bluuebunny/crossref_metadata_2025 huggingface dataset:
Building a framework for evaluation of Fetal Alcohol Spectrum Disorder prevention and support programs: A collaborative Canadian project
Authors: Rutman Deborah , Poole Nancy , Hume Sharon , Hubberstey Carol , Van Bibber Marilyn
Published: March 2014

Rutman, D., Poole, N., Hume, S., Hubberstey, C., & Van Bibber, M. (2014). Building a framework for evaluation of Fetal Alcohol Spectrum Disorder prevention and support programs: A collaborative Canadian project. The International Journal Of Alcohol And Drug Research, 3(1), 81-89. doi:10.7895/ijadr.v3i1.122Aims: This article discusses a Canadian project that is designed to identify promising evaluation methods and create common evaluation frameworks for FASD prevention programs serving pregnant women and mothers, and FASD supportive intervention programs serving youth and adults living with FASD. A social determinants of health perspective guided the project.Design: The project has employed a mixed-methods approach including a literature search, documentary review, and an iterative set of consultations with program providers, program managers, government managers and funders, researchers, and evaluators in the context of their work across Canada and internationally.Results: The project’s processes led to the development of three visual “maps” comprised of concentric rings that depict theoretical foundations; activities and approaches; formative outcomes; and participant, community and systemic outcomes. The three visual frameworks depict evaluation of 1) FASD prevention programs; 2) FASD support programs; and 3) FASD programs in Aboriginal communities.Conclusions: The development of visual maps to depict common evaluation frameworks promotes individual and collective action towards applying the frameworks on the part of community-based services and governments across Canada, on the service and systemic levels. Program providers, researchers, and system planners have indicated that the maps have wide-ranging applications.
Evaluation of a three-year Youth Outreach Program for Aboriginal youth with suspected Fetal Alcohol Spectrum Disorder
Authors: Hubberstey Carol , Rutman Deborah , Hume Sharon
Published: March 2014

Hubberstey, C., Rutman, D., & Hume, S. (2014). Evaluation of a three-year Youth Outreach Program for Aboriginal youth with FASD. The International Journal Of Alcohol And Drug Research, X3(1), 63-70. doi:10.7895/ijadr.v3i1.124Aims: This article discusses the process, findings and lessons learned from the external evaluation of the Youth Outreach Program (YOP), a three-year intensive outreach and support program intended for at-risk Aboriginal youth, 13 to 18, with characteristics and/or behaviors associated with Fetal Alcohol Spectrum Disorder (FASD). The overall purpose of the formative and summative evaluation was to document the development and early implementation of the program, in order to make adjustments as the program unfolded; and to assess, describe, and document early outcomes for youth participants and community partners.Design: The project employed a mixed-method design using qualitative and quantitative data.Setting: The program and evaluation took place in a small, rural community in British Columbia, Canada.Participants: Program managers, program staff, program participants, community partners, family members of participants.Measures and methods: Triangulation, program output data; program-specific data collection tools, such as qualitative interview guides; participant outcome rating scale.Results: Multiple sources of data revealed that the Youth Outreach Program led to a number of positive outcomes for youth in areas of safety, relationships, school attendance, sexual health, substance use, and knowledge and use of community resources.Conclusions: The Youth Outreach Program made an important contribution in developing and implementing a program model for promoting positive change for highly marginalized youth who display characteristics of FASD and have limited community and family support.
Combining visual methods with focus groups: An innovative approach for capturing the multifaceted and complex work experiences of Fetal Alcohol Spectrum Disorder prevention specialists
Authors: Job Jenelle M. , Poth Cheryl-Anne , Pei Jacqueline , Wyper Katherine , Teresa O'Riordan , Taylor Lin
Published: March 2014

Job, J., Poth, C., Pei, J., Wyper, K., Teresa, O., & Taylor, L. (2014). Combining visual methods with focus groups: An innovative approach for capturing the multifaceted and complex work experiences of Fetal Alcohol Spectrum Disorder prevention specialists. The International Journal Of Alcohol And Drug Research, 3(1), 71-80. doi:10.7895/ijadr.v3i1.129Aims: This paper discusses the untapped potential of an innovative methodological approach for capturing the experiences of prevention specialists working with women at risk of drug and/or alcohol-exposed pregnancies and live births. Allowing frontline workers to express their personal and professional experiences through a creative activity enhanced our understanding of the difficult-to-measure programming outcomes of a provincial Fetal Alcohol Spectrum Disorder (FASD) strategy.Design: A multi-method design integrating focus groups with a quilting activity.Setting: Annual General Meeting of the Parent and Child Assistance Program (PCAP)—a prevention program for women at risk for drug and/or alcohol-exposed pregnancies and live births.Participants: Forty-seven FASD prevention specialists from across Alberta, Canada.Measurements: Triangulation across data sources: seven focus groups and 49 quilting pieces.Results: Thematic analysis revealed four themes: change as a process, client-advocate connection, ecological understanding, and evidence-based practice. The findings from this study contribute improved understanding about the significance of relationships, reflection, and research in the work of FASD prevention specialists.Conclusions: A multi-methods approach (focus groups with a quilting activity) provided an appropriate and trustworthy means of accessing the prevention specialists’ programmatic experience; that experience has the strong potential for informing future FASD policy, strategic planning, and programming.
Projections of future summertime ozone over the U.S.
Authors: Pfister G. G. , Walters S. , Lamarque J.‐F. , Fast J. , Barth M. C. , Wong J. , Done J. , Holland G. , Bruyère C. L.
Published: March 2014

