarcoidosis
Authors: Baughman Robert P. , Lower Elyse E.
Published: May 2013

Case History—A 26 yr old man with an odd skin rash and an abnormal chest radiograph.

Sarcoidosis is a disease of unknown cause that is characterized by the presence of noncaseating granulomas in at least two organs. It can present in a wide variety of ways. Differential diagnosis is most commonly from tuberculosis or lymphoma....
Lung transplantation
Authors: Hopkins P. , McNeil K.
Published: May 2013

Lung transplantation offers the only therapeutic option for many patients with a variety of endstage pulmonary and cardiopulmonary diseases, but donors are scarce and the major challenge facing lung transplantation (as with all solid organ transplants) is the critical shortage of donor organs.

Recipient selection—emphysema/chronic obstructive pulmonary disease (COPD), cystic fibrosis, idiopathic pulmonary fibrosis, and pulmonary vascular disease are the main disease groups referred for lung transplantation. Most patients are listed for transplantation when their survival is estimated to be less than 2 years without a transplant. Exclusion criteria include malignancy (excluding localized skin malignancies) within the last 2 years, inability to cooperate or comply with medical therapy/instruction, recent substance addiction, active or noncurable extrapulmonary infection, significant chest wall/spinal deformity, and significant extrathoracic organ dysfunction....
Aplastic anaemia and pure red cell aplasia
Authors: Marsh Judith C.W. , Kulasekararaj Austin , Mufti Ghulam J.
Published: May 2013

Aplastic anaemia (AA) is a rare bone marrow failure (BMF) disorder characterized by pancytopenia and a hypocellular bone marrow. AA is commonly acquired, immune-mediated and idiopathic in nature.

Activate auto-reactive, cytotxic CD8+ T-cells are present but recent work has shown that CD4+ T-cells appear to be more important in the pathogenesis of acquired AA. The immune nature of acquired AA provides the rationale for one of the treatment options, namely immunosuppressive therapy....
Introduction to the lymphoproliferative disorders
Authors: Degar Barbara A. , Berliner Nancy
Published: May 2013

Lymphoproliferative disorders occur when the normal mechanisms of control of proliferation of lymphocytes break down, resulting in autonomous, uncontrolled proliferation of lymphoid cells and typically leading to lymphocytosis and/or lymphadenopathy, and sometimes to involvement of extranodal sites, e.g. bone marrow.

These include (1) malignant—clonal in nature, resulting from the uncontrolled proliferation of a single transformed cell, e.g. lymphoma; (2) nonmalignant—polyclonal lymphoproliferative disorders may result from conditions including (a) infections—lymphocytosis is commonly caused by viral infections, e.g. Epsitein–Barr virus (EBV); lymphadenopathy is a common feature of a very wide variety of infections, (b) reactive—conditions such as systemic lupous erythematosus (SLE) and sarcoidosis frequently cause lymphadenopathy....
Anaemias resulting from defective maturation of red cells
Authors: Fuller Stephen J. , Wiley James S.
Published: May 2013

Defective maturation of red cells leads to premature destruction of nucleated red cell precursors before they leave the haematopoietic bone marrow, which results in expansion of the marrow, haemolytic jaundice, peripheral signs of increased erythroid turnover on blood films, and (in long-standing disorders) iron overload due to enhanced absorption....
Blood transfusion
Authors: Alhumaiden H.S. , Perrotta P.L. , Han Y. , Snyder E.L.
Published: May 2013

Transfusion of blood components is a life-saving treatment for patients with severe haemorrhage: it can also be used to replace coagulation factors and to ameliorate the effects of severe anaemia, thrombocytopenia, and impaired platelet function. However, blood transfusion has many hazards, hence its use should always be considered carefully and restricted to those who will gain benefit that outweighs the risks....
Haemopoietic stem cell transplantation
Authors: Gordon-Smith E.C. , Morris Emma
Published: May 2013

Haemopoietic stem cells (HSC) give rise to the blood cell lineages and the cells of the immune system, and their transplantation may be an appropriate part of the management of conditions including (1) malignant haematological disorders e.g. leukaemia, lymphoma, myeloma (2) bone marrow failure syndromes—e.g. aplastic anaemia; (3) congenital disorders—(a) haematological—e.g. Fanconi’s anaemia; (b) immunological—severe combined immunodeficiency; (c) metabolic—e.g. lysosomal diseases....
Clinical approach to the diagnosis of skin disease
Authors: Venning Vanessa
Published: May 2013

As in most medical specialities, the diagnosis of skin disease relies on careful history taking, and a thorough examination, supported in some cases by appropriate investigation. Astute physicians will also be aware that management outcomes are improved by taking account of the impact of skin disease on patients’ lives, whether through discomfort, disfigurement, or disability. This section, however, is chiefly concerned with aspects of history taking and examination that inform the diagnostic process....
Lung and thorax
Authors: O'Rourke Noelle , Sproule Michael
Published: May 2013

