Identification of 2 Novel ANTXR2 Mutations in Patients With Hyaline Fibromatosis Syndrome and Proposal of a Modified Grading System

Juvenile hyaline fibromatosis (JHF) and infantile systemic hyalinosis (ISH) are rare, autosomal recessive disorders of the connective tissue caused by mutations in the gene encoding the anthrax toxin receptor 2 protein (ANTXR2) located on chromosome 4q21. Characteristically, these conditions present with overlapping clinical features, such as nodules and/or pearly papules, gingival hyperplasia, flexion contractures of the joints, and osteolytic bone defects. The present report describes a pair of sibs and three other JHF/ISH patients whose diagnoses were based on typical clinical manifestations and confirmed by histopathologic analyses and/or molecular analysis. A comparison of ISH and JHF, additional thoughts about new terminology (hyaline fibromatosis syndrome) and a modified grading system are also included. (C) 2012 Wiley Periodicals, Inc.

Toward Global Standards for Comparator Pharmaceutical Products: Case Studies of Amoxicillin, Metronidazole, and Zidovudine in the Americas

This study compared in vitro dissolution characteristics and other quality measures of different amoxicillin, metronidazole, and zidovudine products purchased in the Americas to a comparator pharmaceutical product (CPP). These three drugs are classified as Biopharmaceutics Classification System Class I drugs with the possibility that dissolution findings might be used to document bioequivalence. All investigated zidovudine products were found to be in vitro equivalent to the CPP. Only 3 of 12 tested amoxicillin products were found to be in vitro equivalent to the CPP. None of the tested metronidazole products were in vitro equivalent to the CPP. These findings suggest but do not confirm bioinequivalence where in vitro comparisons failed, given that an in vivo blood level study might have confirmed bioequivalence. At times, identifying a CPP in one of the selected markets proved difficult. The study demonstrates that products sold across national markets may not be bioequivalent. When coupled with the challenge of identifying a CPP in different countries, the results of this study suggest the value of an international CPP as well as increased use of BCS approaches as means of either documenting bioequivalence or signaling the need for further in vivo studies. Because of increased movement of medicines across national borders, practitioners and patients would benefit from these approaches.

Cochlear implanted children present vocal parameters within normal standards

Objective: to compare acoustic and perceptual parameters regarding the voice of cochlear implanted children, with normal hearing children. Method: this is a cross-sectional, quantitative and qualitative study. Methods: Thirty six cochlear implanted children aged between 3y and 3 m to 5y and 9 m and 25 children with normal hearing, aged between 3y and 11 m and 6y and 6 m, participated in this study. The recordings and the acoustics analysis of the sustained vowel/a/and spontaneous speech were performed using the PRAAT program. The parameters analyzed for the sustained vowel were the mean of the fundamental frequency, jitter, shimmer and harmonic-to-noise ratio (HNR). For the spontaneous speech, the minimum and maximum frequencies and the number of semitones were extracted. The perceptual analysis of the speech material was analyzed using visual-analogical scales of 100 points, composing the aspects related to the overall severity of the vocal deviation, roughness, breathiness, strain, pitch, loudness and resonance deviation, and instability. This last parameter was only analyzed for the sustained vowel. Results: The results demonstrated that the majority of the vocal parameters analyzed in the samples of the implanted children disclosed values similar to those obtained by the group of children with normal hearing. Conclusion: implanted children who participate in a (re) habilitation and follow-up program, can present vocal characteristics similar to those vocal characteristics of children with normal hearing. (C) 2012 Elsevier Ireland Ltd. All rights reserved.

White paper sobre Open Source, Open Access, open Standards e o futuro da catalogação

The discussions on the future of cataloging has received increased attention in the last ten years, mainly due to the impact of rapid development of information and communication technologies in the same period, which has provided access to the Web anytime, anywhere. These discussions revolve around the need for a new bibliographic framework to meet the demand of this new reality in the digital environment, ie how libraries can process, store, deliver, share and integrate their collections (physical, digital or scanned), in current post-PC era? Faced with this question, Open Access, Open Source and Open Standards are three concepts that need to receive greater attention in the field of Library and Information Science, as it is believed to be fundamental elements for the change of paradigm of descriptive representation, currently based conceptually on physical item rather than intellectual work. This paper aims to raise and discuss such issues and instigate information professionals, especially librarians, to think, discuss and propose initiatives for such problems, contributing and sharing ideas and possible solutions, in multidisciplinary teams. At the end is suggested the effective creation of multidisciplinary and inter-institutional study groups on the future of cataloging and its impact on national collections, in order to contribute to the area of descriptive representation in national and international level

Laboratory verification of predicted permanent deformation in asphalt materials following climate change.

