bluuebunny/crossref_metadata_2025 huggingface dataset:
Stereospecificity of Ginsenoside Rg3 in the Promotion of Cellular Immunity in Hepatoma H22‐Bearing Mice
Authors: Wu Rihui , Ru Qin , Chen Lin , Ma Baomiao , Li Chaoying
Published: July 2014

Previous investigations have demonstrated that ginsenoside Rg3 (Rg3) has many actions including antitumor, antioxidative, and immunomodulatory effects. However, Rg3 exists as 2 stereoisomeric pairs, 20(S)‐ginsenoside Rg3 [20(S)‐Rg3] and 20(R)‐ginsenoside Rg3 [20(R)‐Rg3], which have disparate pharmacological actions because of their different chemical structures. In this study, the 2 epimers were compared for their effects on the growth of hepatocellular carcinoma H22 transplanted tumors and the immune function of H22‐bearing mice.In vivoefficacy study showed that the growth of H22 transplanted tumors was significantly inhibited when treated with 20(S)‐Rg3 and 20(R)‐Rg3 (P< 0.05), and the inhibition rate of tumor growth was 23.6% and 40.9%, respectively. Furthermore, the cellular immunity of H22‐bearing mice was remarkably enhanced after Rg3 treatment (P< 0.05), which may be due to stimulation of ConA‐induced lymphocyte proliferation and augmentation of Th1‐type cytokines interleukin‐2 and interferon‐γ levels in mice. Interestingly, the effects of 20(R)‐Rg3 were significantly greater than those of the S‐form (P< 0.05). Taken together, these results indicate that Rg3 inhibits H22 tumor growthin vivoat least partly by improving the host's cellular immunity in a stereospecific manner, and 20(R)‐Rg3 is more potent for treating cancers or other immune‐mediated diseases clinically.
Epidemiology of diabetes mellitus, pre‐diabetes, undiagnosed and uncontrolled diabetes and its predictors in general population aged 15 to 75 years: A community‐based study (KERCADRS) in southeastern Iran;
Authors: Najafipour Hamid , Sanjari Mojgan , Shokoohi Mostafa , Haghdoost Ali‐Akbar , Afshari Mehdi , Shadkam Mitra , Etemad Koorosh , Mirzazade Ali
Published: July 2014

Background

The goal of this research was to measure the age‐sex standardized prevalence of pre‐diabetes (pre‐DM) and diabetes (DM), and the effectiveness of diabetes management (using HbA1C as the indicator) in an urban area in Iran.

Methods

Using a randomized cluster household survey, we recruited 5900 individuals whose age ranged from 15 to 75 from Kerman for assessing coronary artery disease risk factors (KERCADRS) including diabetes. In 2010 and 2011, all of the participants were interviewed by trained staff for medical history and physical activities, and were then examined for blood pressure and anthropometric measures. Venus blood sample was also collected for fasting plasma glucose and HbA1c.

Results

The age‐sex standardized prevalence of pre‐diabetes, diagnosed and undiagnosed was 18.7%, 6.3% and 2.7%, respectively. Diabetes increased by age (from 14.7% in the 15–24 years old group to 28.4% in the 65–75 years old group), particularly after 40 years. Occasional opium users had the highest prevalence of Pre‐DM (34.6%). Seventy‐nine percent of the depressed and 75.5% of the anxious participants with diagnosed‐DM were identified as uncontrolled‐DM. More than 60% of diagnosed diabetic cases had impaired HbA1c. Overweight and obesity (adjusted odds ratio (AOR) 1.6) and low physical activity (AOR 1.5) were the most preventable risk factors associated with diabetes.

Conclusion

Considerable prevalence of diabetes, susceptibility in progressing to diabetes and uncontrolled diabetes among individuals living in Kerman, suggested ineffective prevention and treatment of diabetes in urban areas in Iran. Successful experience regarding primary health‐care in rural areas should be expanded to urban settings.
Effect of glycemic control on nocturnal arterial oxygen saturation: A case‐control study in type 2 diabetic patients 血糖控制对夜间动脉血氧饱和度的影响：一项2型糖尿病患者的病例对照研究
Authors: Lecube Albert , Ciudin Andreea , Sampol Gabriel , Valladares Silvia , Hernández Cristina , Simó Rafael
Published: July 2014

Background

There is growing evidence suggesting a deleterious effect of type 2 diabetes on lung function and sleep breathing. The aim of this case‐control study was to evaluate whether or not an improvement in glycemic control could arrest or ameliorate nocturnal hypoxemia in type 2 diabetes.

Methods

Thirty patients with type 2 diabetes with HbA1c ≥8% (cases) and 10 non‐diabetic subjects were analyzed. Controls were closely matched to cases by age, gender, body mass index, and neck circumference. The nocturnal oxygen desaturation index (ODI) was calculated at baseline and 5 days after blood glucose improvement with pharmacological intervention. Four different oxygen desaturation thresholds (reductions in SaO2 ≥ 3%, 4%, 6%, and 8%) as indicators of hypoxemia severity (ODI‐3%, ODI‐4%, ODI‐6%, ODI‐8%) were used.

