bluuebunny/crossref_metadata_2025 huggingface dataset:
Ab initio quantum transport simulation of silicide-silicon contacts
Authors: Gao Qun , Guo Jing
Published: January 2012

Parasitic contact resistance increasingly limits modern CMOS performance. Atomistic scale features and quantum effects play an important role in determining silicide-silicon contact properties. We develop ab initio quantum transport simulation capabilities for silicide-silicon contacts, which provide first principle descriptions of interfacial structural, electronic, and transport properties. It is found that transmission through the CoSi2-Si contact of the primed valleys can be distinctively different from that of the unprimed valleys, due to the size of the CoSi2 Fermi surface. Interfacial atomistic doping can modulate the barrier height, but, at the same time, lower the transmission and induce localized bandgap states. The primary effect of strain is to modulate the barrier height instead of quantum transmission. The physical insights obtained here would not have been possible by tight binding simulations, where reliable interface binding parameters lack.
The effect of InGaAs strain-reducing layer on the optical properties of InAs quantum dot chains grown on patterned GaAs(100)
Authors: Hakkarainen T. V. , Schramm A. , Tommila J. , Guina M.
Published: January 2012

We report the influence of InGaAs strain-reducing layers on the optical properties of quantum dot chains grown on groove patterns oriented along the [011], [01-1], and [010] directions. The site-controlled InAs quantum dot chains were grown by molecular beam epitaxy on GaAs(100) substrates patterned by nanoimprint lithography. The InGaAs capping causes a redshift of photoluminescence, which depends on the groove orientations. Based on the analysis of the surface morphology before and after capping, we attribute this to variation of composition and effective thickness of the InGaAs layer in grooves with different orientations. Furthermore, we analyze the effect of the InGaAs cap thickness on the in-plane polarization anisotropy of the photoluminescence emission and show that the [01-1]-oriented quantum dot chains experience a significant increase of polarization anisotropy with increasing InGaAs cap thickness. The increase of polarization anisotropy is attributed to enhanced interdot coupling due to a reduction of the barrier height and piezoelectronic potential.
Follicular fluid supplementation during in vitro maturation promotes sperm penetration in bovine oocytes by enhancing cumulus expansion and increasing mitochondrial activity in oocytes
Authors: Somfai Tamás , Inaba Yasushi , Watanabe Shinya , Geshi Masaya , Nagai Takashi
Published: January 2012

The aim of this study was to examine the effects of bovine follicular fluid (bFF) on mitochondrial activity in in vitro-matured (IVM) oocytes and to assess its importance for fertilisation and embryo development. Bovine follicular oocytes were subjected to IVM in medium supplemented either with polyvinylpyrrolidone, bovine serum albumin, calf serum or bFF. Nuclear maturation, cumulus expansion, mitochondrial distribution and ATP content in oocytes were compared between groups along with subsequent in vitro fertilisation (IVF) and embryo development. Compared with other supplements, bFF generated significantly enhanced re-distribution of active mitochondria in oocytes and this effect was associated with elevated intracellular ATP content. Furthermore, bFF significantly improved cumulus expansion, which was associated with improved fertilisation rates when cumulus-enclosed oocytes were subjected to IVF; however, its promoting effect was neutralised when denuded oocytes were inseminated. Elevating ATP content in oocytes by bFF did not affect maturation or embryo development but promoted fertilisation when mitochondrial electron transport was blocked in oocytes before IVF by Rotenone. In conclusion, supplementation of IVM medium with bFF promotes sperm penetration both by the improvement of cumulus expansion and by enhancing ATP levels in oocytes, which maintains their ability to be fertilised after mitochondrial stress.
14-3-3 fusion oncogenes in high-grade endometrial stromal sarcoma
Authors: Lee Cheng-Han , Ou Wen-Bin , Mariño-Enriquez Adrian , Zhu Meijun , Mayeda Mark , Wang Yuexiang , Guo Xiangqian , Brunner Alayne L. , Amant Frédéric , French Christopher A. , West Robert B. , McAlpine Jessica N. , Gilks C. Blake , Yaffe Michael B. , Prentice Leah M. , McPherson Andrew , Jones Steven J. M. , Marra Marco A. , Shah Sohrab P. , van de Rijn Matt , Huntsman David G. , Dal Cin Paola , Debiec-Rychter Maria , Nucci Marisa R. , Fletcher Jonathan A.
Published: January 2012