In the past a change in temperature of 5°C most often occurred over intervals of thousands of years. According to estimates by the IPCC, in the XXI century is expected an increase in average temperatures in Europe between 1.8 and 4.0°C in the best case caused by emissions of carbon dioxide and other GHG from human activities. As well as on the environment and economic context, global warming will have effects even on road safety. Several studies have already shown how increasing temperature may cause a worsening of some types of road surface damages, especially rutting, a permanent deformation of the road structures consisting in the formation of a longitudinal depression in the wheelpath, mostly due to the rheological behavior of bitumen. This deformation evolves during the hot season because of the heating capacity of the asphalt layers, in fact, the road surface temperature is up to 24°C higher than air. In this thesis, through the use of Wheeltrack test, it was studied the behavior of some types of asphalt concrete mixtures subjected to fatigue testing at different temperatures. The objectives of this study are: to determine the strain variation of different bituminous mixture subjected to fatigue testing at different temperature conditions; to investigate the effect of aggregates, bitumen and mixtures’ characteristics on rutting. Samples were made in the laboratory mostly using an already prepared mixtures, the others preparing the asphalt concrete from the grading curve and bitumen content. The same procedure was performed for each specimen: preparation, compaction using the roller compactor, cooling and heating before the test. The tests were carried out at 40 - 50 - 60°C in order to obtain the evolution of deformation with temperature variation, except some mixtures for which the tests were carried out only at 50°C. In the elaboration of the results were considered testing parameters, component properties and the characteristics of the mixture. Among the testing parameters, temperature was varied for each sample. The mixtures responded to this variation with a different behavior (linear logarithmic and exponential) not directly correlated with the asphalt characteristics; the others parameters as load, passage frequency and test condition were kept constant. According to the results obtained, the main contribution to deformation is due to the type of binder used, it was found that the modified bitumen have a better response than the same mixtures containing traditional bitumen; to the porosity which affects negatively the behavior of the samples and to the homogeneity ceteris paribus. The granulometric composition did not seem to have interfered with the results. Overall has emerged at working temperature, a decisive importance of bitumen composition, than the other characteristics of the mixture, that tends to disappear with heating in favor of increased dependence of rutting resistance from the granulometric composition of the sample considered. In particular it is essential, rather than the mechanical characteristics of the binder, its chemical properties given by the polymeric modification. To confirm some considered results, the maximum bulk density and the air voids content were determined. Tests have been conducted in the laboratories of the Civil Engineering Department at NTNU in Trondheim according to European Standards.

Export Supply Chain Organization and Food Safety and Quality Standards: a case study of the Moroccan Fruit and Vegetable Sector

Agri-food supply chains extend beyond national boundaries, partially facilitated by a policy environment that encourages more liberal international trade. Rising concentration within the downstream sector has driven a shift towards “buyer-driven” global value chains (GVCs) extending internationally with global sourcing and the emergence of multinational key economic players that compete with increase emphasis on product quality attributes. Agri-food systems are thus increasingly governed by a range of inter-related public and private standards, both of which are becoming a priori mandatory, especially in supply chains for high-value and quality-differentiated agri-food products and tend to strongly affect upstream agricultural practices, firms’ internal organization and strategic behaviour and to shape the food chain organization. Notably, increasing attention has been given to the impact of SPS measures on agri-food trade and notably on developing countries’ export performance. Food and agricultural trade is the vital link in the mutual dependency of the global trade system and developing countries. Hence, developing countries derive a substantial portion of their income from food and agricultural trade. In Morocco, fruit and vegetable (especially fresh) are the primary agricultural export. Because of the labor intensity, this sector (especially citrus and tomato) is particularly important in terms of income and employment generation, especially for the female laborers hired in the farms and packing houses. Hence, the emergence of agricultural and agrifood product safety issues and the subsequent tightening of market requirements have challenged mutual gains due to the lack of technical and financial capacities of most developing countries.

