bluuebunny/crossref_metadata_2025 huggingface dataset:
Recasting ‘Nuclear-Free Korean Peninsula’ as a Sino-American Language for Co-ordination
Authors: TAMAKI TAKU
Published: January 2012

A series of Six-Party Talks involving the United States, China, Japan, South and North Korea, and Russia resulted in the emergence of a narrative of a ‘nuclear-free Korean Peninsula’. Given the prevalence of nuclear weapons amidst Sino-American rivalry, the area is hardly ‘nuclear-free’. Instead, the phrase has evolved into a common signifier for the US and China, suggesting that, despite their rivalries, the North Korean nuclear issue can be detrimental for both – a rare convergence of interests in an often sensitive bilateral relationship. This article provides a Constructivist perspective to this particular aspect of Sino-American balance of power by taking the language of ‘nuclear-free’ seriously, recasting the phrase as borne of both mutual scepticism, as well as convergent interests, over the Korean Peninsula.
Global Goals versus Bilateral Barriers? The International Criminal Court in the Context of US Relations with Germany and Japan
Authors: LUKNER KERSTIN
Published: January 2012

This article deals with the International Criminal Court (ICC) as a point of contention in US relations with Germany and Japan. Both countries rank among America's closest allies, but – quite contrary to the US – they have also been supporting the establishment and operation of the ICC, although each to a different extent. The article analyzes the reasons for the three countries’ diverging attitudes and policies towards the establishment and operation of the Court, and contrasts Germany's and Japan's handling of the ICC issuevis-à-visthe US. It suggests that Berlin's idealistic position and full ICC support on the one hand, as well as Japan's cautious and pragmatic approach on the other, are both rooted not only in their individual evaluations of the ICC's institutional design, but also the varying degrees of their bi/multilateral orientation and the extent of their ‘dependence’ on US security commitments.
Boundary Fluidity and Ideology: A Comparison of Japan's pre-World War II and Present Regionalisms
Authors: YU JOSE LYDIA N.
Published: January 2012

There is a question that has not been raised in the literature on Japan's regionalism: Why does it have a strong tendency toward making the boundary of the proposed East Asian community fluid? By looking back beyond the Greater East Asia Co-Prosperity Sphere of the 1940s, a method hitherto untried, the paper shows that this Japanese propensity was also present in the first half of the twentieth century, especially in the 1920s and 1930s. Moreover, both then and now, Japan did not and does not have a firm adherence to an ideology. These are two similarities between the pre-World War II period and the present (from the 1960s). On the other hand, Japan's present international situation is very different from its pre-World War II position. The paper uses the logic of the ‘most different cases’ comparative method, which states that in two cases that are different in most aspects but the same in some, one or some of the similarities may explain the other similarity or similarities. It concludes that in both periods, the lack of a firm commitment to an ideology explains Japan's prejudice toward boundary fluidity. This explanation has the potential to contribute to a more comprehensive, if not yet a general theory of Japan's approach to regionalism because it applies not only to the present, but to the past as well. And it has to be stressed, the past refersnot onlyto the Greater East Asia Co-Prosperity Sphere of the 1940s but also to the decades before.
Preface: Responses to the Special Issue, ‘Ideas of Asian Regionalism’ (Japanese Journal of Political Science, Vol. 12 Part 2)
Authors: INOGUCHI TAKASHI , HE BAOGANG
Published: January 2012

The Japanese Journal of Political Science published a special issue, ‘Ideas of Asian Regionalism’ in Vol. 12 (2) (August 2011). In the papers that follow, Rosemary Foot and Gilbert Rozman focus on angles they each see as not being adequately addressed in the special issue.
The role of regulatory purpose under Articles III: 2 and 4 – toward consistency between negotiating history and WTO jurisprudence
Authors: ZHOU WEIHUAN
Published: January 2012

After years of debate, the issues of whether and where (i.e. under which legal element) regulatory purposes should be considered under Article III:2 and Article III:4 of the GATT – the most invoked provisions of the National Treatment rule – remain unsolved. This article submits that the preparatory work of the National Treatment rule provides significant interpretative guidance on the issues. In relation to Article III:2, 2nd sentence and Article III:4, the WTO jurisprudence has achieved consistency with the interpretative guidance. However, by expanding the reach of Article III:2, 1st sentence to origin-neutral fiscal measures whereas rejecting the relevance of regulatory purposes to the determination of whether such measures are in violation of that sentence, the WTO judges have failed to respect the functions of Article III:1 and Article III:2, 1st sentence as contemplated by the draftsmen. To remedy this failure, this article proposes that the WTO adjudicators should either approve formal purpose inquiries under Article III:2, 1st sentence, or, alternatively, confine the application of that sentence to origin-specific measures only.
The Composer's Eye: Focalizing Judith in the Cantatas by Jacquet de La Guerre and Brossard
Authors: Cabrini Michele
Published: January 2012

With its intense drama and marked eroticism, the story of Judith's slaying of Holofernes was often represented in baroque visual art and music. The overwhelming majority of musical representations are found in oratorios, with only three cantatas known to have been devoted to the subject. The oratorio's dramatic framework was suited for emphasizing Judith's multifaceted figure through character depiction, contrast and conflict, while the cantata's epic nature and lack of direct character intervention made staging conflict in that genre more difficult. Yet precisely because of these limitations, the cantata constitutes a revealing case study for exploring the strategies composers employed to give agency to Judith.

