bluuebunny/crossref_metadata_2025 huggingface dataset:
HIV pre‐exposure prophylaxis for people who inject drugs: a review of current results and an agenda for future research
Authors: Escudero Daniel J , Lurie Mark N , Kerr Thomas , Howe Chanelle J , Marshall Brandon DL
Published: March 2014

Introduction

Studies examining the use of pre‐exposure prophylaxis (PrEP) to prevent HIV transmission among people who inject drugs (PWIDs) have not been adequately summarized. Recently, the Bangkok Tenofovir Study has shown that PrEP may be effective at reducing new HIV infections among this high‐risk group. This randomized controlled trial was the first study to specifically examine the efficacy of PrEP among PWIDs. In this review, we present the current state of evidence regarding the use of PrEP to prevent HIV infection in PWID populations, and set an agenda for future research to inform the most effective implementation of PrEP in the context of existing evidence‐based HIV prevention strategies.

Discussion

Despite positive trial results confirming that PrEP may prevent HIV transmission among PWIDs, there remain many questions regarding the interpretation of these results, as well as obstacles to the implementation of PrEP regimens within highly diverse drug‐using communities. Aside from the Bangkok Tenofovir Study, we identified only one other published study that has collected empirical data to inform the use of PrEP among PWIDs. The large gap in research regarding the use and implementation of PrEP for PWIDs signals the need for further research and attention.

Conclusions

We recommend that future research efforts focus on elucidating the generalizability of the Bangkok Tenofovir Study results in other injection drug–using populations, examining the willingness of PWIDs to use PrEP in diverse contexts, identifying barriers to adherence to PrEP regimens and determining the most effective ways to implement PrEP programmes within the context of existing evidence‐based prevention strategies, including opioid substitution therapy and needle and syringe distribution programmes.
Suppressing the 1/f noise and noise figure of InP-based high electron mobility transistors
Authors: Arai Tomoyuki , Sato Masaru , Hara Naoki
Published: March 2014

We have developed InP-based high electron mobility transistors (HEMTs) with a structure that significantly suppresses the 1/f noise, noise figure (NF), and drain conductance (g
d) dispersion. These phenomena appear to be caused by the accumulation of holes that are generated by strong electric fields and accumulate at the extrinsic source because of the hole barrier at the carrier-supply-layer/channel interface. Our planar structure has alloyed ohmic contacts that suppress hole accumulation by eliminating the strong electric field and hole barrier at the carrier-supply-layer/channel interface. The 1/f noise and NF of InP-based HEMTs with this planar structure are therefore respectively 15 and 10 dB less than the 1/f noise and NF of InP-based HEMTs with the conventional structure.
Effect with high density nano dot type storage layer structure on 20 nm planar NAND flash memory characteristics
Authors: Sasaki Takeshi , Muraguchi Masakazu , Seo Moon-Sik , Park Sung-kye , Endoh Tetsuo
Published: March 2014

The merits, concerns and design principle for the future nano dot (ND) type NAND flash memory cell are clarified, by considering the effect of storage layer structure on NAND flash memory characteristics. The characteristics of the ND cell for a NAND flash memory in comparison with the floating gate type (FG) is comprehensively studied through the read, erase, program operation, and the cell to cell interference with device simulation. Although the degradation of the read throughput (0.7% reduction of the cell current) and slower program time (26% smaller programmed threshold voltage shift) with high density (10 × 1012 cm−2) ND NAND are still concerned, the suppress of the cell to cell interference with high density (10 × 1012 cm−2) plays the most important part for scaling and multi-level cell (MLC) operation in comparison with the FG NAND. From these results, the design knowledge is shown to require the control of the number of nano dots rather than the higher nano dot density, from the viewpoint of increasing its memory capacity by MLC operation and suppressing threshold voltage variability caused by the number of dots in the storage layer. Moreover, in order to increase its memory capacity, it is shown the tunnel oxide thickness with ND should be designed thicker (>3 nm) than conventional designed ND cell for programming/erasing with direct tunneling mechanism.
Hot carrier effect of a scaled thin-film silicon-on-insulator power metal oxide semiconductor field-effect transistor under constant drain electric field
Authors: Takasugi Tomoya , Matsumoto Satoshi
Published: March 2014

We report a hot carrier effect of the thin-film silicon-on-insulator (SOI) power metal oxide semiconductor field-effect transistor (MOSFET) for scaling under a constant drain electric field. The device degradation caused by the hot carrier effect was enhanced by shrinking a channel length even at the constant drain electric field because of the parasitic bipolar effect.
Floral fraudulence: Do blue Thelymitra species (Orchidaceae) mimic Orthrosanthus laxus (Iridaceae)?
Authors: Edens-Meier Retha Marie , Raguso Robert A , Westhus Eric , Bernhardt Peter
Published: March 2014

