bluuebunny/crossref_metadata_2025 huggingface dataset:
Recent advances in the treatment of gastrointestinal stromal tumors
Authors: Serrano César , George Suzanne
Published: February 2014

Constitutively activating mutations in the KIT and platelet-derived growth factor receptor α (PDGFRA) RTKs play a crucial role in the biology of gastrointestinal stromal tumors (GISTs), and this disease has served as an effective model for targeting gain-of-function kinase mutations in cancer. Imatinib has entered the clinical arena in the last decade and substantially improved the outcome in these formerly untreatable cancers. However, most advanced GISTs responding to imatinib progress within 2–3 years due to heterogeneous subclones harboring a range of imatinib-resistant secondary KIT mutations. Sunitinib, and more recently, regorafenib, have obtained US Food and Drug Administration approval for the treatment of GISTs after imatinib failure, and thus expanded the treatment options in resistant disease. Within this framework, we present an evaluation of current GIST management, emphasizing the most recent advances in the field together with a discussion on future steps to be taken in refractory disease.
Development of an interprofessional program for cardiovascular prevention in primary care: A participatory research approach
Authors: Lalonde Lyne , Goudreau Johanne , Hudon Éveline , Lussier Marie-Thérèse , Bareil Céline , Duhamel Fabie , Lévesque Lise , Turcotte Alain , Lalonde Gilles ,   Group for TRANSIT to Best Practices in Cardiovascular Disease Prevention in Primary Care
Published: February 2014

Background:

The chronic care model provides a framework for improving the management of chronic diseases. Participatory research could be useful in developing a chronic care model–based program of interventions, but no one has as yet offered a description of precisely how to apply the approach.

Objectives:

An innovative, structured, multi-step participatory process was applied to select and develop (1) chronic care model–based interventions program to improve cardiovascular disease prevention that can be adapted to a particular regional context and (2) a set of indicators to monitor its implementation.

Methods:

Primary care clinicians (n = 16), administrative staff (n = 2), patients and family members (n = 4), decision makers (n = 5), researchers, and a research coordinator (n = 7) took part in the process. Additional primary care actors (n = 26) validated the program.

Results:

The program targets multimorbid patients at high or moderate risk of cardiovascular disease with uncontrolled hypertension, dyslipidemia or diabetes. It comprises interprofessional follow-up coordinated by case-management nurses, in which motivated patients are referred in a timely fashion to appropriate clinical and community resources. The program is supported by clinical tools and includes training in motivational interviewing. A set of 89 process and clinical indicators were defined.

Conclusion:

Through a participatory process, a contextualized interventions program to optimize cardiovascular disease prevention and a set of quality indicators to monitor its implementation were developed. Similar approach might be used to develop other health programs in primary care if program developers are open to building on community strengths and priorities.
Interpreting pulmonary function tests
Authors: Hughes J.M.B.
Published: February 2014

Educational aims

To elucidate the purpose of pulmonary function tests (PFTs).

To describe a pathway (algorithm) for interpreting PFTs, in a diagnostic sense, from measurements of spirometry (forced expiratory volume in 1 s (FEV1)) and forced vital capacity (FVC)), lung volume (total lung capacity (TLC)) and gas transfer and coefficient (transfer factor for the lung for carbon monoxide (TL,CO) and transfer coefficient of the lung for carbon monoxide (KCO)).