This article focuses on the baroque cantata settings of the Judith story by Sébastien de Brossard and Élisabeth Jacquet de La Guerre (both from about 1708, both based on a text by La Motte). To illustrate their differing perspectives on Judith, I employ the concept of focalization – used in literary theory to mean point of view or filtered perspective – as a theoretical framework. The well-known Judith paintings by Caravaggio and Artemisia Gentileschi (the so-called Uffizi Judith) provide a lucid example of focalization through the differing perspectives of the two maidservants and offer a valuable methodological tool for understanding the two differing compositional approaches. Whereas Brossard follows La Motte's narrative dutifully by emphasizing swiftness of action at the expense of character depiction, Jacquet de La Guerre bypasses it through instrumental accompaniments and independent symphonies that give voice to Judith, despite a text that downplays her character.
Fibulin-5 binds urokinase-type plasminogen activator and mediates urokinase-stimulated β1-integrin-dependent cell migration
Authors: Kapustin Alexander , Stepanova Victoria , Aniol Natalia , Cines Douglas B. , Poliakov Alexei , Yarovoi Serge , Lebedeva Tatiana , Wait Robin , Ryzhakov Grigory , Parfyonova Yelena , Gursky Yaroslav , Yanagisawa Hiromi , Minashkin Mikhail , Beabealashvilli Robert , Vorotnikov Alexander , Bobik Alex , Tkachuk Vsevolod
Published: January 2012

uPA (urokinase-type plasminogen activator) stimulates cell migration through multiple pathways, including formation of plasmin and extracellular metalloproteinases, and binding to the uPAR (uPA receptor; also known as CD87), integrins and LRP1 (low-density lipoprotein receptor-related protein 1) which activate intracellular signalling pathways. In the present paper we report that uPA-mediated cell migration requires an interaction with fibulin-5. uPA stimulates migration of wild-type MEFs (mouse embryonic fibroblasts) (Fbln5+/+ MEFs), but has no effect on fibulin-5-deficient (Fbln5−/−) MEFs. Migration of MEFs in response to uPA requires an interaction of fibulin-5 with integrins, as MEFs expressing a mutant fibulin-5 incapable of binding integrins (FblnRGE/RGE MEFs) do not migrate in response to uPA. Moreover, a blocking anti-(human β1-integrin) antibody inhibited the migration of PASMCs (pulmonary arterial smooth muscle cells) in response to uPA. Binding of uPA to fibulin-5 generates plasmin, which excises the integrin-binding N-terminal cbEGF (Ca2+-binding epidermal growth factor)-like domain, leading to loss of β1-integrin binding. We suggest that uPA promotes cell migration by binding to fibulin-5, initiating its cleavage by plasmin, which leads to its dissociation from β1-integrin and thereby unblocks the capacity of integrin to facilitate cell motility.
Ubiquitin links to cytoskeletal dynamics, cell adhesion and migration
Authors: Schaefer Antje , Nethe Micha , Hordijk Peter L.
Published: January 2012

Post-translational modifications are used by cells to link additional information to proteins. Most modifications are subtle and concern small moieties such as a phosphate group or a lipid. In contrast, protein ubiquitylation entails the covalent attachment of a full-length protein such as ubiquitin. The protein ubiquitylation machinery is remarkably complex, comprising more than 15 Ubls (ubiquitin-like proteins) and several hundreds of ubiquitin-conjugating enzymes. Ubiquitin is best known for its role as a tag that induces protein destruction either by the proteasome or through targeting to lysosomes. However, addition of one or more Ubls also affects vesicular traffic, protein–protein interactions and signal transduction. It is by now well established that ubiquitylation is a component of most, if not all, cellular signalling pathways. Owing to its abundance in controlling cellular functions, ubiquitylation is also of key relevance to human pathologies, including cancer and inflammation. In the present review, we focus on its role in the control of cell adhesion, polarity and directional migration. It will become clear that protein modification by Ubls occurs at every level from the receptors at the plasma membrane down to cytoskeletal components such as actin, with differential consequences for the pathway's final output. Since ubiquitylation is fast as well as reversible, it represents a bona fide signalling event, which is used to fine-tune a cell's responses to receptor agonists.
Regulation of the intersubunit ammonia tunnel in Mycobacterium tuberculosis glutamine-dependent NAD+ synthetase
Authors: Chuenchor Watchalee , Doukov Tzanko I. , Resto Melissa , Chang Andrew , Gerratana Barbara
Published: January 2012

Glutamine-dependent NAD+ synthetase is an essential enzyme and a validated drug target in Mycobacterium tuberculosis (mtuNadE). It catalyses the ATP-dependent formation of NAD+ from NaAD+ (nicotinic acid–adenine dinucleotide) at the synthetase active site and glutamine hydrolysis at the glutaminase active site. An ammonia tunnel 40 Å (1 Å=0.1 nm) long allows transfer of ammonia from one active site to the other. The enzyme displays stringent kinetic synergism; however, its regulatory mechanism is unclear. In the present paper, we report the structures of the inactive glutaminase C176A variant in an apo form and in three synthetase–ligand complexes with substrates (NaAD+/ATP), substrate analogue {NaAD+/AMP-CPP (adenosine 5′-[α,β-methylene]triphosphate)} and intermediate analogues (NaAD+/AMP/PPi), as well as the structure of wild-type mtuNadE in a product complex (NAD+/AMP/PPi/glutamate). This series of structures provides snapshots of the ammonia tunnel during the catalytic cycle supported also by kinetics and mutagenesis studies. Three major constriction sites are observed in the tunnel: (i) at the entrance near the glutaminase active site; (ii) in the middle of the tunnel; and (iii) at the end near the synthetase active site. Variation in the number and radius of the tunnel constrictions is apparent in the crystal structures and is related to ligand binding at the synthetase domain. These results provide new insight into the regulation of ammonia transport in the intermolecular tunnel of mtuNadE.
Space, Territory, and Territoriality
Authors: Raffestin Claude
Published: January 2012