In Western Australia, Thelymitra crinita Lindl. and T. macrophylla Lindl. are pollinated by female, polylectic bees but offer no edible rewards. Flowers of Orthrosanthus laxus (Endl.) Benth. (Iridaceae) offer granular pollen and previous authorities suggest it is a Batesian model of T. crinita. We analyzed the floral fragrances and measured the floral dimensions of the orchid species, their putative hybrid, and O. laxus. Although the ‘scentless’ T. crinita emitted low levels of monoterpenoids and sesquiterpenoids, the pleasantly discernible fragrance of T. macrophylla was dominated by 2-phenylethanol. Their putative hybrid produced slightly lower levels of 2-phenylethanol compared with T. macrophylla and failed to produce any sesquiterpenoids associated with T. crinita. However, the hybrid produced higher volumes of the monoterpene linalool than either parent species. The fragrance of O. laxus contained 2-phenylethanol but lacked the sesquiterpenoids. We also measured perianth area and symmetry as well as the length and width of contrastingly pigmented floral centres for each taxon. Significant differences in floral area and symmetry were detected between the putative hybrid, the two parent species, and O. laxus. In contrast, the floral reward centre area (tuft of stamens) in O. laxus was significantly larger than the pseudo-reward centres (mitras) of both Thelymitra species and their hybrid. At the peak of their respective, but overlapping flowering periods, an inflorescence of T. macrophylla produced more than twice the number of open flowers as T. crinita and more than four times the number of open flowers on cymes of O. laxus. Based on scent production and visual displays, T. macrophylla appears more likely to be a Batesian floral mimic of O. laxus. We suggest that large-flowered Thelymitra species appear to produce a novel, visual and olfactory attractant pattern of fraudulence we call the ‘New Again, More Again Effect’.
Desmocladus (Restionaceae) enlarged to include the Western Australian Harperia, Kulinia and Onychosepalum
Authors: Briggs Barbara Gillian
Published: March 2014

A recent phylogeny of the restiid clade of Poales based on chloroplast DNA data has shown several currently recognised genera of Leptocarpoideae to be paraphyletic or polyphyletic. In the largely Western Australian Desmocladus clade, Kulinia, Onychosepalum and Harperia appear embedded in Desmocladus. These are now included in Desmocladus and the new combinations D. confertospicatus, D. eludens, D. eyreanus, D. ferruginipes, D. lateriflorus, D. laxiflorus, D. microcarpus and D. nodatus are provided.
Trends in alcohol consumption during pregnancy in Australia, 2001–2010
Authors: Callinan Sarah , Ferris Jason
Published: March 2014

Callinan, S., & Ferris, J. (2014). Trends in alcohol consumption during pregnancy in Australia, 2001–2010. The International Journal Of Alcohol And Drug Research, 3(1), 17-24. doi:10.7895/ijadr.v3i1.108Aim: The aim of the current study is to examine, using cross-sectional data, the role of maternal age, period (year of pregnancy) and cohort (year of birth) as predictors of alcohol consumption during pregnancy over a 10-year period.Design: Four cross-sectional surveys were examined, both separately and together.Setting: Using cross-sectional data, there does appear to be a positive relationship between maternal age and alcohol consumption during pregnancy; however, within any one survey period, it is difficult to determine if these patterns are due to period or cohort effects.Participants: The National Drug Strategy Household Survey (NDSHS) is a large-scale survey administered to more than 20,000 respondents. Across four survey periods, 3,281 women reported being pregnant in the 12 months prior to the survey.Measures: The section on pregnancy and alcohol in the NDSHS 2001, 2004, 2007 and 2010.Findings: Age was a significant positive predictor of alcohol consumption during pregnancy in 2010. However, when the four data sets were combined, period appeared to be a stronger predictor, with younger groups and cohorts decreasing consumption at a faster rate over time than older groups and cohorts.Conclusions: Although age and cohort do play a role in the likelihood of alcohol consumption among Australian women during pregnancy, period is the most important predictor, indicating that alcohol consumption among pregnant women is decreasing. Furthermore, knowledge of pregnancy results in a marked decrease in consumption, suggesting a possible focus for prevention campaigns.
The effectiveness of alcohol warning labels in the prevention of Fetal Alcohol Spectrum Disorder: A brief review
Authors: Thomas Gerald , Gonneau Ginny , Poole Nancy , Cook Jocelynn
Published: March 2014

Thomas, G., Gonneau, G., Poole, N., & Cook, J. (2014). The effectiveness of alcohol warning labels in the prevention of Fetal Alcohol Spectrum Disorder: A brief review. The International Journal Of Alcohol And Drug Research, 3(1), 91-103 doi:10.7895/ijadr.vX3i1.126Aims and Method: Alcohol warning labels are one way of influencing alcohol consumption in pregnancy and thereby preventing Fetal Alcohol Spectrum Disorder (FASD). This scoping review describes the literature on the influence of alcohol warning labels (AWLs) for changing attitudes and behavior related to alcohol use in pregnancy; draws on the larger literature related to effectiveness of AWLs which may have relevance to FASD prevention; and situates AWLs within a continuum of strategies to prevent FASD.Findings: Our review of the published literature suggests that while AWLs are popular with the public, their effectiveness for changing drinking behavior is limited. Available research suggests that for maximum effect, AWLs should speak clearly about the consequences of alcohol consumption and should also be coordinated and integrated with other, broader social messaging campaigns. Use of AWLs related to alcohol and pregnancy must be carefully considered; their messaging has the most influence on low-risk drinkers, and to date they have not been shown to change the drinking behavior of those who drink heavily or binge during pregnancy. However, AWLs have been shown to stimulate conversations about alcohol consumption and may play a role in shifting social norms to reduce risks.Conclusions: Multiple measures are required to increase societal awareness of the risks of drinking in pregnancy, influence alcohol consumption by pregnant women, and improve the quality of support for women with alcohol and related health and social problems.
Women’s receptivity to Fetal Alcohol Spectrum Disorders prevention approaches: A case study of two regions in Russia
Authors: Balachova Tatiana , Bonner Barbara , Bard David , Chaffin Mark , Isurina Galina , Owora Arthur , Tsvetkova Larissa , Volkova Elena
Published: March 2014