Chapter 4 discusses the lung and thorax, and includes clinical backgrounds, diagnosis and staging, imaging for planning, and other intrathoracic malignancies.
Pancreatic tumours
Authors: Miller Ben , Geh Ian , Roy-Choudhury Shuvro
Published: May 2013

Chapter 9 discusses the ninety percent of primary pancreatic tumours that are ductal adenocarcinomas, which have a predilection for the head and neck and are the main focus of discussion here. Tumours of the islet cells are less common and are discussed separately in Chapter 18.
Gastrointestinal stromal tumours
Authors: Mahon Brinder , Seddon Beatrice , Geh Ian
Published: May 2013

Chapter 10 discusses gastrointestinal stromal tumours (GISTs), which are rare tumours arising from the same common mesenchymal stem cell precursor as the interstitial cells of Cajal, which are pacemaker cells of the autonomic nervous system, located within the wall of the gut and responsible for gastrointestinal (GI) tract peristalsis.
Imaging for common complications
Authors: Whittaker Charlotte , Goh Vicky
Published: May 2013

Chapter 21 includes some fundamental scientific aspects of radiation and its effect on the human body, guidance on dosimetry, as well as the regulations themselves.
The law and the criminal justice system
Authors: Plant Martin , Robertson Roy , Plant Moira , Miller Patrick
Published: May 2013

This chapter summarizes the main provisions of the UK's Misuse of Drugs Act (1971) and other legislation related to illicit drug use. It should be noted that this important piece of legislation is derived from the International United National Convention 1961. This Convention sets out the framework for domestic legislation in member countries but often results in slightly different laws with varying penalties and constraints. For this reason differences are often observed between countries when comparisons are made. It also considers some of the recent debates about the operation of the criminal justice system in relation to drugs and drug users. The legal classification of drugs will be critically considered in the light of evidence suggesting that some legal drugs (such as alcohol and tobacco) are at least as dangerous as some of those which are illegal. A review will also be provided of trends in cautions and convictions for drug-related offences. The overall role of drugs in relation to crime and the criminal justice system will also be considered. This discussion will include the issues of drug offenders, drug dependents and drug use in prison, the impact of drugs on the court service, probation, and Customs and Excise.
Mechanisms of disease
Authors: Harrison Dr Mark
Published: May 2013

2.1 Basic terminology, 154

2.2 Mechanisms of attachment, invasion, and persistence, 154

• Colonization: The continuing presence of microorganisms without injury or invasion of our tissues. For example MRSA in the nostrils; normal gut flora.

• Pathogen: A microorganism that parasitizes a human and causes disease....
Clostridial infection
Authors: Harrison Dr Mark
Published: May 2013

3.1 Clostridial colitis, 170

3.2 Clostridial gas gangrene, 171

3.3 Tetanus, 172

• Clostridial bacteria are Gram positive, anaerobic, spore-forming rods.

• Commonly found in GI tract, dust, soil, and vegetation.

• Potent exotoxins cause botulism, tetanus, gas gangrene, and pseudomembranous colitis.

• Pseudomembranous colitis...
Klebsiella, Salmonella, E. coli
Authors: Harrison Dr Mark
Published: May 2013

6.1 Klebsiella, 180

6.2 Salmonella, 181

6.3 Escherichia coli, 182

• Klebsiella pneumoniae and Klebsiella oxytoca

• Enterobacteria

• Gram negative rods

• Encapsulated, produce exotoxins

• Primarily opportunistic and nosocomial pathogen.

• Colonizes skin, nasopharynx, and GI tract.

• Frequently colonizes hospitalized patients and contaminant in critical care areas and ventilators....
Hepatitis
Authors: Harrison Dr Mark
Published: May 2013

13.1 Hepatitis A, 200

13.2 Hepatitis B, 201

13.3 Hepatitis C, 204

• Common.

• Virus shed in faeces, therefore predominantly spread via faecal-oral route; blood spread is rare.

• Can be transmitted by eating uncooked shellfish harvested from sewage-contaminated water.

• Common in underdeveloped countries with poor sanitation and in institutions....
Measles, mumps, rubella
Authors: Harrison Dr Mark
Published: May 2013

14.1 Measles, 206

14.2 Mumps, 207

14.3 Rubella, 207

14.4 MMR, 208

• A disease of childhood now rare in the UK as a result of vaccination.

• Transmission is via respiratory droplets.

• Incubation period is 10-18 days.

• Measles is extremely infectious and patients are infective from 1-2 days before initial symptoms until 5 days after rash appears....
Respiratory viruses
Authors: Harrison Dr Mark
Published: May 2013

15.1 Rhinovirus, 209

15.2 Influenza, 210

15.3 Parainfluenza, 211

15.4 Respiratory syncytial virus (RSV), 211

• There are more than 100 different serotypes of rhinovirus.

• Rhinovirus is chiefly limited to upper respiratory tract infections and is the major cause of the common cold....
Gastrointestinal viruses
Authors: Harrison Dr Mark
Published: May 2013

16.1 Rotavirus, 213

16.2 Norovirus, 214

• Causes severe gastroenteritis, especially in children and infants.

