bluuebunny/crossref_metadata_2025 huggingface dataset:
Rawls, reasonableness, and international toleration
Authors: Porter Thomas
Published: February 2012

Rawls’s account of international toleration in The Law of Peoples has been the subject of vigorous critiques by critics who believe that he unacceptably dilutes the principles of his Law of Peoples in order to accommodate non-liberal societies. One important component in these critiques takes issue specifically with Rawls’s inclusion of certain non-liberal societies (‘decent peoples’) in the constituency of justification for the Law of Peoples. In Rawls’s defence, I argue that the explanation for the inclusion of decent peoples in the constituency of justification is not, as is standardly assumed, that they are the kind of societies that ought to be tolerated in that way on some prior conception of which kinds of societies ought to be tolerated in that way. The real explanation appeals to a methodological principle underlying Rawls’s approach to political justification, according to which liberals owe justification, as a matter of liberal principle, to those who comply with liberal principles for political institutions that apply to them. If such liberal principles can be complied with by agents who nevertheless cannot accept fully liberal justifications for those principles, then liberalism itself requires liberals to seek justifications which they can accept. This approach gives us a new way to view decent peoples: as just such agents, who are therefore owed a justification for the Law of Peoples that they can accept. Decency is thus a concept that is internal to liberal political justification at the international level. Reading Rawls in this way permits a coherent and attractive defence of his strategy of toleration and of his international theory as a whole.
Video-stimulated accounts: Young children accounting for interactional matters in front of peers
Authors: Theobald Maryanne
Published: February 2012

Research in the early years places increasing importance on participatory methods to engage children. The playback of video-recording to stimulate conversation is a research method that enables children’s accounts to be heard and attends to a participatory view. During video-stimulated sessions, participants watch an extract of video-recording of a specific event in which they were involved, and then account for their participation in that event. Using an interactional perspective, this article draws distinctions between video-stimulated accounts and a similar research method, popular in education, that of video-stimulated recall. Reporting upon a study of young children’s interactions in a playground, video-stimulated accounts are explicated to show how the participants worked toward the construction of events in the video-stimulated session. This article discusses how the children account for complex matters within their social worlds, and manage the accounting of others in the video-stimulated session. When viewed from an interactional perspective and used alongside fine grained analytic approaches, video-stimulated accounts are an effective method to provide the standpoint of the children involved and further the competent child paradigm.
Considering the Source
Authors: Basford Tessa E. , Offermann Lynn R. , Wirtz Philip W.
Published: February 2012

Researchers and practitioners have devoted little attention to the impact of different sources of leadership support on follower outcomes. The present study is the first to examine the relationship between two levels of leadership support—immediate supervisors and senior management—on follower motivation and intent to stay. Although positively related, support from each level exerted an independent, positive influence on follower motivation and intent to stay, with senior management support showing greater impact. These findings emerged for employees in low- and high-status positions; however, the levels of support had stronger impact on intent to stay for workers in high-status positions.
Prevention of Type II Endoleak by Laparoscopic Inferior Mesenteric Artery Ligation
Authors: Brenes Robert A. , Panait Lucian , Abbas Hussain M. A. , Tapias Leonidas , Tripodi Giuseppe , Ajemian Michael S. , Macaron Shady H.
Published: February 2012

Abdominal aortic aneurysm repair by endovascular techniques have gained wide acceptance as a treatment option. A potential well-known complication of endovascular repair includes endoleak. Specifically, type II endoleak, which is described as retrograde flow into the aneurysm sac through collateral vessels, can occur in up to 30% of patients. Certain preoperative factors can predict which patients may develop type II endoleak. This article describes laparoscopic inferior mesenteric artery ligation prior to endovascular abdominal aortic aneurysm repair as a viable treatment option in the prevention of type II endoleak.
Primary alveolar epithelial cell surface membrane microdomain function is required for Pneumocystis β-glucan-induced inflammatory responses
Authors: Evans Scott E , Kottom Theodore J , Pagano Richard E , Limper Andrew H
Published: February 2012

Intense lung inflammation characterizes respiratory failure associated with Pneumocystis pneumonia. Our laboratory has previously demonstrated that alveolar epithelial cells (AECs) elaborate inflammatory cytokines and chemokines in response to the Pneumocystis carinii cell wall constituent β-(1→3)-glucan (PCBG), and that these responses require lactosylceramide, a prominent glycosphingolipid constituent of certain cell membrane microdomains. The relevance of membrane microdomains, also termed plasma membrane lipid rafts, in cell signaling and macromolecule handling has been increasingly recognized in many biologic systems, but their role in P. carinii-induced inflammation is unknown. To investigate the mechanisms of microdomain-dependent P. carinii-induced inflammation, we challenged primary rat AECs with PCBG with or without pre-incubation with inhibitors of microdomain function. Glycosphingolipid and cholesterol rich microdomain inhibition resulted in significant attenuation of P. carinii-induced expression of TNF-α and the rodent C-X-C chemokine MIP-2, as well as their known inflammatory secondary signaling pathways. We have previously shown that protein kinase C (PKC) is activated by PCBG challenge and herein show that PKC localizes to AEC microdomains. We also demonstrate by conventional microscopy, fluorescence microscopy, confocal microscopy and spectrophotofluorimetry that AECs internalize fluorescently-labeled PCBG by microdomain-mediated mechanisms, and that anti-microdomain pretreatments prevent internalization. Taken together, these data suggest an important role for AEC microdomain function in PCBG-induced inflammatory responses. This offers a potential novel target for therapeutics for a condition that continues to exert unacceptable morbidity and mortality among immunocompromised populations.
An integrated measurement system for analysing impact biomechanics in the rugby scrum
Authors: Preatoni Ezio , Wallbaum Andreas , Gathercole Nicholas , Coombes Stephen , Stokes Keith A , Trewartha Grant
Published: February 2012

