Novel mutations in the BRCA1 and BRCA2 genes in Iranian women with early-onset breast cancer

BACKGROUND: Breast cancer is the most common female malignancy and a major cause of death in middle-aged women. So far, germline mutations in the BRCA1 and BRCA2 genes in patients with early-onset breast and/or ovarian cancer have not been identified within the Iranian population. METHODS: With the collaboration of two main centres for cancer in Iran, we obtained clinical information, family history and peripheral blood from 83 women under the age of 45 with early-onset breast cancer for scanning of germline mutations in the BRCA1 and BRCA2 genes. We analysed BRCA1 exons 11 and BRCA2 exons 10 and 11 by the protein truncation test, and BRCA1 exons 2, 3, 5, 13 and 20 and BRCA2 exons 9, 17, 18 and 23 with the single-strand conformation polymorphism assay on genomic DNA amplified by polymerase chain reaction. RESULTS: Ten sequence variants were identified: five frameshifts (putative mutations – four novel); three missense changes of unknown significance and two polymorphisms, one seen commonly in both Iranian and British populations. CONCLUSIONS Identification of these novel mutations suggests that any given population should develop a mutation database for its programme of breast cancer screening. The pattern of mutations seen in the BRCA genes seems not to differ from other populations studied. Early-onset breast cancer (less than 45 years) and a limited family history is sufficient to justify mutation screening with a detection rate of over 25% in this group, whereas sporadic early-onset breast cancer (detection rate less than 5%) is unlikely to be cost-effective

An Exploratory Study of Forces and Frictions affecting Large-Scale Model-Driven Development

In this paper, we investigate model-driven engineering, reporting on an exploratory case-study conducted at a large automotive company. The study consisted of interviews with 20 engineers and managers working in different roles. We found that, in the context of a large organization, contextual forces dominate the cognitive issues of using model-driven technology. The four forces we identified that are likely independent of the particular abstractions chosen as the basis of software development are the need for diffing in software product lines, the needs for problem-specific languages and types, the need for live modeling in exploratory activities, and the need for point-to-point traceability between artifacts. We also identified triggers of accidental complexity, which we refer to as points of friction introduced by languages and tools. Examples of the friction points identified are insufficient support for model diffing, point-to-point traceability, and model changes at runtime.Comment: To appear in proceedings of MODELS 2012, LNCS Springe

Do large preterm infants with respiratory distress syndrome benefit from early surfactant?

Large preterm infants are generally not considered good candidates for surfactant treatment until they have been intubated for progressing respiratory distress. This study has been done to detect the effect of electively providing early single-dose surfactant to large preterm babies with mild to moderate respiratory distress syndrome (RDS). A randomized clinical trial was performed on 45 infants with birth weight > 1250 grams, gestational age < 36 weeks, postnatal age 0-12 hours, FiO2 > 40 and no immediate need for intubation. They were randomly divided into two interventional (n = 22) and control (n = 23) groups. Interventional group infants were intubated and received surfactant in the first 12 hours of life with signs of mild to moderate RDS and were extubated as soon as possible. The control group infants were only intubated and received surfactant when clinically or radiographically indicated. The primary outcome was duration of assisted ventilation. Interventional group infants had a median duration of assisted ventilation of 4.45 hours compared to 1.02 hours in the control group in the first 24 hours of life, since only 8 of 23 infants in the control group (34) needed intubation and mechanical ventilation. There were no differences in the two groups for need of subsequent retreatment with surfactant and requirement for supplemental oxygen or mechanical ventilation, hospital stay and adverse outcomes. Results of this study indicate that elective intubation for administration of early single-dose surfactant to large preterm infants is not necessary. © 2008 Tehran University of Medical Sciences. All rights reserved

Model-based tool support for Tactical Data Links: an experience report from the defence domain

The Tactical Data Link (TDL) allows the exchange of information between cooperating platforms as part of an integrated command and control (C2) system. Information exchange is facilitated by adherence to a complex, message-based protocol defined by document-centric standards. In this paper, we report on a recent body of work investigating migration from a document-centric to a model-centric approach within the context of the TDL domain, motivated by a desire to achieve a positive return on investment. The model-centric approach makes use of the Epsilon technology stack and provides a significant improvement to both the level of abstraction and rigour of the network design. It is checkable by a machine and, by virtue of an MDA-like approach to the separation of domains and model transformation between domains, is open to integration with other models to support more complex workflows, such as by providing the results of interoperability analyses in human-readable domain-specific reports conforming to an accepted standard