Balachova, T., Bonner, B., Bard, D., Chaffin, M., Isurina, G., Owora, A., Tsvetkova, L., & Volkova, E. (2014). Women’s receptivity to Fetal Alcohol Spectrum Disorders prevention approaches: A case study of two regions in Russia. The International Journal Of Alcohol And Drug Research, 3(1), 5-15. doi:10.7895/ijadr.v3i1.158Aims: This study obtained data to inform the development of programs for prevention of Fetal Alcohol Spectrum Disorders (FASD) by examining Russian women’s perceptions about the determinants of their decisions regarding alcohol consumption during pregnancy; the importance of educating professionals and community about FASD; and the credibility of various sources of information.Design: Cross-sectional survey.Setting: Seven women’s clinics in St. Petersburg and the Nizhny Novgorod region in Russia.Participants: Six hundred and forty-eight pregnant and non-pregnant women of childbearing age.Measures: A face-to-face structured interview assessed demographic characteristics, pregnancy status, alcohol consumption, and level of trust in and receptivity to FASD prevention messages.Findings: The most influential contributor to women’s decisions regarding alcohol consumption during pregnancy was their own knowledge, followed by information from an obstetrician/gynecologist or nurse. It was most important to women that obstetrics and gynecology professionals and husbands or partners were knowledgeable about the effects of drinking during pregnancy. Physicians’ recommendations and research data were regarded by the women as the most credible sources of information. There were significant variations in responses by socio-demographic characteristics and alcohol consumption levels. Younger women were more likely to report the contributions of husbands, mothers, and friends or coworkers to their decisions about alcohol consumption and indicated the importance of educating these people. Women at risk for alcohol use during pregnancy reported greater influence of husbands or partners and warning labels on containers on their alcohol consumption.Conclusions: This study emphasizes the importance of broadly disseminating information about FASD, particularly research data, through education of health professionals and the general public in Russia. Women’s socio-demographic characteristics and alcohol consumption levels should be considered in designing prevention programs.
Progressive flash heating and the evolution of high‐velocity rock friction
Authors: Chen J. , Rempel A. W.
Published: March 2014

Accurate descriptions of strength evolution are required in predictive models of fault zone behavior during earthquakes. At low sliding rates, frictional resistance between fault rocks is much higher than the shear stress that is typically inferred to be present during earthquakes. Laboratory experiments confirm that the friction coefficient drops at high sliding rates, and it is suggested that strengthening, possibly related to an increase in the area of viscous melt patches, may occur after this initial weakening stage. Most existing weakening mechanisms do not predict such strengthening, which may exert an important control on the thickness of the shear zone. We propose a micromechanical model of flash heating that describes how shear resistance evolves at the asperity scale as a result of distributed deformation over a weak layer that grows during the brief lifetime of each asperity contact. Beyond a threshold weakening velocity, our model predicts that friction should decrease with slip rate since higher sliding speeds cause the weak layer to thicken more rapidly. A comparison with published experimental data from a range of mineral systems shows good agreement with the model predictions. The parameter choices that ensure good model fits to the laboratory friction data are consistent with a priori estimates for the onset of asperity melting at high contact normal stresses. At higher sliding rates and/or elevated temperatures, our model predicts that the frictional rate dependence should transition from velocity weakening to become velocity strengthening because decreases in the contact lifetime with slip rate cause the average asperity strength to increase.
Forcings and feedbacks in the GeoMIP ensemble for a reduction in solar irradiance and increase in CO2
Authors: Huneeus Nicolas , Boucher Olivier , Alterskjær Kari , Cole Jason N. S. , Curry Charles L. , Ji Duoying , Jones Andy , Kravitz Ben , Kristjánsson Jón Egill , Moore John C. , Muri Helene , Niemeier Ulrike , Rasch Phil , Robock Alan , Singh Balwinder , Schmidt Hauke , Schulz Michael , Tilmes Simone , Watanabe Shingo , Yoon Jin‐Ho
Published: March 2014

The effective radiative forcings (including rapid adjustments) and feedbacks associated with an instantaneous quadrupling of the preindustrial CO2 concentration and a counterbalancing reduction of the solar constant are investigated in the context of the Geoengineering Model Intercomparison Project (GeoMIP). The forcing and feedback parameters of the net energy flux, as well as its different components at the top‐of‐atmosphere (TOA) and surface, were examined in 10 Earth System Models to better understand the impact of solar radiation management on the energy budget. In spite of their very different nature, the feedback parameter and its components at the TOA and surface are almost identical for the two forcing mechanisms, not only in the global mean but also in their geographical distributions. This conclusion holds for each of the individual models despite intermodel differences in how feedbacks affect the energy budget. This indicates that the climate sensitivity parameter is independent of the forcing (when measured as an effective radiative forcing). We also show the existence of a large contribution of the cloudy‐sky component to the shortwave effective radiative forcing at the TOA suggesting rapid cloud adjustments to a change in solar irradiance. In addition, the models present significant diversity in the spatial distribution of the shortwave feedback parameter in cloudy regions, indicating persistent uncertainties in cloud feedback mechanisms.
A modified weighted function method for parameter estimation of Pearson type three distribution
Authors: Liang Zhongmin , Hu Yiming , Li Binquan , Yu Zhongbo
Published: March 2014