We use a regional coupled chemistry‐transport model to assess changes in surface ozone over the summertime U.S. between present and a 2050 future time period at high spatial resolution under the A2 climate and Representative Concentration Pathway (RCP) 8.5 anthropogenic precursor emission scenarios. Predicted changes in regional climate and globally enhanced ozone are estimated to increase surface ozone over most of the U.S.; the 95th percentile for daily 8 h maximum surface ozone increases from 79 ppb to 87 ppb. The analysis suggests that changes in meteorological drivers likely will add to increasing ozone, but the simulations do not allow separating meteorological feedbacks from that due to enhanced global ozone. Stringent emission controls can counteract these feedbacks; if implemented as in RCP8.5, the 95th percentile for surface ozone is reduced to 55 ppb. A comparison of regional to global model projections shows that the global model is biased high in surface ozone compared to the regional model and compared to observations. On average, both the global and the regional model predict similar future changes but reveal pronounced differences in urban and rural regimes that cannot be resolved at the coarse resolution of the considered global model. This study confirms the key role of emission control strategies in future air quality projections and demonstrates the need for considering degradation of air quality with future climate change in policy making. It also illustrates the need for high‐resolution modeling when the objective is to address regional and local air quality or establish links to human health and society.
Climate change impacts on the temperature and magnitude of groundwater discharge from shallow, unconfined aquifers
Authors: Kurylyk Barret L. , MacQuarrie Kerry T. B. , Voss Clifford I.
Published: March 2014

Cold groundwater discharge to streams and rivers can provide critical thermal refuge for threatened salmonids and other aquatic species during warm summer periods. Climate change may influence groundwater temperature and flow rates, which may in turn impact riverine ecosystems. This study evaluates the potential impact of climate change on the timing, magnitude, and temperature of groundwater discharge from small, unconfined aquifers that undergo seasonal freezing and thawing. Seven downscaled climate scenarios for 2046–2065 were utilized to drive surficial water and energy balance models (HELP3 and ForHyM2) to obtain future projections for daily ground surface temperature and groundwater recharge. These future surface conditions were then applied as boundary conditions to drive subsurface simulations of variably saturated groundwater flow and energy transport. The subsurface simulations were performed with the U.S. Geological Survey finite element model SUTRA that was recently modified to include the dynamic freeze‐thaw process. The SUTRA simulations indicate a potential rise in the magnitude (up to 34%) and temperature (up to 3.6°C) of groundwater discharge to the adjacent river during the summer months due to projected increases in air temperature and precipitation. The thermal response of groundwater to climate change is shown to be strongly dependent on the aquifer dimensions. Thus, the simulations demonstrate that the thermal sensitivity of aquifers and baseflow‐dominated streams to decadal climate change may be more complex than previously thought. Furthermore, the results indicate that the probability of exceeding critical temperature thresholds within groundwater‐sourced thermal refugia may significantly increase under the most extreme climate scenarios.
Biopolymer‐Based Gel Casting of Ferroelectric Ceramics
Authors: Plucknett Kevin P. , Munro Cameron D.
Published: March 2014

Ferroelectric ceramics have a wide range of industrial applications. While components can be formed through simple ‘press and sinter’ approaches, there is an increasing need for more flexible processing methods. Suspension based forming promotes greater homogeneity, through elimination of processing defects, and allows the formation of more complex shaped components. In the present work, the application of aqueous gel casting technologies is reviewed, and in particular the use of natural biopolymers as gelation aids for such approaches. Recent studies of the application of such technology to complex shape forming of BaTiO3 ferroelectric ceramics are examined. Emphasis is placed upon a simple subtractive rapid prototyping method, utilizing aqueous gel casting in combination with green machining.
Theoretical Comparison, Equivalent Transformation, and Conjunction Operations of Electromagnetic Induction Generator and Triboelectric Nanogenerator for Harvesting Mechanical Energy
Authors: Zhang Chi , Tang Wei , Han Changbao , Fan Fengru , Wang Zhong Lin
Published: March 2014

Triboelectric nanogenerator (TENG) is a newly invented technology that is effective using conventional organic materials with functionalized surfaces for converting mechanical energy into electricity, which is light weight, cost‐effective and easy scalable. Here, we present the first systematic analysis and comparison of EMIG and TENG from their working mechanisms, governing equations and output characteristics, aiming at establishing complementary applications of the two technologies for harvesting various mechanical energies. The equivalent transformation and conjunction operations of the two power sources for the external circuit are also explored, which provide appropriate evidences that the TENG can be considered as a current source with a large internal resistance, while the EMIG is equivalent to a voltage source with a small internal resistance. The theoretical comparison and experimental validations presented in this paper establish the basis of using the TENG as a new energy technology that could be parallel or possibly equivalently important as the EMIG for general power application at large‐scale. It opens a field of organic nanogenerator for chemists and materials scientists who can be first time using conventional organic materials for converting mechanical energy into electricity at a high efficiency.
A Practical Procedure for Iron‐Catalyzed Cross‐Coupling Reactions of Sterically Hindered Aryl‐Grignard Reagents with Primary Alkyl Halides
Authors: Sun Chang‐Liang , Krause Helga , Fürstner Alois
Published: March 2014