Results

At baseline, patients with diabetes showed a higher number of ODI‐3%, ODI‐4%, and ODI‐6% in comparison with controls. A significant reduction in ODI‐3% (29.7 [4.8–107.9] events per hour at baseline versus 24.6 [3.1–97.7] e/h at discharge, P < 0.001), ODI‐4% (21.7 [1.6–79.3] versus 14.7 [0.3– 79.4], P = 0.003), ODI‐6% (9.3 [0.3–71.8] versus 4.0 [0.0–73.7], P = 0.001), and ODI‐8% (4.1 [0.0–64.3] versus 1.1 [0.0–69.8], P = 0.033) was observed in patients with diabetes after 5 days of follow‐up. However, no changes in ODI events were observed in non‐diabetic patients after the same period. No significant changes in weight were observed in either group.

Conclusions

Glycemic control improvement significantly reduces the increased number of nocturnal oxygen desaturations that exist in type 2 diabetes. Although the mechanisms are not yet fully understood, the rapid effect without changes in body weight suggests a central mechanism involving respiratory center output.
Fire‐mediated niche‐separation between two sympatric small mammal species
Authors: Mowat Emily J. , Webb Jonathan K. , Crowther Mathew S.
Published: July 2014

Fire is a key ecological process influencing the population dynamics of small mammals. Whilst shifting competitive advantage amongst small mammal species following a single fire event is well‐documented, there has been little investigation of the potential influence of fire frequency on small mammal interspecific interactions. In this study, we investigated the effect of fire frequency on the abundance of two small dasyurid mammals, Antechinus stuartii and A. flavipes, which occur sympatrically in some parts of their range. The two antechinus species are known to have different habitat preferences, so it is possible that fire regimes may promote their coexistence in areas of sympatry by altering vegetation structure. To investigate this possibility, we estimated the abundance of both species using replicate sites which differed in the number of times burnt (1–4) during the last four decades, but with identical time‐since‐fire. Proportionally, we captured greater numbers of A. stuartii in less frequently burnt sites and greater numbers of A. flavipes in more‐frequently burnt sites. Hence, fire may mediate niche‐separation between these two species. To clarify further this pattern of response to fire frequency, we investigated which structural habitat variables differed between fire frequencies, and compared antechinus abundances with structural vegetation characteristics. We found a trend for lower ground cover density under higher fire frequencies. This offers one potential explanation of the patterns of abundance that we observed. Our study provided insights into the complexities of small mammal responses to fire, and strongly suggests that fire could mediate competitive interactions between species.
The Asthma Control Questionnaire as a clinical trial endpoint: past experience and recommendations for future use
Authors: Barnes P. J. , Casale T. B. , Dahl R. , Pavord I. D. , Wechsler M. E.
Published: July 2014

The goal of asthma treatment is to control the disease according to guidelines issued by bodies such as the Global Initiative for Asthma. Effective control is dependent upon evaluation of symptoms, initiation of appropriate treatment and minimization of the progressive adverse effects of the disease and its therapies. Although individual outcome measures have been shown to correlate with asthma control, composite endpoints are preferred to enable more accurate and robust monitoring of the health of the individual patient. A number of validated instruments are utilized to capture these component endpoints; however, there is no consensus on the optimal instrument for use in clinical trials. The Asthma Control Questionnaire (ACQ) has been shown to be a valid, reliable instrument that allows accurate and reproducible assessment of asthma control that compares favourably with other commonly used instruments. This analysis provides a summary of the use of ACQ in phase II, III and IV asthma trials. Comparisons between the ACQ and other instruments are also presented. Our analysis suggests that the ACQ is a valid and robust measure for use as a primary or secondary endpoint in future clinical trials.
Ophthalmological findings in 10‐year‐old full‐term children – a population‐based study
Authors: Larsson Eva , Holmström Gerd , Rydberg Agneta
Published: July 2014

Purpose

To determine different ophthalmological parameters in 10‐year‐old, healthy, full‐term children in Stockholm County, Sweden.

Methods

Two hundred and seventeen children were included in the study. Best‐corrected distance and near visual acuities (VA) were measured using logMAR charts. Cycloplegic retinoscopy was performed, and spherical equivalent and astigmatism were determined. Examination of ocular movement and cover test for distance and near were performed. Stereopsis was assessed with the TNO test, and contrast sensitivity with the Vistech test. The Royal Air Force rule was used for assessing accommodation, and near point of convergence was measured with the Lang fixation stick. Ophthalmoscopy was performed through dilated pupils.

Results

Eighty‐two per cent of the children had a distance VA of −0.1 logMAR (1.3 Snellen acuity) or better. None of the children were visually impaired [VA >0.6 logMAR (<0.3 Snellen acuity)]. Ninety‐three per cent had a near VA of −0.1 logMAR (1.25 Snellen acuity) or better. Mean spherical equivalent was 0.6 D. Eight (3.6%) children had hypermetropia (≥+2 D), and 17 (7.8%) were myopic (≤−0.5 D). Nine (4.1%) children had an astigmatism ≥1 D, and two (0.9%) had anisometropia of ≥1 D. Manifest strabismus was found in seven (3.2%) children, five of whom had exotropia. Heterophoria for distance and/or near was found in 80.2% of the children. In children without manifest strabismus, stereopsis >60 seconds of arc was found in five (2.4%). Three (1.4%) of 215 children had contrast sensitivity below normal limits. Binocular median near point of accommodation was 14 D, and median near point of convergence 6 cm.