14-3-3 proteins are ubiquitously expressed regulators of various cellular functions, including proliferation, metabolism, and differentiation, and altered 14-3-3 expression is associated with development and progression of cancer. We report a transforming 14-3-3 oncoprotein, which we identified through conventional cytogenetics and whole-transcriptome sequencing analysis as a highly recurrent genetic mechanism in a clinically aggressive form of uterine sarcoma: high-grade endometrial stromal sarcoma (ESS). The 14-3-3 oncoprotein results from a
t
(10;17) genomic rearrangement, leading to fusion between 14-3-3ε (YWHAE) and either of two nearly identical FAM22 family members (FAM22A or FAM22B). Expression of YWHAE–FAM22 fusion oncoproteins was demonstrated by immunoblot in
t
(10;17)-bearing frozen tumor and cell line samples.
YWHAE–FAM22
fusion gene knockdowns were performed with shRNAs and siRNAs targeting various
FAM22A
exons in an
t
(10;17)-bearing ESS cell line (ESS1): Fusion protein expression was inhibited, with corresponding reduction in cell growth and migration. YWHAE–FAM22 maintains a structurally and functionally intact 14-3-3ε (YWHAE) protein-binding domain, which is directed to the nucleus by a FAM22 nuclear localization sequence. In contrast to classic ESS, harboring JAZF1 genetic fusions, YWHAE–FAM22 ESS display high-grade histologic features, a distinct gene-expression profile, and a more aggressive clinical course. Fluorescence in situ hybridization analysis demonstrated absolute specificity of
YWHAE–FAM22A/B
genetic rearrangement for high-grade ESS, with no fusions detected in other uterine and nonuterine mesenchymal tumors (55 tumor types,
n
= 827). These discoveries reveal diagnostically and therapeutically relevant models for characterizing aberrant 14-3-3 oncogenic functions.
Tiling genomes of pathogenic viruses identifies potent antiviral shRNAs and reveals a role for secondary structure in shRNA efficacy
Authors: Tan Xu , Lu Zhi John , Gao Geng , Xu Qikai , Hu Long , Fellmann Christof , Li Mamie Z. , Qu Hongjing , Lowe Scott W. , Hannon Gregory J. , Elledge Stephen J.
Published: January 2012

shRNAs can trigger effective silencing of gene expression in mammalian cells, thereby providing powerful tools for genetic studies, as well as potential therapeutic strategies. Specific shRNAs can interfere with the replication of pathogenic viruses and are currently being tested as antiviral therapies in clinical trials. However, this effort is hindered by our inability to systematically and accurately identify potent shRNAs for viral genomes. Here we apply a recently developed highly parallel sensor assay to identify potent shRNAs for HIV, hepatitis C virus (HCV), and influenza. We observe known and previously unknown sequence features that dictate shRNAs efficiency. Validation using HIV and HCV cell culture models demonstrates very high potency of the top-scoring shRNAs. Comparing our data with the secondary structure of HIV shows that shRNA efficacy is strongly affected by the secondary structure at the target RNA site. Artificially introducing secondary structure to the target site markedly reduces shRNA silencing. In addition, we observe that HCV has distinct sequence features that bias HCV-targeting shRNAs toward lower efficacy. Our results facilitate further development of shRNA based antiviral therapies and improve our understanding and ability to predict efficient shRNAs.
Enhanced HIV-1 neutralization by antibody heteroligation
Authors: Mouquet Hugo , Warncke Malte , Scheid Johannes F. , Seaman Michael S. , Nussenzweig Michel C.
Published: January 2012

Passive transfer of broadly neutralizing human antibodies against HIV-1 protects macaques against infection. However, HIV-1 uses several strategies to escape antibody neutralization, including mutation of the gp160 viral surface spike, a glycan shield to block antibody access to the spike, and expression of a limited number of viral surface spikes, which interferes with bivalent antibody binding. The latter is thought to decrease antibody apparent affinity or avidity, thereby interfering with neutralizing activity. To test the idea that increasing apparent affinity might enhance neutralizing activity, we engineered bispecific anti–HIV-1 antibodies (BiAbs) that can bind bivalently by virtue of one scFv arm that binds to gp120 and a second arm to the gp41 subunit of gp160. The individual arms of the BiAbs preserved the binding specificities of the original anti-HIV IgG antibodies and together bound simultaneously to gp120 and gp41. Heterotypic bivalent binding enhanced neutralization compared with the parental antibodies. We conclude that antibody recognition and viral neutralization of HIV can be improved by heteroligation.
Compatibility between Environment-Induced Decoherence and the Modal-Hamiltonian Interpretation of Quantum Mechanics
Authors: Lombardi Olimpia , Ardenghi Juan Sebastián , Fortin Sebastian , Castagnino Mario
Published: January 2012

Given the impressive success of environment-induced decoherence (EID), nowadays no interpretation of quantum mechanics can ignore its results. The modal-Hamiltonian interpretation (MHI) has proved to be effective for solving several interpretative problems, but since its actualization rule applies to closed systems, it seems to stand at odds with EID. The purpose of this article is to show that this is not the case: the states einselected by the interaction with the environment according to EID (the elements of the “pointer basis”) are the eigenvectors of an actual-valued observable belonging to the preferred context selected by the MHI.
A Defense of Syntax-Based Gene Concepts in Postgenomics: Genes as Modular Subroutines in the Master Genomic Program
Authors: Baetu Tudor M.
Published: January 2012

The purpose of this article is to update and defend syntax-based (conserved DNA-sequence motifs) gene concepts. I show how syntax-based concepts have been and can be extended to accommodate complex cases of genome expression, regulation, and processing. In response to difficult cases and causal parity objections, I argue that the syntax-based approach fleshes out a deflationary concept that defines genes in terms of sequences and organizational features of the genome that contribute to a phenotype.
On Kinematic versus Dynamic Approaches to Special Relativity
Authors: Camp Wesley Van
Published: January 2012

Janssen argues that special relativity is preferable to Lorentzian dynamics due to its kinematic structure. Brown, along with others, raises an objection, arguing that a dynamical understanding of special relativity is explanatorily prior and hence more fundamental than the principle theory-based kinematic structure of Minkowski space-time. This article challenges this objection, arguing that both Janssen and Brown miss the essential aspect of the principles of special relativity that underwrite its interpretational success. It is not its kinematic structure but the constitutive nature of the principles it employs, by providing a coherent conceptual framework, that does the foundational work.
From the Pessimistic Induction to Semantic Antirealism
Authors: Frost-Arnold Greg
Published: January 2012