Although iron‐catalyzed cross‐coupling reactions of arylmagnesium halides with alkyl halides are well established and proceed effectively under a variety of experimental conditions, they often find limitations when working with sterically hindered aryl‐Grignard reagents. Outlined in this paper is a practical solution that allows this gap in coverage to be filled. Specifically, it is shown that bis(diethylphosphino)ethane (depe) crafts an effective coordination environment about Fe(+2). This commercially available ligand is slim enough not to interfere with the loading of the iron center even by ortho,ortho‐disubstituted arylmagnesium halides, yet capable of preventing premature reductive coupling of the resulting organoiron species, which seem to be hardly basic either. The reaction is compatible with various polar functional groups as well as with substrates containing β‐heteroatom substituents. Moreover, the procedure even allows encumbered neopentylic electrophiles to be arylated with donors as bulky as mesitylmagnesium bromide, whereas secondary alkyl halides tend to eliminate.

magnified image
Diastereotopic Group Selection in Hydroxy‐Directed Intramolecular CH Alkenylation of Indole under Oxidative Palladium(II) Catalysis
Authors: Kandukuri Sandeep R. , Jiao Lin‐Yu , Machotta Axel B. , Oestreich Martin
Published: March 2014

Group‐selective palladium(II)‐catalyzed ring closures involving CH bond alkenylation are reported. The cyclization precursors contain a prochiral bis(homoallylic) alcohol unit tethered to either an arene or an indole. The homobenzylic hydroxy group in these substrates is positioned to act as a directing group in the ortho‐selective CH bond activation prior to the cyclization event. Arene‐derived precursors reacted poorly, even when applying a protocol that had proven effective in intermolecular hydroxy‐directed CH bond alkenylations. No asymmetric induction was obtained with chiral ligands, mono‐N‐protected amino acids (MPAAs) in particular. Conversely, the cyclization of indole‐derived precursors was substantially more efficient, and installation of a substituent in the benzylic position rendered these intramolecular CH bond alkenylations diastereoselective. The diastereotopic group selection is high with diastereomeric ratios ranging from dr=91:9 to 94:6.

magnified image
Solution‐Based Silicon in Thin‐Film Solar Cells
Authors: Bronger Torsten , Wöbkenberg Paul H. , Wördenweber Jan , Muthmann Stefan , Paetzold Ulrich W. , Smirnov Vladimir , Traut Stephan , Dagkaldiran Ümit , Wieber Stephan , Cölle Michael , Prodi‐Schwab Anna , Wunnicke Odo , Patz Matthias , Trocha Martin , Rau Uwe , Carius Reinhard
Published: March 2014

Solution‐based semiconductors give rise to the next generation of thin‐film electronics. Solution‐based silicon as a starting material is of particular interest because of its favorable properties, which are already vastly used in conventional electronics. Here, the application of a silicon precursor based on neopentasilane for the preparation of thin‐film solar cells is reported for the first time, and, for the first time, a performance similar to conventional fabrication methods is demonstrated. Because three different functional layers, n‐type contact layer, intrinsic absorber, and p‐type contact layer, have to be stacked on top of each other, such a device is a very demanding benchmark test of performance of solution‐based semiconductors. Complete amorphous silicon n‐i‐p solar cells with an efficiency of 3.5% are demonstrated, which significantly exceeds previously reported values.
Chromogenic factor VIII activity assay
Authors: Moser Karen A. , (Adcock) Funk Dorothy M.
Published: March 2014

Factor VIII (FVIII) may be measured by three different methodologies in the clinical laboratory: one‐stage clotting assay, two‐stage clotting assay, and chromogenic assay. These assays differ in ease of use, variety of reagents available, sensitivity to mild hemophilia A, and interference from lupus anticoagulants. This review will outline the methodology for each of the FVIII activity assays, with a discussion of assay interferences and variability. In some cases, chromogenic FVIII activity assays may be preferable to clot‐based assays, and these clinical situations will be reviewed as well. Am. J. Hematol. 89:781–784, 2014. © 2014 Wiley Periodicals, Inc.
Clinical manifestations of 17 patients affected with mucopolysaccharidosis type VI and eight novel ARSB mutations
Authors: Kantaputra Piranit Nik , Kayserili Hulya , Guven Yeliz , Kantaputra Warissara , Balci Mehmet C. , Tanpaiboon Pranoot , Tananuvat Napaporn , Uttarilli Anusha , Dalal Ashwin
Published: March 2014

