bluuebunny/crossref_metadata_2025 huggingface dataset:
Spectrum and Prevalence of Vasculopathy in Pediatric Neurofibromatosis Type 1
Authors: Kaas Bonnie , Huisman Thierry A. G. M. , Tekes Aylin , Bergner Amanda , Blakeley Jaishri O. , Jordan Lori C.
Published: July 2012

To describe the spectrum and associated clinical features of peripheral and cerebral vasculopathy in pediatric patients with neurofibromatosis type 1, children seen at a single center from 2000 to 2010 with appropriate imaging studies were identified. Scans were assessed for vascular disease by 2 pediatric neuroradiologists. Of 181 children, 80 had pertinent imaging studies: 77 had brain imaging, 6 had peripheral imaging, and 3 had both. Vasculopathy was identified in 14/80 children (18%, minimum prevalence of 14/181; 8%). Of those with vascular abnormalities, 2/14 had peripheral vasculopathy (1% minimum prevalence) and 12/14 had cerebrovascular abnormalities (7% minimum prevalence). No associations were found between vasculopathy and common clinical features of neurofibromatosis type 1, including optic pathway glioma, plexiform neurofibroma, skeletal abnormalities, attention-deficit hyperactivity disorder (ADHD), or suspected learning disability. Both peripheral and cerebral vasculopathy are important complications of pediatric neurofibromatosis type 1 and should be considered in the management of this complex disease.
Unusual Manifestations of Pediatric Neuromyelitis Optica
Authors: Yavuz Halûk , Kireşi Demet
Published: July 2012

Neuromyelitis optica is a rare, severe idiopathic disease that predominantly involves optic nerves and spinal cord. Main clinical features of neuromyelitis optica are visual loss, paraparesis or tetraparesis, sensory loss, and sphincter dysfunction. A 13-year-old girl with vision loss and behavioral change was admitted. Her behavioral changes concerned demanding everything, eating cacik (a kind of meal prepared by yogurt) continuously, calling everyone “father,” and self-throttling during the last 1 month, and blurred vision started 15 days ago. On cranial magnetic resonance imaging (MRI), multiple lesions were seen. The patient was admitted 40 days later with walking difficulty. There were lesions in the medulla and cervical spinal cord on MRI. Neuromyelitis optica was diagnosed. Vomiting was the beginning complaint in 2 of 5 hospitalizations later. We conclude that neuromyelitis optica may involve atypical symptoms such as behavioral change and vomiting. Atypical presentations may delay diagnosis. Vomiting may be a recurrence messenger.
Usefulness of the Tendon Reflex for Assessing Spasticity After Botulinum Toxin-A Injection in Children With Cerebral Palsy
Authors: Jang Dae-Hyun , Sung In Young , Kang Yu Jeong
Published: July 2012

This study sought to investigate the relationships between clinical and neurophysiologic assessments of spasticity after injection of botulinum toxin-A in children with cerebral palsy. A total of 40 children were recruited. Clinical assessments included the modified Ashworth scale and modified Tardieu scale parameters R1, R2, and D. Neurophysiologic assessment included compound motor action potential, Hoffmann, and tendon reflex. Children showed significant decreases in modified Ashworth scale, R1, and R2 at 2, 4, and 12 weeks and in D at 2 and 4 weeks. Amplitude of compound motor action potential decreased at 2 weeks, Hoffmann reflex amplitude decreased at 4 weeks, and tendon reflex amplitude decreased at 2 and 4 weeks. At 12 weeks, none of the neurophysiologic parameters differed from baseline. The correlations among R2, D, and the amplitude of tendon reflex were significant. Neurophysiologic tests could be used to evaluate reduced spasticity after botulinum toxin-A injection. The amplitude of tendon reflex showed the highest correlation with severity of spasticity.
Sturge-Weber Syndrome
Authors: Jagtap Sujit , Srinivas G. , Harsha K. J. , Radhakrishnan Neelima , Radhakrishnan Ashalatha
Published: July 2012

Sturge-Weber syndrome is a heterogeneous neurocutaneous syndrome with facial and leptomeningeal angiomas, glaucoma, seizures, stroke-like episodes, and mental retardation. The authors critically evaluated the clinical manifestations, outcome, and natural history in 30 patients with Sturge-Weber syndrome followed up from January 1985 to May 2010. Of the patients, 15 were males, age at diagnosis ranged from 1 month to 43 years. Typical port-wine stain nevus occurred in 26 (86%), it was bilateral in 2 (8%), and it was absent in 4 (4%). Nine patients had glaucoma (30%), 3 required surgery. Four had transient hemiparesis. All patients had seizures; they were well controlled in 22 (73.3%); in 8 they remained drug resistant. Three patients underwent surgery and became seizure-free. Of the 17 who had mental subnormality, 14 (82.4%) had seizure onset before 2 years. An early age at seizure onset and those with drug-resistant seizures had more severe degree of mental subnormality. Uncontrolled seizures, mental subnormality, visual handicap, and cosmetic disfiguration were the major impediments in life.
Resistance (Weight Lifting) Training in an Adolescent With McArdle Disease
Authors: García-Benítez Sergio , Fleck Steven J. , Naclerio Fernando , Martín Miguel Angel , Lucia Alejandro
Published: July 2012