In this paper, an unconventional method called Modified Weighted Function (MWF) is presented for the conventional moment estimation of a probability distribution function. The aim of MWF is to estimate the coefficient of variation (CV) and coefficient of skewness (CS) from the original higher moment computations to the first‐order moment calculations. The estimators for CVand CSof Pearson type three distribution function (PE3) were derived by weighting the moments of the distribution with two weight functions, which were constructed by combining two negative exponential‐type functions. The selection of these weight functions was based on two considerations: (1) to relate weight functions to sample size in order to reflect the relationship between the quantity of sample information and the role of weight function and (2) to allocate more weights to data close to medium‐tail positions in a sample series ranked in an ascending order. A Monte‐Carlo experiment was conducted to simulate a large number of samples upon which statistical properties of MWF were investigated. For the PE3 parent distribution, results of MWF were compared to those of the original Weighted Function (WF) and Linear Moments (L‐M). The results indicate that MWF was superior to WF and slightly better than L‐M, in terms of statistical unbiasness and effectiveness. In addition, the robustness of MWF, WF, and L‐M were compared by designing the Monte‐Carlo experiment that samples are obtained from Log‐Pearson type three distribution (LPE3), three parameter Log‐Normal distribution (LN3), and Generalized Extreme Value distribution (GEV), respectively, but all used as samples from the PE3 distribution. The results show that in terms of statistical unbiasness, no one method possesses the absolutely overwhelming advantage among MWF, WF, and L‐M, while in terms of statistical effectiveness, the MWF is superior to WF and L‐M.
Processing and Characterization of Aluminum Nitride Ceramics for High Thermal Conductivity
Authors: Lee Hyun Min , Bharathi Kamala , Kim Do Kyung
Published: March 2014

The effects of sintering additives, microstructure, and morphology of second phase on the thermal conductivity of aluminum nitride ceramics are discussed in this review. The thermal conductivity of AlN is highly dependent on the types and amount of sintering additives, second phase morphology and microstructure. The morphology of second phase in AlN ceramics could be controlled by changing the cooling rate. The amount of second phase was able to be minimized by using the transient sintering additives. The thermal conductivity of AlN could be enhanced with the inclusion of the transient sintering additives. The thermal conductivity of AlN ceramics was evaluated by Raman spectroscopy. High temperature AC impedance studies were conducted to characterize the electrical conduction mechanism of AlN ceramics.
Exploring Single Semiconductor Nanowires with a Multimodal Hard X‐ray Nanoprobe
Authors: Martínez‐Criado Gema , Segura‐Ruiz Jaime , Alén Benito , Eymery Joël , Rogalev Andrei , Tucoulou Rémi , Homs Alejandro
Published: March 2014

Semiconductor nanowires offer new opportunities for optoelectronic and spintronic nanodevices. However, their full potential is ultimately dictated by our ability to control multiple property‐function relationships taking place at the nanoscale in the spatial and time domains. Only a combination of high‐resolution analytical techniques can provide a comprehensive understanding of their complex functionalities. Here we describe how a multimodal hard X‐ray nanoprobe addresses fundamental questions in nanowire research. Selected topics ranging from cluster formation, dopant segregation, and phase separations to quantum confinement effects are investigated with sub‐100 nm spatial resolution and sub‐50 ps temporal resolution. This approach opens new avenues for structural, composition and optical studies with broad applicability in materials science.
Ferrocenylalkynes for Ruthenium‐Catalyzed Isohypsic CH/NO Bond Functionalizations
Authors: Kornhaaß Christoph , Kuper Christian , Ackermann Lutz
Published: March 2014

Ruthenium(II) catalysis allowed for regioselective annulations of challenging ferrocenylalkynes by oximes or N‐methoxybenzamides through isohypsic CH/NO bond functionalization to furnish substituted isoquinolines and NH‐free isoquinolones with ample scope.

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Reusing textile waste as reinforcements in composites
Authors: Ramamoorthy Sunil Kumar , Persson Anders , Skrifvars Mikael
Published: March 2014

Polyester (PET) has wide applications in textile industries as textile fiber and its share continues to grow. Substantial quantities of cotton/polyester blend fabrics are disposed every year due to technical challenges, which pose a big environmental and waste‐dumping problem. The aim of this study is to evaluate the potential of discarded cotton/PET fabrics as raw materials for composites. If their inherent reinforcement properties can be used in composites, an ecological footprint issue can be solved. In this study, we investigate three concepts for reuse of cotton/PET fabrics for composites: compression molding above the Tm of PETs, use of a matrix derived from renewable soybean oil, use of thermoplastic copolyester/polyester bi‐component fibers as matrix. All three concepts have been explored to make them available for wider applications. The effects of processing parameters such as compression temperature, time and pressure are considered in all three cases. The third concept gives the most appealing properties, which combine good tensile properties with toughness; more than four times better tensile strength than the first concept; and 2.2 times better than the second concept. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 40687.
A7: Initial Assessment of Multi‐biomarker Disease Activity Assay in JIA
Authors: Ringold Sarah , Lu Lucy , Wallace Carol A. , Sasso Eric H. , Scott Eastman P.
Published: March 2014