Conclusion

Knowledge of various visual functions in normally developing children is crucial to be able to draw conclusions from ophthalmological examinations in children with eye diseases. This population‐based study describes different ophthalmological parameters in full‐term ten‐year‐old children. The material can be used as a control when examining children of similar ages with various ophthalmological conditions, such as groups of children with specific neurological or retinal diseases, and syndromes.
Ocular components during the ages of ocular development
Authors: Hashemi Hassan , Jafarzadehpur Ebrahim , Ghaderi Soraya , Yekta Abbasali , Ostadimoghaddam Hadi , Norouzirad Reza , Khabazkhoob Mehdi
Published: July 2014

Purpose

To determine the distribution of ocular biometric components and their correlation with age and sex during the ages of ocular development in a 6‐ to 18‐year‐old population in Iran.

Method

In this cross‐sectional study, which was performed in October 2012, multi‐stage stratified cluster sampling was used to sample the study population from Dezful schools, a city in the southwest of Iran. Biometric examinations were done by an experienced optometrist using the LENSTAR/BioGraph (WaveLight AG, Erlangen, Germany).

Results

Among 864 selected students, 683 participated in the study (response rate: 79.1%); 377 participants (55.2%) were male, and the mean age of the participants was 12 ± 3.4 years (range: 6–18 years). The mean and 95% confidence interval of axial length (AL) were 23.13 mm (22.93–23.33), anterior chamber depth (ACD) was 3.01 mm (2.96–3.06), lens thickness (LT) was 3.58 mm (3.55–3.61), central corneal thickness (CCT) was 549.33 mic (546.59–552.07), corneal radius (CR) was 7.77 mm (7.74–7.81), corneal diameter (CD) was 12.34 mm (12.31–12.38) and pupil diameter (PD) was 4.97 (4.91–5.03). Mean AL, ACD, CD and CR were significantly higher in boys, and mean LT was significantly higher in girls. AL and ACD increased, while LT decreased significantly with age. Myopia was associated with an increase in AL and ACD, and hyperopia was associated with an increase in LT and a decrease in ACD.

Conclusion

This study evaluated the distribution of the biometric components of the eye during the ages of ocular development in an Iranian population. In this age range, the majority of the changes were observed in the AL and LT.
Expression of cytokines on the iris of patients with neovascular glaucoma
Authors: Hou Xian‐ru , Miao Heng , Tao Yong , Li Xiao‐xin , Wong Ian Y.
Published: July 2014

Purpose

To determine the expression levels of cytokines, including growth factors, inflammatory cytokines, and cell migration associated factors on the iris from subjects with neovascular glaucoma (NVG).

Methods

After receiving formal consent from 12 subjects with NVG secondary to proliferative diabetic retinopathy and 12 subjects with primary open angle glaucoma (POAG), trabeculectomy was performed and iris specimens were collected during the surgery. Each subject with NVG received intravitreal injection of bevacizumab 1 week prior to the surgery. The mRNA level of vascular endothelial growth factor, basic fibroblastic growth factor, placental‐induced growth factor, interleukin‐2, interleukin 6, tumour necrosis factor α, intercellular adhesion molecule 1 (ICAM‐1) and integrin subunit αV were determined by real‐time polymerase chain reaction. The mRNA levels were compared between the two groups.

Results

The mRNA levels of all inflammatory cytokines and integrin subunit αV were significantly increased in the NVG group compared with POAG controls. However, the mRNA level of growth factors and ICAM‐1 did not show any difference between the two groups.

Conclusions

Inflammatory process maybe an important cause of iris neovascularization in subjects with NVG in addition to growth factors alone. Further studies should focus on the effect of growth factors in different phases in the pathogenesis of NVG.
A comparison of three scales for measuring pain in children with cognitive impairment
Authors: Massaro Marta , Ronfani Luca , Ferrara Giovanna , Badina Laura , Giorgi Rita , D'Osualdo Flavio , Taddio Andrea , Barbi Egidio
Published: July 2014

Aim

Pain is a neglected problem in children with cognitive impairments, and few studies compare the clinical use of specific pain scales. We compared the Non‐Communicating Children's Pain Checklist Postoperative Version (NCCPC‐PV), the Echelle Douleur Enfant San Salvador (DESS) and the Children's Hospital of Eastern Ontario Pain Scale (CHEOPS). The first two were developed for children with cognitive impairment, and the third is a more general pain scale.

Methods

Two external observers and the child's caregiver assessed 40 children with cognitive impairment for pain levels. We assessed inter‐rater agreement, correlation, dependence on knowledge of the child's behaviour, simplicity and adequacy in pain rating according to the caregiver for all three scales.

Results

The correlation between the NCCPC‐PV and the DESS was strong (Spearman correlation coefficient = 0.76) and better than between each scale and the CHEOPS. Although the DESS showed better inter‐rater agreement, it was more dependent on familiarity with the child and was judged more difficult to use by all observers. The NCCPC‐PV was the easiest use and the most appropriate for rating the child's pain.

Conclusion

The NCCPC‐PV was the easiest to use for pain assessment in cognitively impaired children and should be adopted in clinical settings.
Preterm born 9‐year‐olds have elevated IGF‐1 and low prolactin, but levels vary with behavioural and eating disorders
Authors: Kistner A , Deschmann E , Legnevall L , Vanpee M
Published: July 2014

Aim

This study examined the relationship between hypothalamic‐associated hormones and behavioural and eating disorders in children with low birthweight.