The Pessimistic Induction (PI) states: most past scientific theories were radically mistaken; therefore, current theories are probably similarly mistaken. But mistaken in what way? On the usual understanding, such past theories are false. However, on widely held views about reference and presupposition, many theoretical claims of previous scientific theories are neither true nor false. And if substantial portions of past theories are truth-valueless, then the PI leads to semantic antirealism. But most current philosophers of science reject semantic antirealism. So PI proponents face a difficult choice: accept either semantic antirealism or an unorthodox position on reference and presupposition.
The Instrumentalist's New Clothes
Authors: Rowbottom Darrell P.
Published: January 2012

This article develops a new version of instrumentalism, in light of progress in the realism debate in recent decades, and thereby defends the view that instrumentalism remains a viable philosophical position on science. The key idea is that talk of unobservable objects should be taken literally only when those objects are assigned properties (or described in terms of analogies involving things) with which we are experientially (or otherwise) acquainted. This is derivative from the instrumentalist tradition insofar as the distinction between unobservable and observable is taken to have significance with respect to meaning.
Some Difficulties for the Problem of Unconceived Alternatives
Authors: Ruhmkorff Samuel
Published: January 2012

P. Kyle Stanford defends the problem of unconceived alternatives, which maintains that scientists are unlikely to conceive of all the scientifically plausible alternatives to the theories they accept. Stanford's argument has been criticized on the grounds that the failure of individual scientists to conceive of relevant alternatives does not entail the failure of science as a corporate body to do so. I consider two replies to this criticism and find both lacking. In the process, I argue that Stanford does not provide evidence that there are likely scientifically plausible unconceived alternatives to scientific theories accepted now and in the future.
The Aharonov Approach to Equilibrium
Authors: Dizadji-Bahmani Foad
Published: January 2012

Using the ‘Aharonov approach’, Linden and colleagues purportedly prove that reaching equilibrium is a universal property of quantum systems. Such a proof would constitute a very significant result in the foundations of statistical mechanics. I argue that, as it stands, this proof is not sound. However, based on the their theorems, I construct an argument for the conclusion that an arbitrary small subsystem of a large quantum system typically tends toward and remains in, or close to, equilibrium. This is the central result of the article. In the final part of the article, I defend the Aharonov approach against anti-interventionist criticisms.
Against Regular and Irregular Characterizations of Mechanisms
Authors: DesAutels Lane
Published: January 2012

This article addresses the question of whether we should conceive of mechanisms as productive of change in a regular way. I argue that, if mechanisms are characterized as fully regular, on the one hand, then not enough processes will count as mechanisms for them to be interesting or useful. If no appeal to regularity is made at all in their characterization, on the other hand, then mechanisms can no longer be useful for grounding prediction and supporting intervention strategies. I conclude that, if the New Mechanistic Philosophy is to be successful, a stochastic characterization of mechanisms must be adopted.
On the Virtues of Cursory Scientific Reductions
Authors: Press Joel K.
Published: January 2012

Many philosophers accept a nonreductive physicalist view of at least some special sciences, which is to say that while they assert that each particular referent of any special science term is identical to some referent of a physical term, or token physicalism, they deny that special science types are identical to physical types. The most commonly cited reason for this position is Jerry Fodor's antireductionist argument based on the multiple realizability of many special science terms. I argue that if token physicalism is true, as nonreductive physicalists believe, then this multiple-realization argument fails to preclude reductive physicalism.
Sequence Matters: Genomic Research and the Gene Concept
Authors: Perini Laura
Published: January 2012

Analysis of two key ways of characterizing genes—as causes of phenotypic effects and as genomic DNA sequences—has yielded widespread pessimism that they can be united in a coherent gene concept. This raises important questions about the epistemology of genomic research: If analysis of a genome sequence cannot yield information about genes defined both in terms of their products and their DNA sequence, then what could we learn from it? I investigate basic tools of genomic analysis, argue that they do not reflect the application of either gene concept, and clarify how we learn from genomic research.
High Proportion of False-Positive Clostridium difficile Enzyme Immunoassays for Toxin A and B in Pediatric Patients
Authors: Toltzis Philip , Nerandzic Michelle M. , Saade Elie , O'Riordan Mary Ann , Smathers Sarah , Zaoutis Theoklis , Kim Jason , Donskey Curtis J.
Published: January 2012

Objectives.

To determine the frequency of false-positive Clostridium difficile toxin enzyme immunoassay (EIA) results in hospitalized children and to examine potential reasons for this false positivity.

Design.

Nested case-control.

Setting.

Two tertiary care pediatric hospitals.

Methods.

As part of a natural history study, prospectively collected EIA-positive stools were cultured for toxigenic C. difficile, and characteristics of children with false-positive and true-positive EIA results were compared. EIA-positive/culture-negative samples were recultured after dilution and enrichment steps, were evaluated for presence of the tcdB gene by polymerase chain reaction (PCR), and were further cultured for Clostridium sordellii, a cause of false-positive EIA toxin assays.

Results.

Of 112 EIA-positive stools cultured, 72 grew toxigenic C. difficile and 40 did not, indicating a positive predictive value of 64% in this population. The estimated prevalence of C. difficile infection (CDI) in the study sites among children tested for this pathogen was 5%–7%. Children with false-positive EIA results were significantly younger than those with true-positive tests but did not differ in other characteristics. No false-positive specimens yielded C. difficile when cultured after enrichment or serial dilution, 1 specimen was positive for tcdB by PCR, and none grew C. sordellii.

