bluuebunny/crossref_metadata_2025 huggingface dataset:
Exceptionally stable, redox-active supramolecular protein assemblies with emergent properties
Authors: Brodin Jeffrey D. , Carr Jessica R. , Sontz Pamela A. , Tezcan F. Akif
Published: February 2014

Significance

Supramolecular assembly is a powerful strategy to generate structural and functional diversity from a limited set of components. Owing to their chemical and structural versatility, proteins represent particularly attractive building blocks for engineering supramolecular materials with new or improved properties. We previously exploited the strength, directionality, and reversibility of designed metal coordination interactions to arrange a monomeric, redox protein into highly ordered supramolecular architectures. Here we demonstrate that metal-directed self-assembly not only yields very stable architectures but that it also leads to a dramatic stabilization of the individual protein components, whose redox activities can now be utilized for controlled growth of inorganic nanocrystals. These emergent physical and functional properties are attained with minimal modification of the original building blocks.
Lévy flights do not always optimize random blind search for sparse targets
Authors: Palyulin Vladimir V. , Chechkin Aleksei V. , Metzler Ralf
Published: February 2014

Significance

Has natural selection led to adaptations of Lévy flight foraging, as stated on the respective Wikipedia page? Random walks with scale-free jump length distributions were indeed shown to optimize the search for sparse targets as supported by extensive movement data of many animal species and humans. Here we demonstrate that small variations of the search conditions strongly modify these claims: In the presence of a bias, underwater currents for sea predators or winds for airborne searchers, a Lévy searcher easily overshoots the target, and Brownian strategies become advantageous. Even in the absence of a bias, there exist conditions for which a Brownian strategy may effect faster target localization. Our results show clear limitations for the universality of Lévy flight foraging.
Hydrogen sulfide cytoprotective signaling is endothelial nitric oxide synthase-nitric oxide dependent
Authors: King Adrienne L. , Polhemus David J. , Bhushan Shashi , Otsuka Hiroyuki , Kondo Kazuhisa , Nicholson Chad K. , Bradley Jessica M. , Islam Kazi N. , Calvert John W. , Tao Ya-Xiong , Dugas Tammy R. , Kelley Eric E. , Elrod John W. , Huang Paul L. , Wang Rui , Lefer David J.
Published: February 2014

Significance

Physiological concentrations of hydrogen sulfide (H
2
S) exert potent prosurvival actions. We demonstrate that the cytoprotective actions of H
2
S are mediated in part via a second gaseous signaling molecule, nitric oxide (NO). We found that cystathionine γ-lyase (CSE) KO mice with reduced H
2
S levels exhibit increased oxidative stress and an exacerbated response to myocardial ischemia/reperfusion injury. CSE KO mice also exhibit reduced levels of NO and reduced NO synthesis via endothelial NO synthase (eNOS). Both oxidative stress and myocardial injury in CSE KO mice were attenuated by exogenous H
2
S therapy, with increased eNOS function and restoration of NO levels. These findings provide insight into H
2
S-mediated cytoprotetion and important information regarding the translation of H
2
S therapy to the clinic.
Differential uptake of nanoparticles by endothelial cells through polyelectrolytes with affinity for caveolae
Authors: Voigt Julia , Christensen Jon , Shastri V. Prasad
Published: February 2014

Significance

Nanoparticles (NPs) can serve as containers for the targeting of therapeutics to tumors. Tumors comprise many cell types including endothelial cells that form the blood vessels. Developing new strategies to target information preferentially to endothelial cells can have major implications in the development of targeted therapeutics. We have discovered that charged polymers containing aromatic sulfonate have pronounced affinity for caveolae, which are highly expressed by endothelial cells. By engineering the surface of lipid NPs to bear sulfonate-containing polymers, lipid NPs that are preferentially taken up by endothelial cells have been demonstrated.
Morphogenesis at criticality
Authors: Krotov Dmitry , Dubuis Julien O. , Gregor Thomas , Bialek William
Published: February 2014

Significance

Biological networks are described by many parameters, and the behavior of a network is qualitatively different (monostable, bistable, oscillating, etc.) in different parts of parameter space. Critical points and surfaces are the borders between such qualitatively different regimes, as with phase transitions in equilibrium thermodynamics. We argue that, as expected from the thermodynamic case, genetic regulatory networks should exhibit behaviors near criticality that are independent of most molecular details. Analyzing recent experiments on the gap gene network in the early
Drosophila
embryo, we find that these signatures of criticality can be seen, quantitatively. This raises the question of why evolution has tuned this network to such a special point in its parameter space.
Differentiated human stem cells resemble fetal, not adult, β cells
Authors: Hrvatin Sinisa , O’Donnell Charles W. , Deng Francis , Millman Jeffrey R. , Pagliuca Felicia Walton , DiIorio Philip , Rezania Alireza , Gifford David K. , Melton Douglas A.
Published: February 2014

Significance

Human pluripotent stem cells (hPSCs) can be produced from any person and have the potential to differentiate into any cell type in the body. This study focuses on the generation of insulin-expressing cells from hPSCs and compares their gene expression, as assayed by transcriptional gene products, to that of insulin-expressing β cells from human fetal and adult samples. We employ a new method to isolate and profile insulin-expressing cells and conclude that several different hPSC lines generate very similar insulin-expressing cells, cells whose transcripts resemble fetal rather than adult β cells. This study advances the possibility of directing the differentiation of stem cells into functional β cells by comparing and cataloging differences between hPSC-derived insulin-expressing cells and human β cells.
Lipid domains control myelin basic protein adsorption and membrane interactions between model myelin lipid bilayers
Authors: Lee Dong Woog , Banquy Xavier , Kristiansen Kai , Kaufman Yair , Boggs Joan M. , Israelachvili Jacob N.
Published: February 2014