Mucopolysaccharidosis (MPS) type VI or Maroteaux‐Lamy syndrome is a very rare autosomal recessive lysosomal storage disease, caused by a deficiency of the enzyme N‐acetylgalactosamine‐4‐sulfatase (Arylsulfatase B, ARSB). Clinical examination, biochemical studies, and molecular genetic analyses have been performed in 17 patients affected with MPS VI from 15 unrelated families from Thailand, India, and Turkey. Large ear lobule appears to be a newly recognized finding of this syndrome. Mutation analysis of the ARSB gene revealed seven missense and three frameshift mutations of which eight were novel. Novel missense mutations were p.Asp53Asn, p.Val376Glu, p.Glu390Lys, p.Pro445Leu, and p.Trp450Cys, while an Indian patient was homozygous for two novel missense mutations (p.Pro445Leu and p.Trp450Cys). Three novel frameshift mutations were p.Pro70fsX123, p.Ser403fs, and p.Thr526fs. Two previously reported mutations, p.Arg160Gln and p.Leu321Pro, were also observed in our cohort. The amino acid Arg160 appears to be the mutational hot spot for the ARSB gene. Five patients homozygous for p.Leu321Pro mutation had early onset of the disease, and haplotype analysis showed that the mutation is a founder mutation in Turkish population © 2014 Wiley Periodicals, Inc.
Adhesion properties of soy protein crosslinked with organic calcium silicate hydrate hybrids
Authors: Kim Min Jung , Sun Xiuzhi Susan
Published: March 2014

The objective of this work was to investigate if inorganic calcium silicate hydrate (CSH) hybrids would improve soy protein wet adhesion properties. 3‐aminopropyltriethoxysilane (APTES) was used as a crosslinking agent to make covalent linkage between organic soy protein and inorganic CSH phases. Soy protein–calcium silicate hydrate (MSP‐CSH) composites with different mole ratio of APTES were prepared and the effect of crosslinking reaction on physicochemical properties such as thermal, rheological, FTIR spectroscopic, and morphological and adhesion properties were studied with physical aging effect. Covalent linkage was observed between CSH and soy protein using the FTIR technique. With aging effect, the denaturation temperature (Td) and enthalpies (ΔHd) of each fraction of soy protein increased in DSC thermograms, representing higher thermal stability, and the viscoelasticity of the composites also increased. The roughly coated surface of the MSP‐CSH composite was observed in SEM images. All these changes further confirmed the interaction between CSH and soy protein molecules. Dry and wet adhesion strength of the MSP‐CSH composites was higher than the control MSP alone. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 40693.
Peace, Prosperity and Safety Nets in Timor‐Leste: Competing Priorities or Complementary Investments?
Authors: Dale Pamela , Lepuschuetz Lena , Umapathi Nithin
Published: March 2014

Social protection cash transfers are a vital policy instrument in tackling poverty, and provide an affordable, broad‐based foundation for inclusive growth and social stability. Yet, international experience has shown that many countries have too many programs, but with coverage gaps and fragmented benefits which leave significant proportions of the population without adequate poverty relief or improved economic security. Here, we examine the design and poverty impact of the primary cash transfer programs in the Democratic Republic of Timor‐Leste using nationally representative survey data. We find that though Timor‐Leste's level of social protection expenditure is high by international standards, the overall poverty impact is incommensurate with spending levels. This is explained by the proportion of expenditure devoted to transfers to veterans, the large proportion of the poor population which is not reached by the current targeting mechanisms, and the small coverage and benefit level of the only program that explicitly targets poor households.
The Rentier State at Work: Comparative Experiences of the Resource Curse in East Asia and the Pacific
Authors: Barma Naazneen H.
Published: March 2014

Countries rich in natural resources do not all experience the resource curse in the same way. The rentier state logic holds that the main political–economic impacts of resource dependence rest on how the state handles windfall resource rents. I differentiate how countries experience the resource curse by disaggregating the rentier effect into how governments generate and distribute resource rents. A simple typology of variation in rentier state experiences explains how the overall credibility of intertemporal commitment and degree of political inclusiveness in a country determine its distinct experience of the resource curse. Four brief country cases—comparing the micro political economy of natural resource governance in Laos, Papua New Guinea, Mongolia, and Timor‐Leste—illustrate how intertemporal credibility and political inclusiveness affect patterns of resource rent generation and rent distribution. Different countries experience the resource curse in different ways, with implications for policy attempts at mitigation.
A31: Vitamin D Status is a Determinant of the Effect of Atorvastatin on Carotid Intima Medial Thickening Progression Rate in Children with Lupus: An Atherosclerosis Prevention in Pediatric Lupus Erythematosus Substudy
Authors: Robinson Angela , Tangpricha Vin , Yow Eric , Gurion Reut , Schanberg Laura E. , McComsey Grace ,   for The APPLE Investigators
Published: March 2014

Background/Purpose:

Epidemiologic associations suggest that vitamin D status may play a role in inflammation and progression of atherosclerosis. Using frozen serum, carotid intima medial thickness (CIMT) measurements, and other existing data from the Atherosclerosis Prevention in Pediatric Lupus Erythematosus (APPLE) trial, we assessed interactions between serum 25‐hydroxyvitamin D [25(OH)D], atorvastatin randomization, and CIMT progression rate.

Methods:

Participants in the 3‐year APPLE trial were randomized to placebo or atorvastatin and CIMT progression rate was measured. Frozen serum collected at baseline was used to measure 25(OH)D levels by chemiluminescent assay (IDS, LTD). Mixed effect longitudinal models for the outcome CIMT progression at 3 years were used to evaluate interaction between vitamin D deficiency [25(OH)D levels <20 ng/mL] at baseline and atorvastatin or placebo treatment, and adjusted for lupus duration, gender, systolic blood pressure, pubertal level, LDL‐cholesterol, and the log of baseline high sensitivity C‐reactive protein.