As part of a wider project investigating the biomechanics of the rugby scrum within rugby union, the focus of the present study was to design, realise and test an unobtrusive measurement system for assessing the kinematics and kinetics of rugby forwards while scrummaging on the pitch in realistic environmental conditions. Currently the study investigates one forward pack (eight players) scrummaging against an instrumented scrum machine, a training aid used widely throughout rugby. The measurement system integrates three different subsystems for: (1) measuring forces exerted by players; (2) capturing players’ movements; and, (3) triggering/synchronising all the sensors involved in (1) and (2). Applied three-dimensional forces were measured by strain gauge circuits attached to each pusher arm of the machine and then summed to produce the components of overall force. Multiple camera views allowed the recording and subsequent analysis of player movements, in the primary transverse (50 Hz and 200 Hz) and sagittal (50 Hz) planes of motion. A control system executed pre-recorded audio commands to players with consistent timings, sent trigger pulses to acquisition devices and collected analogue data at 500 Hz. The overall system has been applied successfully in the field to record data from rugby union forward packs across a range of playing levels and initial results confirm that the measurement system will be useful for its desired purpose to compare the biomechanics of different scrum engagement techniques.
Excess mortality after treatment with fludarabine and cyclophosphamide in combination with alemtuzumab in previously untreated patients with chronic lymphocytic leukemia in a randomized phase 3 trial
Authors: Lepretre Stephane , Aurran Therese , Mahé Beatrice , Cazin Bruno , Tournilhac Olivier , Maisonneuve Herve , Casasnovas Olivier , Delmer Alain , Leblond Veronique , Royer Bruno , Corront Bernadette , Chevret Sylvie , Delépine Roselyne , Vaudaux Sandrine , Van Den Neste Eric , Béné Marie Christine , Letestu Remi , Cymbalista Florence , Feugier Pierre
Published: February 2012

A French and Belgian multicenter phase 3 trial was conducted in medically fit patients with untreated chronic lymphocytic leukemia. Of 178 patients enrolled in the study, 165 were randomly assigned to receive 6 courses of oral fludarabine and cyclophosphamide (FC) in combination with rituximab (FCR; 375 mg/m2 in cycle one, 500 mg/m2 in all subsequent cycles) or alemtuzumab (FCCam; 30 mg subcutaneously injected on cycle days 1-3); each cycle was 28 days. Recruitment was halted prematurely because of excess toxicity; 8 patients died in the FCCam group, 3 from lymphoma and 5 from in-fection. Overall response rates were 91% with FCR and 90% with FCCam (P = .79). Complete remission rates were 33.75% with FCR and 19.2% with FCCam (P = .04). Three-year progression-free survival was 82.6% with FCR and 72.5% with FCCam (P = .21). Three-year overall survival was similar between the 2 arms at 90.1% in the FCR arm and 86.4% in the FCCam arm (P = .27). These results indicate that the FCCam regimen for the treatment of advanced chronic lymphocytic leukemia was not more effective than the FCR regimen and was associated with an unfavorable safety profile, representing a significant limitation of its use. This study is registered with www.clinicaltrials.gov as number NCT00564512.
Risk stratification–directed donor lymphocyte infusion could reduce relapse of standard-risk acute leukemia patients after allogeneic hematopoietic stem cell transplantation
Authors: Yan Chen-Hua , Liu Dai-Hong , Liu Kai-Yan , Xu Lan-Ping , Liu Yan-Rong , Chen Huan , Han Wei , Wang Yu , Qin Ya-Zhen , Huang Xiao-Jun
Published: February 2012

We studied the impact of risk stratification–directed interventions for minimal residual disease (MRD) on relapse and disease-free survival (DFS) prospectively in 814 subjects with standard-risk acute leukemia receiving allotransplantation in first or second complete remission. A total of 709 subjects were MRD− after transplantation (Group A); 105 subjects were MRD+, 49 received low-dose IL-2 (Group B), and 56 received modified donor lymphocyte infusion (DLI) with or without low-dose IL-2 (Group C). Posttransplantation immune suppression for GVHD was also modified based on MRD state. The cumulative risk of relapse was significantly less and DFS was significantly better in subjects in Group C than in subjects in Group B (P = .001 and P = .002, respectively), but was not different from subjects in Group A (P = .269 and P = .688, respectively). Multivariate analyses confirmed that MRD state and modified DLI were significantly correlated with relapse (P = .000, odds ratio [OR] = 0.255 and P = .000, OR = 0.269) and DFS (P = .001, OR = 0.511 and P = .006, OR = 0.436, respectively). These data suggest that risk stratification–directed interventions with modified DLI in patients with standard-risk acute leukemia who are MRD+ after transplantation may improve transplantation outcomes.
The cold-induced basic helix-loop-helix transcription factor gene MdCIbHLH1encodes an ICE-like protein in apple
Authors: Feng Xiao-Ming , Zhao Qiang , Zhao Ling-Ling , Qiao Yu , Xie Xing-Bin , Li Hui-Feng , Yao Yu-Xin , You Chun-Xiang , Hao Yu-Jin
Published: February 2012

Background

Plant growth is greatly affected by low temperatures, and the expression of a number of genes is induced by cold stress. Although many genes in the cold signaling pathway have been identified in Arabidopsis, little is known about the transcription factors involved in the cold stress response in apple.