PFTs are quantitative (for assessment) as well as qualitative (for diagnosis). The assessment aspect asks “are the results normal?”, “how abnormal?”, “has there been a significant change post–bronchodilator, or since the last measurement?”, “can this patient withstand a pneumonectomy?”,etc.The qualitative aspect looks at a portfolio of results (spirometry, lung volumes, gas transfer and muscle pressures) and makes a physiological diagnosis of 1) airflow obstruction: a) intrathoracic or extrathoracic, b) with or without alveolar damage; or 2) restriction: a) intrapulmonary, b) extrapulmonary — chest wall/pleura or neuromuscular. The physiological diagnosis may or may not support the provisional clinical diagnosis as given on the Pulmonary Function Request Form. Interpretation starts with the distinction between obstructive and restrictive disease, based primarily on TLC and the FEV1, the FVC and the FEV1/FVC ratio. The transfer factor and coefficient (TL,CO andKCO) add useful information regarding alveolar damage, pulmonary microvascular pathology, decreased alveolar expansion (neuromuscular disease) and discrete loss of units. A highKCO should prompt measurement of maximal inspiratory (PI,max) and expiratory (PE,max) pressures. Special tests have been developed recently to detect bronchiolar disease (multi–breath nitrogen washout with slope analysis). Exercise testing focuses more on assessment and prognosis than on diagnosis.
The metabolic consequences of obstructive sleep apnoea in children
Authors: Verhulst S.
Published: February 2014

Educational aims

To define the metabolic syndrome in the paediatric population.

To describe the long-term morbidity of paediatric metabolic syndrome in early adulthood.

To investigate the relationship between OSA and metabolic syndrome during childhood, across age ranges and across different degrees of obesity.

To identify future areas of research.

The metabolic syndrome is defined as the clustering of hyperinsulinaemia, obesity, hypertension and hyperlipidaemia. Its prevalence in the paediatric population in the US is estimated at ∼4%, but this can rise to 20–50% in obese children. The presence of aspects of the metabolic syndrome in childhood is closely linked to factors such as obesity, insulin resistance and early signs of cardiovascular disease in young adulthood.

While in adults there is a strong relationship between sleep-disordered breathing and obesity, and hence with other factors associated with the metabolic syndrome, the evidence in children has not been as clear-cut, although factors such as arterial oxygen saturation (Sa,O2) and apnoea–hypopnoea index (AHI) have been shown to correlate with aspects of the metabolic syndrome.

Intervention studies in sleep-disordered breathing with metabolic syndrome, using adenotonsillectomy, continuous positive airway pressure (CPAP) and weight loss, have produced mixed results, and the optimum treatment remains unclear. Randomised controlled trials of these treatments, along with larger-scale and longitudinal studies to tease out the associations between sleep-disordered breathing, obesity and the metabolic syndrome in a paediatric context, are needed.
Mesothelioma: an update
Authors: Berghmans T.
Published: February 2014

Educational aims

To show that malignant pleural mesothelioma (MPM) is an increasing incident cancer, affecting mainly men at older age and related in most of the cases to asbestos exposure.

To emphasise that histology is the key-point for the diagnosis of mesothelioma and should follow the recommendations of the International Mesothelioma Panel.

To demonstrate that the treatment of MPM is palliative in most instances, chemotherapy with cisplatin plus pemetrexed being the standard of care in good performance status patients with surgery being reserved for highly selected patients.

Malignant pleural mesothelioma (MPM) is a relatively rare neoplasm, the incidence of which is now growing due to the large use of asbestos in the last decades. Although asbestos is banned from most of the industrialised countries, it is still largely used in emerging ones suggesting the persistence of the MPM epidemic. Despite observed advances, MPM is still a difficult disease to be diagnosed and treated. Few active therapeutics are currently available and the role of surgery remains debatable. Outside of clinical trials, there is no definite place for radiotherapy. The combination of cisplatin and pemetrexed is nowadays the standard first-line chemotherapy regimen for good performance status patients. New promising therapeutic approaches are under investigation such as histone deacetylase inhibitors vorinostat and valproate. Guidelines recently developed by a combined European Respiratory Society and European Society of Thoracic Surgery Task Force are now available and can serve the pneumologists and oncologists in their daily practice.
Use of country of birth as an indicator of refugee background in health datasets
Authors: Gibson-Helm Melanie , Boyle Jacqueline , Block Andrew , Teede Helena
Published: February 2014

Background

Routine public health databases contain a wealth of data useful for research among vulnerable or isolated groups, who may be under-represented in traditional medical research. Identifying specific vulnerable populations, such as resettled refugees, can be particularly challenging; often country of birth is the sole indicator of whether an individual has a refugee background. The objective of this article was to review strengths and weaknesses of different methodological approaches to identifying resettled refugees and comparison groups from routine health datasets and to propose the application of additional methodological rigour in future research.