Conclusions.

Approximately one-third of EIA tests used to evaluate pediatric inpatients for CDI were falsely positive. This finding was likely due to the low prevalence of CDI in pediatric hospitals, which diminishes the test's positive predictive value. These data raise concerns about the use of EIA assays to diagnosis CDI in children.

Infect Control Hosp Epidemiol 2012;33(2):175-179
Initiation and channelling of a microwave discharge by a plasma filament created in atmospheric air by an intense femtosecond laser pulse
Authors: Bodrov S B , Kulagin D I , Malkov Yu A , Murzanev A A , Smirnov A I , Stepanov A N
Published: January 2012

We study the initiation of a pulsed microwave discharge in atmospheric air by a plasma channel induced by intense femtosecond laser pulses. It is shown that the electric field threshold for the initiated discharge is lowered compared with the self-discharge by about a factor of two, from 25 to 12 kV cm−1. Channelling of the atmospheric-pressure microwave discharge in the direction of the plasma filament has been detected. The time of existence of the initiated discharge plasma was determined by the duration of the microwave pulse and amounted to 1–2 µs for the maximum electron density estimated as about 4 × 1015 cm−3. The developed theory of propagation of the microwave radiation along the plasma channel created by a femtosecond laser pulse predicts that the relatively low conductivity of the plasma and its rapid decay limit the characteristic scale of decay of the microwave fields confined by the plasma channel to a few centimetres.
EPI64 interacts with Slp1/JFC1 to coordinate Rab8a and Arf6 membrane trafficking
Authors: Hokanson David E. , Bretscher Anthony P.
Published: January 2012

Cell function requires the integration of cytoskeletal organization and membrane trafficking. Small GTP-binding proteins are key regulators of these processes. We find that EPI64, an apical microvillar protein with a Tre-2/Bub2/Cdc16 (TBC) domain that stabilizes active Arf6 and has RabGAP activity, regulates Arf6-dependent membrane trafficking. Expression of EPI64 in HeLa cells induces the accumulation of actin-coated vacuoles, a distinctive phenotype seen in cells expressing constitutively active Arf6. Expression of EPI64 with defective RabGAP activity does not induce vacuole formation. Coexpression of Rab8a suppresses the vacuole phenotype induced by EPI64, and EPI64 expression lowers the level of Rab8-GTP in cells, strongly suggesting that EPI64 has GAP activity toward Rab8a. JFC1, an effector for Rab8a, colocalizes with and binds directly to a C-terminal region of EPI64. Together this region and the N-terminal TBC domain of EPI64 are required for the accumulation of vacuoles. Through analysis of mutants that uncouple JFC1 from either EPI64 or from Rab8-GTP, our data suggest a model in which EPI64 binds JFC1 to recruit Rab8a-GTP for deactivation by the RabGAP activity of EPI64. We propose that EPI64 regulates membrane trafficking both by stabilizing Arf6-GTP and by inhibiting the recycling of membrane through the tubular endosome by decreasing Rab8a-GTP levels.
Testing Day's Conjecture that More Nitrogen Decreases Crop Yield Skewness
Authors: Du Xiaodong , Hennessy David A. , Yu Cindy L.
Published: January 2012

While controversy surrounds skewness attributes of typical yield distributions, a better understanding is important for agricultural policy assessment and for crop‐insurance rate setting. Day (1965) conjectured that crop yield skewness declines with an increase in nitrogen use at low levels but not at higher levels. Employing four corn yield experimental plot datasets, we investigate the conjecture by introducing (a) a flexible Bayesian extension of the Just–Pope technology to incorporate skewness and (b) a quantile‐based measure of skewness shift. Bayesian estimation provides strong evidence in favor of negative skewness at commercial nitrogen rates and for Day's conjecture. There was weaker evidence in favor of positively skewed cotton yield and little evidence in favor of the conjecture. The results are confirmed by the quantile‐based measure. We also find evidence that skewness becomes more negative upon moving from corn‐after‐corn to corn‐after‐soybean.
A Structural Model of the Analysis of Retail Market Power: The Case of Fluid Milk
Authors: Hovhannisyan Vardges , Gould Brian W.
Published: January 2012

We derive a structural model of firm behavior that is composed of the Generalized Quadratic Almost Ideal Demand System to represent both consumers’ milk preferences and firm profit maximization conditions that allow for a range of competitive scenarios. The importance of this specification is found in its fuller representation of consumer preferences, as opposed to the Linear Approximate Almost Ideal Demand System used in previous analyses. We apply this structural framework to investigate retailer conduct in the sale of beverage milk in a U.S. market using product‐level data. Our Lerner Index estimates show that retailers are not perfectly competitive. However, this deviation is small.
The role of the seasonal and semi-diurnal tidal cycle on mesozooplankton variability in a shallow mixed estuary (Bahía Blanca, Argentina)
Authors: Menéndez M. Clara , Dutto M. Sofía , Piccolo M. Cintia , Hoffmeyer Mónica S.
Published: January 2012