Methods

We included 100 children (mean age 9.7 years): 39 were born preterm at <32 gestational weeks, 28 were full‐term, but small for gestational age, and 33 were full‐term controls. Behavioural histories were analysed, together with fasting blood samples of leptin, insulin, insulin‐like growth factor‐1 (IGF‐I), prolactin, glucagon and cortisol.

Results

Preterm children had lower prolactin (p = 0.01) and higher IGF‐I than controls (p < 0.05, adjusted for confounders), despite being significantly shorter than the predicted target height (p < 0.001). More preterm children displayed behavioural disorders (38% versus 10%, p < 0.001) and eating disorders (26% versus 8%, p < 0.05) than full‐term children. These disorders were associated with lower leptin (p < 0.01), insulin (p < 0.05) and IGF‐I (p < 0.05), but correlations between these hormones and leptin were similar among the groups. Combined behavioural and eating disorders were only observed in preterm children, who were also the shortest in height.

Conclusion

Behavioural and eating disorders among preterm children were associated with low leptin, insulin and IGF‐1. Low prolactin in all preterm children indicated an increased dopaminergic tonus, which might inhibit body weight incrementation. This raises speculation about IGF‐I receptor insensitivity.
Patients' preferences and health utility assessment with SF‐6D and EQ‐5D in patients with chronic hepatitis C treated with sofosbuvir regimens
Authors: Stepanova M. , Nader F. , Cure S. , Bourhis F. , Hunt S. , Younossi Z. M.
Published: July 2014

Background

Health utilities measure patients' preferences for a health state.

Aim

To assess health utilities for sofosbuvir‐containing therapy for chronic hepatitis C.

Methods

The SF‐6D utility scores were derived from the SF‐36 instrument administered at baseline, during and post‐treatment to participants of the previously reported clinical trials of sofosbuvir. EQ‐5D utility scores were also approximated from the SF‐36 using a regression model.

Results

Nine hundred and ninety‐four patients were enrolled. Baseline SF‐6D and EQ‐5D scores were 0.66 ± 0.13 and 0.71 ± 0.22, respectively (the POSITRON trial), 0.71 ± 0.16 and 0.76 ± 0.23 (FISSION), 0.70 ± 0.14 and 0.75 ± 0.22 (FUSION), 0.72 ± 0.15 and 0.79 ± 0.22 (NEUTRINO). In all studies, SF‐6D and EQ‐5D scores were highly correlated with each other. (r = 0.83–0.87, P < 0.0001). After 12 weeks, patients receiving sofosbuvir + ribavirin (POSITRON) had similar utility scores to placebo (P > 0.05). Patients receiving 12 and 16 weeks of sofosbuvir + ribavirin (FUSION) had similar utility scores (P > 0.05). In FISSION, patients receiving sofosbuvir + ribavirin had significantly better utilities compared to patients receiving interferon + ribavirin (P < 0.001). Patients receiving sofosbuvir + ribavirin + interferon (NEUTRINO) had a decrease in utilities during treatment (SF‐6D: from 0.72 to 0.62, EQ‐5D: 0.79 to 0.65; P < 0.0001) similar to that observed in patients receiving pegylated interferon + ribavirin for 24 weeks in FISSION (0.72 to 0.62 and 0.77 to 0.65, respectively, P < 0.0001). After 12 weeks post‐treatment, patients with SVR (FUSION) had improvement in SF‐6D (+0.026 from baseline, P = 0.013) and EQ‐5D (+0.043, P = 0.013). In multivariate analyses, baseline depression, anxiety, fatigue, insomnia and treatment‐related anaemia were the most consistent predictors of utilities.

Conclusions

Patients' health utilities are minimally impacted by sofosbuvir + ribavirin treatment, as compared to interferon‐based, therapy regardless of treatment duration.

Clinical trials' numbers: NCT01542788 (POSITRON), NCT01497366 (FISSION), NCT01604850 (FUSION), NCT01641640 (NEUTRINO).
Rates of inbreeding and genetic diversity in Iranian Holstein Cattle
Authors: Dadar Mohsen , Mahyari Saeid Ansari , Rokouei Mohammad , Edriss Mohammd Ali
Published: July 2014

The accumulation of inbreeding and the loss of genetic diversity is a potential problem in Holstein dairy cattle. The goal of this study was to estimate inbreeding levels and other measures of genetic diversity, using pedigree information from Iranian Holstein cattle. Edited pedigree included 1 048 572 animals. The average number of discrete generation equivalents and pedigree completeness index reached 13.4 and 90%, respectively. The rate of inbreeding was 0.3% per year. Effective number of founders, founder genomes, non‐founders and ancestors of animals born between 2003 and 2011 were 503, 15.6, 16.1 and 25.7, respectively. It was proven that the unequal founder contributions as well as bottlenecks and genetic drift were important reasons for the loss of genetic diversity in the population. The top 10 ancestors with the highest marginal genetic contributions to animals born between 2003 and 2011 and with the highest contributions to inbreeding were 48.20% and 63.94%, respectively. Analyses revealed that the most important cause of genetic diversity loss was genetic drift accumulated over non‐founder generations, which occurred due to small effective population size. Therefore, it seems that managing selection and mating decisions are controlling future co‐ancestry and inbreeding, which would lead to better handling of the effective population size.
Leptospiral lipopolysaccharide stimulates the expression of toll‐like receptor 2 and cytokines in pig fibroblasts
Authors: Guo Yijie , Fukuda Tomokazu , Donai Kenichiro , Kuroda Kengo , Masuda Mizuki , Nakamura Shuichi , Yoneyama Hiroshi , Isogai Emiko
Published: July 2014