Owing to the risk of severe rhabdomyolysis, clinicians advise McArdle disease patients to refrain from strenuous exercise, particularly weight lifting. A 15-year-old male McArdle disease patient performed a 6-week, supervised, light- to moderate-intensity (∼65-70% of one-repetition-maximum) resistance (weight lifting) training program (2 sessions/week). Training resulted in ∼27% and ∼6% increase in one-repetition-maximum bench press and multipower squat performance while inducing no myoglobinuria. The patient changed to a lower disease severity class, that is, he became virtually asymptomatic in terms of exercise limitations. The authors’ preliminary data suggest that supervised, light to moderate resistance training is feasible in children with McArdle disease and has potential clinical benefits.
Disaster Mitigation and Preparedness
Authors: Chikoto Grace L. , Sadiq Abdul-Akeem , Fordyce Erin
Published: July 2012

Few studies have compared the mitigation and preparedness activities adopted by nonprofit, private, and public organizations. This study contributes to this important literature by comparing the adoption of mitigation and preparedness activities by nonprofit, private, and public organizations in Memphis, Tennessee. The findings show that although nonprofit organizations may be more resource-constrained compared with private corporations, they adopt more mitigation and preparedness activities than private corporations. In addition, public organizations adopt more mitigation and preparedness activities than private organizations. The results are inconclusive on the comparison between nonprofits and public agencies.
The Effect of Individuals’ Organization Affiliation on Their Internet Donations
Authors: Reddick Christopher G. , Ponomariov Branco
Published: July 2012

Based on a national representative sample of U.S. internet users, this article examines the impact of associational participation on the likelihood of making an online donation to a charity. The results indicated that internet users engaged in more offline groups and networks are more likely to donate online. Frequency of use of internet and social media do not influence general propensity to donate, thereby suggesting that online donations are a function of actual engagement in social groups, rather than of frequent exposure to the internet media. Individuals involved in choice-based groups were the most likely to donate online, compared to other types of organization participation and/or affiliation. The authors also find that general propensity to donate online (including charities respondents are unaffiliated with) and making monetary contributions specifically to the particular organizations individuals are active in have somewhat distinct determinants.
Evaluation of potential near-term operational changes to mitigate environmental impacts of aviation
Authors: Marais Karen B , Reynolds Tom G , Uday Payuna , Muller Delri , Lovegren Jonathan , Dumont Jean-Marie , Hansman R John
Published: July 2012

Changing aircraft operational procedures is one way of mitigating the environmental impacts of aviation in relatively short timeframes with existing aircraft types. However, to date these mitigations have not been evaluated or compared in a systematic manner that considers both their environmental impact reduction potential and their ability to be successfully implemented. This article presents a comprehensive identification and systematic evaluation of potential near-term operational changes to determine their relative environmental mitigation benefits. The research also evaluated the potential for successful implementation by identifying possible barriers to implementation for each mitigation. The analysis identifies the most promising mitigations offering a combination of environmental impact reduction and ease of implementation.
Adaptive backstepping control for a hypersonic vehicle with uncertain parameters and actuator faults
Authors: Qi Ruiyun , Huang Yuhai , Jiang Bin , Tao Gang
Published: July 2012

For a hypersonic vehicle with redundant elevators, an adaptive backstepping fault-tolerant control scheme is designed for its longitudinal motion model. In the backstepping design, the dynamic surface control strategy is adopted to eliminate the explosion of complexity in calculating the derivatives of virtual control inputs by introducing two first-order filters. An appropriate controller structure is proposed and the matching conditions are derived for adaptive fault compensation for the vehicle with redundant elevators subject to uncertain actuator faults. The adaptation laws are designed to update parameter estimates to implement the adaptive controller. The closed-loop stability under the proposed adaptive actuator fault compensation scheme is analyzed. Both analytical and simulation results are given to verify the effectiveness of the design and demonstrate the desired performance for altitude and velocity control.
Application and limitations of the Artemisia/Chenopodiaceae pollen ratio in arid and semi-arid China
Authors: Zhao Yan , Liu Hongyan , Li Furong , Huang Xiaozhong , Sun Jinghui , Zhao Wenwei , Herzschuh Ulrike , Tang Yu
Published: July 2012

The Artemisia/Chenopodiaceae (A/C) ratio is assumed to be a useful index for reconstructing moisture changes in arid and semi-arid regions. Thorough modern pollen studies are still lacking to understand the reliability and limitation of A/C ratio as a moisture indicator, however. Here we review how well this ratio can be applied in arid and semi-arid China on the basis of new surface pollen data, previous data synthesis and other publications. Results indicate that variance in the A/C ratio can permit identification of modern vegetation types and that the A/C ratio generally has a positive relationship with annual precipitation. However, soil salinity, vegetation community composition, human activity and sample provenance (e.g. soil and lake sediments) will affect the values of the A/C ratio in different vegetation zones and therefore the A/C ratio is not comparable in different regions. We argue that the A/C ratio can only be used to reconstruct vegetation types and climate change in regions with precipitation <450–500 mm, and in steppe, steppe desert and desert areas. Careful studies should be undertaken to understand the modern pollen–vegetation–climate relationships in various regions before using the A/C ratio to interpret vegetation and climate.
Juvenile onset systemic lupus erythematosus: a possible role for vitamin D in disease status and bone health
Authors: Casella CB , Seguro LPC , Takayama L , Medeiros D , Bonfa E , Pereira RMR
Published: July 2012