Discussion

Methodological approaches to selecting refugee and comparison groups from existing routine health datasets vary widely and are often explained in insufficient detail. Linked data systems or datasets from specialized refugee health services can accurately select resettled refugee and asylum seeker groups but have limited availability and can be selective. In contrast, country of birth is commonly collected in routine health datasets but a robust method for selecting humanitarian source countries based solely on this information is required. The authors recommend use of national immigration data to objectively identify countries of birth with high proportions of humanitarian entrants, matched by time period to the study dataset. When available, additional migration indicators may help to better understand migration as a health determinant. Methodologically, if multiple countries of birth are combined, the proportion of the sample represented by each country of birth should be included, with sub-analysis of individual countries of birth potentially providing further insights, if population size allows. United Nations-defined world regions provide an objective framework for combining countries of birth when necessary. A comparison group of economic migrants from the same world region may be appropriate if the resettlement country is particularly diverse ethnically or the refugee group differs in many ways to those born in the resettlement country.

Routine health datasets are valuable resources for public health research; however rigorous methods for using country of birth to identify resettled refugees would optimize usefulness of these resources.
Do early onset and pack-years of smoking increase risk of type II diabetes?
Authors: Kim Sun Jung , Jee Sun Ha , Nam Jung Mo , Cho Woo Hyun , Kim Jae-Hyun , Park Eun-Cheol
Published: February 2014

Background

Type II diabetes is not only major public health problem but also heavy fiscal burden to each nation’s health care system around the world. This study aimed to investigate the effect of early onset and pack-years of smoking on type II diabetes risk.

Methods

We used the most recent cross-sectional National Health and Nutrition Examination Survey set of South Korea (2010) and the United States (2009–2010). Participants who were diagnosed with diabetes after age 20 were included (South Korea: n = 7273, 44% male; U.S.: n = 3271, 52% male). Cox proportional models, stratified by sex and country, were used to estimate hazard ratios.

Results

7.1% of South Korean men, 5.5% of South Korean women, 15.5% of U.S. men, and 12.4% of U.S. women had type II diabetes; 40% of South Korean men, 34% of U.S. men, and 21% of U.S. women began smoking before age 20 (57%, 49%, 36% of those who had type II diabetes, respectively). Type II diabetic participants were older and married; have a higher BMI, low income, and less education; lack moderate physical activity, smoked more and earlier compared to those without type II diabetes. Differences in risk factors including life-style behaviors and SES were found in both diabetic and non-diabetic populations. Men who began smoking before age 16 had a higher type II diabetes risk than who never smoked (South Korea: hazard ratio [HR] 2.46, 95% confidence interval [CI] 1.04–5.79; U.S.: HR 1.64, 95% CI 1.01–2.67), as did U.S. men who began smoking between 16 and 20 years (HR 1.58, 95% CI 1.05–2.37). Smoking pack-years were also associated with type II diabetes in U.S. men (HR 1.07, 95% CI 1.01–1.12). In women population, however, associations were not found.

Conclusions

Early onset of smoking increases type II diabetic risk among men in South Korea and the U.S., and type II diabetic risk increases with higher pack-years in U.S. men, however, no associations were found in women population. Underage tobacco policy and education programs are strongly needed in both countries.
The effect of high‐top and low‐top shoes on ankle inversion kinematics and muscle activation in landing on a tilted surface
Authors: Fu Weijie , Fang Ying , Liu Yu , Hou Jianfu
Published: February 2014

Background

There is still uncertainty concerning the beneficial effects of shoe collar height for ankle sprain prevention and very few data are available in the literature regarding the effect of high‐top and low‐top shoes on muscle responses during landing. The purpose of this study was to quantify the effect of high‐top and low‐top shoes on ankle inversion kinematics and pre‐landing EMG activation of ankle evertor muscles during landing on a tilted surface.