Results:

201/221 APPLE participants had available samples and were included in this analysis; 61/201 (30%) had vitamin D deficiency at baseline. In univariable linear regression modeling, baseline vitamin D deficiency was associated with increased baseline mean‐max IMT (p = 0.01). In multivariable longitudinal modeling, there was a significant interaction effect between baseline vitamin D deficiency and atorvastatin treatment in 3‐year progression of mean‐max CIMT (see Figure). In 4 out of 6 carotid segments, there was a greater decrease in mean‐max CIMT progression rate in subjects who were treated with atorvastatin compared to placebo if they had baseline 25(OH)D levels ≥20ng/mL.

image

Conclusion:

Subjects with higher serum 25(OH)D (≥ 20ng/mL) had lower mean‐max CIMT progression following 3 years of atorvastatin treatment. Results from secondary analyses must be interpreted cautiously, but these findings suggest that treating underlying vitamin D deficiency may optimize benefits from statin therapy.
A54: Insulin Sensitivity Is Improved in sJIA Children With Insulin Resistance After Tocilizumab Treatment: Results From the TENDER Study
Authors: Mirjafari Hoda , Ruperto Nicolino , Brunner Hermine I. , Zuber Zbigniew , Zulian Francesco , Maldonado‐Velázquez Maria del Rocio , Mantzourani Evangelia , Murray Kevin , Roth Johannes , Rovensky Jozef , Vougiouka Olga , Wang Jianmei , Harari Olivier , Lovell Daniel J. , Martini Alberto , De Benedetti Fabrizio
Published: March 2014

Background/Purpose:

In adults with inflammatory arthritis, insulin resistance (IR) is associated with diabetes and cardiovascular disease. Interleukin‐6 (IL‐6) is postulated to play a mechanistic role in IR. The aim of this study was to evaluate the degree of IR among children with systemic juvenile idiopathic arthritis (sJIA) and to determine whether treatment with tocilizumab (TCZ) results in attenuation of IR in sJIA.

Methods:

Patients from TENDER were included if baseline and week 6 fasting insulin were measured. Glucocorticoid tapering was not permitted until week 6. Insulin sensitivity was quantified using the homeostatic model of insulin resistance (HOMA‐IR). Patients were classified as having IR if their HOMA‐IR was ≥2.2 U. Change in HOMA‐IR after 6 weeks was assessed using paired t‐test. Baseline associations with HOMA‐IR and factors predicting change of HOMA‐IR from baseline were assessed using regression analyses. Factors changing in association with HOMA‐IR change were assessed.

Results:

Ninety‐two patients with sJIA were analyzed. 62 were randomly assigned to TCZ and 30 to placebo, 12 of whom required escape therapy with TCZ by week 6. At baseline, 40 patients (43%) had IR. Baseline HOMA‐IR was associated with higher standardized body mass index and higher IL‐6 levels (β‐coefficients [95% CI]: 0.20 [0.05, 0.35] and 0.019 [0.001, 0.038], respectively) but not with JADAS, CRP, active joint count, or presence of fever. Of the 74 patients who received TCZ, 34 (46%) had IR at baseline, including 4 patients who escaped from the placebo arm, compared with 6/18 (33%) who received only placebo. IR patients treated with TCZ but not placebo had significant reductions in HOMA‐IR at week 6 (). Across all IR patients, improvement in JADAS and active joint count was not associated with improvement in HOMA‐IR (β‐coefficients [95% CI]: 0.04 [−0.07, 0.14] and 0.08 [−0.06, 0.22], respectively).

Change in HOMA‐IR After 6 Weeks of TCZ Treatment in Children With sJIA in the TENDER Study

Change in HOMA‐IR Mean (95% CI)
p

TCZ (n = 34)
−0.2 (−3.8, −0.2)
0.03

PBO (n = 6)
0 (−1.7, 1.6)
NS

NS, not significant; PBO, placebo. aPaired t‐test.

Conclusion:

After only 6 weeks of TCZ treatment, HOMA‐IR was improved in IR patients with sJIA in the presence of unchanged glucocorticoid dose. These data support a mechanistic contribution of IL‐6 to IR in vivo in humans.
A108: Linking Exercise, Activity and Pathophysiology in Childhood Arthritis: An Innovative Canadian Knowledge Translation Strategy
Authors: Gibbon Michele , Tucker Lori B. , Feldman Debbie Ehrmann , McKay Heather A. , Sims‐Gould Joanie , Stinson Jennifer N. , Stringer Elizabeth , Tse Shirley M. L. ,   LEAP Study Investigators, Duffy Ciarán M.
Published: March 2014

Background/Purpose:

We implemented a novel knowledge translation (KT) initiative called the LEAP Ambassador Program to disseminate findings from the “Linking Exercise, Activity and Pathophysiology (LEAP) in Children with JIA study.” The main hypothesis of the study is that increased levels of physical activity will improve the outcomes (such as quality of life) of youth with juvenile idiopathic arthritis (JIA). The aim of this initiative is to inspire youth with JIA to be physically active through the creation of a community of athletes and youth with JIA, who model different levels of physical activity.