Purpose: In juvenile onset systemic lupus erythematosus (JoSLE), evidence for the association between vitamin D status, lupus activity, and bone health is very limited and not conclusive. The aim of this study was, therefore, to assess in JoSLE patients the possible relevance of vitamin D deficiency in disease and bone parameters. Methods: Fifty-seven JoSLE patients were initially compared to 37 age, race and body mass index (BMI) -matched healthy controls. The serum concentration of 25 hydroxyvitamin D (25OHD) was determined by radioimmunoassay. Patients with 25OHD deficiency (≤20 ng/mL) were compared to those with levels >20 ng/mL. Disease activity was evaluated by SLE Disease Activity Index (SLEDAI). Bone mineral density (BMD) and body composition (BC) were measured using dual-energy X-ray absorptiometry (DXA). Results: 25OHD levels were similar in patients and controls (21.44 ± 7.91 vs 22.54 ± 8.25 ng/mL, p = 0.519), regardless of supplementation (65% of patients and none in controls). Thirty-one patients with 25OHD deficiency (≤20 ng/mL) were further compared to the 26 JoSLE patients with levels >20 ng/mL. These two groups were well-balanced regarding vitamin D confounding variables: age ( p = 0.100), ethnicity ( p = 1.000), BMI ( p = 0.911), season (p = 0.502 ), frequency of vitamin D supplementation ( p = 0.587), creatinine ( p = 0.751), renal involvement ( p = 0.597 ), fat mass ( p = 0.764), lean mass ( p = 0.549), previous/current use of glucocorticoids(GC) ( p = 1.0), immunosuppressors ( p = 0.765), and mean current daily dose of GC ( p = 0.345). Patients with vitamin D deficiency had higher SLEDAI (3.35 ± 4.35 vs 1.00 ± 2.48, p = 0.018), lower C4 levels (12.79 ± 6.78 vs 18.38 ± 12.24 mg/dL, p = 0.038), lower spine BMD (0.798 ± 0.148 vs 0.880 ± 0.127 g/cm2, p = 0.037 ) and whole body BMD (0.962 ± 0.109 vs 1.027 ± 0.098 g/cm2, p = 0.024). Conclusion: JoSLE vitamin D deficiency, in spite of conventional vitamin D supplementation, affects bone and disease activity status independent of therapy and fat mass reinforcing the recommendation to achieve adequate levels.
Gendered working-time arrangements and their policy implications: Korean experiences
Authors: Won Sook-Yeon
Published: July 2012

This study is to explore the reality of gendered work time and its policy implications. With the dual-earner model of family, the amount and manner in which time is spent for paid work, as opposed to unpaid work, constructs gender relations in Korea. This article raises the following questions. What is the impact of exceptionally long working hours on gender relations in the workplace and the family in Korea? In terms of time spent, to what extent are there changes in the unquestioned exclusive care responsibility by women and traditional notions of fatherhood? To what extent has the Confucian dichotomy of public (workplace) and private (family) been altered, in terms of the workplace practice of long working hours? In doing so, this study applies quantitative and qualitative data from various sources. The findings show that, despite moving towards a dual-earner reality, the Confucian dichotomy of unpaid work and fatherhood is still tenacious. Furthermore, the practice of extremely long working hours provides a ‘good’ reason for a father’s absence in unpaid work, which in turn reflects the Confucian fatherhood. Also, this prevents mothers from achieving fuller integration into the labour market. Given these findings, we can see that the practices of long working hours and Confucian traditions combine to generate a vicious circle of gender inequality in the labour market and the family. The policy implications of these practices are discussed.
Data-driven techniques to estimate parameters in the homogenized energy model for shape memory alloys
Authors: Crews John H , Smith Ralph C , Pender Kyle M , Hannen Jennifer C , Buckner Gregory D
Published: July 2012

The homogenized energy model is a unified framework for modeling hysteresis in ferroelectric, ferromagnetic, and ferroelastic materials. The homogenized energy model framework combines energy analysis at the lattice level with stochastic homogenization techniques, based on the assumption that quantities such as interaction and coercive fields are manifestations of underlying densities, to construct macroscopic material models. In this article, we focus on the homogenized energy model for shape memory alloys. Specifically, we develop techniques for estimating model parameters based on attributes of measured data. Both the local (mesoscopic) and macroscopic models are described, and the model parameters’ relationship to the material’s response is discussed. Using these relationships, techniques for estimating model parameters are presented. The techniques are applied to constant-temperature stress–strain and resistance–strain data. These estimates are used in two manners. In one method, the estimates are considered fixed and only the homogenized energy model density functions are optimized. For SMA, the HEM incorporates densities for the interaction and relative stress (the width of the hysteresis loop). In the second method, the estimates are included in the optimization algorithm. Both cases are compared to experimental data at various temperatures, and the optimized model parameters are compared to the initial estimates.
On Doing the Wrong Things for the Wrong Reasons
Authors: Nord Walter R.
Published: July 2012