In this paper I reconstitute my own approach to the notions of space, territory, and territoriality. Developing from the early 1970s, my thoughts resided in the effort devoted to deriving from space the idea of territory qua production by the projection of labor, a Janus-faced category composed of energy and information. The construction of territory is the consequence of territoriality—defined as the ensemble of relations that a society maintains with exteriority and alterity for the satisfaction of its needs, towards the end of attaining the greatest possible autonomy compatible with the resources of the system. I also propose a descriptive model utilizable in the production of territory as well as in the production of representations of this territory in making available ‘images’ or landscapes. In the conclusion I draw attention to the fact that if labor is always a mediator, it is not thereby any less subordinated to the money whose possessors are in a position to alienate labor by subjecting it to orientations that can be undesirable. Money accelerates the process of territorialization, deterritorialization, and reterritorialization. Geography, by considering only territorial productions, has neglected to take up the issue of labor; consequently, it has not been able to demonstrate the effects on labor of money as a mediator that has rendered everything more and more fluid.
Entente Territorial: Sack and Raffestin on Territoriality
Authors: Murphy Alexander B
Published: January 2012

Two of the most prolific contributors to the theoretical literature on territoriality—Robert Sack and Claude Raffestin—treat territoriality in fundamentally different ways. Sack conceives of territoriality as a spatial strategy that individuals, groups, and organizations use to achieve particular social and political ends. Raffestin, in contrast, takes a relational approach to territoriality—seeing it as arising out of, integral to, and reinforcing of interactions and structural circumstances. These contrasting approaches reflect different types of scholarly projects. The reading of one against the other shows that Raffestin's relational approach is critical to capturing the territorial ideas and practices of everyday life, as these are not reducible to simple strategies to control space. But as these ideas and practices congeal into territorial structures and norms of the sort exemplified by the emergence of the modern state system they produce understandings and arrangements that lend themselves to the type of theorization of territoriality proposed by Sack. Rather than treating the relationship between Raffestin's and Sack's approaches to territoriality as strictly oppositional, it is more constructive to explore the circumstances in which relational territoriality, as developed by Raffestin, produces understandings and arrangements that can be effectively captured through the territoriality-as-spatial-strategy approach of Sack.
Claude Raffestin's Italian Travels
Authors: Minca Claudio
Published: January 2012

This paper is focused on the contribution that French Swiss geographer Claude Raffestin has made to Italian geography studies and, more generally, on his role in linking Italian geography to social theory and philosophy. It also explores the adoption of, and the engagement with, his ideas by a select group of Italian geographers during the last three decades or so. The first part of this paper claims that one reason for such an influence is Raffestin's capacity to be often conceptually ‘ahead of time’ and to his extraordinary capacity to present his theoretical approach in a very accessible way. While reflecting on how his concepts of ‘territory’ and ‘territoriality’, together with his speculation on the relationship between semiotics, power, and space, left a deep mark on the ways in which the discipline is practised in Italy today, the paper also shows how and why other aspects of Raffestin's work were less received. The second part of this paper is thus focused on four key ‘intersections’ of people, concepts, events, etc in which Raffestin's specific contribution to the Italian intellectual scene became particularly remarkable. The conclusion, while restating that any clear cultural mapping of Raffestin's ‘Italian travels’ is, perhaps, an operation doomed to failure (if anything, because of the complexity of his diverse interventions), at the same time highlights how his work has been and continues today to be of extraordinary relevance for Italian geographers and for their practice.
Functional characterization of the guanine nucleotide exchange factor (GEF) motif of GIV protein reveals a threshold effect in signaling
Authors: Garcia-Marcos Mikel , Kietrsunthorn Patrick S. , Pavlova Yelena , Adia Michelle A. , Ghosh Pradipta , Farquhar Marilyn G.
Published: January 2012

Heterotrimeric G proteins are critical signal-transducing molecules controlled by a complex network of regulators. GIV (a.k.a. Girdin) is a unique component of this network and a nonreceptor guanine nucleotide exchange factor (GEF) that functions via a signature motif. GIV's GEF motif is involved in the regulation of critical biological processes such as phosphoinositide 3 kinase (PI3K)-Akt signaling, actin cytoskeleton remodeling, cell migration, and cancer metastasis. Here we investigated how the GEF function of GIV affects the wiring of its signaling pathway to shape different biological responses. Using a structure-guided approach, we designed a battery of GIV mutants with different Gαi-binding and -activating properties and used it to dissect the specific impact of changes in GIV's GEF activity on several cellular responses. In vivo signaling assays revealed a threshold effect of GEF activity for the activation of Akt by GIV in different cell lines and by different stimuli. Akt signaling is minimal at low GEF activity and is sharply increased to reach a maximum above a threshold of GEF activity, suggesting that GIV is a critical signal amplifier and that activation of Akt is ultrasensitive to changes in GIV's GEF activity. A similar threshold dependence was observed for other biological functions promoted by GIV such as remodeling of the actin cytoskeleton and cell migration. This functional characterization of GIV's GEF motif provides insights into the molecular interactions between nonreceptor GEFs and G proteins and the mechanisms that govern this signal transduction pathway.
Nerve growth factor regulates axial rotation during early stages of chick embryo development
Authors: Manca Annalisa , Capsoni Simona , Di Luzio Anna , Vignone Domenico , Malerba Francesca , Paoletti Francesca , Brandi Rossella , Arisi Ivan , Cattaneo Antonino , Levi-Montalcini Rita
Published: January 2012