Methods:

The LEAP Ambassador program was developed by the LEAP study program manager and approved by the LEAP Steering Committee. Various levels of athletes, ranging from international, national, college/university level, and local LEAP study participants (youth with JIA, aged 8–16 years), were sought. Individuals agreeing to participate signed consent for use of their personal photo(s) and interview on the LEAP website (www.leapjia.com). Participants were asked to provide a photo of themselves involved in a sport or physical activity, and to answer 6 brief questions about their motivation to engage in sport/physical activities, in the face of disease flares and/or injuries. Each of the participating LEAP sites was encouraged to seek local LEAP ambassadors through their clinics and community connections, to ensure representation across the country.

Results:

To date, 15 LEAP ambassadors have been engaged in the program, including 3 international/national level athletes, 2 college/provincial level athletes and 10 youth with JIA. Different levels of physical activity and sports, including freestyle skiing, soccer, walking, horseback riding, speed skating, hockey, cycling and rowing, have been represented. The 10 youth with JIA who have agreed to be LEAP ambassadors come from across the country. Both English and Frenchspeaking ambassadors have been included.

Conclusion:

The LEAP ambassador program is a unique KT initiative aimed at developing a robust community across the country to support the research messages of the LEAP study, relating to the promotion of physical activity in youth with arthritis. A supportive network is being developed, in which athletes act as role models, inspiring youth with JIA to engage in physical activity, and the youth themselves encourage and motivate each other through shared experiences. Future plans include expansion of the program to include more athletes and youth with JIA, and increased use of social media to connect patients and athletes. An evaluation of the effectiveness of the program is also planned.
A110: The Impact of Shoe Wear on the 6 Minute Walk Test in Adolescents with Juvenile Idiopathic Arthritis
Authors: Blitz Jill R. , Stern Sara , Marzan Katherine AB
Published: March 2014

Background/Purpose:

Health care professionals recommend appropriate athletic shoe wear to patients with juvenile idiopathic arthritis, particularly during exercise and activities to prevent pain or foot injury. Adolescents, however, tend to choose their shoe wear based on fashion rather than practical factors. The purpose of this study was to determine whether the type of shoe wear utilized had any impact on walking endurance in adolescents with juvenile idiopathic arthritis.

Methods:

27 patients who participated in a walking program were included and assessed for exercise endurance using the 6‐Minute Walk Test (6MWT). 14 subjects were tested once and 13 subjects were tested 4 times with an interval of 6–8 weeks, for a total of 56 6MWTs. Patients were allowed to wear whatever type of shoes they wanted for each test. The type of shoe wear utilized by each patient was recorded for each 6 MWT. Type of shoe‐wear used by subjects varied, and was grouped into 3 categories for analysis purposes: athletic sneakers (n = 9); flat unsupportive sneakers, boots/ballet flats (n = 38); and flip‐flops/sandals (n = 10). Data were analyzed using analysis of variance.

Results:

27 patients (23 F, 4M, aged 11–19 years) enrolled in the study. The majority of 56 6MWT were done in flat shoes (38/56, 68 %) with athletic shoes utilized the least (9/56, 16%). Patients wearing athletic shoes walked the longest distance (503.94 + 64.03 m) followed by flats (494.56 + 58.45m) and sandals (480.29 + 72.39 m). These differences in 6MWT distance were not statistically significant (p = 0.61) likely due to small sample size.

Conclusion:

Though no statistically significant impact of shoe wear on walking endurance was found, subjects walked longer distances in 6 minutes when wearing athletic shoes. The difference seen may be clinically meaningful to this patient population. Based on the results of this small pilot study, further research on a larger population appears warranted.
A158: CpG‐Induced Macrophage Activation Syndrome Develops Through an Organism Level Resistance to Toll‐like Receptor 9 Tolerance
Authors: Weaver Lehn K. , Behrens Edward M.
Published: March 2014

Background/Purpose:

Macrophage activation syndrome (MAS) is a cytokine storm syndrome known to complicate severe inflammatory diseases, and can be seen in patients with systemic rheumatologic conditions. Recent data implicates repeated adjuvant stimulation using the CpG Toll‐like Receptor 9 (TLR9) agonist as a model of the feed forward inflammatory cycle seen in cytokine storm syndromes. These results contradict the well known phenomenon of TLR tolerance, whereby repeated doses of TLR agonists result in diminishing inflammatory responses to additional stimuli. In contrast, CpG‐induced MAS results in a dose‐dependent increase in systemic inflammation in a process dependent on TLR9, Interferon‐γ (IFNγ), and Interleukin (IL)‐12.

Methods:

C57BL/6 and Yet40 IL‐12 reporter mice were treated with 0–4 doses of CpG before harvesting tissues to measure parameters of MAS. Analysis of ex vivo and in vitro cellular TLR9 tolerance was performed on whole splenocytes, bone marrow‐derived dendritic cells (BMDC) and bone marrow‐derived macrophages (BMMP). IL‐12 production was measured from supernatants by ELISA and intracellular IL‐12 was assessed by flow cytometry.