Significance

The proper functioning of multilayer membrane systems, such as myelin, requires the multilamellar membranes to be tightly wrapped around the axon fibers, thereby allowing efficient electric signal transmission. Slight changes in lipid composition in myelin membranes will alter their domain sizes and distributions, and the intermembrane adhesive properties. Using the surface forces apparatus and atomic force microscope, we studied the adsorption of myelin basic protein (MBP) to model myelin lipid bilayer membranes of varying compositions, and their effects on the structure, equilibrium spacing (swelling), and adhesion force between them. We find that MBP preferentially adsorbs to “disordered” submicron domains, affecting regular spacing and adhesion. These findings provide insights into lipid–protein interactions and membrane-associated (e.g., demyelinating) diseases.
Introduction to structured argumentation
Authors: Besnard Philippe , Garcia Alejandro , Hunter Anthony , Modgil Sanjay , Prakken Henry , Simari Guillermo , Toni Francesca
Published: February 2014

In abstract argumentation, each argument is regarded as atomic. There is no internal structure to an argument. Also, there is no specification of what is an argument or an attack. They are assumed to be given. This abstract perspective provides many advantages for studying the nature of argumentation, but it does not cover all our needs for understanding argumentation or for building tools for supporting or undertaking argumentation. If we want a more detailed formalisation of arguments than is available with abstract argumentation, we can turn to structured argumentation, which is the topic of this special issue of Argument and Computation. In structured argumentation, we assume a formal language for representing knowledge, and specifying how arguments and counterarguments can be constructed from that knowledge. An argument is then said to be structured in the sense that normally the premises and claim of the argument are made explicit, and the relationship between the premises and claim is formally defined (for instance using logical entailment). In this introduction, we provide a brief overview of the approaches covered in this special issue on structured argumentation.
A tutorial on assumption-based argumentation
Authors: Toni Francesca
Published: February 2014

We give an introductory tutorial to assumption-based argumentation (referred to as ABA) – a form of argumentation where arguments and attacks are notions derived from primitive notions of rules in a deductive system, assumptions and contraries thereof. ABA is equipped with different semantics for determining ‘winning’ sets of assumptions and – interchangeably and equivalently – ‘winning’ sets of arguments. It is also equipped with a catalogue of computational techniques to determine whether given conclusions can be supported by a ‘winning’ set of arguments. These are in the form of disputes between (fictional) proponent and opponent players, provably correct w.r.t. the semantics. Albeit simple, ABA is powerful in that it can be used to represent and reason with a number of problems in AI and beyond: non-monotonic reasoning, preferences, decisions. While doing so, it encompasses the expressive and computational needs of these problems while affording the transparency and explanatory power of argumentation.
A bidirectional antagonism between aPKC and Yurt regulates epithelial cell polarity
Authors: Gamblin Clémence L. , Hardy Émilie J.-L. , Chartier François J.-M. , Bisson Nicolas , Laprise Patrick
Published: February 2014

During epithelial cell polarization, Yurt (Yrt) is initially confined to the lateral membrane and supports the stability of this membrane domain by repressing the Crumbs-containing apical machinery. At late stages of embryogenesis, the apical recruitment of Yrt restricts the size of the apical membrane. However, the molecular basis sustaining the spatiotemporal dynamics of Yrt remains undefined. In this paper, we report that atypical protein kinase C (aPKC) phosphorylates Yrt to prevent its premature apical localization. A nonphosphorylatable version of Yrt dominantly dismantles the apical domain, showing that its aPKC-mediated exclusion is crucial for epithelial cell polarity. In return, Yrt counteracts aPKC functions to prevent apicalization of the plasma membrane. The ability of Yrt to bind and restrain aPKC signaling is central for its role in polarity, as removal of the aPKC binding site neutralizes Yrt activity. Thus, Yrt and aPKC are involved in a reciprocal antagonistic regulatory loop that contributes to segregation of distinct and mutually exclusive membrane domains in epithelial cells.
Analysis on a generalized algorithm for the strong discrete logarithm problem with auxiliary inputs
Authors: Kim Minkyu , Cheon Jung Hee , Lee In-Sok
Published: February 2014

We investigate a recently proposed algorithm solving the strong discrete logarithm problem with auxiliary inputs, and show that this algorithm in general is not more efficient than ordinary discrete-logarithm-solving algorithms such as Pollard’s rho method, by analyzing a lower bound on the sum of digits of integers.
SurvMicro: assessment of miRNA-based prognostic signatures for cancer clinical outcomes by multivariate survival analysis
Authors: Aguirre-Gamboa Raul , Trevino Victor
Published: February 2014

Summary: MicroRNAs (miRNAs) play a key role in post-transcriptional regulation of mRNA levels. Their function in cancer has been studied by high-throughput methods generating valuable sources of public information. Thus, miRNA signatures predicting cancer clinical outcomes are emerging. An important step to propose miRNA-based biomarkers before clinical validation is their evaluation in independent cohorts. Although it can be carried out using public data, such task is time-consuming and requires a specialized analysis. Therefore, to aid and simplify the evaluation of prognostic miRNA signatures in cancer, we developed SurvMicro, a free and easy-to-use web tool that assesses miRNA signatures from publicly available miRNA profiles using multivariate survival analysis. SurvMicro is composed of a wide and updated database of >40 cohorts in different tissues and a web tool where survival analysis can be done in minutes. We presented evaluations to portray the straightforward functionality of SurvMicro in liver and lung cancer. To our knowledge, SurvMicro is the only bioinformatic tool that aids the evaluation of multivariate prognostic miRNA signatures in cancer.