Nerve growth factor (NGF) was discovered because of its neurotrophic actions on sympathetic and sensory neurons in the developing chicken embryo. NGF was subsequently found to influence and regulate the function of many neuronal and non neuronal cells in adult organisms. Little is known, however, about the possible actions of NGF during early embryonic stages. However, mRNAs encoding for NGF and its receptors TrkA and p75
NTR
are expressed at very early stages of avian embryo development, before the nervous system is formed. The question, therefore, arises as to what might be the functions of NGF in early chicken embryo development, before its well-established actions on the developing sympathetic and sensory neurons. To investigate possible roles of NGF in the earliest stages of development, stage HH 11–12 chicken embryos were injected with an anti-NGF antibody (mAb αD11) that binds mature NGF with high affinity. Treatment with anti-NGF, but not with a control antibody, led to a dose-dependent inversion of the direction of axial rotation. This effect of altered rotation after anti NGF injection was associated with an increased cell death in somites. Concurrently, a microarray mRNA expression analysis revealed that NGF neutralization affects the expression of genes linked to the regulation of development or cell proliferation. These results reveal a role for NGF in early chicken embryo development and, in particular, in the regulation of somite survival and axial rotation, a crucial developmental process linked to left–right asymmetry specification.
CHARACTERIZING CO FOURTH POSITIVE EMISSION IN YOUNG CIRCUMSTELLAR DISKS
Authors: Schindhelm Rebecca N. , France Kevin , Burgh Eric B. , Herczeg Gregory J. , Green James C. , Brown Alexander , Brown Joanna M. , Valenti Jeff A.
Published: January 2012

Carbon monoxide is a commonly used IR/submillimeter tracer of gas in protoplanetary disks. We present an analysis of ultraviolet CO emission in Hubble Space Telescope Cosmic Origins Spectrograph spectra for 12 Classical T Tauri stars (CTTSs). Several ro-vibrational bands of the CO A
1Π–X
1Σ+ (Fourth Positive) electronic transition system are spectrally resolved from emission of other atoms and H2. The CO A
1Π v′ = 14 state is populated by absorption of Lyα photons, created at the accretion column on the stellar surface. For targets with strong CO emission, we model the Lyα radiation field as an input for a simple fluorescence model to estimate CO rotational excitation temperatures and column densities. Typical column densities range from N
CO = 1018 to 1019 cm−2. Our measured excitation temperatures are mostly below T
CO = 600 K, cooler than typical M-band CO emission. These temperatures and the emission line widths imply that the UV emission originates in a different population of CO than that which is IR-emitting. We also find a significant correlation between CO emission and the disk accretion rate

and age. Our analysis shows that ultraviolet CO emission can be a useful diagnostic of CTTS disk gas.
Numerical analysis of guiding a microwave radiation using a set of plasma filaments: dielectric waveguide concept
Authors: Alshershby Mostafa , Lin Jingquan , Hao Zuoqiang
Published: January 2012

A proposed model for a circular bunch of plasma filaments used as a virtual waveguide for microwave radiation is presented. The virtual circular guiding system is shown to support guided modes of electromagnetic radiation in the millimetre and sub-millimetre wavelength range. Transmission is due to total internal reflection of the wave on the less dense plasma cladding. The energy loss of microwave radiation propagating in such a virtual waveguide is calculated. Optimum spatial configurations of circular plasma filament waveguides are proposed. Plasma filament waveguides are shown to enhance microwave transmission relative to free space propagation of microwave radiation over limited distances.
Equi-frequency contour of photonic crystals with the extended Dirichlet-to-Neumann wave vector eigenvalue equation method
Authors: Jiang Bin , Zhang Yejing , Wang Yufei , Liu Anjin , Zheng Wanhua
Published: January 2012

We present the extended Dirichlet-to-Neumann wave vector eigenvalue equation (DtN-WVEE) method to calculate the equi-frequency contour (EFC) of square lattice photonic crystals (PhCs). With the extended DtN-WVEE method and Snell's law, the effective refractive index of the mode with a circular EFC can be obtained, which is further validated with the refractive index weighted by the electric field or magnetic field. To further verify the EFC calculated by the DtN-WVEE method, the finite-difference time-domain method is also used. Compared with other wave vector eigenvalue equation methods that calculate EFC directly, the size of the eigenmatrix used in the DtN-WVEE method is much smaller, and the computation time is significantly reduced. Since the DtN-WVEE method solves wave vectors for given arbitrary frequencies, it can also find applications in studying the optical properties of a PhC with dispersive, lossy and magnetic materials.
Dynamic simulator of RWM control for fusion devices: modelling and experimental validation on RFX-mod
Authors: Marchiori G. , Baruzzo M. , Bolzonella T. , Liu Y.Q. , Soppelsa A. , Villone F.
Published: January 2012

A new integrated simulator for experiments of resistive wall mode (RWM) closed-loop control and its benchmark against experimental data are presented. The numerical tool couples in a self-consistent way a full 3D finite element description of the machine boundaries (Cariddi code), a 2D toroidal model of RFP plasma stability (MARS-F code) and a realistic representation of the RFX-mod control system producing an overall dynamic model cast in the state variable space. In this way a full dynamic ‘flight simulator’ of RWM control experiments has been implemented where the interaction of proportional–integral–derivative controller gains and plasma equilibrium parameters can be explored.

