bluuebunny/crossref_metadata_2025_split huggingface dataset:
Japanese guidelines for fingolimod in multiple sclerosis: Putting into practice
Authors: Matsui Makoto , Shimizu Yuko , Doi Hikaru , Tomioka Ryo , Nakashima Ichiro , Niino Masaaki , Kira Jun‐ichi 
Published: February 2014

AbstractFingolimod functions as a modulator of sphingosine‐1‐phosphate (S1P) receptors expressed on the surface of T and B lymphocytes, leading to their internalization. Loss of S1P receptors results in sequestration of central memory T cells enriched by Th17 cells in lymph nodes. After successful treatment of an animal model of multiple sclerosis (MS), clinical trials of oral fingolimod in patients with relapsing‐remitting MS showed a 60% reduction in the annualized rate of relapse. The United States Food and Drug Administration approved fingolimod as a first‐line drug for MS treatment in 2010, and data have been accumulated thereafter. However, MS experts recommend that the drug should remain as a second‐line option, because the long‐term risks for infection and malignancy have not been fully elucidated. Also, because of different genetic backgrounds, Asian MS patients might require special attention regarding other infectious agents and secondary cancer as compared with those reported in Caucasian patients. Furthermore, some Japanese patients who developed severe symptoms were later shown to be positive for the anti‐aquaporin‐4 antibody. In addition, reports of some Western MS patients have noted worsening after initiation, as well as discontinuation of fingolimod treatment. Finally, the optic spinal type of MS and neuromyelitis optica spectrum disorders are more prevalent in Asian than Western countries. Thus, establishment of criteria for determining which Asian MS patients would benefit from fingolimod treatment is mandatory.
Clinical features of Japanese myasthenia gravis
Authors: Suzumura Akio 
Published: February 2014

AbstractA nationwide multicenter analysis of Japanese patients with myasthenia gravis (MG) is reported in this issue by Murai et al. (Clin Exp Neuroimmunol. 2014; 5(1) 84–91. The study has revealed the characteristics of three subgroups of Japanese MG; early onset, late onset and thymoma‐associated MG.
Position and practical use of fingolimod in Europe
Authors: Comi Giancarlo 
Published: February 2014

AbstractApproval of fingolimod in 2011 heralded the era of oral therapies for multiple sclerosis (MS) in the European Union. Uptake of fingolimod across Europe was widespread, even though its indication was predominantly second‐line; that is, for patients with a lack of response to interferon beta or those with highly active relapsing–remittingMS(RRMS). Safety concerns raised with the European Medicines Agency culminated in the revision of the European Union labeling for first‐dose management in 2012. However, in addition to evidence from the pivotal clinical trials, cumulating real‐world fingolimod experience in Europe provides reassurance on its safety and efficacy. Studies show that switching to fingolimod from approved first‐line injectable therapies is beneficial for patients who might otherwise switch to another interferon beta or glatiramer acetate. Furthermore, in several recent European studies of patients who switched to fingolimod from natalizumab, disease control was improved compared with drug withdrawal and no immunomodulatory treatment, or withdrawal and first‐line treatment, including the Disease Control and Safety in Patients withRRMSSwitching from NatalizumabTO FINGOlimod (TOFINGO) study, which supported a shorter washout period before switching. The safety profile shown in clinical trials is supported by post‐marketing observations; any first‐dose effects on heart rate are managed easily, and severe complications as a result of herpes viral infections are rare. The use of newer oral drugs remains a key topic of discussion, in light of the recognized importance of an early shift of suboptimal responders to another therapy. The information on fingolimod summarized in the present review may contribute to define its role further in RRMS treatment in Europe.
Effects of sea surface warming on marine plankton
Authors: Lewandowska Aleksandra M. , Boyce Daniel G. , Hofmann Matthias , Matthiessen Birte , Sommer Ulrich , Worm Boris 
Published: February 2014