Menéndez, M. C., Dutto, M. S., Piccolo, M. C., and Hoffmeyer, M. S. 2012. The role of the seasonal and semi-diurnal tidal cycle on mesozooplankton variability in a shallow mixed estuary (Bahía Blanca, Argentina). – ICES Journal of Marine Science, 69: 389–398. The role of the seasonal and semi-diurnal tidal cycle on mesozooplankton dynamics was investigated in the inner zone of the Bahía Blanca Estuary (BBE), Argentina. Hydrological data and mesozooplankton samples were obtained bimonthly from December 2004 to April 2006, during 14 h tidal cycles. The mesozooplankton community was represented by 33 taxa. Taxa richness was greater near the bottom, where the contribution of benthic forms was notable. Abundances were greatest during summer (>5500 ind. m−3) and lowest during winter (<70 ind. m−3). The mesozooplankton community was dominated by Acartia tonsa and Eurytemora americana. Multivariate analyses revealed significant seasonal differences in community structure, especially in terms of density. Seasonal differences in community structure are well explained by the natural change of abiotic and biotic conditions, but temperature played a key role in structuring the mesozooplankton community. The zooplankton was significantly more abundant during the ebb, suggesting that local hydrological conditions are responsible for the spatial variations. The results demonstrate how variable the mesozooplankton community structure can be over different time-scales and provide a better understanding of zooplankton variability in the BBE and other temperate, turbid, mixed systems.
Prescribing for the eye
Authors: Beckwith Sue , Franklin Penny
Published: January 2012

NB: the advice given in this chapter is for non-medical prescribers who are not optometrists
Prescribing for gastrointestinal problems
Authors: Beckwith Sue , Franklin Penny
Published: January 2012

Many of the medications for treatment of the conditions included in this section are available as over-the-counter (OTC) medications at less cost than a prescription and prescribers should consider this before writing a prescription. Over-the-counter (OTC) drugs, p. 422.
Oxford Handbook of Gastroenterology and Hepatology
Authors: Bloom Stuart , Webster George , Marks Daniel
Published: January 2012

This resource provides up-to-date, practical advice on the management of common conditions for trainees and specialists in gastroenterology and hepatology. It covers approaches to clinical problems, including infectious disease and gastrointestinal problems in developing countries.
F
Authors: Bloom Stuart , Webster George , Marks Daniel
Published: January 2012

Fabry's disease 304

Faecal incontinence: see Approach to faecal
incontinence 304

Faecal occult blood tests (FOBT): see ‘Faecal
occult blood tests (FOBT)’ (p.
123)
304

Familial adenomatous polyposis (FAP)
304

Familial Mediterranean fever (FMF)
306

Familial pancreatitis: see Hereditary pancreatitis 306

Fat malabsorption: see ...
I
Authors: Bloom Stuart , Webster George , Marks Daniel
Published: January 2012

Ileal pouch–anal anastomosis (IPAA): see ‘Ileal
pouch–anal anastomosis’ (p.
192)
368

Ileostomy: see
‘Ileostomy’ (p.
189)
368

Ileus 368

Immunoglobulin deficiency 369

Inflammatory bowel disease: see Crohn's disease, Microscopic colitis, and
Ulcerative colitis 369

Intestinal ischaemia 369

Intramural haematoma 370

Intrinsic factor (IF) ...
M
Authors: Bloom Stuart , Webster George , Marks Daniel
Published: January 2012

Mallory–Weiss tears396

Magnification endoscopy396

MALT lymphoma: see Lymphomas in GI
tract396

Manometry396

Meckel's diverticulum396

Megacolon397

Melanosis coli398

MELD score: see Liver
transplantation398

Ménétrier's disease398

Mesenteric venous thrombosis399

Microscopic colitis399

Microsporidia401

Mirizzi's syndrome401...
Juvenile idiopathic arthritis
Authors: Hakim Alan J. , Clunie Gavin P.R. , Haq Inam
Published: January 2012

Introduction 304

Oligoarthritis 306

Systemic arthritis 310

Rheumatoid factor negative polyarthritis in childhood 316

Chronic, infantile, neurological, cutaneous, and articular syndrome 319

• The classification of childhood onset arthritis has seen several changes over recent years. In this chapter we will discuss juvenile arthritis using headings and criteria from the International League of Associations for Rheumatology (ILAR.) The terms ‘juvenile rheumatoid arthritis’ (JIA) and ‘juvenile chronic arthritis’ (JCA) were discarded in the ILAR classification. The term ‘juvenile idiopathic arthritis’ was adopted to indicate arthritis present for at least 6 weeks and currently of no known cause in a patient <16 years....
The antiphospholipid (antibody) syndrome
Authors: Hakim Alan J. , Clunie Gavin P.R. , Haq Inam
Published: January 2012

Introduction 344

Epidemiology and pathology 345

Clinical features of antiphospholipid syndrome 346

Treatment of antiphospholipid syndrome 348

Catastrophic antiphospholipid syndrome 350

The antiphospholipid syndrome (APS) was first described in the 1980s and comprises arterial and venous thrombosis with or without pregnancy morbidity in the presence of anticardiolipin (ACL) antibodies or the lupus anticoagulant (LAC). It can be primary, or secondary to other autoimmune diseases, most commonly systemic lupus erythematosus (SLE) (...
Sjögren's syndrome
Authors: Hakim Alan J. , Clunie Gavin P.R. , Haq Inam
Published: January 2012