As an application of the new integrated tool, closed-loop RWM stability analyses have been benchmarked against experimental data. In this way it was possible to experimentally prove that the control simulator correctly reproduces closed-loop RWM growth rates under different control conditions. Time domain simulations were also run to assess the overall accuracy of the model including the presence of non-linear blocks. The achieved results are discussed in connection with the broader international effort towards an effective control of RWMs in both tokamak and RFP configurations.
Adherence
Authors: Wiffen Philip , Mitchell Marc , Snelling Melanie , Stoner Nicola
Published: January 2012

Introduction to adherence 2

Assessing adherence 4

Strategies to improve adherence 6

Adherence counselling 8

Writing patient information leaflets 10

‘To be taken as directed’ is an instruction that frequently appears on medicine labels. It suggests that a patient will obey the doctor's ‘orders’ without question. However, as most pharmacists are well aware, patients frequently choose not to ‘take as directed’....
Clinical trials
Authors: Wiffen Philip , Mitchell Marc , Snelling Melanie , Stoner Nicola
Published: January 2012

Clinical trial regulations 108

Licensing of a clinical trial 109

Clinical trial development phases 110

Trial design, randomization, and blinding 111

European Clinical Trials Directive 112

Clinical trials: hospital pharmacy guidance 114

Ethical committees 116

Clinical trials form a fundamental part in the research, development, and licensing of new medicines. Research of how the drug interacts in humans is essential to ensure safe and effective medicines are licensed as new treatments. It is an exciting and varied role at the cutting edge of modern research with trials ranging across all therapeutic specialities. Clinical Trial pharmacists are therefore required to have a broad clinical knowledge and a specialist knowledge of the regulations that clinical trials have to follow....
Therapy-related issues: gastrointestinal system
Authors: Wiffen Philip , Mitchell Marc , Snelling Melanie , Stoner Nicola
Published: January 2012

Diarrhoea 314

Constipation in adults 318

Management of nausea and vomiting 322

Dyspepsia, peptic ulcer disease, and gastro-oesophageal reflux disease 326

Pharmaceutical care in gastrointestinal stoma patients 334

• ‘Diarrhoea’ is a term generally understood to mean an ↑ frequency of bowel movement relative to normal for an individual patient....
Therapy-related issues: obstetrics, gynaecology, and urinary tract disorders
Authors: Wiffen Philip , Mitchell Marc , Snelling Melanie , Stoner Nicola
Published: January 2012

Hormonal contraception 460

Contraception has been an important part of human lives since the time of the early Egyptians. While methods have changed dramatically over the years, the purpose remains the same—to control fertility.

Most methods used today are female-driven and involve hormones. These methods are very effective in preventing pregnancy when taken or used as directed. Barrier methods rely on their availability at the time of intercourse and are more efficacious when used with spermicides....
Therapy-related issues: miscellaneous
Authors: Wiffen Philip , Mitchell Marc , Snelling Melanie , Stoner Nicola
Published: January 2012

Introduction to critical care 592

Delirium/acute confusional state 596

Stress ulcer prophylaxis 598

Motility stimulants 600

Mechanical ventilation 602

Vasoactive agents 604

Renal replacement therapy 606

Treatment of alcohol withdrawal 610

Dealing with poisoning enquiries 614

Drug desensitization 618

Drug interference with laboratory tests 620...
Introduction
Authors: Lam Raymond W.
Published: January 2012

• Depression is a common and disabling psychiatric condition that must be recognized by all physicians and health professionals.

• The principles of care for major depressive disorder include: thorough assessment and diagnosis, selection of appropriate and evidence-based treatments, and careful follow up using measurement-based care....
Clinical management
Authors: Lam Raymond W.
Published: January 2012

• Clinical management of depression includes screening, assessment, developing a therapeutic alliance, selecting treatment(s), monitoring, and follow up.

• The treatment of depression has two phases: the acute phase to achieve full remission of symptoms, and the maintenance phase to prevent relapse and recurrence.

•...
Special populations
Authors: Lam Raymond W.
Published: January 2012

• The keys to optimal management of treatment-resistant depression and depression in special populations include careful assessment, selection of evidence-based treatments tailored to the individual, and ongoing monitoring of response and outcome.