Background/Purpose:

Current measures of disease activity in JIA, including physician global assessment of disease activity and active joint count, are subjective and potentially confounded by disease heterogeneity and comorbid conditions. A multi‐biomarker disease activity assay (MBDA) incorporating a panel of biomarkers may provide objective and quantitative data regarding disease activity that would be of great value to physicians caring for children with JIA. The objective of this investigation was to measure the feasibility of a MBDA developed for RA (Vectra DA, Crescendo Bioscience, Inc), and its individual biomarker components as a measure of disease activity in patients with JIA.

Methods:

Samples were analyzed from a prior cross‐sectional, observational study that included 31 children with rheumatoid factor (RF) positive polyarticular JIA (n = 4), RF negative polyarticular JIA (n = 18), or extended oligoarticular JIA (n = 8). All children had established disease and were on treatment (mean disease duration 5 years; range 0–15 years). The Juvenile Arthritis Disease Activity Score (JADAS) based on 10 joints was calculated for each sample and each sample was classified as clinically inactive disease or active disease using the ACR provisional criteria for clinically inactive disease (CID). Samples were analyzed for 18 individual biomarkers, 12 of which comprise Vectra DA and a total Vectra DA score was calculated. Biomarker assays were also performed for a cohort of 44 healthy 18 year‐old controls obtained from the ProMeDx specimen bank.

Results:

The mean JADAS value for the cohort was 4.9 (range 0–16.3). The mean Vectra DA score for the healthy controls was 14 (maximum possible score is 100). The mean score was 20 for the children with CID, and 27 for children with active disease. The correlation between the Vectra DA and JADAS was moderate (r = 0.68; Figure 1). The individual biomarker profiles for the control cohort and the children who met criteria for inactive disease appeared similar, but several individual biomarkers, including SAA, CRP, IL‐6 and MMP‐3 were elevated in the active disease group as compared to the children with CID and controls (Figure 2).

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Conclusion:

These data support the feasibility of the development of a JIA‐specific MBDA that will reflect the underlying heterogeneity of the disease process and provide physicians with an objective measure of disease activity. Additional analyses of larger sets of biomarkers using samples with a broad range of disease activities will inform the next steps of assay development.
A9: Exploring Systemic Lupus Erythematosus from the Molecular Level and Dissecting the Disease Mechanism by Molecular Imaging
Authors: Hu Shaofan , Ke Shi , Wang Wei , Ran Henry , Chen Meipu , Zhang Fujun , Qiu Xiuchun , Jiang Ming , Zou Chaoxia , Zhang Rufeng , Cao Li , Fu Rui , Chen Chaoying
Published: March 2014

Background/Purpose:

One and a half million Americans suffer from systemic lupus erythematosus (SLE), with increased death rate in the 15–44 year age group. SLE has a wide range of symptoms and affects multiple organs and tissues. SLE affects each person differently over time. Treatment options are limited with potential serious side effects. There is no cure currently due to the lack of understanding of the mechanism of disease at molecular levels. However, recent developments in the field of molecular imaging provide a tool for noninvasive, target‐specific and longitudinal study of multiple disease components at the same time as well as understanding the dynamic change of the disease. We hypothesize genetic differences play a role in development and severity of the disease. In addition, multiple different disease molecules in different organs at one time point make SLE difficult to treat by standard regiments.

Methods:

We tested our hypothesis in animal models with two different genetic backgrounds and three target‐specific molecular imaging agents. Two groups of mice carrying normal or mutant Fas gene with SLE were utilized in the study. Optical imaging agents that specifically target to pro‐inflammatory cytokine (IL‐11), cytokine from T‐cells (CXCR4), or disease stroma (matrix metalloproteinase, MMP) were injected through the tail vein. Mice were imaged immediately after injection and for as long as 48 hours afterward. SAS software was used to analyze data by one‐way‐ANOVA or the general linear model. Data comparison was presented in notched box‐and whisker plots. The significant level was set at 0.05 with two‐tailed test.

Results:

Mice with a normal Fas gene have statistical higher signal intensities for all agents in the joint regions than the Fas mutant mice (P = 0.0139). Target‐specific agents have different organ distributions in Fas mutant mice. The MMP signals are in the kidney (Fig. 1A) and IL‐11 signals are in the lung (Fig. 1B). Both agents have statistical low signal intensities in the same organs in the control mice with normal Fas gene (P<0.0002). The animal with normal Fas gene has high IL‐11 signal intensity in the knee (Fig. 1C). On contrary, CXCR4 has significantly low signal intensity in the Fas mutant mice. Fas mutant mice also have enlarged spleen and kidney by either size or weight than control mice (P<0.0001).