Methods

Thirteen physical education students landed on four types of surfaces wearing either high‐top shoes (HS) or low‐top shoes (LS). The four conditions were 15° inversion, 30° inversion, combined 25° inversion + 10° plantar flexion, and combined 25° inversion + 20° plantar flexion. Ankle inversion kinematics and EMG data of the tibialis anterior (TA), peroneus longus (PL), and peroneus brevis (PB) muscles were measured simultaneously. A 2 × 4 (shoe × surface) repeated measures ANOVA was performed to examine the effect of shoe and landing surfaces on ankle inversion and EMG responses.

Results

No significant differences were observed between the various types of shoes in the maximum ankle inversion angle, the ankle inversion range of motion, and the maximum ankle inversion angular velocity after foot contact for all conditions. However, the onset time of TA and PB muscles was significantly later wearing HS compared to LS for the 15° inversion condition. Meanwhile, the mean amplitude of the integrated EMG from the 50 ms prior to contact (aEMGpre) of TA was significantly lower with HS compared to LS for the 15° inversion condition and the combined 25° inversion + 20° plantarflexion condition. Similarly, the aEMGpre when wearing HS compared to LS also showed a 37.2% decrease in PL and a 31.0% decrease in PB for the combined 25° inversion + 20° plantarflexion condition and the 15° inversion condition, respectively.

Conclusion

These findings provide preliminary evidence suggesting that wearing high‐top shoes can, in certain conditions, induce a delayed pre‐activation timing and decreased amplitude of evertor muscle activity, and may therefore have a detrimental effect on establishing and maintaining functional ankle joint stability.
Which components or attributes of biodiversity influence which dimensions of poverty?
Authors: Roe Dilys , Fancourt Max , Sandbrook Chris , Sibanda Mxolisi , Giuliani Alessandra , Gordon-Maclean Andrew
Published: February 2014

Background

There is an explicit assumption in international policy statements that biodiversity can help in efforts to tackle global poverty. This systematic map was stimulated by an interest in better understanding the evidence behind this assumption by disaggregating the terms and asking - as our review question - which components or attributes of biodiversity influence which dimensions of poverty?

Methods

We employed a search strategy that covered peer-reviewed and grey literature. Relevant studies included in the map were those that described an interaction by poor people with biodiversity in non-OECD countries and documented some kind of contribution (positive or negative) to different aspects of their well-being.

Results

A total of 387 studies were included in the final systematic map. Of these 248 met our additional criteria that studies should include a measure of the contribution to poverty alleviation. The studies were widely distributed geographically. Ecological distribution was less well spread, however, with the largest number of studies focussed on forests. We found studies addressing 12 different dimensions of poverty/well-being – although the most commonly studied was income. Similarly we found studies addressing all levels of biodiversity from genes to ecosystems. The largest number of studies was focussed on groups of resources – particularly non-timber forest products. In most cases, abundance was the attribute that made biodiversity important for poverty alleviation/well-being, while diversity was the least frequently noted attribute.

Conclusions

The map highlights a number of apparent gaps in the evidence base. Very few studies documented any causal link between use of biodiversity and an impact on poverty. In the majority of the studies biodiversity was framed in terms of its value as a resource – in the form of specific goods that can be used to generate tangible benefits such as cash, food fuel. Very few studies explored the underpinning role of biodiversity in ecosystem service delivery for poverty alleviation, and fewer investigated the benefits of diversity as a form of insurance or adaptive capacity. This is where we suggest research should be prioritised.
Atherosclerotic plaques occur in absence of intima-media thickening in both systemic sclerosis and systemic lupus erythematosus: a duplexsonography study of carotid and femoral arteries and follow-up for cardiovascular events
Authors: Frerix Marc , Stegbauer Johannes , Kreuter Alexander , Weiner Stefan Markus
Published: February 2014

Introduction

The objective of this cross-sectional and retrospective cohort study was (1) to determine the usefulness of intima-media thickness (IMT) in contrast to plaque assessment, (2) to examine the value of additive femoral artery sonography and (3) to identify potential risk factors for atherosclerosis and incident cardiovascular events in systemic sclerosis (SSc) and systemic lupus erythematosus (SLE) patients.