Availability and implementation: SurvMicro and its tutorial are freely available at http://bioinformatica.mty.itesm.mx/SurvMicro.

Contact:  vtrevino@itesm.mx or victor.trevino@gmail.com

Supplementary Information:  Supplementary data are available at Bioinformatics online.
New Light on Candles on the Seventeenth-Century French Stage
Authors: Hawcroft Michael
Published: February 2014

Modern accounts of the seventeenth-century French stage have repeatedly asserted that plays were divided into short acts of some twenty to thirty minutes in performance because the candles that lit the theatres had to be snuffed at frequent intervals. This article claims that there is no evidence for this assertion and aims to evoke the technological constraints of candle usage at the time so as to suggest that candles could be managed in such a way that they did not actually dictate dramaturgical practice. The article considers seventeenth-century theoretical discussion of the division of plays into acts: such discussion never alludes to candles, but refers to historical precedent and spectator attention spans as perceived explanations for the phenomenon of act division. It aims to adduce compelling evidence against the traditional view and concludes that the snuffing of candles took advantage of the opportunity offered by act division, but was never its cause.
The contribution of quota to the discards problem: a case study on the complexity of common megrim Lepidorhombus whiffiagonis discarding in the northern North Sea
Authors: Macdonald P. , Cleasby I. R. , Angus C. H. , Marshall C. T.
Published: February 2014

The common megrim Lepidorhombus whiffiagonis is a commercially important, high-value flatfish species. From the early 2000s, discarding of common megrim in the northern North Sea has been widespread. In this study, we investigated temporal variation in megrim discarding in the mixed demersal fishery in the northern North Sea before, and following recent quota increases. Furthermore, logistic regression models were applied to investigate the effects of a range of explanatory factors on the probability of individual fish being discarded. Results indicate that discarding on the vessels sampled has declined from an average of 54% of the total common megrim catch in 2009 to 20% in 2012. The decrease in total discards was primarily a result of a decrease in the proportions of discards categorized by the crew as small within the catches from 0.39 (±0.02 s.e.) in 2009 to 0.10 (±0.01 s.e.) in 2012. Model outputs also suggest that the likelihood of a fish being discarded decreases significantly (p < 0.001) with increasing quota. The current megrim total allowable catch serves only to regulate landings and does little to regulate fishing mortality. Additionally, the proposed reform of the CFP, including the move towards a discards ban and the implementation of maximum sustainable yield, raises a number of concerns that need to be addressed if the northern North Sea mixed demersal fishery is to be managed sustainably and remain economically viable in the future.
Distributed Cognitive Functions
Authors: Hodges John R.
Published: February 2014

Chapter 1 describes three broad domains of cognition that have a distributed neural basis: arousal/attention, memory and executive function, including applied anatomy, personality, and behaviour.
Standardized Mental Test Schedules: Their Uses and Abuses
Authors: Hodges John R.
Published: February 2014

Chapter 6 discusses various mental test schedules used over the years, from the 10-item Hodgkinson Mental Test, to the much more complex Dementia Rating Scale (DRS. For practical purposes, however, such tests can be divided into two broad groups: (i) the brief schedules that can easily be used in the clinic, or at the bedside, and do not require specialized equipment or training, and (ii) the more elaborate scales, which are used largely, at least at present, in research studies, and require the purchase of test materials and some training in their administration. The Addenbrooke’s Cognitive Examination (ACE) was developed in an attempt to bridge this divide and to provide a test with greater sensitivity to early cognitive decline than the Mini-Mental State Examination (MMSE) and which could also differentiate between different brain diseases. The remainder of this chapter covers possible alternative cognitive screening instruments. It describes three of the most commonly used brief assessment schedules: the MMSE, the Information–Memory–Concentration (IMC) Test, and the 10-item Hodgkinson Mental Test, which is derived from the IMC Test; plus two longer tests, which are widely used in dementia research: the Mattis Dementia Rating Scale (DRS) and the Cambridge Cognitive Examination—Revised (CAMCOG-R). Finally it also includes a description of the Alzheimer’s Disease Assessment Scale (ADAS-Cog) since it has been used widely in drug evaluation studies.
Chondrodysplasia Punctata, Autosomal Dominant Type (Mim 118650; 215105)
Authors: Spranger Jürgen W. , Brill Paula W. , Nishimura Gen , Superti-Furga Andrea , Unger Sheila
Published: February 2014

Chapter 20 covers chondrodysplasia punctata, autosomal dominant type (MIM 118650, 215105), including major clinical findings, radiographic features, and differential diagnoses.
Progressive Pseudorheumatoid Chondrodysplasia (Mim 208230)
Authors: Spranger Jürgen W. , Brill Paula W. , Nishimura Gen , Superti-Furga Andrea , Unger Sheila
Published: February 2014

Chapter 32 covers progressive pseudorheumatoid chondrodysplasia (MIM 208230), including major clinical findings, radiographic features, and differential diagnoses.
Odontochondrodysplasia (Mim 184260)
Authors: Spranger Jürgen W. , Brill Paula W. , Nishimura Gen , Superti-Furga Andrea , Unger Sheila
Published: February 2014

Chapter 35 covers odontochondrodysplasia (MIM 184260), including major clinical findings, radiographic features, and differential diagnoses.
Spondylometaphyseal Dysplasia with Cone-Rod Dystrophy (Mim 608940)
Authors: Spranger Jürgen W. , Brill Paula W. , Nishimura Gen , Superti-Furga Andrea , Unger Sheila
Published: February 2014