Epidemiology and pathology 354

Clinical manifestations of Sjögren's syndrome 356

Investigation of Sjögren's syndrome 360

Treatment of Sjögren's syndrome 362

• Sjögren's syndrome (SS) is a chronic autoimmune disease of unknown aetiology, characterized by lymphocyte infiltration of exocrine glands resulting in xerostomia and keratoconjunctivitis sicca....
Systemic sclerosis and related disorders
Authors: Hakim Alan J. , Clunie Gavin P.R. , Haq Inam
Published: January 2012

Epidemiology and diagnostic criteria 364

Cutaneous features of scleroderma and their treatment 368

Systemic features of the disease, investigation, and treatment 372

Antifibrotic and immunosuppressive therapies for systemic sclerosis 378

Summary—the approach to systemic sclerosis 380

Scleroderma-like fibrosing disorders 382

• Scleroderma is a spectrum of rare disorders ranging from limited to generalized, non-systemic to systemic, and environmental to autoimmune rheumatic disease. Generalized scleroderma, systemic sclerosis, predominantly affects women and is associated with production of collagen, widespread microvascular damage, and inflammation....
Idiopathic inflammatory myopathies: polymyositis and dermatomyositis
Authors: Hakim Alan J. , Clunie Gavin P.R. , Haq Inam
Published: January 2012

Epidemiology and diagnosis 386

Clinical features of polymyositis and dermatomyositis 388

Investigation of polymyositis and dermatomyositis 392

Autoantibodies in myositis 394

Treatment of polymyositis and dermatomyositis 398

Inclusion-body myositis 401

Polymyositis and dermatomyositis in children 402

• The idiopathic inflammatory myopathies are characterized by proximal muscle weakness and evidence of autoimmune-mediated muscle breakdown. These disorders include:...
Miscellaneous conditions
Authors: Hakim Alan J. , Clunie Gavin P.R. , Haq Inam
Published: January 2012

Behçet's disease 490

Sarcoidosis 494

Miscellaneous skin conditions associated with arthritis 498

Complex regional pain syndrome 504

Relapsing polychondritis 506

Miscellaneous disorders of synovium 508

Amyloidosis 510

Fibromyalgia and chronic widespread pain 514

• Behçet's disease is a systemic inflammatory disorder of unknown aetiology. It is most common in the Mediterranean basin, the Middle East, and Asia....
Drugs used in rheumatology
Authors: Hakim Alan J. , Clunie Gavin P.R. , Haq Inam
Published: January 2012

Introduction 546

Principles of rehabilitation 548

Pain relief 550

Opioid analgesics 554

Non-steroidal anti-inflammatory drugs 556

Antidepressants 560

Anticonvulsants 562

Glucocorticoids 564

(Non-biologic) disease-modifying anti-rheumatic drugs 566

Biologic therapies 580

Other medication 586

Drugs used in the management of hyperuricaemia, pulmonary hypertension, and osteoporosis are discussed in ...
Corticosteroid injection therapy
Authors: Hakim Alan J. , Clunie Gavin P.R. , Haq Inam
Published: January 2012

Introduction 590

Principles of injection techniques 592

The shoulder 593

The elbow 594

The wrist and hand 595

The hip and peri-articular lesions 596

The knee and peri-articular lesions 597

The ankle and foot 598

Anatomical drawings for each region of the body are found in ...
Distinct Gut Microbiota in Southeastern African and Northern European Infants
Authors: Grześkowiak Łukasz , Collado Maria Carmen , Mangani Charles , Maleta Kenneth , Laitinen Kirsi , Ashorn Per , Isolauri Erika , Salminen Seppo
Published: January 2012

Background and Objective:

The intestinal microbiota composition in infants reflects the early environment. Our objective was to compare the gut microbiota in 6‐month‐old infants living in rural Malawi with children of the same age living in urban Finland, both being breast‐fed and having an age‐appropriate diet typical for each area.

Methods:

Malawian 6‐month‐old infants (n = 44) were compared with Finnish infants (n = 31) of the same age. In both cohorts, infant stool samples were available for microbiota characterization by flow cytometry‐fluorescent in situ hybridization and quantitative polymerase chain reaction methods.

Results:

Bifidobacteria were dominant at 6 months of age in all of the infants, although in greater proportions in Malawian (70.8%) than in Finnish infants (46.8%; P < 0.001). Additional distinctions in bacterial group composition comprised Bacteroides‐Prevotella (17.2% vs 4.7%; P < 0.001) and Clostridium histolyticum (4.4% vs 2.8%; P = 0.01), respectively. The species Bifidobacterium adolescentis, Clostridium perfringens, and Staphylococcus aureus were absent in Malawian but detected in Finnish infants.

Conclusions:

The gut microbiota of 6‐month‐old infants in a low‐income country differs significantly from that in a high‐income country. This may have an effect on both the energy harvest from the diet typifying malnutrition and diarrheal diseases in low‐income countries and Western lifestyle diseases in high‐income countries.
Integration of intrinsic muscle properties, feed-forward and feedback signals for generating and stabilizing hopping
Authors: Haeufle D. F. B. , Grimmer S. , Kalveram K.-T. , Seyfarth A.
Published: January 2012