Results

Here, we show that the apple bHLH (basic helix-loop-helix) gene MdCIbHLH1 (Cold-Induced bHLH1), which encodes an ICE-like protein, was noticeably induced in response to cold stress. The MdCIbHLH1 protein specifically bound to the MYC recognition sequences in the AtCBF3 promoter, and MdCIbHLH1 overexpression enhanced cold tolerance in transgenic Arabidopsis. In addition, the MdCIbHLH1 protein bound to the promoters of MdCBF2 and favorably contributed to cold tolerance in transgenic apple plants by upregulating the expression of MdCBF2 through the CBF (C-repeat-binding factor) pathway. Our findings indicate that MdCIbHLH1 functions in stress tolerance in different species. For example, ectopic MdCIbHLH1 expression conferred enhanced chilling tolerance in transgenic tobacco. Finally, we observed that cold induces the degradation of the MdCIbHLH1 protein in apple and that this degradation was potentially mediated by ubiquitination and sumoylation.

Conclusions

Based on these findings, MdCIbHLH1 encodes a transcription factor that is important for the cold tolerance response in apple.
Effect of calcification on the mechanical stability of plaque based on a three-dimensional carotid bifurcation model
Authors: Wong Kelvin KL , Thavornpattanapong Pongpat , Cheung Sherman CP , Sun Zhonghua , Tu Jiyuan
Published: February 2012

Background

This study characterizes the distribution and components of plaque structure by presenting a three-dimensional blood-vessel modelling with the aim of determining mechanical properties due to the effect of lipid core and calcification within a plaque. Numerical simulation has been used to answer how cap thickness and calcium distribution in lipids influence the biomechanical stress on the plaque.

Method

Modelling atherosclerotic plaque based on structural analysis confirms the rationale for plaque mechanical examination and the feasibility of our simulation model. Meaningful validation of predictions from modelled atherosclerotic plaque model typically requires examination of bona fide atherosclerotic lesions. To analyze a more accurate plaque rupture, fluid-structure interaction is applied to three-dimensional blood-vessel carotid bifurcation modelling. A patient-specific pressure variation is applied onto the plaque to influence its vulnerability.

Results

Modelling of the human atherosclerotic artery with varying degrees of lipid core elasticity, fibrous cap thickness and calcification gap, which is defined as the distance between the fibrous cap and calcification agglomerate, form the basis of our rupture analysis. Finite element analysis shows that the calcification gap should be conservatively smaller than its threshold to maintain plaque stability. The results add new mechanistic insights and methodologically sound data to investigate plaque rupture mechanics.

Conclusion

Structural analysis using a three-dimensional calcified model represents a more realistic simulation of late-stage atherosclerotic plaque. We also demonstrate that increases of calcium content that is coupled with a decrease in lipid core volume can stabilize plaque structurally.
The associations between body and knee height measurements and knee joint structure in an asymptomatic cohort
Authors: Teichtahl Andrew J , Wluka Anita E , Strauss Boyd J , Wang Yuanyuan , Berry Patricia , Davies-Tuck Miranda , Cicuttini Flavia M
Published: February 2012

Background

It has been suggested that knee height is a determinant of knee joint load. Nonetheless, no study has directly examined the relationship between anthropometric measures of height and knee joint structures, such as cartilage.

Methods

89 asymptomatic community-based adults aged 25-62 with no diagnosed history of knee arthropathy were recruited. Anthropometric data (knee height and body height) were obtained by standard protocol, while tibial cartilage volume and defects, as well as bone area were determined from magnetic resonance imaging. Static knee alignment was measured from the joint radiograph.

Results

All anthropometric height measures were associated with increasing compartmental tibial bone area (p ≤ 0.05). Although knee height was associated with tibial cartilage volume (e.g. β = 27 mm3 95% CI 7- 48; p = 0.009 for the medial compartment), these relationship no longer remained significant when knee height as a percentage of body height was analysed. Knee height as a percentage of body height was associated with a reduced risk of medial tibial cartilage defects (odds ratio 0.6; 95% confidence interval 0.4 - 1.0; p = 0.05).

Conclusion

The association between increased anthropometric height measures and increased tibial bone area may reflect inherently larger bony structures. However the beneficial associations demonstrated with cartilage morphology suggest that an increased knee height may confer a beneficial biomechanical environment to the chondrocyte of asymptomatic adults.
Preventing Pseudomonas aeruginosa and Chromobacterium violaceum infections by anti-adhesion-active components of edible seeds
Authors: Rachmaninov Ofra , Zinger-Yosovich Keren D , Gilboa-Garber Nechama
Published: February 2012

Background

Pseudomonas aeruginosa adhesion to animal/human cells for infection establishment involves adhesive proteins, including its galactose- and fucose-binding lectins PA-IL (LecA) and PA-IIL (LecB). The lectin binding to the target-cell receptors may be blocked by compatible glycans that compete with those of the receptors, functioning as anti-adhesion glycodecoys. The anti-adhesion treatment is of the utmost importance for abrogating devastating antibiotic-resistant P. aeruginosa infections in immunodeficient and cystic fibrosis (CF) patients. This strategy functions in nature in protecting embryos and neonates. We have shown that PA-IL, PA-IIL, and also CV-IIL (a PA-IIL homolog produced in the related pathogen Chromobacterium violaceum) are highly useful for revealing natural glycodecoys that surround embryos in diverse avian eggs and are supplied to neonates in milks and royal jelly. In the present study, these lectins were used as probes to search for seed embryo-protecting glycodecoys.