AbstractOcean warming has been implicated in the observed decline of oceanic phytoplankton biomass. Some studies suggest a physical pathway of warming via stratification and nutrient flux, and others a biological effect on plankton metabolic rates; yet the relative strength and possible interaction of these mechanisms remains unknown. Here, we implement projections from a global circulation model in a mesocosm experiment to examine both mechanisms in a multi‐trophic plankton community. Warming treatments had positive direct effects on phytoplankton biomass, but these were overcompensated by the negative effects of decreased nutrient flux. Zooplankton switched from phytoplankton to grazing on ciliates. These results contrast with previous experiments under nutrient‐replete conditions, where warming indirectly reduced phytoplankton biomass via increased zooplankton grazing. We conclude that the effect of ocean warming on marine plankton depends on the nutrient regime, and provide a mechanistic basis for understanding global change in marine ecosystems.
Stance phase kinematics and kinetics of horses trotting over poles
Authors: Clayton H. M. , Stubbs N. C. , Lavagnino M. 
Published: February 2014

SummaryReason for performing studyTrotting over poles is frequently used therapeutically to restore swing phase ranges of joint motion. It is not known whether ground reaction forces (GRFs) increase as the swing phase limbs are lifted higher to clear the poles. HigherGRFsmight be painful or jeopardise healing of musculoskeletal injuries.ObjectivesTo measure stance phase kinematics andGRFsin the forelimbs and hindlimbs of horses trotting on level ground, over low poles and over high poles, and to test the hypothesis that trotting over poles is associated with increases in peakGRFsand impulses in the supporting hindlimb and forelimb compared with trotting over level ground.Study designRepeated measures experimental study on horses with normal gait.MethodsKinematic andGRFdata were collected from 8 horses trotting on level ground under 3 conditions performed in random order: no poles, low (11 cm) poles and high (20 cm) poles spaced 1.05 ± 0.05 m apart. Spatiotemporal and angular kinematic variables andGRFswere measured during stance. Comparisons among conditions were made using repeated measuresANOVA(P<0.05) with Bonferroni correction forpost hoctesting.ResultsThe onlyGRFcomponent that increased when trotting over poles was peak forelimb brakingGRF. Forelimb vertical and braking impulses increased and the transverse impulse changed from medially to laterally directed. Extension of the metatarsophalangeal and metacarpophalangeal joints did not change.ConclusionsThe fact that peak vertical forces and extension of the metatarsophalangeal and metacarpophalangeal joints did not increase when trotting over poles suggests that loading of the musculoskeletal tissues is comparable with that associated with trotting on level ground in horses with symmetrical movement at trot. The findings support the use of trot poles during rehabilitation from lameness in horses that move symmetrically. The generation of laterally directed forelimb transverse forces suggests that trotting over poles may recruit the forelimb adductor musculature.
Effect of hoof orientation and ballast on acceleration and vibration in the hoof and distal forelimb following simulated impactsex vivo
Authors: McCarty C. A. , Thomason J. J. , Gordon K. , Burkhart T. , Bignell W. 
Published: February 2014