• Responsible for 50% of cases of severe diarrhoea in children under 2 years.

• Seasonal variation in incidence, peaking in winter months.

• Faecal-oral transmission from contaminated food, water, and surfaces....
Yeasts and fungi
Authors: Harrison Dr Mark
Published: May 2013

17.1 Candida, 215

17.2 Cryptococcus, 216

17.3 Dermatophytes, 217

• Candida occurs as part of the normal flora of the mouth, skin, vagina, and GI tract.

• Opportunistic infection, frequently presenting in association with immunocompromise and antibiotic use.

• The use of broad spectrum antibiotics eliminates competing bacterial flora allowing the yeast to overgrow....
Worms
Authors: Harrison Dr Mark
Published: May 2013

18.1 Threadworm, 218

18.2 Tapeworm (pork and beef), 218

18.3 Roundworm, 220

18.4 Hookworm, 220

• Also known as pinworm or ‘enterobiasis’, caused by Enterobius vernicularis.

• Common, especially in children.

• Humans are the only host.

• Transmission is via ingestion of eggs....
Cardiovascular physiology
Authors: Harrison Dr Mark
Published: May 2013

3.1 Systemic overview, 259

3.2 Cardiac cycle I, 262

3.3 Cardiac cycle II, 267

3.4 Cardiac cycle III, 269

3.5 Cardiac output, 272

3.6 Peripheral vascular physiology I, 276

3.7 Peripheral vascular physiology II, 278

3.8 Peripheral vascular physiology III, 282

See Table C.3.1...
Gastrointestinal physiology
Authors: Harrison Dr Mark
Published: May 2013

4.1 Functional anatomy of the gastrointestinal tract - outline of structure, 288

4.2 Saliva, 289

4.3 Swallowing (deglutition), 292

4.4 Stomach, 293

4.5 Small intestine, 297

4.6 Pancreas, 300

4.7 Liver, 302

4.8 Gallbladder, 305

4.9 Large intestine, 306

• The gastrointestinal tract has a fairly consistent general structure that is arranged into 4 concentric layers (see Figure ...
Infections
Authors: Harrison Dr Mark
Published: May 2013

5.1 Notifiable diseases, 385

5.2 Antibacterial drugs, 385

5.3 Penicillins, 390

5.4 Cephalosporins, 393

5.5 Tetracyclines, 394

5.6 Aminoglycosides, 395

5.7 Macrolides, 396

5.8 Other antibiotic agents, 396

5.9 Management of tuberculosis, 398

5.10 Quinolones, 399

5.11 Urinary tract infections, 400

5.12 Antifungal preparations, 401...
Immunological products and vaccines
Authors: Harrison Dr Mark
Published: May 2013

9.1 Active immunity, 416

9.2 Passive immunity, 418

9.3 Specific vaccines and preparations, 418

9.4 Immunoglobulins (Ig), 421

Vaccines stimulate production of antibodies and other components of the immune mechanism.

• Inactivated

▪ Heat/chemically inactivated virulent microorganism (virus or bacteria).

▪ May require a primary series of injections of vaccine to produce an adequate antibody response, and in most cases booster (reinforcing) injections are required; the duration of immunity varies from months to many years. Some inactivated vaccines are adsorbed onto an adjuvant (such as aluminium hydroxide) to enhance the antibody response....
Respiratory
Authors: Harrison Dr Mark
Published: May 2013

1.1 Control of ventilation, 436

1.2 Reflexes in ventilatory control, 437

1.3 Pressure, chemical, and irritant receptors, 438

1.4 J receptors, 438

1.5 Pulmonary stretch receptors, 438

1.6 Golgi tendon organs, 438

1.7 Muscle spindles, 438

1.8 Lung volumes, 438

1.9 Pulmonary mechanics, 439

1.10...
Neurology
Authors: Harrison Dr Mark
Published: May 2013

3.1 Intracranial pressure, 465

3.2 Sensory pathways, 466

3.3 Motor pathways, 467

3.4 Nerve conduction, 468

3.5 Pain, 469

3.6 Sight, 470

3.7 Auditory system, 471

3.8 Brainstem reflexes and death, 472

3.9 Temperature, 472

3.10 Effect of altitude and dysbarism, 474

• The Munro-Kelly doctrine describes the skull as a rigid cavity of fixed volume...
Metabolic response to insult
Authors: Harrison Dr Mark
Published: May 2013

6.1 Control of energy production, 488

6.2 Metabolic responses to stress including injury, infection, infarction, temperature, and burns, 489

• Initial hyperglycaemia resulting from increased glucose production and reduced uptake in peripheral tissues

• Peripherally reduced uptake due to an injury - proportionate insulin resistance, postulated to be due to action of cytokines and dysfunction of glucose transporter proteins...
Respiratory
Authors: Stacey Victoria
Published: May 2013

Asthma - Chronic obstructive pulmonary disease (COPD) - Non-invasive ventilation - Venous thromboembolism - Pneumonia - Spontaneous pneumothorax - Respiratory failure and oxygen therapy - Arterial blood gas analysis - SAQs