Methods

The lectin-blocking glycodecoy activities were shown by the hemagglutination-inhibition test. Lectin-binding glycoproteins were detected by Western blotting with peroxidase-labeled lectins.

Results

The present work reports the finding - by using PA-IL, PA-IIL, and CV-IIL - of rich glycodecoy activities of low (< 10 KDa) and high MW (> 10 kDa) compounds (including glycoproteins) in extracts of cashew, cocoa, coffee, pumpkin, and tomato seeds, resembling those of avian egg whites, mammal milks, and royal jelly.

Conclusions

Edible seed extracts possess lectin-blocking glycodecoys that might protect their embryos from infections and also might be useful for hampering human and animal infections.
High serum alkaline phosphatase cooperating with MMP-9 predicts metastasis and poor prognosis in patients with primary osteosarcoma in Southern China
Authors: Han Ju , Yong Bicheng , Luo Canqiao , Tan Pingxian , Peng Tingsheng , Shen Jingnan
Published: February 2012

Background

Osteosarcoma is a malignant tumor with high ability to form invasion and metastasis. Identifying prognostic factor in osteosarcoma is helpful to select those patients for more aggressive management. Our study evaluated serum alkaline phosphatase (ALP) cooperating with matrix metalloproteinase-9 (MMP-9) as an important prognostic predictor for local recurrence and distant metastasis of osteosarcoma.

Methods

177 cases were included from the osteosarcoma patients treated at 1st Affiliated Hospital of Sun Yat-sen University (1999-2008). Pre-chemotherapy serum ALP (pre-ALP) were studied and correlated with tumor recurrence, lung metastasis and patient survival. MMP-9 protein in tumor tissues was detected by immunohistochemistry and correlated with pre-ALP level.

Results

Pre-ALP were partitioned into normal, high, and very high groups, in each group the incidence of metastases was 12.2%, 21.2% and 34.6%, respectively (p = 0.007). In the three groups the mean disease-free survival (DFS) was 57 ± 3.15, 28 ± 3.57 and 14 ± 3.35 months, respectively (p < 0.001); overall survival (OS) was 92 ± 26.89, 39 ± 8.61 and 17 ± 5.07 months, respectively (p < 0.001). By multivariate analysis, elevated serum pre-ALP were associated with shorter DFS (p = 0.018) and OS (p = 0.031). If elevated ALP levels decreased after clinical treatment, the incidence of lung metastasis rate decreased (p = 0.028); DFS and OS were both prolonged (p < 0.001). Pre-ALP was also positively correlated with MMP-9 expression (p = 0.015) in tumor tissue.

Conclusions

Pre-ALP was an independent prognostic factor for the survival of osteosarcoma patients in south China, and correlated with MMP-9 expression and lung metastasis. ALP can also serve as a prognostic marker for treatment, and merit large-scale validation studies.
Robust reconstruction algorithm for compressed sensing in Gaussian noise environment using orthogonal matching pursuit with partially known support and random subsampling
Authors: Sermwuthisarn Parichat , Auethavekiat Supatana , Gansawat Duangrat , Patanavijit Vorapoj
Published: February 2012

The compressed signal in compressed sensing (CS) may be corrupted by noise during transmission. The effect of Gaussian noise can be reduced by averaging, hence a robust reconstruction method using compressed signal ensemble from one compressed signal is proposed. The compressed signal is subsampled for L times to create the ensemble of L compressed signals. Orthogonal matching pursuit with partially known support (OMP-PKS) is applied to each signal in the ensemble to reconstruct L noisy outputs. The L noisy outputs are then averaged for denoising. The proposed method in this article is designed for CS reconstruction of image signal. The performance of our proposed method was compared with basis pursuit denoising, Lorentzian-based iterative hard thresholding, OMP-PKS and distributed compressed sensing using simultaneously orthogonal matching pursuit. The experimental results of 42 standard test images showed that our proposed method yielded higher peak signal-to-noise ratio at low measurement rate and better visual quality in all cases.
Up-regulation of brain-derived neurotrophic factor in primary afferent pathway regulates colon-to-bladder cross-sensitization in rat
Authors: Xia Chun-Mei , Gulick Melisa A , Yu Sharon J , Grider John R , Murthy Karnam S , Kuemmerle John F , Akbarali Hamid I , Qiao Li-Ya
Published: February 2012

Background

In humans, inflammation of either the urinary bladder or the distal colon often results in sensory cross-sensitization between these organs. Limited information is known about the mechanisms underlying this clinical syndrome. Studies with animal models have demonstrated that activation of primary afferent pathways may have a role in mediating viscero-visceral cross-organ sensitization.