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Conclusion:

We found that different genetic backgrounds predispose to different disease manifestations. Each organ has different disease components even with same the genetic background at the same disease stage The method we developed here can be used as a tool to better understand genetic and disease components and improve the treatment plan for individual patient needs.
A13: The Research in Arthritis in Canadian Children Emphasizing Outcomes (ReACCh Out) Cohort: Prospective Determination of the Incidence of New Onset Uveitis in Juvenile Idiopathic Arthritis
Authors: Watanabe Duffy Karen N , Lee Jennifer , Guzman Jaime , Barrowman Nick , Morishita Kimberly , Spiegel Lynn R. , Stringer Elizabeth , Gibbon Michele , Yeung Rae SM , Tucker Lori B. , Oen Kiem , Duffy Ciarán M. ,   ReACChOut Investigators
Published: March 2014

Background/Purpose:

Previous studies of uveitis in Juvenile Idiopathic Arthritis (JIA) patients have reported prevalence and not incidence. The ReACCh Out cohort, a large inception cohort of newly diagnosed JIA patients provided the opportunity to prospectively ascertain the true incidence of new onset uveitis. The objectives of this study were to determine the overall incidence rate and its trajectory over time.

Methods:

ReACCh Out recruited newly diagnosed JIA patients between January 2005 and December 2010, from 16 Canadian centres across the country. Prospective data was collected every 6 months for the first 2 years, then yearly. Data was collected on numerous clinical and laboratory measures including the diagnosis of uveitis and its complications, determined by an ophthalmologist. A Poisson model was used to estimate the overall incidence rate. A Kaplan‐Meier plot was used to evaluate the time from diagnosis of JIA to the time of diagnosis of new onset uveitis.

Results:

1104 patients with newly diagnosed (≤6 months) JIA with ≥1 follow‐up visit were reviewed. Patients were predominantly female (63%), age at diagnosis was 9.3 (3.9, 13.0) years. Time from diagnosis to enrollment was 0.3 (0, 1.6) months. Follow‐up to last visit or study end was 34.2 (21.5, 48) months. 23 patients whose uveitis status was not available, were excluded. 77 patients with new onset uveitis were identified during the study period. The overall incidence rate of new cases of uveitis following the diagnosis of JIA was 2.9% per year (95% confidence interval 2.3–3.6). Following the trajectory of new cases of uveitis over time, the incidence of new cases showed a slow decline over time (Figure ). Importantly, new cases of uveitis occurred as far out from diagnosis as the end of the study period. Kaplan‐Meier plots were also used to evaluate age at diagnosis of new onset uveitis and gender. Results support previously identified risk factors for uveitis including younger age (<5 years) and female gender. The frequency of uveitis occurred in the JIA patients in the following distribution according to subtype: oligoarthritis (43, 56%), polyarthritis RF negative (18, 23%), polyarthritis RF positive (1, 1%), psoriatic (4, 5%), ERA (1, 1%), systemic (1, 1%) and undifferentiated (9, 12%).

Time (confidence intervals) from diagnosis of JIA to diagnosis of new onset uveitis

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Conclusion:

In a large inception cohort of newly diagnosed JIA patients followed prospectively, the overall incidence rate of new cases of uveitis was 2.9% per year. The slow decrease in incidence over time and the development of new cases of uveitis years later, highlight the importance of ongoing and long term surveillance.
A15: Predicting Macrophage Activation Syndrome in Pediatric Systemic Lupus Erythematosus Patients at Diagnosis
Authors: Gerstein Maya , Sukhdeo Sharon , Levy Deborah M. , Feldman Brian M. , Benseler Susanne M. , Ng Lawrence W.K. , Abdelhaleem Mohamed , Silverman Earl D. , Hiraki Linda
Published: March 2014

Background/Purpose:

Macrophage activation syndrome (MAS), a life‐threatening inflammatory emergency of children with rheumatic diseases, is increasingly recognized in pediatric systemic lupus erythematosus (pSLE). The challenge is to differentiate active pSLE from MAS in order to make correct treatment decisions. The purpose of this study is to generate a decision tree for the recognition of MAS in newly diagnosed pSLE and test the performance of these proposed criteria in an independent pSLE cohort.

Methods:

A retrospective cohort study of consecutive patients requiring admission to SickKids Hospital with newly diagnosed, active pSLE between January 2002 and July 2007 (training cohort) was performed. All patients met ≥4/11 ACR criteria. Data collection on: 1) Clinical features including fever, CNS dysfunction, splenomegaly, hepatomegaly and hemorrhage; 2) laboratory parameters; CBC, ESR, CRP, C3, C4, ferritin, AST, ALT, LDH, albumin, bilirubin, triglycerides, LDL, HDL, urea, creatinine, sodium, coagulation parameters including INR, PTT, fibrinogen and D‐Dimer, and soluble IL‐2 receptor (sIL‐2R) and CD163. Patients were assigned to one of 2 cohorts exclusively (MAS/non‐MAS). Putative predictor variables were compared between cohorts. A decision tree analysis for diagnosis of MAS in pSLE was constructed using recursive partitioning, and decision rules were subsequently applied to an independent cohort of newly diagnosed, active pSLE diagnosed and admitted to SickKids between July 2007 and July 2013 (testing cohort) to determine the sensitivity and specificity of the proposed criteria.

Results:

The training cohort consisted of 56 pSLE patients: 9 (16%) diagnosed with MAS and 47 non‐MAS patients. Splenomegaly was more common in the non‐MAS cohort, with no other differences in clinical characteristics between cohorts. Of all the available laboratory data, ALT ≥ 45 units/L, neutrophils < 1.65 × 103/mm3 and ferritin < 836 µg/L identified 56% of the patients with MAS (R2 = 0.75) with 100% specificity. The testing cohort consisted of 9 (20%) MAS and 37 non‐MAS pSLE patients. The proposed thresholds for ALT, neutrophil count and ferritin demonstrated a sensitivity of 11% and specificity of 97%.