• Given the still limited evidence base, use and selection of antidepressants depends on an individual risk-benefit assessment in elderly patients, those with other medical illnesses, pregnant and breastfeeding women, and children and adolescents....
Risk models predicting survival after reduced‐intensity transplantation for myelofibrosis
Authors: Alchalby Haefaa , Yunus Dinah‐Rohina , Zabelina Tatjana , Kobbe Guido , Holler Ernst , Bornhäuser Martin , Schwerdtfeger Rainer , Bethge Wolfgang , Kvasnicka Hans Michael , Büsche Guntram , Ayuk Francis , Bacher Ulrike , Zander Axel. R. , Kröger Nicolaus
Published: January 2012

To define a prognostic model for predicting outcome of reduced‐intensity allogeneic stem cell transplantation (RIC‐ASCT) for myelofibrosis we evaluated 150 homogenously treated patients and developed a new risk score for overall survival (OS). In a multivariate Cox model for OS, only JAK2 V617F wild‐type, age ≥57 years and constitutional symptoms were independently predictive for OS (Hazard Ratio: 2·02; 2·43 and 2·80 respectively). Depending on the presence of one, two or all of these factors, HR of death was 3·08; 4·70 and 16·61 respectively (P < 0·001). This score was compared to the Lille, Cervantes, International Prognostic Scoring System (IPSS), dynamic IPSS (DIPSS) and modified European Blood and Marrow Transplantation Group (EBMT) scores. Lille score correlated significantly with OS but discriminated poorly between the intermediate and high‐risk groups (5‐year OS 56% and 51% respectively). IPSS and DIPSS correlated significantly with OS but differences between intermediate‐1 and intermediate‐2 groups were not significant (5‐year OS 78% vs. 78% and 70%, 60% respectively). Modified EBMT and Cervantes models did not predict OS post‐ASCT. In conclusion, a simple model which includes: age, JAK2 V617F‐status and constitutional symptoms can clearly separate distinct risk groups and can be used in addition to the Lille model to predict OS after RIC‐ASCT for myelofibrosis.
The major royal jelly proteins 8 and 9 (Api m 11) are glycosylated components of Apis mellifera venom with allergenic potential beyond carbohydrate‐based reactivity
Authors: Blank S. , Bantleon F. I. , McIntyre M. , Ollert M. , Spillner E.
Published: January 2012

Background

As hymenoptera venoms are one of the allergen sources causing the highest incidence of anaphylaxis and sometimes fatal consequences, the detailed characterization of all venom allergens is imperative for design of component‐resolved diagnostic approaches and improved intervention strategies.

Objective

Our aim was the immunochemical characterization of major royal jelly proteins (MRJP) 8 and 9, both components identified in honeybee venom (HBV) and putative allergens.

Methods

Both MRJPs were recombinantly produced as soluble differentially glycosylated proteins providing a defined degree of reactivity to cross‐reactive carbohydrate determinants (CCD) in insect cells. Allergen‐specific IgE(sIgE) reactivity of HBV‐allergic patients was analysed by ELISA and immunoblotting.

Results

MRJP8 and MRJP9 were identified as venom components by MS‐based proteomic analyses. In a population of 47 HBV‐allergic patients, reactivities with CCD‐carrying MRJPs were in the range of 56% (61%), underlining the contribution of CCDs to allergen‐binding. Beyond CCD‐reactivity, 15% of patients showed sIgEreactivity with MRJP8 and 34% with MRJP9 respectively. These reactivities roughly in the range of Api m 2 render the MRJPs minor, but important allergens.

Conclusion and Clinical Relevance

The glycosylated MRJP8 and MRJP9 of HBV have IgE‐sensitizing potential in HBV‐allergic patients beyond CCD reactivity and have to be considered as allergens, which might be potentially important for a fraction of venom allergic patients. They are valuable tools to elucidate individual component‐resolved reactivity profiles of venom allergic patients and to provide insights into the role of particular venom components. Due to their allergenic properties, MRJP8 and MRJP9 were designated as isoallergens Api m 11.0101 and Api m 11.0201 respectively.
Serum thyrotrophin at baseline predicts the natural course of subclinical hyperthyroidism
Authors: Das G. , Ojewuyi T. A. , Baglioni P. , Geen J. , Premawardhana L. D. , Okosieme O. E.
Published: January 2012

Objective

Optimal therapeutic strategies for subclinical hyperthyroidism are undecided. Overt disease develops in a minority of cases, but the risk factors for progression remain unclear. We examined whether a baseline thyrotrophin (TSH) predicted progression to overt hyperthyroidism in asymptomatic individuals with subclinical hyperthyroidism.

Design, patients and measurements

This was a retrospective study of 323 patients with subclinical hyperthyroidism seen in our institution from 2003 to 2010 (mean age 71 years, males 26·9%, females 73·1%, mean follow‐up duration 32 months, range 6–93 months). Serum TSH and free thyroxine (FT4) were documented at baseline and during follow‐up. After excluding individuals with nonthyroid causes of low TSH, patients were grouped according to initial TSH as: TSH 0·10–0·39 mU/l (grade I) and TSH < 0·10 mU/l (grade II).

Results

Only 38 patients (11·8%) developed overt hyperthyroidism with annual progression rates of 0·6–3·7%. Most patients reverted to normal thyroid status (31·6%) or remained subclinically hyperthyroid (56·7%). Progression to frank hyperthyroidism was higher in grade II than in grade I patients (20·3% vs 6·8%, P < 0·001, Chi square test). Kaplan–Meier curves showed faster progression rates in grade II than grade I (P < 0·001, log rank test). In stepwise multivariate Cox regression analysis, TSH < 0·1 mU/l was associated with overt hyperthyroidism (hazard ratio 3·4, confidence interval 1·6–7·0), whereas age, gender, FT4 and aetiological diagnosis were not associated with hyperthyroidism.