Methods

Colonic inflammation was induced by a single dose of tri-nitrobenzene sulfonic acid (TNBS) instilled intracolonically. The histology of the colon and the urinary bladder was examined by hematoxylin and eosin (H&E) stain. The protein expression of transient receptor potential (TRP) ion channel of the vanilloid type 1 (TRPV1) and brain-derived neurotrophic factor (BDNF) were examined by immunohistochemistry and/or western blot. The inter-micturition intervals and the quantity of urine voided were obtained from analysis of cystometrograms.

Results

At 3 days post TNBS treatment, the protein level of TRPV1 was increased by 2-fold (p< 0.05) in the inflamed distal colon when examined with western blot. TRPV1 was mainly expressed in the axonal terminals in submucosal area of the distal colon, and was co-localized with the neural marker PGP9.5. In sensory neurons in the dorsal root ganglia (DRG), BDNF expression was augmented by colonic inflammation examined in the L1 DRG, and was expressed in TRPV1 positive neurons. The elevated level of BDNF in L1 DRG by colonic inflammation was blunted by prolonged pre-treatment of the animals with the neurotoxin resiniferatoxin (RTX). Colonic inflammation did not alter either the morphology of the urinary bladder or the expression level of TRPV1 in this viscus. However, colonic inflammation decreased the inter-micturition intervals and decreased the quantities of urine voided. The increased bladder activity by colonic inflammation was attenuated by prolonged intraluminal treatment with RTX or treatment with intrathecal BDNF neutralizing antibody.

Conclusion

Acute colonic inflammation increases bladder activity without affecting bladder morphology. Primary afferent-mediated BDNF up-regulation in the sensory neurons regulates, at least in part, the bladder activity during colonic inflammation.
Polysaccharide and extracts from Lentinula edodes: structural features and antiviral activity
Authors: Rincão Vinicius Pires , Yamamoto Kristie Aimi , Silva Ricardo Nágila Maria Pontes , Soares Sandra Aguiar , Paccola Meirelles Luzia Doretto , Nozawa Carlos , Carvalho Linhares Rosa Elisa
Published: February 2012

Background

Lentinula edodes, known as shiitake, has been utilized as food, as well as, in popular medicine, moreover, compounds isolated from its mycelium and fruiting body have shown several therapeutic properties. The aim of this study was to determine the antiviral activity of aqueous (AqE) and ethanol (EtOHE) extracts and polysaccharide (LeP) from Lentinula edodes in the replication of poliovirus type 1 (PV-1) and bovine herpes virus type 1 (BoHV-1).

Methods

The time-of-addition assay was performed at the times -2, -1, 0, 1 and 2 h of the infection. The virucidal activity and the inhibition of viral adsorption were also evaluated. Plaque assay was used to monitor antiviral activity throughout.

Results

The AqE and LeP were more effective when added at 0 h of infection, however, EtOHE was more effective at the times 1 h and 2 h of the infection. AqE, EtOHE and LeP showed low virucidal activity, and the inhibition of viral adsorption was not significant.

Conclusions

The results allowed us to conclude that AqE, EtOHE and LeP act on the initial processes of the replication of both strains of virus.
Epidemics of viral meningitis caused by echovirus 6 and 30 in Korea in 2008
Authors: Kim Hye-Jin , Kang Byounghak , Hwang Seoyeon , Hong Jiyoung , Kim Kisang , Cheon Doo-Sung
Published: February 2012

Background

Enteroviruses (EVs) are the leading cause of aseptic meningitis, which is the most frequent central nervous system infection worldwide. We aimed to characterize the EVs involved in an aseptic meningitis outbreak in Korea in 2008. In Korea, Echovirus type 30 (E30) and E6 have been associated with outbreaks and frequent meningitis.

Methods

During 2008, through nationwide surveillance, we collected specimens from 758 patients with aseptic meningitis-related clinical manifestations. The detection of EVs from specimens was subjected to a diagnostic real-time RT-PCR in the 5' NCR. A semi-nested polymerase chain reaction (PCR) to amplify sequences from the VP1 region and sequence comparison with reference strains registered in Genbank was performed for the genotype determination.

Results

Most patients (98%) in this outbreak were children < 15 years of age. The temporal distribution of the E6 and E30 epidemics showed an obvious seasonal pattern during the short period from June to July. A large majority of the EV-positive patients experienced fever, headache, vomiting, and neck stiffness. Some patients also showed cold symptoms, sore throat, altered mental status, and seizures. We did not observe a higher fatality rate in children with E6 or E30 infection. Most of the patients recovered uneventfully. In most cases, the cerebrospinal fluid (CSF) profile was studied, and generally showed a higher than normal white blood cell count (≥ 5/mm3). We detected EVs from 513 patients (67.68%) and identified the EV genotype in 287 patients. E30 (n = 155, 50.4%) and E6 (n = 95, 33.1%) were the predominant genotypes. E9, E1, E7, E16, coxsackievirus A3, 4, 6, coxsackievirus B1, 3, and 10 were also identified. According to phylogenetic analysis, E30 belonged to subgroup 4b, and E6, to the C4 subgroup.