Pigs throughout the world are afflicted with leptospirosis, causing serious economic losses and potential hazards to human health. Although it has been known that leptospiral lipopolysaccharide (L‐LPS) is involved in an immunological reaction between an antigen and a host cell, little is known about how the immune system of pigs can respond to L‐LPS. Here, we stimulated pig fibroblasts by L‐LPS and then quantitatively measured gene and protein expression levels of two toll‐like receptors (TLRs), TLR2 and TLR4, by real‐time PCR and Western blotting. As a result, expression of TLR2 was found to be significantly up‐regulated within 24 h after L‐LPS stimulation whereas induction of TLR4 expression was relatively weak. We also revealed that of myeloid differentiation primary response gene 88 (MyD88), interleukin 6 (IL‐6) and IL‐8 gene expressions were markedly up‐regulated by L‐LPS stimulation. These results may suggest that the pig cell can activate TLR2 rather than TLR4 by L‐LPS stimulation, thereby inducing expression of cytokines.
Perceived therapist genuineness predicts therapeutic alliance in cognitive behavioural therapy for psychosis
Authors: Jung Esther , Wiesjahn Martin , Rief Winfried , Lincoln Tania M.
Published: July 2014

Objectives

The quality of therapeutic alliance is a consistent and stable predictor of therapy outcome. Recent studies have shown therapist characteristics to be relevant predictors of the alliance in psychological therapies in general. However, little is known about the specific therapist characteristics that explain differences in therapeutic alliance in cognitive behavioural therapy for psychosis (CBTp). The aim of this study was to identify relevant therapist characteristics that predict early therapeutic alliance in CBTp.

Design and methods

Forty‐eight patients with a DSM‐IV diagnosis of a psychotic disorder participating in a CBTp trial and 11 therapists were included in the analysis. Therapist characteristics as perceived by the patients (empathy, genuineness, positive regard, competence, and convincingness) were assessed at baseline. Alliance was assessed after the fifth therapy session. Data were analyzed using bivariate correlations and multivariate hierarchic regression analysis.

Results

All therapist characteristics were positively associated with patient‐rated alliance. Patient characteristics were not significantly associated with alliance and did not predict alliance in the multivariate analysis. Regression analysis revealed therapist genuineness and competence to significantly predict higher patient‐rated alliance.

Conclusions

Our results suggest that perceived therapist genuineness is the most relevant predictor of patient‐rated therapeutic alliance in CBTp. Future trials using control samples with other mental disorders could clarify whether this finding is specific to CBTp. Therapist training concepts for increasing beneficial therapist qualities are needed.

Practitioner points

The patients' perception of the therapist as empathic, genuine, accepting, competent and convincing is associated with therapeutic alliance in CBTp.

Perceived therapist genuineness and competence are the most relevant predictors of patient‐rated therapeutic alliance.

Training and supervision should focus on increasing basic therapist qualities.

Limitations of this study include homogeneity of therapists, small sample size, and lack of a control group.
Development and validation of a model to predict platelet response to romiplostim in patients with lower‐risk myelodysplastic syndromes
Authors: Sekeres Mikkael A. , Giagounidis Aristoteles , Kantarjian Hagop , Mufti Ghulam J. , Fenaux Pierre , Jia Catherine , Yang Allen S. , Platzbecker Uwe
Published: July 2014

Low endogenous erythropoietin levels and limited red blood cell transfusion history can predict response to erythropoiesis‐stimulating agents in anaemic patients with myelodysplastic syndromes (MDS). The relationship between endogenous thrombopoietin (THPO) levels and platelet response to romiplostim is unknown. Variables including baseline endogenous THPO levels, transfusion needs, and platelet response were analysed in a randomized trial of 250 thrombocytopenic, lower‐risk MDS patients (International Prognostic Scoring System low/intermediate‐1). A predictive scoring system was developed based on log–likelihood ratios and logistic coefficients. Patients with HI–P (haematological improvement – platelets) responses had lower mean baseline THPO levels (P = 0·0497) and were more likely to have <6 platelet units transfused in the past year (P = 0·0027), as did patients with platelet responses ≥50% of weeks on romiplostim (P = 0·001 and P = 0·0037, respectively). A model for predicting response to romiplostim was developed and validated in a separate MDS cohort (N = 72). Patients in low‐, intermediate‐, and high‐response groups had response rates of 17·4%, 29·6%, and 50·7%, respectively, for HI‐P, and 17·4%, 33·8%, and 65·2%, respectively, for ≥50% response. For thrombocytopenic patients with lower‐risk MDS, lower baseline THPO levels (<500 pg/ml) and limited platelet transfusion history predicted a greater likelihood of a subsequent platelet response to romiplostim.
Metabolic characteristics of 13‐cis‐retinoic acid (isotretinoin) and anti‐tumour activity of the 13‐cis‐retinoic acid metabolite 4‐oxo‐13‐cis‐retinoic acid in neuroblastoma
Authors: Sonawane Poonam , Cho Hwang Eui , Tagde Ashujit , Verlekar Dattesh , Yu Alice L , Reynolds C Patrick , Kang Min H
Published: July 2014

Background and Purpose

Isotretinoin (13‐cis‐retinoic acid; 13‐cRA) is a differentiation inducer used to treat minimal residual disease after myeloablative therapy for high‐risk neuroblastoma. However, more than 40% of children develop recurrent disease during or after 13‐cRA treatment. The plasma concentrations of 13‐cRA in earlier studies were considered subtherapeutic while 4‐oxo‐13‐cis‐RA (4‐oxo‐13‐cRA), a metabolite of 13‐cRA considered by some investigators as inactive, were greater than threefold higher than 13‐cRA. We sought to define the metabolic pathways of 13‐cRA and investigated the anti‐tumour activity of its major metabolite, 4‐oxo‐13‐cRA.