Conclusions

Thyrotrophin predicts overt hyperthyroidism in asymptomatic individuals with subclinical hyperthyroidism. Patients with TSH < 0·10 mU/l have a higher risk of progressing to hyperthyroidism than those with TSH 0·10–0·39 mU/l.
Accumulation of polyunsaturated fatty acids by cladocerans: effects of taxonomy, temperature and food
Authors: MASCLAUX HÉLÈNE , BEC ALEXANDRE , KAINZ MARTIN J. , PERRIÈRE FANNY , DESVILETTES CHRISTIAN , BOURDIER GILLES
Published: January 2012

1. Zooplankton are important in transferring dietary nutrients, including polyunsaturated fatty acids (PUFA), up through aquatic food webs.

2. We tested the hypothesis that the taxonomic composition of zooplankton affects the retention and subsequent transfer of PUFA from upwards through the food web. Using laboratory experiments, we investigated dietary PUFA accumulation and bioconversion capacities of six cladoceran species (Ceriodaphnia sp., Daphnia longispina, Daphnia magna, Daphnia pulex, Scapholeberis mucronata and Simocephalus vetulus) fed on two diets (Scenedesmus obliquus and Cryptomonas sp.) that differed in their PUFA profiles. We performed experiments at two different temperatures (14 and 20 °C) to assess the role of temperature in the trophic transfer of PUFA.

3. There was little variation in the concentrations of PUFA in these cladocerans which were controlled by dietary PUFA supply. Moreover, as expected, the concentrations of PUFA in all cladoceran species were higher at low temperature.

4. However, even if the composition of PUFA in the cladoceran species generally corresponded to that in their diet, preferential accumulation of some PUFA was recorded in all these taxa. When fed on a highly unsaturated fatty acid‐deficient diet, all the cladocerans showed some ability to convert C18‐PUFA into arachidonic acid and eicosapentaenoic acid. Interspecific variation in the ability to accumulate and bioconvert PUFA in cladocerans was more pronounced at low temperature (14 °C) for both diets.

5. Our results strongly suggest that in heterogeneous habitats with food partitioning between co‐existing cladocerans, foraging behaviour may affect the transfer of PUFA more strongly than interspecific variation in accumulating and/or bioconverting dietary PUFA.
Spatial scale influences the outcome of the predator–prey space race between tadpoles and predatory dragonflies
Authors: Hammond John I. , Luttbeg Barney , Brodin Tomas , Sih Andrew
Published: January 2012

1. How predators and prey distribute themselves across space can have large population and community‐level consequences by affecting the frequency and potential strength of interactions between and within trophic levels. The general pattern that emerges from numerous studies is that predators seek areas with higher prey densities and prey avoid areas with higher predation risk. However, little is known about the behavioural mechanisms underlying the emergent spatial patterns between freely interacting predators and prey.

2. We examined the behaviour and space use of groups ofPseudacris regilla(Pacific treefrog) tadpole prey and larvalRhionaeschna multicolor(blue‐eyed darner) odonate predators in arenas consisting of four patches of the prey’s resources divided into two spatial scales over two observation periods a day apart. Distributions were assayed both alone and together. We predicted scale should inherently affect the resulting spatial patterns because factors such as selection, competition, interference, movement ability and prey responses to predators all have potentially similar effects as scale become larger or smaller. These factors predict that prey should be more able to dictate the spatial pattern at smaller scales and predators at larger scales.

3. Results generally match these predictions with measures of joint space being consistent with the predators dictating the joint space use more than expected at the larger scale. Moreover, at the smaller scale, either the predator and prey responses offset or reverse to favour the prey. We used a model selection approach to look at the underlying behavioural rules shaping these spatial patterns. Prey were more likely to leave patches with lower resources across both scales. However, their response to predators and competitors differed between the scales, with prey appearing to become trapped with predators only at the larger scale and only avoiding other prey at the small scale.

4. These results highlight the importance of investigating freely interacting predators and prey and the factors that are likely to affect the predator’s or prey’s ability to dictate spatial patterns. An ability to predict predator–prey spatial outcomes should be a great benefit with habitat fragmentation and shifting population densities, distributions and community compositions.
The temperature‐size rule emerges from ontogenetic differences between growth and development rates
Authors: Forster Jack , Hirst Andrew G.
Published: January 2012

1. The temperature‐size rule (TSR) is a widespread phenomenon, which describes the phenotypic plastic response of species’ size to temperature: individuals reared at colder temperatures mature as larger adults than at warmer temperatures.

2. The TSR is driven by an unequal thermal response of growth and development rates. However, we currently lack an understanding of how these rates change through ontogeny and their decoupling. Further, we do not know how this decoupling varies across generations.

3. Using the brine shrimp Artemia franciscana as a model, we examine growth and development rates through ontogeny at different temperatures across two generations.

4. The slopes of natural‐logged weight‐specific growth rates against temperature are steeper in earlier than later larval stages, indicating their greater temperature dependence, whereas development rates maintain the same temperature dependence across life stages. An inverse TSR is generated in early larval stages; the typical TSR (smaller size at warmer temperatures) is only established later in ontogeny.

5. Phase‐specific temperature dependence of growth and development rates is not significantly different across the 1st and 2nd generation, suggesting the TSR is primarily a within‐generation outcome.