Conclusions

Conclusively, aseptic meningitis was the most common manifestation in children with either echovirus 30 or 6 infection. Identification of E6 and E30 as the prominent EVs in the 2008 outbreak in South Korea shows the potential of EVs to cause a serious disease in an unpredictable (fashion. Our findings provide new) insights into the clinical and virological features of the aseptic meningitis outbreak caused by E30 and E6.
Phylogenetic and molecular characterization of coxsackievirus A24 variant isolates from a 2010 acute hemorrhagic conjunctivitis outbreak in Guangdong, China
Authors: De Wu , Huanying Zheng , Hui Li , Corina Monagin , Xue Guo , Leng Liu , Hanri Zeng , Ling Fang , Yanling Mo , Huiqiong Zhou , Huan Zhang , Jing Kou , Caiyun Long , Yoshida Hiromu , Changwen Ke
Published: February 2012

Background

Acute hemorrhagic conjunctivitis is a common disease in China. As a notifiable disease, cases are registered by ophthalmologists on the AHC surveillance system. An AHC outbreak caused by CA24v was observed in Guangdong Province in 2007 by the National Disease Supervision Information Management System. Three years later, a larger outbreak occurred in Guangdong during the August-October period (2010). To characterize the outbreak and compare the genetic diversity of CA24v, which was determined to be the cause of the outbreak, the epidemiology and the molecular characterization of CA24v were analyzed in this study.

Results

A total of 69,635 cases were reported in the outbreak. 73.5% of index cases originated from students, children in kindergarten and factory workers, with the ≦ 9 age group at the highest risk. The male to female ratio was 1.84:1 among 0-19 years. 56 conjunctival swabs were collected to identify the causative agent from five cities with the AHC outbreak. 30 virus strains were isolated, and two of the genomes had the highest identity values (95.8%) with CA24v genomes. Four CA24v genotypes were identified by phylogenetic analysis for the VP1 and 3C regions. CA24v which caused the outbreak belonged to genotype IV. Furthermore, full nucleotide sequences for four representative isolates in 2010 and 2007 were determined and compared. 20 aa mutations, two nt insertions and one nt deletion were observed in the open reading frame, with 5'- and 3'- UTR respectively between them.

Conclusions

CA24v was determined to be the pathogen causing the outbreak and belongs to genotype IV. VP1 is more informative than 3CPro for describing molecular epidemiology and we hypothesize that accumulative mutations may have promoted the outbreak.
Serum levels of CXCL13 are associated with ultrasonographic synovitis and predict power Doppler persistence in early rheumatoid arthritis treated with non-biological disease-modifying anti-rheumatic drugs
Authors: Bugatti Serena , Manzo Antonio , Benaglio Francesca , Klersy Catherine , Vitolo Barbara , Todoerti Monica , Sakellariou Garifallia , Montecucco Carlomaurizio , Caporali Roberto
Published: February 2012

Introduction

Biological markers specifically reflecting pathological processes may add value in the assessment of inter-individual variations in the course of rheumatoid arthritis (RA). The current study was undertaken to investigate whether baseline serum levels of the chemokine CXCL13 might predict clinical and ultrasonographic (US) outcomes in patients with recent-onset RA.

Methods

The study included 161 early RA patients (disease duration < 12 months) treated according to a disease activity score (DAS) driven step-up protocol aiming at DAS < 2.4. Clinical disease activity measures were collected at baseline, 2, 4, 6, 9 and 12 months, and US examination of the hands was performed at baseline, 6 and 12 months. Grey-Scale (GS) and Power Doppler (PD) synovitis were scored (0 to 3), with overall scores as the sum of each joint score. CXCL13 levels were measured at baseline by enzyme-linked immunosorbent assay and evaluated in relation to the achievement of low disease activity (LDA, DAS < 2.4) and US residual inflammation (PD ≤ 1) at 12 months.

Results

Baseline levels of CXCL13 were significantly higher in RA compared to healthy controls (n = 19) (P = 0.03) and correlated with measures of synovitis, such as the swollen joint count (R 0.28, P < 0.001), the US-GS (R 0.27, P = 0.003) and US-PD (R 0.26, P = 0.005) score. Although CXCL13 did not predict the likelihood of achieving clinical LDA at 12 months within a structured treat-to-target protocol, elevated levels of CXCL13 were associated with more frequent increases of methotrexate dosage (P < 0.001). Using adjusted analyses, the highest levels of CXCL13 (> 100 pg/ml) were the only independent predictor of residual imaging inflammation (P = 0.005), irrespective of initial US-PD scores, disease activity status, acute phase reactants and autoantibodies. Among the patients in clinical LDA at 12 months, US-PD scores ≤ 1 were less frequently achieved in the high baseline CXCL13 (> 100 pg/ml) group, with an adjusted OR = 0.06 (95% CI 0.01 to 0.55, P = 0.01).

Conclusions

CXCL13 emerges as a new biological marker in early RA, accurate in assessing the severity of synovitis and the persistence of US-PD activity over time in response to conventional treatments.
Early use of imipenem/cilastatin and vancomycin followed by de-escalation versus conventional antimicrobials without de-escalation for patients with hospital-acquired pneumonia in a medical ICU: a randomized clinical trial
Authors: Kim Jong Wook , Chung Joowon , Choi Sang-Ho , Jang Hang Jea , Hong Sang-Bum , Lim Chae-Man , Koh Younsuck
Published: February 2012

Introduction

Although early use of broad-spectrum antimicrobials in critically ill patients may increase antimicrobial adequacy, uncontrolled use of these agents may select for more-resistant organisms. This study investigated the effects of early use of broad-spectrum antimicrobials in critically ill patients with hospital-acquired pneumonia.