Conclusion:

MAS is a life threatening complication of pSLE. Early recognition is challenging yet critical for appropriate therapy. PSLE patient with and without MAS have many similar clinical and laboratory features. Using statistical modeling, the initial criteria developed maintained excellent specificity but poor sensitivity for distinguishing MAS from active SLE at diagnosis in the testing cohort. Hence, new validated models are required for the early recognition of MAS among pSLE patients. Future analyses are planned to address these issues.
A16: Long‐term follow‐up of 36 Pediatric Antiphospholipid Syndrome Patients: A Retrospective Study
Authors: Gomes Francisco Hugo , Carvalho Luciana , Pinheiro Paola , Resende Tamara , Ferriani Virgínia
Published: March 2014

Background/Purpose:

Antiphospholipid syndrome (APS) is a multisystem autoimmune disease characterized by arterial and/or venous thrombosis and persistent presence of antiphospholipid antibodies. Long term follow‐up studies in children are still scarce. The aim of this study was to evaluate clinical data and long‐term outcome of patients with confirmed antiphospholipid syndrome in childhood.

Methods:

Between 1993 and 2013, 36 patients with confirmed pediatric antiphospholipid syndrome (22 female; aged 8 months‐18 years, mean 9 years) were followed at the Pediatric Rheumatology Unit of the University Hospital of USP‐RP. Clinical data and long‐term outcome of these patients were reviewed retrospectively.

Results:

The median follow‐up period was 8.5 years (0.6–20 years), fourteen (38.8%) had underlying autoimmune diseases (30% systemic lupus erytematosous, 5% Behcet's disease and 2.5% systemic juvenile idiopathic arthritis). Venous and arterial thrombosis on the first episode occurred in 14 (38%) and 22 (61%) patients, respectively. Ischemic stroke was the most frequent thrombotic event (50%). Three patients had thrombosis in two different sites on the first episode (inferior vena cava and cerebral sinus vein; lower extremities deep vein thrombosis and pulmonary thromboembolism; portal vein and jugular vein thrombosis). The most frequent associated nonthrombotic clinical manifestations were hematologic manifestations (27%), hypertension (22%), and valvulopaties, identified in 10/27 echocardiograms performed (37%), including one case of Libmann‐Sachs endocarditis. The frequency of antiphospholipid antibodies identified were: IgG anticardiolipin in 24/35 (68%) patients, IgM anticardiolipin in 21/35 (60%), IgG anti‐beta(2)‐glycoprotein I in 6/31 (19%), IgM anti‐beta(2)‐glycoprotein I in 7/31(22%), and lupus anticoagulant in 17/35 (48%). Six patients were positive for all antiphospholipid antibodies investigated. During the follow‐up period new thrombotic events occurred in 9 patients (25%), with catastrophic antiphospholipid syndrome in one of these patients. One patient had two new events (jugular vein thrombosis and pulmonary thromboembolism). Major hemorrhagic events, including intracranial hemorrhage and minor hemorrhagic events, including epistaxis, hematomas and hypermenorrhea occurred in 47% of the patients during the use of oral anticoagulants.

Conclusion:

Despite of prophylaxis with anticoagulants, new thrombotic events occurred in 25% of the patients and reaching the ideal prothrombin time to prevent thrombotic episodes was the major challenge, as nearly half of the patients had hemorrhagic events. Studies are necessary to identify ideal parameters for treating and monitoring children with antiphospholipid syndrome.
A23: Favorable Response to Belimumab in Childhood‐Onset Systemic Lupus Erythematosus
Authors: Hui‐Yuen Joyce S , Bermudez‐Santiago Liza Mariel , Isgro Josephine , Eichenfield Andrew H. , Starr Amy J. , Imundo Lisa F. , Askanase Anca
Published: March 2014

Background/Purpose:

Belimumab (Benlysta) is a human monoclonal antibody inhibiting soluble B‐lymphocyte stimulator that was approved by the Food and Drug Administration in 2011 for treatment of active, autoantibody‐positive, systemic lupus erythematosus (SLE) in adults. To date, there have been no published data on the use of belimumab in childhood‐onset SLE.

Methods:

This is a case series of patients with childhood‐onset SLE treated with belimumab at our institution. Data were collected on demographic and disease characteristics, clinical manifestations requiring treatment, concomitant medications, disease course, and treatment outcomes. Descriptive statistics were used when appropriate.