Experimental Approach

Effects of 13‐cRA and 4‐oxo‐13‐cRA on human neuroblastoma cell lines were assessed by DIMSCAN and flow cytometry for cell proliferation, MYCN down‐regulation by reverse transcription PCR and immunoblotting, and neurite outgrowth by confocal microscopy. 13‐cRA metabolism was determined using tandem MS in human liver microsomes and in patient samples.

Key Results

Six major metabolites of 13‐cRA were identified in patient samples. Of these, 4‐oxo‐13‐cRA was the most abundant, and 4‐oxo‐13‐cRA glucuronide was also detected at a higher level in patients. CYP3A4 was shown to play a major role in catalysing 13‐cRA to 4‐oxo‐13‐cRA. In human neuroblastoma cell lines, 4‐oxo‐13‐cRA and 13‐cRA were equi‐effective at inducing neurite outgrowth, inhibiting proliferation, decreasing MYCN mRNA and protein, and increasing the expression of retinoic acid receptor‐β mRNA and protein levels.

Conclusions and Implications

We showed that 4‐oxo‐13‐cRA is as active as 13‐cRA against neuroblastoma cell lines. Plasma levels of both 13‐cRA and 4‐oxo‐13‐cRA should be evaluated in pharmacokinetic studies of isotretinoin in neuroblastoma.
Attachment‐Related Biases in Adolescents’ Memory
Authors: Dykas Matthew J. , Woodhouse Susan S. , Jones Jason D. , Cassidy Jude
Published: July 2014

Attachment theorists propose that individuals’ internal working models influence their social information processing. This study explored links between attachment representations and social information processing by examining adolescents’ (n = 189; Mage = 16.5 years) attachment‐related memory biases. Participants completed laboratory tasks assessing memory for (a) emotionally salient childhood events, (b) adjectives describing their parents, and (c) generalized parent‐related characteristics not specific to their own parents. As expected, dismissing attachment (assessed using the Adult Attachment Interview) was linked across tasks to a deactivating strategy in which memory for emotional childhood events and attachment‐relevant stimuli was reduced. In contrast, evidence that preoccupied attachment was linked to a hyperactivating strategy in which memory was heightened emerged only in relation to emotional childhood events.
Sets of Globally Optimal Stream Surfaces for Flow Visualization
Authors: Schulze M. , Esturo J. Martinez , Günther T. , Rössl C. , Seidel H.‐P. , Weinkauf T. , Theisel H.
Published: July 2014

Stream surfaces are a well‐studied and widely used tool for the visualization of 3D flow fields. Usually, stream surface seeding is carried out manually in time‐consuming trial and error procedures. Only recently automatic selection methods were proposed. Local methods support the selection of a set of stream surfaces, but, contrary to global selection methods, they evaluate only the quality of the seeding lines but not the quality of the whole stream surfaces. Global methods, on the other hand, only support the selection of a single optimal stream surface until now. However, for certain flow fields a single stream surface is not sufficient to represent all flow features.

In our work, we overcome this limitation by introducing a global selection technique for a set of stream surfaces. All selected surfaces optimize global stream surface quality measures and are guaranteed to be mutually distant, such that they can convey different flow features. Our approach is an efficient extension of the most recent global selection method for single stream surfaces. We illustrate its effectiveness on a number of analytical and simulated flow fields and analyze the quality of the results in a user study.
Opacity Optimization for Surfaces
Authors: Günther Tobias , Schulze Maik , Esturo Janick Martinez , Rössl Christian , Theisel Holger
Published: July 2014

In flow visualization, integral surfaces rapidly tend to expand, fold and produce vast amounts of occlusion. While silhouette enhancements and local transparency mappings proved useful for semi‐transparent depictions, they still introduce visual clutter when surfaces grow more complex. An effective visualization of the flow requires a balance between the presentation of interesting surface parts and the avoidance of occlusions that hinder the view. In this paper, we extend the concept of opacity optimization to surfaces to obtain a global approach to the occlusion problem. Starting with a partition of the surfaces into patches, we compute per‐patch opacity as minimizer of a bounded‐variable least‐squares problem. For the final rendering, opacity is interpolated on the surfaces. The resulting visualization technique is interactive, frame‐coherent, view‐dependent and driven by domain knowledge.
Parallel Irradiance Caching for Interactive Monte‐Carlo Direct Volume Rendering
Authors: Khlebnikov Rostislav , Voglreiter Philip , Steinberger Markus , Kainz Bernhard , Schmalstieg Dieter
Published: July 2014