Methods

We compared the early use of broad-spectrum antimicrobials plus subsequent de-escalation (DE) with conventional antimicrobial treatment (non-de-escalation, NDE) in critically ill patients with hospital-acquired pneumonia (HAP). This open-label, randomized clinical trial was performed in patients in a tertiary-care center medical intensive care unit (MICU) in Korea. Patients (n = 54) randomized to the DE group received initial imipenem/cilastatin plus vancomycin with subsequent de-escalation according to culture results, whereas patients randomized to the NDE group (n = 55) received noncarbapenem, nonvancomycin empiric antimicrobials.

Results

Between November 2004 and October 2006, 109 MICU patients with HAP were enrolled. Initial antimicrobial adequacy was significantly higher in the DE than in the NDE group for Gram-positive organisms (100% versus 14.3%; P < 0.001), but not for Gram-negative organisms (64.3% versus 85.7%; P = 0.190). Mean intensive care unit (ICU) stay, and 14-day, 28-day, and overall mortality rates did not differ in the two groups. Among culture-positive patients, mortality from methicillin-resistant Staphylococcus aureus (MRSA) pneumonia was higher in the DE group, even after early administration of vancomycin. Multidrug-resistant organisms, especially MRSA, were more likely to emerge in the DE group (adjusted hazard ratio for emergence of MRSA, 3.84; 95% confidence interval, 1.06 to 13.91).

Conclusions

The therapeutic advantage of early administration of broad-spectrum antimicrobials, especially with vancomycin, was not evident in this study.
Multicomponent joint migration velocity analysis in the angle domain for PP-waves and PS-waves
Authors: Du Qizhen , Li Fang , Ba Jing , Zhu Yitong , Hou Bo
Published: February 2012

Employing the vector processing of multicomponent seismic data, elastic Kirchhoff migration is used to conduct a multicomponent joint migration velocity analysis (MVA) of PP- and PS-waves in the angle domain. In vector-wavefield imaging, the elastic imaging condition has been extended to nonzero time and space shifts. We apply the extended imaging condition to elastic Kirchhoff migration to extract angle-domain common-image gathers (ADCIGs) of PP- and PS-waves. This method, which is derived from 3D wave propagation theory, directly operates on the vector wavefields and automatically resolves the problem of PS-wave polarity reversal in the migration sections. Based on the kinematic characteristics of PP- and PS-waves in the incident-angle domain, the velocity updating functions for P- and S-waves are derived. By combining the ADCIGs flatness criterion and the PP- and PS-wave image-depth consistency principle, the accuracy of P- and S-wave velocities can be assessed. The method was tested on a 2D thin-interbed model and the 2D Marmousi2 model. We found that the proposed method extracts the PP- and PS-wave ADCIGs effectively and produces appropriate P- and S-wave velocity fields. This method can be applied to time-delay gathers and to vertical or inline gathers in the 3D case.
Joint inversion of marine seismic AVA and CSEM data using statistical rock-physics models and Markov random fields
Authors: Chen Jinsong , Hoversten G. Michael
Published: February 2012

Joint inversion of seismic AVA and CSEM data requires rock-physics relationships to link seismic attributes to electric properties. Ideally, we can connect them through reservoir parameters (e.g., porosity and water saturation) by developing physical-based models, such as Gassmann’s equations and Archie’s law, using nearby borehole logs. This could be difficult in the exploration stage because information available is typically insufficient for choosing suitable rock-physics models and for subsequently obtaining reliable estimates of the associated parameters. The use of improper rock-physics models and the inaccuracy of the estimates of model parameters may cause misleading inversion results. Conversely, it is easy to derive statistical relationships among seismic and electric attributes and reservoir parameters from distant borehole logs. In this study, we developed a Bayesian model to jointly invert seismic AVA and CSEM data for reservoir parameters using statistical rock-physics models; the spatial dependence of geophysical and reservoir parameters were carried out by lithotypes through Markov random fields. We applied the developed model to a synthetic case that simulates a CO2 monitoring application. We derived statistical rock-physics relations from borehole logs at one location and estimated seismic P- and S-wave velocity ratio, acoustic impedance, density, electric resistivity, lithotypes, porosity, and water saturation at three different locations by conditioning to seismic AVA and CSEM data. Comparison of the inversion results with their corresponding true values showed that the correlation-based statistical rock-physics models provide significant information for improving the joint inversion results.
On the topography of the cost functional in linear and nonlinear inverse problems
Authors: Fernández Martínez Juan L. , Fernández Muñiz M. Zulima , Tompkins Michael J.
Published: February 2012

We analyze, through linear algebra, the topography of the cost functional in linear and nonlinear inverse problems with the aim of illuminating general characteristics. To a first-order approximation, the local data misfit function in any inverse problem is valley-shaped and elongated in the directions of the null space of the Jacobian and/or in the directions of the smallest singular values. In nonlinear inverse problems, valleys persist; however, local minima might also coexist in the misfit space and might be related to nonlinear effects ignored by the Gauss-Newton approximation to the Hessian, the regularization term designed to provide convexity to the misfit function, or to noise in the data. Furthermore, noise perturbs the size of the equivalence region making location of solutions easier but finding a global minimum harder (in the case of existence). Understanding the behavior of the cost functional is an important step in the developing techniques to appraise inverse solutions and estimate uncertainties caused by noise, incomplete sampling, regularization, and more fundamentally, simplified physical models.
Conditional Inactivation of Noggin in the Postnatal Skeleton Causes Osteopenia
Authors: Canalis Ernesto , Brunet Lisa J. , Parker Kristen , Zanotti Stefano
Published: February 2012