Chapter 38 covers spondylometaphyseal dysplasia with cone-rod dystrophy (MIM 608940), including major clinical findings, radiographic features, and differential diagnoses.
Spondylometaepiphyseal Dysplasia, Short Limb-Abnormal Calcification Type (Mim 271665)
Authors: Spranger Jürgen W. , Brill Paula W. , Nishimura Gen , Superti-Furga Andrea , Unger Sheila
Published: February 2014

Chapter 43 covers spondylometaepiphyseal dysplasia, short limb-abnormal calcification type (MIM 271665), including major clinical findings, radiographic features, and differential diagnoses.
Desbuquois Syndrome (Mim 251450)
Authors: Spranger Jürgen W. , Brill Paula W. , Nishimura Gen , Superti-Furga Andrea , Unger Sheila
Published: February 2014

Chapter 47 covers Desbuquois syndrome (MIM 251450), including major clinical findings, radiographic features, and differential diagnoses.
Pseudodiatrophic Dysplasia (Mim 264180)
Authors: Spranger Jürgen W. , Brill Paula W. , Nishimura Gen , Superti-Furga Andrea , Unger Sheila
Published: February 2014

Chapter 49 covers pseudodiatrophic dysplasia (MIM 264180), including major clinical findings, radiographic features, and differential diagnoses.
Opsismodysplasia (MIM 258480)
Authors: Spranger Jürgen W. , Brill Paula W. , Nishimura Gen , Superti-Furga Andrea , Unger Sheila
Published: February 2014

Chapter 53 covers opsismodysplasia (MIM 258480), including major clinical findings, radiographic features, and differential diagnoses.
Thoracolaryngopelvic Dysplasia (Mim 187760, 187770)
Authors: Spranger Jürgen W. , Brill Paula W. , Nishimura Gen , Superti-Furga Andrea , Unger Sheila
Published: February 2014

Chapter 56 covers thoracolaryngopelvic dysplasia (MIM 187760, 187770), including major clinical findings, radiographic features, and differential diagnoses.
Omodysplasia, Autosomal Recessive (MIM 258315, 251455, 268250)
Authors: Spranger Jürgen W. , Brill Paula W. , Nishimura Gen , Superti-Furga Andrea , Unger Sheila
Published: February 2014

Chapter 61 covers omodysplasia, autosomal recessive (MIM 258315, 251455, 268250), including major clinical findings, radiographic features, and differential diagnoses.
Mesomelic Dysplasia, Werner Type (Mim 135750; 174500; 188740; 188770)
Authors: Spranger Jürgen W. , Brill Paula W. , Nishimura Gen , Superti-Furga Andrea , Unger Sheila
Published: February 2014

Chapter 66 covers mesomelic dysplasia, Werner type (MIM 135750, 174500, 188740, 188770), including major clinical findings, radiographic features, and differential diagnoses.
Mesomelic Dysplasia, Nievergelt-Savarirayan Type (Mim 163400; 605274)
Authors: Spranger Jürgen W. , Brill Paula W. , Nishimura Gen , Superti-Furga Andrea , Unger Sheila
Published: February 2014

Chapter 68 covers mesomelic dysplasia, Nievergelt-Savarirayan type (MIM 163400, 605274), including major clinical findings, radiographic features, and differential diagnoses.
Acromesomelic Dysplasia, Maroteaux Type (Mim 602875)
Authors: Spranger Jürgen W. , Brill Paula W. , Nishimura Gen , Superti-Furga Andrea , Unger Sheila
Published: February 2014

Chapter 70 covers acromesomelic dysplasia, Maroteaux type (MIM 602875), including major clinical findings, radiographic features, and differential diagnoses.
Grebe Dysplasia (MIM 200700, 201250, 228900)
Authors: Spranger Jürgen W. , Brill Paula W. , Nishimura Gen , Superti-Furga Andrea , Unger Sheila
Published: February 2014

Chapter 71 covers Grebe dysplasia (MIM 200700, 201250, 228900), including major clinical findings, radiographic features, and differential diagnoses.
Angel-Shaped Phalangoepiphyseal Dysplasia (MIM 105835)
Authors: Spranger Jürgen W. , Brill Paula W. , Nishimura Gen , Superti-Furga Andrea , Unger Sheila
Published: February 2014

Chapter 76 covers angel-shaped phalangoepiphyseal dysplasia (MIM 105835), including major clinical findings, radiographic features, and differential diagnoses.
Geleophysic Dysplasia (Mim 231050)
Authors: Spranger Jürgen W. , Brill Paula W. , Nishimura Gen , Superti-Furga Andrea , Unger Sheila
Published: February 2014

Chapter 80 covers geleophysic dysplasia (MIM 231050), including major clinical findings, radiographic features, and differential diagnoses.
Cousin Dysplasia (Mim 260660)
Authors: Spranger Jürgen W. , Brill Paula W. , Nishimura Gen , Superti-Furga Andrea , Unger Sheila
Published: February 2014

Chapter 86 covers cousin dysplasia (MIM 260660), including major clinical findings, radiographic features, and differential diagnoses.
Cumming Dysplasia (Mim 211890)
Authors: Spranger Jürgen W. , Brill Paula W. , Nishimura Gen , Superti-Furga Andrea , Unger Sheila
Published: February 2014

Chapter 87 covers Cumming dysplasia (MIM 211890), including major clinical findings, radiographic features, and differential diagnoses.
3M Syndrome (Mim 273750)
Authors: Spranger Jürgen W. , Brill Paula W. , Nishimura Gen , Superti-Furga Andrea , Unger Sheila
Published: February 2014