It was hypothesized that a tight integration of feed-forward and feedback-driven muscle activation with the characteristic intrinsic muscle properties is a key feature of locomotion in challenging environments. In this simulation study it was investigated whether a combination of feed-forward and feedback signals improves hopping stability compared with those simulations with one individual type of activation. In a reduced one-dimensional hopping model with a Hill-type muscle (one contractile element, neither serial nor parallel elastic elements), the level of detail of the muscle's force–length–velocity relation and the type of activation generation (feed-forward, feedback and combination of both) were varied to test their influence on periodic hopping. The stability of the hopping patterns was evaluated by return map analysis. It was found that the combination of feed-forward and proprioceptive feedback improved hopping stability. Furthermore, the nonlinear Hill-type representation of intrinsic muscle properties led to a faster reduction of perturbations than a linear approximation, independent of the type of activation. The results emphasize the ability of organisms to exploit the stabilizing properties of intrinsic muscle characteristics.
Untargeted Metabolic Quantitative Trait Loci Analyses Reveal a Relationship between Primary Metabolism and Potato Tuber Quality
Authors: Carreno-Quintero Natalia , Acharjee Animesh , Maliepaard Chris , Bachem Christian W.B. , Mumm Roland , Bouwmeester Harro , Visser Richard G.F. , Keurentjes Joost J.B.
Published: January 2012

Recent advances in -omics technologies such as transcriptomics, metabolomics, and proteomics along with genotypic profiling have permitted dissection of the genetics of complex traits represented by molecular phenotypes in nonmodel species. To identify the genetic factors underlying variation in primary metabolism in potato (Solanum tuberosum), we have profiled primary metabolite content in a diploid potato mapping population, derived from crosses between S. tuberosum and wild relatives, using gas chromatography-time of flight-mass spectrometry. In total, 139 polar metabolites were detected, of which we identified metabolite quantitative trait loci for approximately 72% of the detected compounds. In order to obtain an insight into the relationships between metabolic traits and classical phenotypic traits, we also analyzed statistical associations between them. The combined analysis of genetic information through quantitative trait locus coincidence and the application of statistical learning methods provide information on putative indicators associated with the alterations in metabolic networks that affect complex phenotypic traits.
Low prevalence of Helicobacter pylori infection among patients with inflammatory bowel disease
Authors: Sonnenberg A. , Genta R. M.
Published: January 2012

Background

There is some preliminary evidence to suggest that patients with inflammatory bowel disease (IBD) are less frequently infected with Helicobacter pylori than the general population.

Aim

To examine whether the prevalence of Helicobacter pylori (H. pylori) is lower among IBD patients compared with non‐IBD individuals based on results from surgical pathology.

Methods

From a database of surgical pathology reports, we recruited a sample of unique patients who underwent a same‐day bidirectional gastrointestinal endoscopy with biopsies. Of the total 65 515 patients, 1061 served as cases with IBD and 64 451 as controls without IBD. The histological presence of H. pylori was correlated with the patients’ demographic characteristics and histological presence of any oesophageal disease, Crohn's disease (CD), ulcerative colitis (UC) and indeterminate colitis (IND). Results were expressed as odds ratios (OR), using multivariate logistic regression to adjust for the cofounding influence of comorbidities and demographic characteristics.

Results

The presence of H. pylori was inversely associated with IBD, the adjusted OR and their 95% confidence intervals being 0.48 (0.27–0.79) for CD, 0.59 (0.39–0.84) for UC and 0.43 (0.15–0.95) for IND. In contradistinction, H. pylori – negative gastritis was positively associated with IBD, the adjusted OR being 11.06 (7.98–15.02) for CD, 2.25 (1.31–3.60) for UC and 6.91 (3.50–12.30) for IND.

Conclusions

Our study confirms an inverse association between H. pylori and IBD and a positive association between the H. pylori – negative gastritis and IBD. These relationships may open new avenues to study the pathogenesis of IBD.
Agricultural encroachment: implications for carbon sequestration in tropical African wetlands
Authors: Saunders Matthew J. , Kansiime Frank , Jones Michael B.
Published: January 2012

Tropical wetlands have been shown to exhibit high rates of net primary productivity and may therefore play an important role in global climate change mitigation through carbon assimilation and sequestration. Many permanently flooded areas of tropical East Africa are dominated by the highly productive C4 emergent macrophyte sedge, Cyperus papyrus L. (papyrus). However, increasing population densities around wetland margins in East Africa are reducing the extent of papyrus coverage due to the planting of subsistence crops such as Colocasia esculenta (cocoyam). In this paper, we assess the impact of this land use change on the carbon cycle and in particular the impacts of land conversion on net ecosystem carbon dioxide exchange. Eddy covariance techniques were used, on a campaign basis, to measure fluxes of carbon dioxide over both papyrus and cocoyam dominated wetlands located on the Ugandan shore of Lake Victoria. Peak rates of net photosynthetic CO2 assimilation, derived from monthly diurnal averages of net ecosystem exchange, of 28–35 μmol CO2 m−2 s−1 and 15–20 μmol CO2 m−2 s−1 were recorded in the papyrus and cocoyam wetlands, respectively, whereas night‐time respiratory losses ranged between 10 and 15 μmol CO2 m−2 s−1 at the papyrus wetland and 5–10 μmol CO2 m−2 s−1 at the cocoyam site. The integration of the flux data suggests that papyrus wetlands have the potential to act as a sink for significant amounts of carbon, in the region of 10 t C ha−1 yr−1. The cocoyam vegetation assimilated ~7 t C ha−1 yr−1 but when carbon exports from crop biomass removal were accounted for these wetlands represent a significant net loss of carbon of similar magnitude. The development of sustainable wetland management strategies are therefore required to promote the dual wetland function of crop production and the mitigation of greenhouse gas emissions especially under future climate change scenarios.
Relationship between diagnosis and intervention in women with inherited bleeding disorders and menorrhagia
Authors: SANDERS S. , PURCELL S. , SILVA M. , PALERME S. , JAMES P.
Published: January 2012