Over the years, a number of scholars have questioned the merits of two core organization studies’ practices – null hypothesis statistical testing (NHST) and obsession with theory (OWT). I used neo-institutional organization theory to study the history of these two practices. I found that both may owe their core positions, at least as much or more, to their value for gaining legitimacy, as to substantive merit. Consequently, following the perspective of neo-institutional theory, it appears both may lack sufficient technical justification. Such a condition could account for some of our field’s leaders recently expressed concerns about our field’s slow progress.
The Rhetoric of Power
Authors: Robinson Jill L. , Topping Danielle
Published: July 2012

Charismatic leaders present intriguing examples of the use of power through language. The prevailing neo-charismatic perspective, however, is based predominately on Western theories and research examining U.S. presidents. This study moves beyond this sample by examining language differences between a moral and a toxic leader. Content analysis was used to explore the rhetoric of Martin Luther King Jr. and Adolf Hitler, whose distinct motives play out over their careers and during crises. Although some differences were predictable (i.e., Martin Luther King Jr. used more Optimistic language, whereas Hitler was higher in Power and Aggression), the changes over time suggest keys to their differing motives. Among other findings, Martin Luther King Jr. was remarkably consistent in his rhetoric, whereas Hitler used increasing Power and Aggressive language as his career progressed. While not providing definitive answers, these preliminary results suggest that further study is warranted into the complex interactions between rhetoric and leadership.
SALL4 and SF-1 Are Sensitive and Specific Markers for Distinguishing Granulosa Cell Tumors From Yolk Sac Tumors
Authors: Bai Shuting , Wei Shi , Ziober Amy , Yao Yuan , Bing Zhanyong
Published: July 2012

Granulosa cell tumors are classified as juvenile and adult types. They may be misinterpreted as a yolk sac tumor when they exhibit a “reticular” growth pattern and contain prominent mitotic activity. In this study, the authors performed immunohistochemical stains for SALL4 and steroidogenic factor-1 (SF-1) on 27 cases of yolk sac tumors and 24 granulosa cell tumors. Nuclear stains for both antibodies were considered as positive and the intensity of staining was graded as negative, weak, moderate, and strong. All the yolk sac tumors were positive for SALL4 (100%) with moderate to strong grade staining and negative for SF-1 (100%). In contrast, all the granulosa cell tumors were positive for SF-1 (85% moderate to strong grade staining and 15% weak staining) and negative for SALL4 (100%). The difference was significant ( P < .01, Student’s t test). This result indicates that these 2 markers could be used to distinguish these 2 tumors in a difficult situation.
The Intimacy Prism
Authors: Milrod Christine , Weitzer Ronald
Published: July 2012

A growing but still limited body of research has examined the views and experiences of clients of sex workers. The current study is based on a content analysis of 2,442 postings on a popular forum where clients review sex workers and discuss their interactions with them. The article explores the reported experiences of a sample of clients who become involved in extended relationships with escorts and the emotional aspects of these associations. Findings show that there is a spectrum of experiences, ranging from counterfeit intimacy to an authentic emotional bond between the two parties. Many clients struggle with the unanticipated demands of an evolving romantic relationship and experience ongoing tension between its instrumental and expressive dimensions.
Mediating mega events and manufacturing multiculturalism: The cultural politics of the world game in Australia
Authors: Baker Stephanie Alice , Rowe David
Published: July 2012

Contemporary global politics is characterized by intense debate about the status of multiculturalism. Framed within discourses of crime, counter-terrorism and moral decline, multiculturalism has been declared redundant just as the Australian government has rehabilitated the term in local citizenship legislation and policy making. Tensions between the local and the global are complex and multifaceted, taking place beyond the formal political arena, with the multicultural image of international mega events, such as the FIFA World Cup, conflicting with local representations of association football in Australia. Our case study of FIFA’s Sydney Live Site (in 2010) investigates latent tensions involving the representation of national interests at mediated local events with global implications. Ambivalence towards multiculturalism in sport is symptomatic, we argue, of a wider conflictual politics of national identity and fealty, with football (soccer) in Australia operating as a specific site where anxieties about multiculturalism are publicly expressed and new forms of governmentality ‘trialled’.
The effectiveness of the pervasive method in ethics pedagogy: A longitudinal study of journalism and mass communication students
Authors: Groshek Jacob , Conway Michael
Published: July 2012

This study answers Christians’ (1978) call for research on the ‘pervasive method’ of ethics instruction. Longitudinal student surveys identified a robust level of concern and suggested penalties for the core ethical issues of plagiarism and fabrication in professional media careers that increased as students progressed through their program of study. Similar, positive findings were also observed among students from many disparate areas of vocational interest. Qualitative instructor assessments of specific techniques for teaching ethics in an introductory skills course and a senior-level capstone seminar further explicate observed increases in students’ ethical growth. Results suggest that the pervasive model as an approach to ethical instruction through socialization can be effective in advancing students’ ethical development.
Parental consent to participation in a randomised trial in children: Associated child, family, and physician factors
Authors: Sureshkumar Premala , Caldwell Patrina , Lowe Alison , Simpson Judy M , Williams Gabrielle , Craig Jonathan C
Published: July 2012

Background

Low participation rates in randomised controlled trials involving children are almost a universal problem, leading to high cost and low statistical power. Trial, parent/family, child, and physician factors have been reported to influence parental willingness to consent for paediatric trials.