Mining tissue microarray data to uncover combinations of biomarker expression patterns that improve intermediate staging and grading of clear cell renal cell cancer

PURPOSE: Tumor stage and nuclear grade are the most important prognostic parameters of clear cell renal cell carcinoma (ccRCC). The progression risk of ccRCC remains difficult to predict particularly for tumors with organ-confined stage and intermediate differentiation grade. Elucidating molecular pathways deregulated in ccRCC may point to novel prognostic parameters that facilitate planning of therapeutic approaches. EXPERIMENTAL DESIGN: Using tissue microarrays, expression patterns of 15 different proteins were evaluated in over 800 ccRCC patients to analyze pathways reported to be physiologically controlled by the tumor suppressors von Hippel-Lindau protein and phosphatase and tensin homologue (PTEN). Tumor staging and grading were improved by performing variable selection using Cox regression and a recursive bootstrap elimination scheme. RESULTS: Patients with pT2 and pT3 tumors that were p27 and CAIX positive had a better outcome than those with all remaining marker combinations. A prolonged survival among patients with intermediate grade (grade 2) correlated with both nuclear p27 and cytoplasmic PTEN expression, as well as with inactive, nonphosphorylated ribosomal protein S6. By applying graphical log-linear modeling for over 700 ccRCC for which the molecular parameters were available, only a weak conditional dependence existed between the expression of p27, PTEN, CAIX, and p-S6, suggesting that the dysregulation of several independent pathways are crucial for tumor progression. CONCLUSIONS: The use of recursive bootstrap elimination, as well as graphical log-linear modeling for comprehensive tissue microarray (TMA) data analysis allows the unraveling of complex molecular contexts and may improve predictive evaluations for patients with advanced renal cancer.

[Analgesia for pediatric patients. Standards and special aspects]

In this paper we describe the assessment and medical treatment of pain in children according to the concept of the Centre of Pediatrics and Adolescent Medicine at the university of Freiburg, Germany. Opiate therapy in children as well as novel data about the association of paracetamol (acetaminophen) and wheezing/asthma bronchiale in children are discussed. Special aspects of analgesia for painful procedures and a nitrous oxide/oxygen mixture which has been recently introduced in Germany are described. The second part of the paper presents results of our prospective study about continuous infusion of fentanyl and midazolam in a fixed combination in 19 critically ill patients with a median age of 46 months, 40% of these patients had an ARDS. The mortality rate was 21%. A median dose of fentanyl of 3.9 microg/kg/h (midazolam 0.26 mg/kg/h) was infused. The fentanyl serum level (median 4.2 ng/ml, range 1.7-17.8 ng/ml) correlated significantly with the administered dose while the midazolam serum levels (median 911 ng/ml, range 234-4 651 ng/ml) correlated neither with the administered dose nor with any of the analysed parameters. Conclusion: A standard protocol for the assessment and treatment of pain should be established in every pediatric hospital. The data about the association of asthma bronchiale and paracetamol cannot be interpreted conclusively, but show that even for well known substances clinical trials may lead to new awareness. The study data about continuous infusion of fentanyl and midazolam show a good correlation of the fentanyl application to serum levels, while midazolam appears to be not the optimal substance for continuous sedation in this setting.

Stimulation of the subthalamic nucleus at an earlier disease stage of Parkinson's disease: Concept and standards of the EARLYSTIM-study

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an established treatment for advanced Parkinson's disease (PD) with disabling motor complications. However, stimulation may be beneficial at an earlier stage of PD when motor fluctuations and dyskinesia are only mild and psychosocial competence is still maintained. The EARLYSTIM trial was conducted in patients with recent onset of levodopa-induced motor complications (<3 years) whose social and occupational functioning remained preserved. This is called 'early' here. The study was a randomized, multicenter, bi-national pivotal trial with a 2 year observation period. Quality of life was the main outcome measure, and a video-based motor score was a blinded secondary outcome of the study. Motor, neuropsychological, psychiatric and psychosocial aspects were captured by established scales and questionnaires. The patient group randomized here is the earliest in the disease course and the youngest recruited in controlled DBS trials so far. The methodological innovation for DBS-studies of this study lies in novel procedures developed and used for monitoring best medical treatment, neurosurgical consistency, best management of stimulation programming, blinded video assessment of motor disability, and prevention of suicidal behaviors.