SummaryReasons for performing studyWe wished to add to the existing baseline data on impact loading of the distal limb as a precursor to assessing the potential role of impact in injury and joint disease.ObjectivesTo examine the effect of 3 hoof‐strike conditions (toe first, flat and heel first) and 2 specimen masses (with and without a ballast of ∼2% body mass) on impact deceleration and vibration frequencies and energies at the hoof, first phalanx and third metacarpal.Study designBiomechanical experiments in cadaver material.MethodsEight cadaver limbs were subjected to randomised, repeated controlled trials, in which the hoof was struck by a pendulum impact‐testing machine (impact velocity, 3.55 m/s) in the 3 strike and 2 mass conditions. Data from triaxial accelerometers on the hoof, first phalanx and third metacarpal quantified, for all trials, the peak impact acceleration, frequencies in the first 6.4 ms following impact, the frequency with the most energy, 95% of the total energy and the frequency at 95% cumulative energy. The effects of the strike and mass conditions on each variable were statistically tested using repeated‐measuresANOVA(α = 0.05).ResultsSignal energy reaching the third metacarpal was 6–31% of that at the hoof. A heel‐first strike produced the largest peak accelerations and highest frequencies among all strike conditions, and changing the mass had no effect regardless of strike condition.ConclusionsLarge accelerations that occur upon impact of the hoof with the ground are attenuated by the distal structures of the equine limb, but still carry considerable energy within the signal that could be damaging to tissue and are dependent on hoof‐strike condition but not ballast. Our results suggest that impact loading on the hoof could be a factor in contributing to bone injury and joint disease in the distal limb.
Prediction of the key binding site of odorant‐binding protein of Holotrichia oblita Faldermann (Coleoptera: Scarabaeida)
Authors: Zhuang X. , Wang Q. , Wang B. , Zhong T. , Cao Y. , Li K. , Yin J. 
Published: February 2014

AbstractThe scarab beetle Holotrichia oblita Faldermann (Coleoptera: Scarabaeidae) is a predominant underground pest in the northern parts of China, and its larvae (grubs) cause great economic losses because of its wide range of host plants and covert habitats. Environmentally friendly strategies for controlling adults would have novel and broad potential applications. One potential pest management measure is the regulation of olfactory chemoreception to control target insect pests. In the process of olfactory recognition, odorant‐binding proteins (OBPs) are believed to carry hydrophobic odorants from the environment to the surface of olfactory receptor neurons. To obtain a better understanding of the relationship between OBP structures and their ligands, homology modelling and molecular docking have been conducted on the interaction between HoblOBP1 and hexyl benzoate in the present study. Based on the results, site‐directed mutagenesis and binding experiments were combined to describe the binding sites of HoblOBP1 and to explore its ligand‐binding mechanism. After homology modelling of HoblOBP1, it was found that the three‐dimensional structure of HoblOBP1 consists of six α‐helices and three disulphide bridges that connect the helices, and the hydrophobic pockets are both composed of five helices. Based on the docking study, we found that van der Waals interactions and hydrophobic interactions are both important in the bonding between HoblOBP1 and hexyl benzoate. Intramolecular residues formed the hydrogen bonds in the C terminus of the protein and the bonds are crucial for the ligand‐binding specificity. Finally, MET48, ILE80 and TYR111 are binding sites predicted for HoblOBP1. Using site‐directed mutagenesis and fluorescence assays, it was found that ligands could not be recognized by mutant of Tyr111. A possible explanation is that the compound could not be recognized by the mutant, and remains in the binding cavity because of the loss of the intramolecular hydrogen bonding that acts as a holder. So we believe that Tyr111 of HoblOBP1 is a key binding site. We also believe that Ile80A is a very important binding site, especially to some ligands.
The antenna‐specific odorant‐binding protein AlinOBP13 of the alfalfa plant bug Adelphocoris lineolatus is expressed specifically in basiconic sensilla and has high binding affinity to terpenoids
Authors: Sun L. , Xiao H‐J. , Gu S‐H. , Zhou J‐J. , Guo Y‐Y. , Liu Z‐W. , Zhang Y‐J. 
Published: February 2014