Results:

Our data recapitulate the well described phenomenon of TLR9 tolerance whereby repeated stimulation with CpG leads to reduced cytokine production using in vitro cultures of whole splenocytes, BMDC and BMMP. Interestingly, IFNγ does not alter the responsiveness of cells to a TLR9 tolerizing stimulus, as the addition of exogenous IFNγ does not rescue TLR9 tolerance in vitro. In contrast, repeated injections of CpG in whole animals results in a dose‐dependent increase in cytokine production, cellular tissue infiltration, cellular responsiveness to CpG, and immunopathology. This dose responsive systemic inflammation correlates with the continued responsiveness of splenic, liver, and bone marrow leukocytes to CpG after in vivo systemic CpG stimuli.

Conclusion:

Despite demonstrating TLR9 tolerance in multiple cell types in vitro, we show that cells remain responsive to CpG stimulation ex vivo even in mice previously treated with systemic CpG. Without the negative regulatory mechanisms of TLR tolerance, repeated injections of CpG lead to a feed forward systemic inflammatory response resulting in systemic immunopathology. These observations elucidate a novel mechanism whereby persistent adjuvant is sufficient to drive the uncontrolled inflammatory responses seen in MAS because of in vivo failure of TLR9 tolerance.
A178: Development of Tools to Facilitate Shared Decision Making about Medications for Juvenile Idiopathic Arthritis—A Project of the Pediatric Rheumatology Care and Outcomes Improvement Network
Authors: DeWitt Esi Morgan , Lipstein Ellen A. , Staun Katie , Scherer Linda , Taylor Janalee , Lannon Carole M. , Brinkman William B.
Published: March 2014

Background/Purpose:

Medication options for juvenile idiopathic arthritis (JIA) are increasing. Medications differ on a variety of attributes, including mechanisms of action, dosing intervals, modes of administration, safety profiles, and cost. Some parents of children with JIA are left with questions and concerns about medications suggesting a need for improved clinician‐parent communication. Decisions like this, with multiple reasonable options that differ in ways that matter to families, are conducive to “Shared Decision Making” (SDM). SDM is a process whereby clinicians share information about the options and patients/parents share information about their goals and preferences. Together, a treatment plan is developed that is the best fit for the individual patient and their family. We conducted a project to develop tools to facilitate SDM within the Pediatric Rheumatology Care and Outcomes Improvement Network (PR‐COIN). PR‐COIN is a learning network designed to improve outcomes of JIA care using quality improvement (QI) approaches.

Methods:

Development of issue cards to facilitate SDM involved multiple steps including qualitative interviews with clinicians and care providers, direct observation of clinical encounters, and an iterative design process involving a graphic designer and a stakeholder panel of clinicians, allied health professionals and parents. We introduced the prototype issue cards for use in clinics using Plan‐Do‐Study‐Act (PDSA) cycles. We elicited feedback to guide card revisions from PR‐COIN members via weekly electronic surveys and discussions during monthly webinars and following direct observation of encounters using the cards.

Results:

We identified the medication attributes deemed most important to discuss by our stakeholders, including “How Soon” will therapies take effect, “How Often” are they given, “Side Effects”, “Cost”, “How Long” will need to stay on the medication, and “Other Considerations.” We used these attributes to organize the issue cards and symbols to convey key concepts (see Figure). Intended use of the cards involves clinicians showing the cards to patient and parent and asking which card they would like to discuss first. By selecting a card, the family reveals what is important to them. After 18 revisions, PR‐COIN stakeholders at 6 sites found the issue cards to be acceptable for regular use.

image

Conclusion:

PR‐COIN issue cards are well accepted by clinicians and families within network sites. PDSA cycles continue as we seek to implement the issue cards in routine clinical care to facilitate SDM across the network. Our ultimate goal is to drive improvement in child JIA outcomes by reliably engaging patients/parents in SDM to select a medication that is a good fit.
Effectiveness of three‐dimensional digital animation in teaching human anatomy in an authentic classroom context
Authors: Hoyek Nady , Collet Christian , Di Rienzo Franck , De Almeida Mickael , Guillot Aymeric
Published: March 2014

Three‐dimensional (3D) digital animations were used to teach the human musculoskeletal system to first year kinesiology students. The purpose of this study was to assess the effectiveness of this method by comparing two groups from two different academic years during two of their official required anatomy examinations (trunk and upper limb assessments). During the upper limb section, the teacher used two‐dimensional (2D) drawings embedded into PowerPoint® slides and 3D digital animations for the first group (2D group) and the second (3D group), respectively. The same 3D digital animations were used for both groups during the trunk section. The only difference between the two was the multimedia used to present the information during the upper limb section. The 2D group surprisingly outperformed the 3D group on the trunk assessment. On the upper limb assessment no difference in the scores on the overall anatomy examination was found. However, the 3D group outperformed the 2D group in questions requiring spatial ability. Data supported that 3D digital animations were effective instructional multimedia material tools in teaching human anatomy especially in recalling anatomical knowledge requiring spatial ability. The importance of evaluating the effectiveness of a new instructional material outside laboratory environment (e.g., after a complete semester and on official examinations) was discussed. Anat Sci Educ 7: 430–437. © 2014 American Association of Anatomists.
Integrin signaling in skeletal development and function
Authors: Docheva Denitsa , Popov Cvetan , Alberton Paolo , Aszodi Attila
Published: March 2014