Chapter 88 covers 3M syndrome (MIM 273750), including major clinical findings, radiographic features, and differential diagnoses.
Kenny-Caffey syndrome (Mim 244460 [Type I]; 127000 [Type 2])
Authors: Spranger Jürgen W. , Brill Paula W. , Nishimura Gen , Superti-Furga Andrea , Unger Sheila
Published: February 2014

Chapter 89 covers Kenny-Caffey syndrome (MIM 244460 [type 1], 127000 [type 2]), including major clinical findings, radiographic features, and differential diagnoses.
Pyknodysostosis (Mim 265800)
Authors: Spranger Jürgen W. , Brill Paula W. , Nishimura Gen , Superti-Furga Andrea , Unger Sheila
Published: February 2014

Chapter 97 covers pyknodysostosis (MIM 265800), including major clinical findings, radiographic features, and differential diagnoses.
Osteopetrosis, Ectodermal Dysplasia, Immune Defect (Mim 300301)
Authors: Spranger Jürgen W. , Brill Paula W. , Nishimura Gen , Superti-Furga Andrea , Unger Sheila
Published: February 2014

Chapter 99 covers osteopetrosis, ectodermal dysplasia, immune defect (MIM 300301), including major clinical findings, radiographic features, and differential diagnoses.
Pachydermoperiostosis, Autosomal Dominant (Mim 167100)
Authors: Spranger Jürgen W. , Brill Paula W. , Nishimura Gen , Superti-Furga Andrea , Unger Sheila
Published: February 2014

Chapter 109 covers pachydermoperiostosis, autosomal dominant (MIM 167100), including major clinical findings, radiographic features, and differential diagnoses.
Pachydermoperiostosis, Autosomal Recessive (Mim 259100)
Authors: Spranger Jürgen W. , Brill Paula W. , Nishimura Gen , Superti-Furga Andrea , Unger Sheila
Published: February 2014

Chapter 110 covers pachydermoperiostosis, autosomal recessive (MIM 259100), including major clinical findings, radiographic features, and differential diagnoses.
Diaphyseal Medullary Stenosis with Bone Malignancy (Mim 112250)
Authors: Spranger Jürgen W. , Brill Paula W. , Nishimura Gen , Superti-Furga Andrea , Unger Sheila
Published: February 2014

Chapter 111 covers diaphyseal medullary stenosis with bone malignancy (MIM 112250), including major clinical findings, radiographic features, and differential diagnoses.
Geroderma Osteodysplasticum (Mim 231070)
Authors: Spranger Jürgen W. , Brill Paula W. , Nishimura Gen , Superti-Furga Andrea , Unger Sheila
Published: February 2014

Chapter 123 covers geroderma osteodysplasticum (MIM 231070), including major clinical findings, radiographic features, and differential diagnoses.
Weismann-Netter Syndrome (Mim 112350)
Authors: Spranger Jürgen W. , Brill Paula W. , Nishimura Gen , Superti-Furga Andrea , Unger Sheila
Published: February 2014

Chapter 124 covers Weismann-Netter syndrome (MIM 112350), including major clinical findings, radiographic features, and differential diagnoses.
Spondyloocular Dysplasia (Mim 605822)
Authors: Spranger Jürgen W. , Brill Paula W. , Nishimura Gen , Superti-Furga Andrea , Unger Sheila
Published: February 2014

Chapter 127 covers spondyloocular dysplasia (MIM 605822), including major clinical findings, radiographic features, and differential diagnoses.
Hypophosphatasia (Mim 146300, 241500)
Authors: Spranger Jürgen W. , Brill Paula W. , Nishimura Gen , Superti-Furga Andrea , Unger Sheila
Published: February 2014

Chapter 129 covers hypophosphatasia (MIM 146300, 241500) including major clinical findings, radiographic features, and differential diagnoses.
Hereditary Rickets (Mim 307800, 193100, 241520, 613312, 241530, 264700, 600081, 277440, 600785)
Authors: Spranger Jürgen W. , Brill Paula W. , Nishimura Gen , Superti-Furga Andrea , Unger Sheila
Published: February 2014

Chapter 131 covers hereditary rickets (MIM 307800, 193100, 241520, 613312, 241530, 264700, 600081, 277440, 600785), including major clinical findings, radiographic features, and differential diagnoses.
Familial Expansile Osteolysis (MIM 174810)
Authors: Spranger Jürgen W. , Brill Paula W. , Nishimura Gen , Superti-Furga Andrea , Unger Sheila
Published: February 2014

Chapter 135 covers familial expansile osteolysis (MIM 174810), including major clinical findings, radiographic features, and differential diagnoses.
Mandibuloacral Dysplasia (MIM 248370; 608612)
Authors: Spranger Jürgen W. , Brill Paula W. , Nishimura Gen , Superti-Furga Andrea , Unger Sheila
Published: February 2014

Chapter 137 covers mandibuloacral dysplasia (MIM 248370, 608612), including major clinical findings, radiographic features, and differential diagnoses.
Progeria (MIM 176670)
Authors: Spranger Jürgen W. , Brill Paula W. , Nishimura Gen , Superti-Furga Andrea , Unger Sheila
Published: February 2014

Chapter 138 covers progeria (MIM 176670), including major clinical findings, radiographic features, and differential diagnoses.
Hajdu-Cheney Osteolysis (MIM 102500)
Authors: Spranger Jürgen W. , Brill Paula W. , Nishimura Gen , Superti-Furga Andrea , Unger Sheila
Published: February 2014

Chapter 140 covers Hajdu-Cheney osteolysis (MIM 102500), including major clinical findings, radiographic features, and differential diagnoses.
Multiple Cartilaginous Exostoses (MIM 133700)
Authors: Spranger Jürgen W. , Brill Paula W. , Nishimura Gen , Superti-Furga Andrea , Unger Sheila
Published: February 2014