AbstractOdorant‐binding proteins (OBPs) are crucial in the olfactory pathway of insects. In the present study, the antenna‐enriched OBP AlinOBP13 was investigated because of its potential contribution to the peripheral olfactory perception in the alfalfa plant bug Adelphocoris lineolatus. The results of quantitative reverse transcriptase‐PCR showed that the transcript level of AlinOBP13 was higher in the adult stage than in the nymph stages. The transcript levels of AlinOBP13 in the male and female antennae significantly increased after 4 and 8 h of starvation, respectively. Fine ultrastructures of different types of chemosensilla in both female and male antennae were investigated using transmission electron microscopy and immunocytochemical labelling. The results revealed that the anti‐AlinOBP13 antiserum strongly and specifically labelled short basiconic sensilla; this antiserum was restricted to the inner lumen and the cavities below the sensillum base of the sensilla. By contrast, multiporous sensilla trichodea, medium long sensilla basiconica, and aporous sensilla chaetica were not labelled. The present study is the first to report an OBP showing specific expression in the short basiconic sensilla of a member of the Hemipteran species. The results of a fluorescence displacement binding assay indicated that recombinant AlinOBP13 showed a more specific binding preference to terpenoids than to sex pheromones and other classes of chemicals. This binding ability was dramatically affected by pH; higher binding affinities were displayed at pH 10.0 than at pH 7.4 and 5.0. In addition, the results of dose‐dependent electroantennogram recordings from the antennae showed that both female and male adult bugs responded to the terpenoids tested, suggesting an apparent physiological relevance of AlinOBP13 in A. lineolatus chemoreception. The results of this study suggest that AlinOBP13 functions as a specific carrier of terpenoids and provide insights into the mechanism of A. lineolatus in response to green volatiles.
The Ethics of Producing In Vitro Meat
Authors: Schaefer G. Owen , Savulescu Julian 
Published: February 2014

AbstractThe prospect of consumable meat produced in a laboratory setting without the need to raise and slaughter animals is both realistic and exciting. Not only could such in vitro meat become popular due to potential cost savings, but it also avoids many of the ethical and environmental problems with traditional meat productions. However, as with any new technology, in vitro meat is likely to face some detractors. We examine in detail three potential objections: 1) in vitro meat is disrespectful, either to nature or to animals; 2) it will reduce the number of happy animals in the world; and 3) it will open the door to cannibalism. While each objection has some attraction, we ultimately find that all can be overcome. The upshot is that in vitro meat production is generally permissible and, especially for ethical vegetarians, worth promoting.
The Tragedy of the Commons as an Essentially Aggregative Harm
Authors: Kahn Elizabeth 
Published: February 2014

AbstractThis article identifies ‘the tragedy of the commons’ as an essentially aggregative harm and considers what agents in such a scenario owe to one another. It proposes that the duty to take reasonable precautions requires that agents make efforts to establish collective solutions to any essentially aggregative harm to which they would otherwise contribute.Baylor Johnson has argued that the general obligation to promote the common good requires that agents make efforts to establish a collective agreement to avert a potential tragedy of the commons. This article agrees with Johnson's analysis but argues that there are also negative duties, which give commons users additional moral reason to take collective action to prevent the destruction of the utility of the commons. These duties link commons users to resolving this particular problem and provide grounds to demand that they make greater efforts to prevent the destruction of the commons compared to bystanders.The article suggests that fulfilling negative duties can require establishing collective institutions with the power to regulate human action and interaction. This analysis could be applied to a range of social problems which result from the aggregation of actions and practices.
Stop Thinking So Much About ‘Sexual Harassment’
Authors: Saul Jennifer 
Published: February 2014

AbstractThis article explores two related widespread mistakes in thinking about sexual harassment. One is a mistake made by philosophers doing philosophical work on the topic of sexual harassment: an excessive focus on attempting to define the term ‘sexual harassment’. This is a perfectly legitimate topic for discussion and indeed a necessary one, but its dominance of the literature has tended to prevent philosophers from adequately exploring other topics that are of at least equal importance, particularly that of bystanders' responsibilities. The other mistake is one made not just by philosophers but by most people attempting to deal with real‐world behaviour that is either sexual harassment or closely related to sexual harassment: an excessive focus on whether or not formal charges of sexual harassment are possible or appropriate. (This is clearly related to the first mistake in that a part of deciding whether charges are appropriate is deciding whether the behaviour meets the definition of sexual harassment.) I argue that these are not merely unfortunate errors in attempting to conceptualise certain problematic behaviours; they have extremely damaging real world effects.
Operational Aspects of a Hypothetical Demise of the Euro
Authors: Papadia Francesco 
Published: February 2014