Methods

In this study, 90 SSc and 100 SLE patients were examined by duplexsonography. IMT was measured in common carotid and common femoral arteries, plaques were assessed in common, internal and external carotid and common, proximal superficial and deep femoral arteries. Different definitions of pathological IMT (pIMT) were compared with the presence of plaque. Results were evaluated in relation to traditional and non-traditional risk factors for baseline atherosclerosis (logistic regression) and their predictive value for cardiovascular events during follow-up (cox regression).

Results

Definite atherosclerosis occurred frequently without signs of subclinical atherosclerosis in both diseases: pIMT >0.9 mm was present in only 17/59 (28.9%) SSc and 13/49 (26.5%) SLE patients with already present atherosclerotic plaques. Using age-adjusted pIMT definitions, this rate was even lower (5.1-10.3% in SSc, 14.3-26.5% in SLE). Plaques were located only at the carotid or only at the femoral arteries in 26 (13.7%) and 24 (12.6%) patients, respectively. Age and nicotine pack-years were independently associated with atherosclerotic plaques in SLE and SSc patients, as well as the cumulative prednisolone dose in SSc subgroup, and ssDNA positive SLE patients had a lower risk for atherosclerotic plaque. During follow-up (available for 129/190 (67.9%) patients, 650 person-years), cardiovascular events occurred more often in patients with coronary heart disease (adjusted-hazards ratio (HR) 10.19, 95% confidence interval (CI) 3.04 to 34.17, P <0.001), male patients (adjusted-HR 8.78, 95% CI 2.73 to 28.19, P <0.001) and in patients with coexistent carotid and femoral plaques (adjusted-HR 5.92, 95% CI 1.55 to 22.67, P = 0.009). Patients with solely carotid or femoral plaque were not at higher risk.

Conclusion

Atherosclerotic plaque lesions can be found frequently in absence of intima-media thickening in both SSc and SLE patients. As well as routine sonography of carotid arteries, the sonography of femoral arteries is recommended to identify additional atherosclerotic lesions and to detect patients at a high risk for cardiovascular events.
Phosphorylation of SRSF1 by SRPK1 regulates alternative splicing of tumor-related Rac1b in colorectal cells
Authors: Gonçalves Vânia , Henriques Andreia , Pereira Joana , Neves Costa Ana , Moyer Mary Pat , Moita Luís Ferreira , Gama-Carvalho Margarida , Matos Paulo , Jordan Peter
Published: February 2014

The premessenger RNA of the majority of human genes can generate various transcripts through alternative splicing, and different tissues or disease states show specific patterns of splicing variants. These patterns depend on the relative concentrations of the splicing factors present in the cell nucleus, either as a consequence of their expression levels or of post-translational modifications, such as protein phosphorylation, which are determined by signal transduction pathways. Here, we analyzed the contribution of protein kinases to the regulation of alternative splicing variant Rac1b that is overexpressed in certain tumor types. In colorectal cells, we found that depletion of AKT2, AKT3, GSK3β, and SRPK1 significantly decreased endogenous Rac1b levels. Although knockdown of AKT2 and AKT3 affected only Rac1b protein levels suggesting a post-splicing effect, the depletion of GSK3β or SRPK1 decreased Rac1b alternative splicing, an effect mediated through changes in splicing factor SRSF1. In particular, the knockdown of SRPK1 or inhibition of its catalytic activity reduced phosphorylation and subsequent translocation of SRSF1 to the nucleus, limiting its availability to promote the inclusion of alternative exon 3b into the Rac1 pre-mRNA. Altogether, the data identify SRSF1 as a prime regulator of Rac1b expression in colorectal cells and provide further mechanistic insight into how the regulation of alternative splicing events by protein kinases can contribute to sustain tumor cell survival.
Auxiliary reproductive technologies: Orthodoxy and law
Authors: Романовский Георгий , Romanovskiy Gyeorgiy
Published: February 2014