Chapter 145 covers multiple cartilaginous exostoses (MIM 133700), including major clinical findings, radiographic features, and differential diagnoses.
Osteoglophonic Dysplasia (MIM 166250)
Authors: Spranger Jürgen W. , Brill Paula W. , Nishimura Gen , Superti-Furga Andrea , Unger Sheila
Published: February 2014

Chapter 146 covers osteoglophonic dysplasia (MIM 166250), including major clinical findings, radiographic features, and differential diagnoses.
Dysplasia Epiphysealis Hemimelica (MIM 127800)
Authors: Spranger Jürgen W. , Brill Paula W. , Nishimura Gen , Superti-Furga Andrea , Unger Sheila
Published: February 2014

Chapter 148 covers dysplasia epiphysealis hemimelica (MIM 127800), including major clinical findings, radiographic features, and differential diagnoses.
Genochondromatosis (MIM 137360)
Authors: Spranger Jürgen W. , Brill Paula W. , Nishimura Gen , Superti-Furga Andrea , Unger Sheila
Published: February 2014

Chapter 151 covers genochondromatosis (MIM 137360), including major clinical findings, radiographic features, and differential diagnoses.
Apert Syndrome (MIM 101200)
Authors: Spranger Jürgen W. , Brill Paula W. , Nishimura Gen , Superti-Furga Andrea , Unger Sheila
Published: February 2014

Chapter 156 covers Apert syndrome (MIM 101200), including major clinical findings, radiographic features, and differential diagnoses.
Jarcho-Levin Syndrome (MIM 277300)
Authors: Spranger Jürgen W. , Brill Paula W. , Nishimura Gen , Superti-Furga Andrea , Unger Sheila
Published: February 2014

Chapter 164 covers Jarcho-Levin syndrome (MIM 277300), including major clinical findings, radiographic features, and differential diagnoses.
Shorter Oxford Textbook of Psychiatry
Authors: Cowen Philip , Harrison Paul , Burns Tom
Published: February 2014

Widely recognised as the standard text for trainee psychiatrists, the Shorter Oxford Textbook of Psychiatry stands head and shoulders above the competition. Honed over five editions it displays a rare fluency, authority and insight, and it makes the process of assimilating information as smooth and enjoyable as possible. The resource provides an introduction to all the clinical topics required by the trainee psychiatrist, including all the sub-specialties and major psychiatric conditions. Throughout, the authors emphasize the basic clinical skills required for the full assessment and understanding of the patient. Discussion of treatment includes not only scientific evidence, but also practical problems in the management of patients their family and social context. It emphasizes an evidence-based approach to practice and gives full attention to ethical and legal issues. Introductory chapters focus on recognition of signs and symptoms, classification and diagnosis, psychiatric assessment, and aetiology. Further chapters deal with all the major psychiatric syndromes as well as providing detailed coverage of pharmacological and psychological treatments. It also gives equal prominence to ICD and DSM classification - often with direct comparisons.
Schizophrenia
Authors: Cowen Philip , Harrison Paul , Burns Tom
Published: February 2014

Chapter 11 discusses how, of all the major psychiatric syndromes, schizophrenia is the most difficult to define and describe. This partly reflects the fact that, over the past 100 years, widely divergent concepts have been held in different countries and by different psychiatrists. Although there is now a greater consensus, substantial uncertainties remain. Indeed, schizophrenia remains the best example of the fundamental issues with which psychiatry continues to grapple—concepts of disease, classification, and aetiology. Having noted the complexities, we start with an introduction to acute schizophrenia and chronic schizophrenia. The reader should bear in mind that these will be idealized descriptions and comparisons, but it is useful to oversimplify at first before introducing the controversial issues.
Psychiatry of the elderly
Authors: Cowen Philip , Harrison Paul , Burns Tom
Published: February 2014

When considering psychiatric disorder in the elderly, the clinician must be able to collect and integrate information from a variety of sources, and produce a management plan which takes account of physical and social needs, as well as psychological ones. This plan is likely to involve the cooperation of several professionals. It is in this clinical complexity that much of the challenge and fascination of old age psychiatry lies. Chapter 18 deals with the psychiatry of old age, with two important exceptions, both of which were covered in Chapter 13: delirium, and the clinical features, aetiology, and investigation of dementia.
Learning disability (mental retardation)
Authors: Cowen Philip , Harrison Paul , Burns Tom
Published: February 2014

This chapter is concerned with a general outline of the features, epidemiology, and aetiology of learning disability (mental retardation), the organization of services and, more specifically, with the psychiatric disorders that affect these people. Many of the psychiatric problems of children with learning disability are similar to those of children of normal intelligence; an account of these problems is given in the previous chapter on child psychiatry.
The Many Faces of Parkinsonism
Authors: Schneider Susanne A. , Klein Christine
Published: February 2014

Parkinson’s disease (PD), and more so ‘parkinsonian syndromes’, have many faces. In recent years numerous genetic causes of parkinsonism have been identified in addition to idiopathic PD and secondary form. In this chapter we review the genetic causes of parkinsonism, with particular focus on mimics of idiopathic PD. These include disorders assigned a PARK locus that present with either classic parkinsonism or with parkinsonism with additional atypical features, causes of classic parkinsonism associated with mutations in a non-PARK or ‘other than-PARK’ gene (e.g. in a DYT or SCA gene) where parkinsonism is a well-recognized concomitant or even isolated feature, and disorders of atypical parkinsonism as a rare presentation of a genetic disorder which is usually characterized by features other than parkinsonism. We will summarize clinical characteristics, results of investigations (e.g. imaging, electrophysiology, or pathological data), and main genetic findings in order to provide a useful overview for clinicians and scientists who may be puzzled by this evolving area.
Primary Dementia Syndromes and Parkinsonism
Authors: Lemstra A.W. , Seelaar H. , van Swieten J.C.
Published: February 2014