We propose a technique to build the irradiance cache for isotropic scattering simultaneously with Monte Carlo progressive direct volume rendering on a single GPU, which allows us to achieve up to four times increased convergence rate for complex scenes with arbitrary sources of light. We use three procedures that run concurrently on a single GPU. The first is the main rendering procedure. The second procedure computes new cache entries, and the third one corrects the errors that may arise after creation of new cache entries. We propose two distinct approaches to allow massive parallelism of cache entry creation. In addition, we show a novel extrapolation approach which outputs high quality irradiance approximations and a suitable prioritization scheme to increase the convergence rate by dedicating more computational power to more complex rendering areas.
Distortion‐Guided Structure‐Driven Interactive Exploration of High‐Dimensional Data
Authors: Liu S. , Wang B. , Bremer P.‐T. , Pascucci V.
Published: July 2014

Dimension reduction techniques are essential for feature selection and feature extraction of complex high‐dimensional data. These techniques, which construct low‐dimensional representations of data, are typically geometrically motivated, computationally efficient and approximately preserve certain structural properties of the data. However, they are often used as black box solutions in data exploration and their results can be difficult to interpret. To assess the quality of these results, quality measures, such as co‐ranking [LV09], have been proposed to quantify structural distortions that occur between high‐dimensional and low‐dimensional data representations. Such measures could be evaluated and visualized point‐wise to further highlight erroneous regions [MLGH13]. In this work, we provide an interactive visualization framework for exploring high‐dimensional data via its two‐dimensional embeddings obtained from dimension reduction, using a rich set of user interactions. We ask the following question: what new insights do we obtain regarding the structure of the data, with interactive manipulations of its embeddings in the visual space? We augment the two‐dimensional embeddings with structural abstractions obtained from hierarchical clusterings, to help users navigate and manipulate subsets of the data. We use point‐wise distortion measures to highlight interesting regions in the domain, and further to guide our selection of the appropriate level of clusterings that are aligned with the regions of interest. Under the static setting, point‐wise distortions indicate the level of structural uncertainty within the embeddings. Under the dynamic setting, on‐the‐fly updates of point‐wise distortions due to data movement and data deletion reflect structural relations among different parts of the data, which may lead to new and valuable insights.
GuideME: Slice‐guided Semiautomatic Multivariate Exploration of Volumes
Authors: Zhou L. , Hansen C.
Published: July 2014

Multivariate volume visualization is important for many applications including petroleum exploration and medicine. State‐of‐the‐art tools allow users to interactively explore volumes with multiple linked parameter‐space views. However, interactions in the parameter space using trial‐and‐error may be unintuitive and time consuming. Furthermore, switching between different views may be distracting. In this paper, we propose GuideME: a novel slice‐guided semiautomatic multivariate volume exploration approach. Specifically, the approach comprises four stages: attribute inspection, guided uncertainty‐aware lasso creation, automated feature extraction and optional spatial fine tuning and visualization. Throughout the exploration process, the user does not need to interact with the parameter views at all and examples of complex real‐world data demonstrate the usefulness, efficiency and ease‐of‐use of our method.
Comparative Exploration of Document Collections: a Visual Analytics Approach
Authors: Oelke D. , Strobelt H. , Rohrdantz C. , Gurevych I. , Deussen O.
Published: July 2014

We present an analysis and visualization method for computing what distinguishes a given document collection from others. We determine topics that discriminate a subset of collections from the remaining ones by applying probabilistic topic modeling and subsequently approximating the two relevant criteria distinctiveness and characteristicness algorithmically through a set of heuristics. Furthermore, we suggest a novel visualization method called DiTop‐View, in which topics are represented by glyphs (topic coins) that are arranged on a 2D plane. Topic coins are designed to encode all information necessary for performing comparative analyses such as the class membership of a topic, its most probable terms and the discriminative relations. We evaluate our topic analysis using statistical measures and a small user experiment and present an expert case study with researchers from political sciences analyzing two real‐world datasets.
A Gaze‐enabled Graph Visualization to Improve Graph Reading Tasks
Authors: Okoe Mershack , Alam Sayeed Safayet , Jianu Radu
Published: July 2014

Performing typical network tasks such as node scanning and path tracing can be difficult in large and dense graphs. To alleviate this problem we use eye‐tracking as an interactive input to detect tasks that users intend to perform and then produce unobtrusive visual changes that support these tasks. First, we introduce a novel fovea based filtering that dims out edges with endpoints far removed from a user's view focus. Second, we highlight edges that are being traced at any given moment or have been the focus of recent attention. Third, we track recently viewed nodes and increase the saliency of their neighborhoods. All visual responses are unobtrusive and easily ignored to avoid unintentional distraction and to account for the imprecise and low‐resolution nature of eye‐tracking. We also introduce a novel gaze‐correction approach that relies on knowledge about the network layout to reduce eye‐tracking error. Finally, we present results from a controlled user study showing that our methods led to a statistically significant accuracy improvement in one of two network tasks and that our gaze‐correction algorithm enables more accurate eye‐tracking interaction.
SimilarityExplorer: A Visual Inter‐Comparison Tool for Multifaceted Climate Data
Authors: Poco J. , Dasgupta A. , Wei Y. , Hargrove W. , Schwalm C. , Cook R. , Bertini E. , Silva C.
Published: July 2014

Inter‐comparison and similarity analysis to gauge consensus among multiple simulation models is a critical visualization problem for understanding climate change patterns. Climate models, specifically, Terrestrial Biosphere Models (TBM) represent time and space variable ecosystem processes, like, simulations of photosynthesis and respiration, using algorithms and driving variables such as climate and land use. While it is widely accepted that interactive visualization can enable scientists to better explore model similarity from different perspectives and different granularity of space and time, currently there is a lack of such visualization tools.