Integrins are cell surface receptors that connect extracellular matrix (ECM) components to the actin cytoskeleton and transmit chemical and mechanical signals into the cells through adhesion complexes. Integrin‐activated downstream pathways have been implicated in the regulation of various cellular functions, including proliferation, survival, migration, and differentiation. Integrin‐based attachment to the matrix plays a central role in development, tissue morphogenesis, adult tissue homeostasis, remodeling and repair, and disturbance of the ECM‐integrin‐cytoskeleton signaling axis often results in diseases and tissue dysfunction. Increasing amount of in vitro and in vivo evidences suggest that integrins are pivotal for proper development, function, and regeneration of skeletal tissues. In this paper, we will summarize and discuss the role of integrins in skeletogenesis and their influence on the physiology and pathophysiology of cartilage, bone, and tendon. Birth Defects Research (Part C) 102:13–36, 2014. © 2014 Wiley Periodicals, Inc.
Chondrocyte hypertrophy in skeletal development, growth, and disease
Authors: Sun Margaret Man‐Ger , Beier Frank
Published: March 2014

Most of our bones form through the process of endochondral ossification, which is tightly regulated by the activity of the cartilage growth plate. Chondrocyte maturation through the various stages of growth plate physiology ultimately results in hypertrophy. Chondrocyte hypertrophy is an essential contributor to longitudinal bone growth, but recent data suggest that these cells also play fundamental roles in signaling to other skeletal cells, thus coordinating endochondral ossification. On the other hand, ectopic hypertrophy of articular chondrocytes has been implicated in the pathogenesis of osteoarthritis. Thus, a better understanding of the processes that control chondrocyte hypertrophy in the growth plate as well as in articular cartilage is required for improved management of both skeletal growth disorders and osteoarthritis. This review summarizes recent findings on the regulation of hypertrophic chondrocyte differentiation, the cellular mechanisms involved in hypertrophy, and the role of chondrocyte hypertrophy in skeletal physiology and pathophysiology. Birth Defects Research (Part C) 102:74–82, 2014. © 2014 Wiley Periodicals, Inc.
Robust, microfabricated culture devices with improved control over the soluble microenvironment for the culture of embryonic stem cells
Authors: Macown Rhys J. , Veraitch Farlan S. , Szita Nicolas
Published: March 2014

The commercial use of stem cells continues to be constrained by the difficulty and high cost of developing efficient and reliable production protocols. The use of microfabricated systems combines good control over the cellular microenvironment with reduced use of resources in process optimization. Our previously reported microfabricated culture device was shown to be suitable for the culture of embryonic stem cells but required improvements to robustness, ease of use, and dissolved gas control. In this report, we describe a number of improvements to the design of the microfabricated system to significantly improve the control over shear stress and soluble factors, particularly dissolved oxygen. These control improvements are investigated by finite element modeling. Design improvements also make the system easier to use and improve the robustness. The culture device could be applied to the optimization of pluripotent stem cell growth and differentiation, as well as the development of monitoring and control strategies and improved culture systems at various scales.
Techniques and best practices for optical coherence tomography
Authors: Lopez John J. , Arain Salman A. , Madder Ryan , Parekh Niraj , Shroff Adhir R. , Westerhausen Don
Published: March 2014

Optical coherence tomography (OCT) is a novel intracoronary imaging modality that utilizes near‐infrared light to provide information regarding lesion length and severity, vessel lumen diameter, plaque morphology, as well as the opportunity for stent procedure guidance and follow‐up. While analogous to intravascular ultrasound (IVUS), the specific imaging properties, including significantly higher resolution, and technical specifications of OCT offer the ability for intracoronary diagnostic and interventional procedure guidance roles that require a thorough understanding of the technology. We provide coronary interventionalist's a user's guide to OCT, focusing on techniques and approaches to optimize imaging, with a focus on efficiency, safety and strategies for effective imaging. © 2014 Wiley Periodicals, Inc.
A fast polygon inflation algorithm to compute the area of feasible solutions for three‐component systems. II: Theoretical foundation, inverse polygon inflation, and FAC‐PACK implementation
Authors: Sawall Mathias , Neymeyr Klaus
Published: March 2014

The area of feasible solutions (AFS) of a multivariate curve resolution method is the continuum of feasible solutions under the given constraints. In the current paper, the AFS is computed only on the condition of nonnegative solutions. This work is a continuation of a paper (J. Chemometrics 28:106–116, 2013) on the polygon inflation algorithm for AFS computations. In this second part, various properties of the AFS are analyzed. First, its boundedness is proved, which is a necessary condition for its numerical computation. Second, it is shown that the origin is never contained in the area of feasible solutions. This fact is the basis for the inverse polygon inflation algorithm, which allows to compute specific types of an AFS containing a hole.

The numerical computation of the AFS is a complicated and computationally expensive process. The construction of proper objective functions for the AFS optimization problem appears to be decisive. The paper contains a comparative analysis of two objective functions and describes the ideas of the new FAC‐PACK toolbox for MATLAB. This freely available toolbox contains a numerical implementation of the polygon inflation and of the inverse polygon inflation algorithm. Copyright © 2014 John Wiley & Sons, Ltd.