This chapter addresses neurodegenerative diseases that are primarily dementia syndromes but are frequently or by definition accompanied by parkinsonism. In many neurodegenerative diseases cognitive dysfunction and extrapyramidal signs occur during the course of the disease. This chapter is limited to those diseases in which dementia is a core feature and parkinsonism is mostly present early in the disease. We will discuss dementia with Lewy bodies (DLB) and frontotemporal lobar degeneration (FTLD), syndromes which present with parkinsonism. DLB is part of the spectrum of Parkinson’s disease, and is clinically challenging from the diagnostic and management perspective. Recent advances in genetic and molecular research have greatly improved insight into disease mechanisms in FTLD, with mutations in two MAPT and GRN genes on chromosome 17. We will discuss the clinical and pathological overlap between FTDP-17 and other parkinsonian syndromes. The combination of cognitive dysfunction and extrapyramidal symptoms in corticobasal degeneration and progressive supranuclear palsy may overlap with FTLD, but these diseases are not considered to be primary dementia syndromes.
Other Dystonias
Authors: Phukan Julie , Warner Thomas
Published: February 2014

Primary forms of dystonia represent around 70 per cent of all cases and are described in Chapter 18. The remainder comprise those cases where dystonia is part of a more complex movement disorder or neurological syndrome. These can be divided into four broad categories: dystonia-plus syndromes, heredodegenerative disorders, secondary (or symptomatic dystonia), and dystonia that is a feature of another neurological condition. The key difference from primary dystonia is the presence of other neurological features in addition to dystonia. Many have underlying neurodegeneration, often genetic in origin.
Huntington’s Disease
Authors: Barker Roger A. , Priller Josef
Published: February 2014

Huntington’s disease (HD) is a rare autosomal dominant neurodegenerative condition that commonly presents in mid life with a combination of a movement disorder and psychiatric and cognitive problems. The identification of the gene underlying HD in 1993 has led to many major breakthroughs in our understanding of this disease, but it remains incurable and fatal to the present time. Our better understanding of the range of clinical features seen in this complex neuropsychiatric disorder and our ability to detect those earliest changes is leading to a new era of drugs trials for HD with the prospect of identifying disease-modifying agents. There is also a new impetus to look at drugs to better treat the symptoms and signs of HD as well as better support patients and their families in the community. In this chapter we outline some of these therapies, and provide clinical tips on how best to assess the HD patient.
Non-degenerative Choreas
Authors: Cardoso Francisco
Published: February 2014

Non-genetic choreas can have a myriad of causes which fit into the following categories: autoimmune, vascular, drug-induced, infectious, metabolic and toxic encephalopathy, and miscellaneous. Sydenham’s chorea, an autoimmune condition related to streptococcal infection, is the most common cause of chorea in children worldwide. In contrast, vascular disease, particularly in association with diabetes mellitus type 2, accounts for the majority of non-genetic choreas in adults. HIV infection, systemic lupus erythematosus, drugs, paraneoplastic syndromes, hyperthyroidism, brain neoplasms, etc. are also causes of chorea. The aim of this chapter is to discuss the epidemiology, clinical features, diagnosis, pathogenesis, and management of acquired causes of chorea.
Wilson Disease
Authors: Bandmann Oliver
Published: February 2014

Wilson disease (WD) is an autosomal recessively inherited monogenic copper storage disease. At least 50% of all patients with WD first present with neurological or psychiatric problems. If treated early, patients can make a full recovery and then lead a near-normal life, but failure to make the diagnosis can result in severe irreversible brain damage and untimely death.
Tic Disorders and Stereotypies
Authors: Augustine Erika F. , Mink Jonathan W.
Published: February 2014

Tics and stereotypies are common childhood movement disorders, each characterized by repetitive stereotyped movements. Older age at onset, a fluctuating and evolving course, and the presence of a premonitory urge are all helpful features that help to differentiate tics from stereotypies. Tics are frequently associated with comorbid disorders, including attention deficit–hyperactivity disorder (ADHD), obsessive–compulsive disorder (OCD), anxiety, mood disorders, and behavioural difficulties. These co-occurring neuropsychiatric disorders may be the main source of functional impairment. When tics result in functional impairment, α2-adrenergic agonists and dopamine receptor antagonists are the mainstay of therapy. Stereotypies are commonly found in healthy, typically developing children. Yet, they are also prominent in children with neurodevelopmental disabilities. Stereotypies typically do not require treatment. When part of a more complex neurodevelopmental disorder, behavioural strategies can be beneficial. For both types of involuntary movement, assessment of phenomenology and review of social, emotional, neurobehavioural, and cognitive factors are key to diagnosis as well as further evaluation and treatment.

Tics and stereotypies are among the most common movement disorders in childhood. These early-onset involuntary movements are stereotyped in nature, but differ in phenomenology, age at onset, and comorbid conditions. This chapter will outline the key identifying features, natural history, and treatment of each.
Hereditary and Acquired Cerebellar Ataxias
Authors: Koutsis George , Wood Nicholas W.
Published: February 2014

‘Cerebellar ataxia’ refers to a clinical syndrome caused by damage to the cerebellum and its connections and characterized by lack of coordination most evident in gait, use of the extremities, speech, and ocular movement. Although individual ataxic disorders are relatively rare, the ataxias as a whole represent a common clinical problem. Acquired ataxias are the most frequent, but heredoataxias also contribute a substantial proportion of cases. Over the past two decades, neuroimaging and molecular genetics have revolutionized the field, shedding light on the aetiology of these diverse disorders.