The effect of volume guarantee ventilation on the incidence of retinopathy of prematurity

Background: Newer technologies in neonatal ventilation such as combining volume guarantee with other modes of ventilation could reduce some complications of artificial ventilation by reducing the duration of ventilation and oxygen needs and fluctuations. Retinopathy of prematurity (ROP) is a multifactorial problem mainly affecting preterm infants with different risk factors. Although gestational age (GA) is the main risk factor for ROP, oxygen saturation and fluctuations, arterial pressure of carbon dioxide, and some other parameters of ventilation such as ventilation duration have great impacts on ROP incidence and severity. Methods: One hundred and twelve infants with birthweight (BW) under 2000 g or GA under 36 weeks that needed artificial ventilation after admission to the neonatal intensive care unit were randomly assigned into two groups. In the first group, neonates underwent synchronized intermittent mandatory ventilation (SIMV), pressure support ventilation (PSV), or SIMV + PSV with volume guarantee (VG); and in the second group, neonates received ventilation without VG mode. All of the survived infants had ophthalmologic examination at the proper age by a retinal subspecialist to find the different stages of ROP. Results: Mean duration of ventilation was reduced using VG mode from 74.08 ± 47.99 to 47.91 ± 30.47 hours (P < 0.05). The oxygen requirement was less in the ones underwent VG modes and the peak fractional inspired oxygen (FiO2) was higher in infants receiving SIMV + PSV without VG compared to that of infants ventilated with VG mode (52.8 ± 18.4 vs. 40.3 ± 13.0, respectively). The difference between highest and lowest FiO2 was more in the group ventilated without VG (�FiO2 = 9.52 in the group I and 18.30 in the group II, P < 0.05). Fluctuation of arterial pressure of carbon dioxide (PaCO2) was less prominent in the VG group as compared to the ones ventilated without VG and the mean difference between maximum and minimum PaCO2 was 7.16 in the group I and 13.36 in the group II (P < 0.05). Only three infants were diagnosed with ROP in the group I (with VG mode) in comparison with eight infants in the group II (odds ratio (OR) = 3.25, 95 confidence interval (CI): 1.13 - 9.36). Severe ROP needing treatment was diagnosed in one infant in the group I vs. four infants in the group II (OR = 3, 95CI: 0.63 - 14.23). Conclusions: ROP incidence in preterm infants could be reduced using VG mode of ventilation, since it is a safer ventilation mode in neonates due to reduction in the mean duration of ventilation, peak FiO2 requirement, and PaCO2 fluctuation. Copyright © 2019, Journal of Comprehensive Pediatrics

Stress-testing centralised model stores

One of the current challenges in model-driven engineering is enabling effective collaborative modelling. Two common approaches are either storing the models in a central repository, or keeping them under a traditional file-based version control system and build a centralized index for model-wide queries. Either way, special attention must be paid to the nature of these repositories and indexes as networked services: they should remain responsive even with an increasing number of concurrent clients. This paper presents an empirical study on the impact of certain key decisions on the scalability of concurrent model queries, using an Eclipse Connected Data Objects model repository and a Hawk model index. The study evaluates the impact of the network protocol, the API design and the internal caching mechanisms and analyzes the reasons for their varying performance

Comparison of risk factors related to intraventricular hemorrhage between preterm infants born after normal and in vitro fertilization conceptions

Objectives We aimed to compare the level of significance of risk factors related Intraventricular hemorrhage (IVH) between preterm infants born after IVF and non-IVF conceptions. Materials & Methods This historical cohort study was done in four Iranian Hospitals in 2013-2014. Overall, 155 preterm newborns were divided into case (IVF) and control (normal conception) groups. Both groups� demographic data were extracted and recorded. The incidence of IVH and its grades were compared between case and control groups. Significant related risk factors were also considered. Results No differences were observed between 2 groups except for gestational age and mode of delivery. The incidence of IVH especially grades II and III were significantly higher in the case group (P=0.003). Results showed no correlations between Gestational age (GA), birth weight and number of gestations with the incidence of IVH in the case group (0.059, 0.85 and 0.49, respectively). On the other hand, among GA, birth weight and number of gestations; multi gestations (P=0.0001) was an effective risk factor for IVH occurrence in the controls. Conclusion The incidence of IVH in the IVF group was significantly higher than in the non-IVF group. IVF as an independent risk factor may cause high-grade IVH; however, in the controls, multi gestational pregnancy (P=0.0001) was an effective risk factor for IVH occurrence. © 2019, Iranian Child Neurology Society. All rights reserved