Summary.  Menorrhagia is the most common bleeding manifestation in women with inherited bleeding disorders. There is little known about whether the management of menorrhagia is altered in specific bleeding disorders. Optimizing treatment strategies for each specific diagnosis may improve quality of life in these women. This work aimed to look for a potential relationship between the specific diagnosis of an inherited bleeding disorder and the intervention required to control the menorrhagia. A retrospective chart review was performed for all women seen in the Kingston Women and Bleeding Disorders Clinic. Patients were categorized by diagnosis into two groups: Haemophilia carriers and all others. Treatment options were grouped into two categories: Medical or gynecological/surgical. Overall, 85.7% of haemophilia carriers required gynaecological surgical management, whereas only 31.4% of patients with all other diagnoses required gynaecological/surgical management (P = 0.012, Fisher’s exact test). Therefore, carriers of Haemophilia were more likely to have a better outcome in treating their menorrhagia with gynaecological or surgical management compared with medical management. This information may 1 day help to guide treatment choice for menorrhagia in women with bleeding disorders.
Sexual expression, fulfilment and haemophilia: reflections from the 16th Australian and New Zealand Haemophilia Conference
Authors: DUNE T.
Published: January 2012

Summary.  Following a presentation given at the 16th Australian and New Zealand Haemophilia Conference; Enjoying your sex life: Issues and solutions for men with physical impairment [Dune TM. Enjoying your sex life: issues and solutions for men with physical impairment. 16th Australian and New Zealand Haemophilia Conference: Health and Wellbeing – The Decade Ahead. Sydney, Australia: Haemophilia Foundation Australia, 2011], this note summarizes some of the issues and discusses solutions men with haemophilia and chronic illness highlight when negotiating their sexuality. This note also purports that the lack of clinical expertise and empirical research on sexuality and haemophilia hinders to provision of holistic health care.
Deregulation of the CXCL12/CXCR4 axis in methotrexate chemotherapy–induced damage and recovery of the bone marrow microenvironment
Authors: Georgiou Kristen R. , Scherer Michaela A. , King Tristan J. , Foster Bruce K. , Xian Cory J.
Published: January 2012

Cancer chemotherapy disrupts the bone marrow (BM) microenvironment affecting steady‐state proliferation, differentiation and maintenance of haematopoietic (HSC) and stromal stem and progenitor cells; yet the underlying mechanisms and recovery potential of chemotherapy‐induced myelosuppression and bone loss remain unclear. While the CXCL12/CXCR4 chemotactic axis has been demonstrated to be critical in maintaining interactions between cells of the two lineages and progenitor cell homing to regions of need upon injury, whether it is involved in chemotherapy‐induced BM damage and repair is not clear. Here, a rat model of chemotherapy treatment with the commonly used antimetabolite methotrexate (MTX) (five once‐daily injections at 0.75 mg/kg/day) was used to investigate potential roles of CXCL12/CXCR4 axis in damage and recovery of the BM cell pool. Methotrexate treatment reduced marrow cellularity, which was accompanied by altered CXCL12 protein levels (increased in blood plasma but decreased in BM) and reduced CXCR4 mRNA expression in BM HSC cells. Accompanying the lower marrow CXCL12 protein levels (despite its increased mRNA expression in stromal cells) was increased gene and protein levels of metalloproteinase MMP‐9 in bone and BM. Furthermore, recombinant MMP‐9 was able to degrade CXCL12 in vitro. These findings suggest that MTX chemotherapy transiently alters BM cellularity and composition and that the reduced cellularity may be associated with increased MMP‐9 expression and deregulated CXCL12/CXCR4 chemotactic signalling.
Difference in dental arch size between obese and non‐obese patients with obstructive sleep apnoea
Authors: MAEDA K. , TSUIKI S. , ISONO S. , NAMBA K. , KOBAYASHI M. , INOUE Y.
Published: January 2012

Summary  A large tongue is recognised as a factor that increases the collapsibility of the upper airway in obstructive sleep apnoea (OSA) patients. We hypothesised that the propensity to develop severe OSA could be minimised if the dental arches were enlarged in obese OSA people who are thought to have a large tongue. We therefore compared the size of the dental arches in obese and non‐obese OSA patients. Using a lateral cephalogram and study models, we compared the sizes of the tongue and dental arches in 23 obese and 23 non‐obese Japanese male OSA patients, who were matched for age, apnoea hypopnea index (AHI) and maxillomandibular size. The median age (years) and AHI (events per hour) for the obese and non‐obese groups were 36·5 and 39·0, and 13·4 and 14·3, respectively. The maxillomandibular size was matched with regard to SNA, SNB and lower face cage obtained from cephalometric measurements. The parameters that were measured for the study model included dental arch width, dental arch length, overjet and overbite. Tongue size (P < 0·05) and both upper (P < 0·01) and lower (P < 0·05) dental arch widths were significantly larger in obese than in non‐obese OSA patients, and there was no difference in the severity of OSA between the two groups. These findings suggest that the tongue was larger and dental arches were enlarged in obese patients compared with non‐obese patients under the same disease severity. Wider dental arches in obese OSA patients may help to offset the impact of the enlarged tongue on upper airway patency.