Noggin is an antagonist of bone morphogenetic proteins (BMP), and its overexpression causes suppressed osteoblastogenesis and osteopenia. Global inactivation of Noggin results in severe developmental defects and prenatal lethality, but the consequences of the conditional inactivation of Noggin on the postnatal skeleton are not known. To study the function of noggin in osteoblasts, we generated tissue-specific null Noggin mice by mating Noggin conditional mice, where the Noggin allele is flanked by loxP sequences, with mice expressing the Cre recombinase under the control of the osteocalcin promoter (Oc-Cre). Noggin conditional null mice exhibited decreased weight, shortened femoral length, and generalized osteopenia. Bone histomorphometric and microarchitectural analyses of distal femurs revealed decreased bone volume due to a reduced number of trabeculae in 1- and 3-month-old Noggin conditional null mice. Vertebral microarchitecture confirmed the osteopenia observed in Noggin conditional null mice. Osteoclast number was increased in 1-month-old male Noggin conditional null mice, and bone formation was increased in 3-month-old mice, but female mice did not exhibit increased bone remodeling. In conclusion, Noggin inactivation causes osteopenia, suggesting that BMP in excess have a detrimental effect on bone or that noggin has a BMP-independent role in skeletal homeostasis.
Synapsins I and II Are Not Required for Insulin Secretion from Mouse Pancreatic β-cells
Authors: Wendt Anna , Speidel Dina , Danielsson Anders , Esguerra Jonathan L. S. , Bogen Inger Lise , Walaas S. Ivar , Salehi Albert , Eliasson Lena
Published: February 2012

Synapsins are a family of phosphoproteins that modulate the release of neurotransmitters from synaptic vesicles. The release of insulin from pancreatic β-cells has also been suggested to be regulated by synapsins. In this study, we have utilized a knock out mouse model with general disruptions of the synapsin I and II genes [synapsin double knockout (DKO)]. Stimulation with 20 mm glucose increased insulin secretion 9-fold in both wild-type (WT) and synapsin DKO islets, whereas secretion in the presence of 70 mm K+ and 1 mm glucose was significantly enhanced in the synapsin DKO mice compared to WT. Exocytosis in single β-cells was investigated using patch clamp. The exocytotic response, measured by capacitance measurements and elicited by a depolarization protocol designed to visualize exocytosis of vesicles from the readily releasable pool and from the reserve pool, was of the same size in synapsin DKO and WT β-cells. The increase in membrane capacitance corresponding to readily releasable pool was approximately 50fF in both genotypes. We next investigated the voltage-dependent Ca2+ influx. In both WT and synapsin DKO β-cells the Ca2+ current peaked at 0 mV and measured peak current (Ip) and net charge (Q) were of similar magnitude. Finally, ultrastructural data showed no variation in total number of granules (Nv) or number of docked granules (Ns) between the β-cells from synapsin DKO mice and WT control. We conclude that neither synapsin I nor synapsin II are directly involved in the regulation of glucose-stimulated insulin secretion and Ca2-dependent exocytosis in mouse pancreatic β-cells.
Dual-Specificity Phosphatases Are Implicated in Severe Hyperplasia and Lack of Response to FGF23 of Uremic Parathyroid Glands from Rats
Authors: Román-García Pablo , Carrillo-López Natalia , Naves-Díaz Manuel , Rodríguez Isabel , Ortiz Alberto , Cannata-Andía Jorge B.
Published: February 2012

Phosphate load accelerates the progression of secondary hyperparathyroidism (sHPT). In advanced stages of sHPT, there is a marked hyperplasia and resistance to classical regulatory endocrine factors such as calcium, calcitriol, or fibroblast growth factor 23 (FGF23), which suppresses PTH secretion by an ERK-dependent mechanism. Nephrectomized rats were fed with a high- or normal-phosphorus diet for different periods of time to induce sHPT. Biochemical parameters, parathyroid gland microarrays, quantitative real-time PCR, and immunohistochemistry (ERK/phospho-ERK) were performed. To test the role of dual-specificity phosphatases (Dusp) on parathyroid gland regulation, normal parathyroid glands were cultured with FGF23 and Dusp. Uremic rats fed with a high-phosphorus diet showed more severe sHPT, higher serum FGF23 levels and mortality, and decreased parathyroid Klotho gene expression. In all stages of sHPT, parathyroid microarrays displayed a widespread gene expression down-regulation; only a few genes were overexpressed, among them, Dusp5 and -6. In very severe sHPT, a significant reduction in phospho-ERK (the target of Dusp) and a significant increase of Dusp5 and -6 gene expression were observed. In ex vivo experiments with parathyroid glands, Dusp partially blocked the effect of FGF23 on PTH secretion, suggesting that Dusp might play a role in parathyroid regulation. The overexpression of Dusp and the inactivation of ERK found in the in vivo studies together with the ex vivo results might be indicative of the defense mechanism triggered to counteract hyperplasia, a mechanism that can also contribute to the resistance to the effect of FGF23 on parathyroid gland observed in advanced forms of chronic kidney disease.