Purpose

To identify modifiable and unmodifiable factors associated with parental consent.

Methods

Demographic and clinical characteristics of children and their families and physician characteristics associated with parental consent were evaluated in a recent randomised placebo-controlled trial of prophylactic antibiotics to prevent recurrent urinary tract infection.

Results

Of 1109 eligible children identified (mean age, 2.0 years), 412 parents (37.2%) consented. On a multivariate analysis, the only modifiable factor associated with consent was request for consent by a member of the research study team rather than by a member of the clinical team (risk ratio (RR) = 1.9, 95% confidence interval (CI): 1.2–2.9). The unmodifiable factors significantly associated with consent were age of the child (≥4 years) (RR = 1.2, 95% CI: 1.1–1.4), presence of vesicoureteric reflux (RR = 1.5, 95% CI: 1.3–1.8), inpatient management of the index infection (RR = 0.8, 95% CI: 0.7–0.9), and multiple (≥4) symptoms at presentation (RR = 1.3, 95% CI: 1.1–1.5).

Limitations

We have reported data from only one of the four participating centres in this trial. Data on non-consenters in other participating centres were not completely collected. Data on characteristics of the recruiting physician were limited. These findings are applicable for those considering a single randomised controlled trial.

Conclusions

Parent, child, and physician factors are associated with consent for trial participation, with most not being modifiable. Having a member of the research study team approach the parent for consent appears to be the only feasible strategy for increasing recruitment to randomised trials in this setting.
Technique Tip
Authors: Haque Syed , Sarkar Jay
Published: July 2012

Background. The use of intramedullary nail fixation for tibio-talo-calcaneal fusion is gaining popularity. There is chance of failure of procedure following faulty operative technique specially alignment. Methods. The article describes a useful application of tibial tunnel jig in inserting the calcanio-talo-tibial guide wire. Results. There is precision of few millimeters in the exit point of guide wire on talus. Conclusions. The authors believe that this helps in better positioning of nail and hence better alignment and better operative outcome.

Level of Evidence: Expert opinion, Level V
Hydroxyurea and a cGMP-amplifying agent have immediate benefits on acute vaso-occlusive events in sickle cell disease mice
Authors: Almeida Camila Bononi , Scheiermann Christoph , Jang Jung-Eun , Prophete Colette , Costa Fernando Ferreira , Conran Nicola , Frenette Paul S.
Published: July 2012

Inhibition of leukocyte adhesion to the vascular endothelium represents a novel and important approach for decreasing sickle cell disease (SCD) vaso-occlusion. Using a humanized SCD–mouse-model of tumor necrosis factor-α–induced acute vaso-occlusion, we herein present data demonstrating that short-term administration of either hydroxyurea or the phosphodiesterase 9 (PDE9) inhibitor, BAY73-6691, significantly altered leukocyte recruitment to the microvasculature. Notably, the administration of both agents led to marked improvements in leukocyte rolling and adhesion and decreased heterotypic red blood cell-leukocyte interactions, coupled with prolonged animal survival. Mechanistically, these rheologic benefits were associated with decreased endothelial adhesion molecule expression, as well as diminished leukocyte Mac-1-integrin activation and cyclic guanosine monophosphate (cGMP)–signaling, leading to reduced leukocyte recruitment. Our findings indicate that hydroxyurea has immediate beneficial effects on the microvasculature in acute sickle-cell crises that are independent of the drug's fetal hemoglobin-elevating properties and probably involve the formation of intravascular nitric oxide. In addition, inhibition of PDE9, an enzyme highly expressed in hematopoietic cells, amplified the cGMP-elevating effects of hydroxyurea and may represent a promising and more tissue-specific adjuvant therapy for this disease.
A phase 2 study of single-agent carfilzomib (PX-171-003-A1) in patients with relapsed and refractory multiple myeloma
Authors: Siegel David S. , Martin Thomas , Wang Michael , Vij Ravi , Jakubowiak Andrzej J. , Lonial Sagar , Trudel Suzanne , Kukreti Vishal , Bahlis Nizar , Alsina Melissa , Chanan-Khan Asher , Buadi Francis , Reu Frederic J. , Somlo George , Zonder Jeffrey , Song Kevin , Stewart A. Keith , Stadtmauer Edward , Kunkel Lori , Wear Sandra , Wong Alvin F. , Orlowski Robert Z. , Jagannath Sundar
Published: July 2012