6. Ontogenetic size responses in Artemia are compared to other crustacean species to identify patterns within this subphylum. Data for a range of crustaceans follow the same ontogenetic pattern: early larval stages show an inverse or no TSR, with TSR being only established in later stages. Adults often, but not always, show the greatest response.
Sodium hypochlorite accident with evaluation by cone beam computed tomography
Authors: Behrents K. T. , Speer M. L. , Noujeim M.
Published: January 2012

Behrents KT, Speer ML, Noujeim M. Sodium hypochlorite accident with evaluation by cone beam computed tomography. International Endodontic Journal, 45, 492–498, 2012.

Aim  To show the radiographic manifestation of sodium hypochlorite after accidental injection past the apical foramen and into the soft tissues.

Summary  A female patient was seen for an emergency visit after suffering a sodium hypochlorite accident at her general dentist’s office. The patient was seen within 1 h of the accident and was in pain associated with facial swelling. Radiographs, including a Cone Beam Computed Tomography (CBCT), and photographs were taken. Endodontic emergency treatment was initiated. The patient was reassured and given pain medication and antibiotics. Follow‐up visits were scheduled over 6 days when the swelling had resolved.

Key learning points 

Importance of multiple radiographic images during preoperative endodontic evaluation when undertaking endodontic retreatment.

Knowledge of apical anatomy as related to surrounding structures.

Effect of sodium hypochlorite when injected in the soft tissues.
Bone marrow‐derived cells contribute to cerulein‐induced pancreatic fibrosis in the mouse
Authors: Lin Wey‐Ran , Inatomi Osamu , Lee Chung Y. , Kallis Yiannis N. , Otto William R. , Jeffery Rosemary , Poulsom Richard , Alison Malcolm R.
Published: January 2012

Bone marrow (BM) cells may transdifferentiate into circulating fibrocytes and myofibroblasts in organ fibrosis. In this study, we investigated the contribution and functional roles of BM‐derived cells in murine cerulein‐induced pancreatic fibrosis. C57/BL6 female mice wild‐type (WT) or Col 1α1r/r male BM transplant, received supraphysiological doses of cerulein to induce pancreatic fibrosis. The CD45+Col 1+ fibrocytes isolated from peripheral blood (PB) and pancreatic tissue were examined by in situ hybridization for Y chromosome detection. The number of BM‐derived myofibroblasts, the degree of Sirius red staining and the levels of Col 1α1 mRNA were quantified. The Y chromosome was detected in the nuclei of PB CD45+Col 1+ fibrocytes, confirming that circulating fibrocytes can be derived from BM. Co‐expression of α‐smooth muscle actin illustrated that fibrocytes can differentiate into myofibroblasts. The number of BM‐derived myofibroblasts, degree of collagen deposition and pro‐collagen I mRNA expression were higher in the mice that received Col 1α1r/r BM, (cells that produce mutated, collagenase‐resistant collagen) compared to WT BM, indicating that the genotype of BM cells can alter the degree of pancreatic fibrosis. Our data indicate that CD45+Col 1+ fibrocytes in the PB can be BM‐derived, functionally contributing to cerulein‐induced pancreatic fibrosis in mice by differentiating into myofibroblasts.
RF9 Powerfully Stimulates Gonadotrophin Secretion in the Ewe: Evidence for a Seasonal Threshold of Sensitivity
Authors: Caraty A. , Blomenröhr M. , Vogel G. M. T. , Lomet D. , Briant C. , Beltramo M.
Published: January 2012

GPR147 and its endogenous ligands, RFRPs, are emerging as important actors in hypothalamic‐pituitary axis control. The role of this system would be to inhibit gonadotrophin secretion. However, data on the subject are contradictory. The discovery of RF9 (adamantanecarbonyl‐RF‐2‐NH2), a GPR147 antagonist, prompted us to use this new tool to further investigate this system in the ewe. Accordingly, we tested the effect of i.c.v. administration of RF9 on gonadotrophin secretion in the ewe during anoestrous and the breeding season. Intracerebroventricular injections of RF9 (from 50–450 nmol) caused a clear elevation in peripheral blood plasma luteinising hormone (LH) concentrations. The effect of RF9 on LH was more pronounced during the anoestrous season. Furthermore, peripheral administration of RF9 as a bolus (2.1, 6.2 and 12.4 μmol per ewe) or as a constant i.v. infusion (2.1, 6.2, 12.4 and 18.6 μmol/h per ewe) to anoestrous acyclic ewes induced a sustained increase in LH plasma concentrations. A pharmacokinetic study showed that RF9 (12.4 μmol bolus i.v.) has an effective half life of 5.5 h in the plasma. Conversely, RF9 is not detectable in the cerebrospinal fluid, suggesting that it does not cross the blood–brain barrier. The increase in LH plasma concentrations induced by RF9 was blocked by previous administration of 1.3 μmol per ewe of gondotrophin‐releasing hormone (GnRH) antagonist Teverelix. This suggests that GnRH is involved in the stimulatory effect of RF9 on gonadotrophin secretion. Finally, no variation in LH plasma concentrations could be detected in ovariectomised ewes injected either i.c.v. or i.v. with RFRP3 (VPNLPQRF‐NH2). The lack of effect of RFRP3 in our experimental setting suggests that the mechanisms involved in RF9 action are probably more complex than previously assumed. Our results indicate that delivery of RF9 in the ewe greatly increases gondadotrophin secretion in both the oestrus and anoestrus season, suggesting a potential new way of controlling reproduction in mammals.