The differential diagnosis of cerebellar ataxia is complex and consists of an extensive list of acquired and an ever-expanding list of recognized hereditary causes. Acquired causes include viral cerebellitis, space-occupying lesions, multiple sclerosis, alcoholic cerebellar degeneration, drug toxicity, paraneoplastic cerebellar degeneration, superficial siderosis, multiple system atrophy, and idiopathic late-onset cerebellar ataxia. Hereditary causes include inborn errors of metabolism, episodic ataxias, autosomal recessive cerebellar ataxias, autosomal dominant cerebellar ataxias (also known as spinocerebellar ataxias), X-linked ataxias, and mitochondrial ataxias. A systematic approach based on relatively straightforward clinical rules can be a useful guide to the diagnostic process. Determining the age of onset can limit the differential to congenital, early-onset (<25 years) and late-onset (> 25 years) causes. Clarifying the mode of onset can further narrow down the list to acute-onset, subacute-onset, and insidious-onset causes. The presence of a non-progressive, intermittent, or progressive course can focus the diagnosis further. Deciding whether an acquired or hereditary cause should be sought reduces the differential to a manageable list. Finally, specific information gathered from the history, the examination (including extracerebellar and extraneural findings), and routine or directed investigations allows the correct diagnosis to be made in most cases.
Systemic Disease and Movement Disorders
Authors: Cloud Leslie J. , Jankovic Joseph
Published: February 2014

Systemic illness is often complicated by the development of movement disorders, and the spectrum of movement disorders occurring in systemic diseases is as diverse as the spectrum of diseases eliciting them. While movement disorders often develop in patients with a known systemic illness, they can sometimes be the presenting feature of a systemic disease (1). Although pregnancy is not considered an “illness” there are many movement disorders associated with this condition(2). Recognition and treatment of the underlying condition or a systemic disorder is essential for the optimal management of associated abnormal movements. Therefore, when evaluating patients with movement disorders, clinicians should carefully consider all medical historical details, associated symptoms and signs, and risk factors for systemic diseases as these may provide important clues to the underlying aetiology of both the systemic and the associated movement disorders. The information presented in this chapter should serve as a guide not only to movement disorder clinicians but also to general and primary care physicians. Recognizing the movement disorder phenomenology is the first step that eventually leads to the aetiologic diagnosis.

This chapter reviews movement disorders occurring in conjunction with several broad categories of systemic disease, including paraneoplastic, autoimmune, endocrine, metabolic, nutritional, and infectious diseases.
Haematology
Authors: Longmore Murray , Wilkinson Ian B. , Baldwin Andrew , Wallin Elizabeth
Published: February 2014

On the taking of blood and of holidays

Anaemia

Iron-deficiency anaemia

Anaemia of chronic disease

Sideroblastic anaemia

The peripheral blood film

The differential white cell count

Macrocytic anaemia

b12 deficiency and pernicious anaemia

An approach to haemolysis

Causes of haemolysis

Sickle-cell anaemia

Thalassaemia

Bleeding disorders...
Infectious diseases
Authors: Longmore Murray , Wilkinson Ian B. , Baldwin Andrew , Wallin Elizabeth
Published: February 2014

Classification of pathogens –

An approach to infectious diseases:

Travel advice

Antibiotics: penicillins

Cephalosporins and others

Empirical ‘blind’ treatment

Using a side-room laboratory

Drug abuse & infectious diseases

PUO and the tropical traveller –

Gastroenteritis

Immunization

Nosocomial infections

Some specific infections:

Malaria

Tuberculosis (MDR-TB )

Infectious mononucleosis...
Oncology and palliative care
Authors: Longmore Murray , Wilkinson Ian B. , Baldwin Andrew , Wallin Elizabeth
Published: February 2014

Looking after people with cancer

Oncology and genetics

Oncological emergencies

Cancer therapies

Radiotherapy

Urgent referral in possible malignancy

Tumour markers

Palliative care:

Principles and symptom relief

Pain relief

Relevant pages for specific cancers:

Anal (p633)

Breast (p604)

cns (...
The child patient
Authors: Tucker Lori B.
Published: February 2014

The child with a rheumatic disease often presents a diagnostic and therapeutic challenge. A broad knowledge of paediatric development and rheumatic diseases of childhood, as well as the ability to work through a diverse paediatric differential diagnosis, is required to properly evaluate children presenting with musculoskeletal or rheumatic complaints. Extensive work has been done in recent years to improve the definitions of the various childhood rheumatic diseases and define the disease course and outcomes.
Young people and transitional care in rheumatology
Authors: McDonagh Janet E. , Gleeson Helena
Published: February 2014

Young people are distinctly different from children and adults and as such require developmentally appropriate, youth-friendly rheumatology services to meet their medical and psychosocial needs. Adolescent development continues into the third decade of life and both influences and is affected by, health and illness (including rheumatic disease) during this time. Effective transitional care in rheumatology is underpinned by the core principles of adolescent medicine, self-management of long-term conditions, and a youth-friendly rheumatology service including staff trained in adolescent health.
The elderly patient
Authors: Birrell Fraser , O’Connell Janice
Published: February 2014

In this chapter, we describe how the process of ageing can itself affect the diagnosis and treatment of musculoskeletal conditions. We outline general principles concerning the clinical presentation of rheumatological diseases in older patients, as well as providing specific guidance on the diagnosis and management of the commoner conditions encountered in practice in the United Kingdom.