Carfilzomib is a next-generation, selective proteasome inhibitor being evaluated for the treatment of relapsed and refractory multiple myeloma. In this open-label, single-arm phase 2 study (PX-171-003-A1), patients received single-agent carfilzomib 20 mg/m2 intravenously twice weekly for 3 of 4 weeks in cycle 1, then 27 mg/m2 for ≤ 12 cycles. The primary endpoint was overall response rate (≥ partial response). Secondary endpoints included clinical benefit response rate (≥ minimal response), duration of response, progression-free survival, overall survival, and safety. A total of 266 patients were evaluable for safety, 257 for efficacy; 95% were refractory to their last therapy; 80% were refractory or intolerant to both bortezomib and lenalidomide. Patients had median of 5 prior lines of therapy, including bortezomib, lenalidomide, and thalidomide. Overall response rate was 23.7% with median duration of response of 7.8 months. Median overall survival was 15.6 months. Adverse events (AEs) were manageable without cumulative toxicities. Common AEs were fatigue (49%), anemia (46%), nausea (45%), and thrombocytopenia (39%). Thirty-three patients (12.4%) experienced peripheral neuropathy, primarily grades 1 or 2. Thirty-three patients (12.4%) withdrew because of an AE. Durable responses and an acceptable tolerability profile in this heavily pretreated population demonstrate the potential of carfilzomib to offer meaningful clinical benefit. This trial was registered at www.clinicaltrials.gov as #NCT00511238.
GiA Roots: software for the high throughput analysis of plant root system architecture
Authors: Galkovskyi Taras , Mileyko Yuriy , Bucksch Alexander , Moore Brad , Symonova Olga , Price Charles A , Topp Christopher N , Iyer-Pascuzzi Anjali S , Zurek Paul R , Fang Suqin , Harer John , Benfey Philip N , Weitz Joshua S
Published: July 2012

Background

Characterizing root system architecture (RSA) is essential to understanding the development and function of vascular plants. Identifying RSA-associated genes also represents an underexplored opportunity for crop improvement. Software tools are needed to accelerate the pace at which quantitative traits of RSA are estimated from images of root networks.

Results

We have developed GiA Roots (General Image Analysis of Roots), a semi-automated software tool designed specifically for the high-throughput analysis of root system images. GiA Roots includes user-assisted algorithms to distinguish root from background and a fully automated pipeline that extracts dozens of root system phenotypes. Quantitative information on each phenotype, along with intermediate steps for full reproducibility, is returned to the end-user for downstream analysis. GiA Roots has a GUI front end and a command-line interface for interweaving the software into large-scale workflows. GiA Roots can also be extended to estimate novel phenotypes specified by the end-user.

Conclusions

We demonstrate the use of GiA Roots on a set of 2393 images of rice roots representing 12 genotypes from the species Oryza sativa. We validate trait measurements against prior analyses of this image set that demonstrated that RSA traits are likely heritable and associated with genotypic differences. Moreover, we demonstrate that GiA Roots is extensible and an end-user can add functionality so that GiA Roots can estimate novel RSA traits. In summary, we show that the software can function as an efficient tool as part of a workflow to move from large numbers of root images to downstream analysis.
Stillbirths and newborn deaths in slum settlements in Mumbai, India: a prospective verbal autopsy study
Authors: Bapat Ujwala , Alcock Glyn , More Neena Shah , Das Sushmita , Joshi Wasundhara , Osrin David
Published: July 2012

Background

Three million babies are stillborn each year and 3.6 million die in the first month of life. In India, early neonatal deaths make up four-fifths of neonatal deaths and infant mortality three-quarters of under-five mortality. Information is scarce on cause-specific perinatal and neonatal mortality in urban settings in low-income countries. We conducted verbal autopsies for stillbirths and neonatal deaths in Mumbai slum settlements. Our objectives were to classify deaths according to international cause-specific criteria and to identify major causes of delay in seeking and receiving health care for maternal and newborn health problems.

Methods

Over two years, 2005–2007, births and newborn deaths in 48 slum areas were identified prospectively by local informants. Verbal autopsies were collected by trained field researchers, cause of death was classified by clinicians, and family narratives were analysed to investigate delays on the pathway to mortality.

Results

Of 105 stillbirths, 65 were fresh (62%) and obstetric complications dominated the cause classification. Of 116 neonatal deaths, 87 were early and the major causes were intrapartum-related (28%), prematurity (23%), and severe infection (22%). Bereavement was associated with socioeconomic quintile, previous stillbirth, and number of antenatal care visits. We identified 201 individual delays in 121/187 birth narratives (65%). Overall, delays in receiving care after arrival at a health facility dominated and were mostly the result of referral from one institution to another. Most delays in seeking care were attributed to a failure to recognise symptoms of complications or their severity.

Conclusions

In Mumbai’s slum settlements, early neonatal deaths made up 75% of neonatal deaths and intrapartum-related complications were the greatest cause of mortality. Delays were identified in two-thirds of narratives, were predominantly related to the provision of care, and were often attributable to referrals between health providers. There is a need for clear protocols for care and transfer at each level of the health system, and an emphasis on rapid identification of problems and communication between health facilities.

Trial registration

ISRCTN96256793
Application of concentrated deep sea water inhibits the development of atopic dermatitis-like skin lesions in NC/Nga mice
Authors: Bak Jong-Phil , Kim Yong-Min , Son Jeonghyun , Kim Chang-Ju , Kim Ee-Hwa
Published: July 2012

Background

Mineral water from deep-sea bedrock, formed over thousands of years, is rich in minerals such as Ca, Mg, Na, K, Fe and others. Our present study was to investigate the preventive effects of natural deep-sea water on developing atopic dermatitis (AD).