Results:

We describe 7 patients with childhood‐onset SLE treated with belimumab, 5 of whom are still receiving belimumab infusions at our institution, with a mean follow‐up of 9.3 months on belimumab. The mean age was 18.5 years old, mean disease duration 5.8 years at initiation of belimumab. Eighty‐six percent of the patients were female, 57% African American, 28% Hispanic, and 14% Caucasian. All patients were taking other background medications prior to initiation of belimumab (hydroxychloroquine 7/7, prednisone 7/7, azathioprine 2/7, mycophenolate mofetil 3/7). The most common indications for initiation of therapy were the inability to taper steroids (100%, mean prednisone equivalent dose 0.54mg/kg/day), rash (43%), fatigue (29%), and arthritis (14%), accompanied by worsening serologic activity (increasing anti‐dsDNA titers and hypocomplementemia). At the last follow‐up (mean 9.3 months after initiation of belimumab), average SLEDAI decreased from 6.4 to 4. We were able to taper steroids in 57% of patients, with 3/7 (43%) able to completely discontinue steroids. The average complement levels increased from 71 to 74 (lower limit of normal 83) for C3 and 8 to 10 (lower limit of normal 16) for C4. Six of the seven patients clinically responded to belimumab within three months, with marked improvement in rash, arthritis, and fatigue. Six of seven patients tolerated infusions well, with 1 patient who discontinued treatment due to recurrent vaginal moniliasis.

Conclusion:

This is the first study investigating the use of belimumab in childhood‐onset SLE across major ethnic groups. Our data demonstrate favorable clinical outcomes including the discontinuation of steroids in 3/7 (43%) of our patients, and improvement in C3 and C4 as early as 3 months after the initiation of belimumab, suggesting a quicker onset of action for belimumab in children than that observed in adult studies, which may support a larger role for belimumab in childhood‐onset SLE.
A43: Juvenile Idiopathic Arthritis in Relation to Maternal Prenatal Smoking
Authors: Shenoi Susan , Bell Samantha , Wallace Carol , Mueller Beth
Published: March 2014

Background/Purpose:

Cigarette smoking increases the risk of seropositive adult Rheumatoid arthritis. Juveinile idiopathic arthritis (JIA) is a heterogenous group of 7 mutually exclusive categories of chronic childhood inflammatory arthritides.

Objectives:

To determine the association between JIA and its categories with maternal prenatal smoking.

Methods:

This case‐control study used ICD‐9 codes from hospital records to identify 1196 JIA cases born in Washington State and diagnosed at a tertiary pediatric center during 1997—2010. Controls (n = 5618) were randomly selected from birth records of children without JIA, frequency matched on birth year. Prenatal smoking exposure was assessed from subjects' birth certificates. Chart review categorized JIA into ILAR categories. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using logistic regression adjusted for maternal age and marital status.

Results:

We did not observe an increased risk of JIA in relation to maternal prenatal smoking. Prenatal smoking was reported less often among mothers of JIA cases (11%), than among control mothers (17%, OR 0.71, 95% CI: 0.58—0.87), a relationship somewhat more marked for oligoarticular/ extended oligoarticular JIA. Although the inverse relationship persisted after adjustment for maternal education or health insurance status, we cannot rule out the possibility that this effect may have been at least partially due to residual confounding by socio‐economic status.

Conclusion:

We did not observe an increased risk of JIA with maternal prenatal smoking.
A57: Four Prolonged Cases of Eosinophilic Fasciitis in Children
Authors: Hui‐Yuen Joyce S , Lauren Christine , Garzon Maria , Starr Amy J. , Imundo Lisa F.
Published: March 2014

Background/Purpose:

Eosinophilic fasciitis (EF) is a rare connective tissue disease characterized by a progressive inflammatory thickening of skin and soft tissues. Diagnosis is often based on characteristic clinical and biopsy findings, and treatment remains challenging. Pediatric data describing clinical course and treatment recommendations remain scarce.

Methods:

This is a case series of all patients diagnosed with EF at our institution in the last 8 years. A retrospective chart review was conducted and data collected on clinical signs and symptoms and laboratory data at diagnosis, disease course, and treatment outcomes. Descriptive statistics were used when appropriate.

Results:

We describe four pediatric patients with EF, with a mean follow‐up of 54 months. Three of the four patients had preceding diagnoses before beginning treatment for EF. All patients had peripheral eosinophilia at diagnosis, two had positive anti‐thyroid antibodies, and two had high levels of total cholesterol. Treatment induction in all patients consisted of intravenous methylprednisone (30mg/kg/day to a maximum of 1g daily for 3 days). All patients required at least one steroid‐sparing agent (methotrexate at 15mg/m2/dose and/or mycophenolate mofetil (MMF) at 600mg/m2/dose) for disease maintenance post‐induction. The mean length of treatment with methotrexate was 23 months, discontinued in only one patient. The mean length of treatment with MMF was 8.3 months. All patients had improvement in skin findings, and all abnormal laboratory findings normalized after treatment with intravenous corticosteroid. One patient had a disease flare less than 12 months after being weaned off cortico‐steroids and methotrexate. Another patient developed a second autoimmune disease five years after treatment for EF. All patients had residual skin changes, and 3 patients had signs of lipodystrophy and/or subcutaneous fat atrophy after treatment.

Conclusion:

EF is often difficult to diagnose and has a variable course in children. We report four cases of prolonged EF, the only four EF patients diagnosed in our practice. Our data suggest a more severe course at earlier age of onset, with higher likelihood of recurrence. Our data also confirm the efficacy of corticosteroid treatment as first‐line therapy, and suggest a role for methotrexate as a promising steroid‐sparing agent. This is the first case series to describe successful treatment of EF with the addition of mycophenolate mofetil to a treatment course of methotrexate and corticosteroid therapy. Three of our four patients required triple therapy for disease control, which may be suggestive of a more severe disease course in the pediatric population.