The short-term effects of intravitreal injection of bevacizumab on the plasma levels of vascular endothelial growth factor, insulin-like growth factor-1, and growth parameters in infants with retinopathy of prematurity

Purpose: To determine the changes in serum levels of free vascular endothelial growth factor (VEGF), insulin-like growth factor-1 (IGF-1), and growth parameters in infants with retinopathy of prematurity (ROP) who received intravitreal injection of the bevacizumab (IVB). Methods: A prospective interventional case series study, including 10 infants with Type 1 ROP was conducted. Using the enzyme-linked immunosorbent assay, serum levels of VEGF and IGF-1 were measured before, 1 month and 2 months after treatment with IVB in both eyes. Growth parameters, including weight, length, and head circumference and their Fenton's z-score, were also measured. Results: Serum VEGF levels were suppressed 1 month after IVB (P = 0.007) and then increased between 1 and 2 months (P = 0.064). Z-scores of all growth parameters except weight z-score decreased in the 1st and 2nd months. Conclusion: Serum VEGF levels showed a transient reduction after IVB which lasted at least 2 months. Growth velocity of premature infants may be affected by anti-VEGF therapy and should be followed with particular attention. © 2020 Journal of Current Ophthalmology | Published by Wolters Kluwer-Medknow

The needs of parents of preterm infants in Iran and a comparison with those in other countries: A systematic review and meta-analysis

Context: Proper accountability to needs of preterm infants� parents requires recognition of these needs and how they change in different conditions. The aim of this study was to assess the needs of parents of preterm infants in Iran, as compared to those in other regions in the world. Evidence Acquisition: A search of Iranian databases (IranMedex, Magiran, and SID) and international resources (PubMed, Scopus, and Google Scholar) was conducted, with no time limitations, to 5 October 2014. Using standard tools, all quantitative studies that considering the parental needs of preterm infants and parental support were extracted. The STROBE checklist was used for the evaluation of the studies. Thirty-one studies were extracted in the qualitative evaluation, of which 17 were included in the metaanalysis. The variance between the studies was analyzed using tau-squared (Tau2) and review manager 5 software. Results: The results obtained using the nurse-parent support tool (NPST) showed that mothers considered that all the fields of support were of great importance. The parental needs in Iran were similar to those of parents in other regions worldwide. However, the mean score for Iranian parents� assessment of the support they received was 2.20 ± 0.06, whereas it was 3.84 ± 0.72 for other countries. The mean scores for parents� assessment of the provision of emotional, informational appraisal, and instrumental support in Iran were 1.73±0.06, 2.1±0.06, 1.54±0.6, and 3.44±0.04, respectively, compared to 3.18±1.34, 4.11±0.5, 4.26±0.18, and 4.51±0.14, respectively, in other countries. Conclusions: Parents always prefer the priorities of their babies to their individual needs. Given the lower scores for the parental assessment of received support in Iran, it is important to focus on these specific items in providing interventions to meet the needs of Iranian parents. © 2016, Growth & Development Research Center

Systematic review of available guidelines on fertility preservation of young patients with breast cancer

Background: Since the survival rate of breast cancer patients has improved, harmful effects of new treatment modalities on fertility of the young breast cancer patients has become a focus of attention. This study aimed to systematically review and critically appraise all available guidelines for fertility preservation in young breast cancer patients. Materials and Methods: Major citation databases were searched for treatment guidelines. Experts from relevant disciplines appraised the available guidelines. The AGREE II Instrument that includes 23 criteria in seven domains (scope and purpose of the guidelines, stakeholder involvement, rigor of development, clarity, applicability, editorial independence, and overall quality) was used to apprise and score the guidelines. Results: The search strategy retrieved 2,606 citations; 72 were considered for full-text screening and seven guidelines were included in the study. There was variability in the scores assigned to different domains among the guidelines. ASCO (2013), with an overall score of 68.0, had the highest score, and St Gallen, with an overall score of 24.7, had the lowest scores among the guidelines. Conclusions: With the promising survival rate among breast cancer patients, more attention should be given to include specific fertility preservation recommendations for young breast cancer patients