Methods

We elicited AD by application of DNCB (2,4-dinitro-chlorobezene) in Nc/Nga mouse dorsal skin. Deep Sea water (DSW) was filtered and concentrated by a nanofiltration process and reverse osmosis. We applied concentrated DSW (CDSW) to lesions five times per week for six weeks, followed by evaluation. 1% pimecrolimus ointment was used as positive control. The severity of skin lesions was assessed macroscopically and histologically. Levels of inflammatory mediators and cytokines in the serum were detected by Enzyme-linked immunosorbent assay (ELISA) and the levels of CD4+ and CD8+ spleen lymphocytes were determined by flow cytometry analysis.

Results

DNCB-treated mice showed atopic dermatitis-like skin lesions. Treatment of mice with CDSW reduced the severity of symptoms in the skin lesions, including edema, erythema, dryness, itching, and transepidermal water loss (TEWL). Histological analyses demonstrated that epidermal thickness and infiltration of inflammatory cells were decreased after CDSW treatment. Given these interesting observations, we further evaluated the effect of CDSW on immune responses in this AD model. Treatment AD mice with CDSW inhibited up-regulation of IgE, histamine, and pro-inflammatory cytokines in the serum. Also, the CD4+/CD8+ ratio in spleen lymphocyte was down-regulated after treatment with CDSW. Finally, cytokines, especially IL-4 and IL-10 which are important for Th2 cell development, were reduced.

Conclusions

Our data suggests that topical application of CDSW could be useful in preventing the development of atopic dermatitis.
Increased risks of malaria due to limited residual life of insecticide and outdoor biting versus protection by combined use of nets and indoor residual spraying on Bioko Island, Equatorial Guinea
Authors: Bradley John , Matias Abrahan , Schwabe Christopher , Vargas Daniel , Monti Feliciano , Nseng Gloria , Kleinschmidt Immo
Published: July 2012

Background

Malaria is endemic on Bioko Island, Equatorial Guinea, with year-round transmission. In 2004 an intensive malaria control strategy primarily based on indoor residual spraying (IRS) was launched. The limited residual life of IRS poses particular challenges in a setting with year-round transmission, such as Bioko. Recent reports of outdoor biting by Anopheles gambiae are an additional cause for concern. In this study, the effect of the short residual life of bendiocarb insecticide and of children spending time outdoors at night, on malaria infection prevalence was examined.

Methods

Data from the 2011 annual malaria indicator survey and from standard WHO cone bioassays were used to examine the relationship between time since IRS, mosquito mortality and prevalence of infection in children. How often children spend time outside at night and the association of this behaviour with malaria infection were also examined.

Results

Prevalence of malaria infection in two to 14 year-olds in 2011 was 18.4%, 21.0% and 28.1% in communities with median time since IRS of three, four and five months respectively. After adjusting for confounders, each extra month since IRS corresponded to an odds ratio (OR) of 1.44 (95% CI 1.15–1.81) for infection prevalence in two to 14 year-olds. Mosquito mortality was 100%, 96%, 81% and 78%, at month 2, 3, 4 and 5 respectively after spraying. Only 4.1% of children spent time outside the night before the survey between the hours of 22.00 and 06.00 and those who did were not at a higher risk of infection (OR 0.87, 95% CI 0.50–1.54). Sleeping under a mosquito net provided additive protection (OR 0.68, 95% CI 0.54–0.86).

Conclusions

The results demonstrate the epidemiological impact of reduced mosquito mortality with time since IRS. The study underscores that in settings of year-round transmission there is a compelling need for longer-lasting IRS insecticides, but that in the interim, high coverage of long-lasting insecticidal nets (LLINs) may ameliorate the loss of effect of current shorter-lasting IRS insecticides. Moreover, continued use of IRS and LLINs for indoor-oriented vector control is warranted given that there is no evidence that spending time outdoors at night increases infection prevalence in children.
What is the role and authority of gatekeepers in cluster randomized trials in health research?
Authors: Gallo Antonio , Weijer Charles , White Angela , Grimshaw Jeremy M , Boruch Robert , Brehaut Jamie C , Donner Allan , Eccles Martin P , McRae Andrew D , Saginur Raphael , Zwarenstein Merrick , Taljaard Monica
Published: July 2012

This article is part of a series of papers examining ethical issues in cluster randomized trials (CRTs) in health research. In the introductory paper in this series, we set out six areas of inquiry that must be addressed if the CRT is to be set on a firm ethical foundation. This paper addresses the sixth of the questions posed, namely, what is the role and authority of gatekeepers in CRTs in health research? ‘Gatekeepers’ are individuals or bodies that represent the interests of cluster members, clusters, or organizations. The need for gatekeepers arose in response to the difficulties in obtaining informed consent because of cluster randomization, cluster-level interventions, and cluster size. In this paper, we call for a more restrictive understanding of the role and authority of gatekeepers.