AbstractThis article illustrates what would be the operational implications of a hypothetical demise of the euro. In order to do this, it examines what were the operational implications of establishing the euro and shows that the opposite endeavour would not just be its symmetric counterpart. The paper also looks at two developments that took place after the launch of the euro – the emergence of very large Target2 balances during the crisis that started in 2010 and the move towards financial integration – showing that they would add to the formidable operational complications that would be created by the demise of the euro. The paper concludes that the logistical difficulties considered here only look minor in comparison with the fundamental reasons that led governments and central banks to fight with determination the risk of a demise of the euro. In absolute terms, they are important enough to tilt the balance of costs and benefits in the direction of preserving the eurozone.
Does National Identity Matter? Political Conditionality and the Crucial Case of Serbia's (Non‐)Co‐operation with the ICTY
Authors: Pawelec Maria , Grimm Sonja 
Published: February 2014

AbstractSeeking to explain the difficult cases of delayed democratic transition in the Western Balkans, recent literature argues that ‘national identity’ significantly limits the effectiveness of external actors’ political conditionality. This argument is tested in this article by investigating Serbia's co‐operation with the International Criminal Tribunal for the former Yugoslavia (ICTY), which was demanded by the United States and the European Union (EU). The findings show that incidents of Serbian co‐operation with the ICTY were not preceded by widespread national identity change; rather, co‐operation occurred when Serbia was faced with consistent external pressure and the immediate prospect of small‐scale rewards. Conditionality thus remained effective. These findings challenge theoretical arguments that issues of national identity may impede external actors’ projection of power, independently of domestic actors’ cost‐benefit calculations. Moreover, they suggest that, in the future, external actors such as the EU may continue to rely upon political conditionality for their democratization agenda, even concerning domestically sensitive issue‐areas.
Prevalence and predictors of PTSD and depression among adolescent victims of the Spring 2011 tornado outbreak
Authors: Adams Zachary W. , Sumner Jennifer A. , Danielson Carla Kmett , McCauley Jenna L. , Resnick Heidi S. , Grös Kirstin , Paul Lisa A. , Welsh Kyleen E. , Ruggiero Kenneth J. 
Published: February 2014

BackgroundRelatively few studies have examined prevalence and predictors of posttraumatic stress disorder (PTSD) or major depressive episode (MDE) in disaster‐affected adolescents. Fewer still have administered diagnostic measures or studied samples exposed to tornadoes, a common type of disaster. Further, methodologic problems limit the generalizability of previous findings. This study addressed prevalence estimates and risk factors for PTSD and MDE among adolescents exposed to the Spring 2011 tornado outbreak in Alabama and Joplin, Missouri.MethodsA large (N = 2000), population‐based sample of adolescents and caregivers, recruited randomly from tornado‐affected communities, participated in structured telephone interviews. PTSD and MDE prevalence were estimated for the overall sample, by gender, and by age. Hierarchical logistic regression was used to identify risk factors for PTSD and MDE.ResultsOverall, 6.7% of adolescents met diagnostic criteria for PTSD and 7.5% of adolescents met diagnostic criteria for MDE since the tornado. Girls were significantly more likely than boys to meet diagnostic criteria for MDE, and older adolescents were more likely than younger adolescents to report MDE since the tornado. Female gender, prior trauma exposure, and an injured family member were associated with greater risk for PTSD and MDE. Specific incident characteristics (loss of services, concern about others’ safety) were associated with greater PTSD risk; prior disaster exposure was associated with lower MDE risk.ConclusionsHowever, most adolescents were resilient following tornado exposure, roughly 1 in 15 developed PTSD, 1 in 13 developed MDE, and many more endorsed subclinical mental health problems. Information regarding specific risk factors can guide early screening, prevention, and intervention efforts in disaster‐affected communities.