In this paper we present three main contributions. First, we propose a domain characterization for the TBM community by systematically defining the domain‐specific intents for analyzing model similarity and characterizing the different facets of the data. Second, we define a classification scheme for combining visualization tasks and multiple facets of climate model data in one integrated framework, which can be leveraged for translating the tasks into the visualization design. Finally, we present SimilarityExplorer, an exploratory visualization tool that facilitates similarity comparison tasks across both space and time through a set of coordinated multiple views. We present two case studies from three climate scientists, who used our tool for a month for gaining scientific insights into model similarity. Their experience and results validate the effectiveness of our tool.
Lyra: An Interactive Visualization Design Environment
Authors: Satyanarayan Arvind , Heer Jeffrey
Published: July 2014

We present Lyra, an interactive environment for designing customized visualizations without writing code. Using drag‐and‐drop interactions, designers can bind data to the properties of graphical marks to author expressive visualization designs. Marks can be moved, rotated and resized using handles; relatively positioned using connectors; and parameterized by data fields using property drop zones. Lyra also provides a data pipeline interface for iterative, visual specification of data transformations and layout algorithms. Visualizations created with Lyra are represented as specifications in Vega, a declarative visualization grammar that enables sharing and reuse. We evaluate Lyra's expressivity and accessibility through diverse examples and studies with journalists and visualization designers. We find that Lyra enables users to rapidly develop customized visualizations, covering a design space comparable to existing programming‐based tools.
Authoring Narrative Visualizations with Ellipsis
Authors: Satyanarayan Arvind , Heer Jeffrey
Published: July 2014

Data visualization is now a popular medium for journalistic storytelling. However, current visualization tools either lack support for storytelling or require significant technical expertise. Informed by interviews with journalists, we introduce a model of storytelling abstractions that includes state‐based scene structure, dynamic annotations and decoupled coordination of multiple visualization components. We instantiate our model in Ellipsis: a system that combines a domain‐specific language (DSL) for storytelling with a graphical interface for story authoring. User interactions are automatically translated into statements in the Ellipsis DSL. By enabling storytelling without programming, the Ellipsis interface lowers the threshold for authoring narrative visualizations. We evaluate Ellipsis through example applications and user studies with award‐winning journalists. Study participants find Ellipsis to be a valuable prototyping tool that can empower journalists in the creation of interactive narratives.
Visual Analysis of Sets of Heterogeneous Matrices Using Projection‐Based Distance Functions and Semantic Zoom
Authors: Behrisch Michael , Davey James , Fischer Fabian , Thonnard Olivier , Schreck Tobias , Keim Daniel , Kohlhammer Jörn
Published: July 2014

Matrix visualization is an established technique in the analysis of relational data. It is applicable to large, dense networks, where node‐link representations may not be effective. Recently, domains have emerged in which the comparative analysis of sets of matrices of potentially varying size is relevant. For example, to monitor computer network traffic a dynamic set of hosts and their peer‐to‐peer connections on different ports must be analysed. A matrix visualization focused on the display of one matrix at a time cannot cope with this task.

We address the research problem of the visual analysis of sets of matrices. We present a technique for comparing matrices of potentially varying size. Our approach considers the rows and/or columns of a matrix as the basic elements of the analysis. We project these vectors for pairs of matrices into a low‐dimensional space which is used as the reference to compare matrices and identify relationships among them. Bipartite graph matching is applied on the projected elements to compute a measure of distance. A key advantage of this measure is that it can be interpreted and manipulated as a visual distance function, and serves as a comprehensible basis for ranking, clustering and comparison in sets of matrices. We present an interactive system in which users may explore the matrix distances and understand potential differences in a set of matrices. A flexible semantic zoom mechanism enables users to navigate through sets of matrices and identify patterns at different levels of detail. We demonstrate the effectiveness of our approach through a case study and provide a technical evaluation to illustrate its strengths.
Surface morphology analysis of dental implants following insertion into bone using scanning electron microscopy: a pilot study
Authors: Deppe Herbert , Grünberg Christina , Thomas Mücke , Sculean Anton , Benner Klaus‐Ulrich , Bauer Florian J. M.
Published: July 2014

Background

Dental implants have become essential in reconstructive dentistry. Primary healing is determined by the design of their surface. The aim of this pilot study has been to investigate whether the morphology of the sandblasted and acid‐etched (SLA®) surface remains unaffected after the insertion process into human bone.

Materials and Methods

Two edentulous‐atrophied human jaw specimens were used. Six brand new Straumann Standard RN implants with an SLA® surface and having a diameter of 3.3 mm and a length of 12 mm were inserted. Another two implants of the same type, but not inserted into bone, served as a reference. After explantation, the four implants were cleaned in an ultrasonic bath and two were left uncleaned. All eight implants were inspected by SEM for qualitative surface changes.

Results

All four implants showed relevant changes of the topography at the apical thread flanks. The non‐cleaned implants showed an almost complete coverage of the surface by a honeycomb‐like structure, consistent with bone residues. The reference implants showed no changes.

Discussion

The results indicate that, for the osseointegration of dental implants, subtractive modifications of implant surfaces are less important than the reestablishment of the destroyed TiO2 layer. Further studies of other implant surfaces are required to verify the present results.