Previous papers in this series have provided solutions to the challenges posed by informed consent in CRTs without the need to invoke gatekeepers. We considered that consent to randomization is not required when cluster members are approached for consent at the earliest opportunity and before any study interventions or data-collection procedures have started. Further, when cluster-level interventions or cluster size means that obtaining informed consent is not possible, a waiver of consent may be appropriate. In this paper, we suggest that the role of gatekeepers in protecting individual interests in CRTs should be limited. Generally, gatekeepers do not have the authority to provide proxy consent for cluster members. When a municipality or other community has a legitimate political authority that is empowered to make such decisions, cluster permission may be appropriate; however, gatekeepers may usefully protect cluster interests in other ways. Cluster consultation may ensure that the CRT addresses local health needs, and is conducted in accord with local values and customs. Gatekeepers may also play an important role in protecting the interests of organizations, such as hospitals, nursing homes, general practices, and schools. In these settings, permission to access the organization relies on resource implications and adherence to institutional policies.
Small incision lenticule extraction (SMILE) versus laser in-situ keratomileusis (LASIK): study protocol for a randomized, non-inferiority trial
Authors: Ang Marcus , Tan Donald , Mehta Jodhbir S
Published: July 2012

Background

Small incision lenticule extraction or SMILE is a novel form of ‘flapless’ corneal refractive surgery that was adapted from refractive lenticule extraction (ReLEx). SMILE uses only one femtosecond laser to complete the refractive surgery, potentially reducing surgical time, side effects, and cost. If successful, SMILE could potentially replace the current, widely practiced laser in-situ keratomileusis or LASIK. The aim of this study is to evaluate whether SMILE is non-inferior to LASIK in terms of refractive outcomes at 3 months post-operatively.

Methods/Design

Single tertiary center, parallel group, single-masked, paired-eye design, non-inferiority, randomized controlled trial. Participants who are eligible for LASIK will be enrolled for study after informed consent. Each participant will be randomized to receive SMILE and LASIK in each eye. Our primary hypothesis (stated as null) in this non-inferiority trial would be that SMILE differs from LASIK in adults (>21 years old) with myopia (> −3.00 diopter (D)) at a tertiary eye center in terms of refractive predictability at 3 months post-operatively. Our secondary hypothesis (stated as null) in this non-inferiority trial would be that SMILE differs from LASIK in adults (>21 years old) with myopia (> −3.00 D) at a tertiary eye center in terms of other refractive outcomes (efficacy, safety, higher-order aberrations) at 3 months post-operatively. Our primary outcome is refractive predictability, which is one of several standard refractive outcomes, defined as the proportion of eyes achieving a postoperative spherical equivalent (SE) within ±0.50 D of the intended target. Randomization will be performed using random allocation sequence generated by a computer with no blocks or restrictions, and implemented by concealing the number-coded surgery within sealed envelopes until just before the procedure. In this single-masked trial, subjects and their caregivers will be masked to the assigned treatment in each eye.

Discussion

This novel trial will provide information on whether SMILE has comparable, if not superior, refractive outcomes compared to the established LASIK for myopia, thus providing evidence for translation into clinical practice.

Trial registration

Clinicaltrials.gov NCT01216475.
Omentin as a novel biomarker of metabolic risk factors
Authors: Shibata Rei , Ouchi Noriyuki , Takahashi Ryotaro , Terakura Yuya , Ohashi Koji , Ikeda Nobuo , Higuchi Akiko , Terasaki Hiroko , Kihara Shinji , Murohara Toyoaki
Published: July 2012

Background

Omentin is an adipocytokine that is abundantly expressed in visceral fat tissue. We investigated the association of omentin with the number of metabolic risk factors.

Finding

The study population comprised 201 Japanese men who underwent annual health checkups. Plasma omentin levels were determined by enzyme-linked immunosorbent assay. We divided the subjects into 4 groups according to omentin levels. A reduction of plasma omentin levels significantly correlated with an increase in the mean number of metabolic risk factors such as increased waist circumference, dyslipidemia, high blood pressure and glucose intolerance.

Conclusions

Circulating omentin levels negatively correlated with the multiplicity of metabolic risk factors, suggesting that omentin acts as a biomarker of metabolic disorders.
AP2-type transcription factors determine stem cell identity in the moss Physcomitrella patens
Authors: Aoyama Tsuyoshi , Hiwatashi Yuji , Shigyo Mikao , Kofuji Rumiko , Kubo Minoru , Ito Motomi , Hasebe Mitsuyasu
Published: July 2012

Stem cells are formed at particular times and positions during the development of multicellular organisms. Whereas flowering plants form stem cells only in the sporophyte generation, non-seed plants form stem cells in both the sporophyte and gametophyte generations. Although the molecular mechanisms underlying stem cell formation in the sporophyte generation have been extensively studied, only a few transcription factors involved in the regulation of gametophyte stem cell formation have been reported. The moss Physcomitrella patens forms a hypha-like body (protonema) and a shoot-like body (gametophore) from a protonema apical cell and a gametophore apical cell, respectively. These apical cells have stem cell characteristics and are formed as side branches of differentiated protonema cells. Here, we show that four AP2-type transcription factors orthologous to Arabidopsis thaliana AINTEGUMENTA, PLETHORA and BABY BOOM (APB) are indispensable for the formation of gametophore apical cells from protonema cells. Quadruple disruption of all APB genes blocked gametophore formation, even in the presence of cytokinin, which enhances gametophore apical cell formation in the wild type. All APB genes were expressed in emerging gametophore apical cells, but not in protonema apical cells. Heat-shock induction of an APB4 transgene driven by a heat-shock promoter increased the number of gametophores. Expression of all APB genes was induced by auxin but not by cytokinin. Thus, the APB genes function synergistically with cytokinin signaling to determine the identity of the two types of stem cells.