The article analyzes the bioethical issues of reproductive technologies in the Russian Federation, states that numerous issues affecting basic human rights are governed by bylaws. In Russia there is no any official advisory body to give a bioethical evaluation injected biomedical technologies. The author considers the content of the Basic Social Concept of the Russian Orthodox Church, as well as the ethical appeal of Pope John Paul II (in particular, “Evangelium Vitae”, March 25, 1995). The article examines bioethical issues arising in the application of surrogacy program.
Problems of Risk-Oriented Approaches for Use in Nuclear Power Industry
Authors: Комаров  , Komarov Yuriy
Published: February 2014

Risk-informed approaches (RIA) analysis in relation to nuclear power industry has been presented. Limitations of safety’s probabilistic analysis (SPA) as a main tool for RIA have been demonstrated. In particular, such SPA problems as statistics uncertainty related to equipment reliability and a problem of accidents modelling uncertainty using thermal-hydraulic codes have been analyzed. Recommendations for accounting of these uncertainties have been given. Ways of RIA further development and results of their application for substantiation and implementation of measures to improve the safety and operation efficiency of nuclear power plants have been presented. Results of the RIA application for such measures as equipment change-over to on-condition maintenance, reduction of amount of testing related to hermetic shell, measurement system accuracy evaluation, some systems’ modernisation feasibility study have been illustrated.
Determination of Radon’s Average Annual Volume Activity on Workplaces
Authors: Андреев  , Andreev A. , Пупатенко  , Pupatenko K.
Published: February 2014

Radiation safety under the influence of radiation’s natural sources, in particular radon, is provided by control related to a value

of average annual equivalent equilibrium volume activity of radon and thoron affiliated products in facilities’ air. Definition of

radon’s average annual equivalent equilibrium volume activity according to single measurements of radon’s volume activity may

lead to essential mistakes in assessment related to radiation situation on workplaces. Radiation control techniques carrying out on

compliance to hygienic requirements on indicators of facilities’ radiation safety are analyzed in this paper. Results of experimental

studies related to radon’s volume activity in rooms with permanent human presence are considered. Recommendations on

determination of actual values of radon’s average annual volume activity and of radon’s volume activity measurements frequency

carrying out are given.
Minding the gap: Approaches to addressing the Middle East within the social science standards
Authors: Bush Amanda
Published: February 2014

In this article the author argues that the current academic standards for social science instruction in California are largely devoid of Middle East concepts and examination. While the standards are a guide for instruction, quality lessons can be inserted into the tenth-grade World History survey course as a start to move towards a more balanced global education. Through the use of primary sources and enrichment activities, students are exposed to major events such as the role of the Middle East in World War I, the creation of the state of Israel and the foundation of current world events. This article does not attempt to cover all major events in Middle East history for the past 500 years, but does offer solutions for teaching more enhanced Middle East content in the secondary classroom over the course of one academic year.
Z notation: A roadmap, �This paper has been withdrawn�
Authors: Singh Monika , Sharma A .K.
Published: February 2014

This paper has been withdrawn.
Cheap Talk and Editorial Control
Authors: Newton Jonathan
Published: February 2014

This paper analyzes simple models of editorial control. Starting from the framework developed by Krishna and Morgan (2001a), we analyze two-sender models of cheap talk where one or more of the senders has the power to veto messages before they reach the receiver. A characterization of the most informative equilibria of such models is given. It is shown that editorial control never aids communication and that for small biases in the senders’ preferences relative to those of the receiver, necessary and sufficient conditions for information transmission to be adversely affected are (i) that the senders have opposed preferences relative to the receiver and (ii) that both senders have powers of editorial control. It is shown that the addition of further senders beyond two weakly decreases information transmission when senders exercising editorial control are anonymous, and weakly increases information transmission when senders exercising editorial control are observed.
Homogeneous (α,β)-metrics of Douglas type
Authors: Liu Huaifu , Deng Shaoqiang
Published: February 2014

In this paper, we consider two related problems concerning homogeneous (α,β)-metrics. In the first part we consider homogeneous (α,β)-spaces of Douglas type. We prove that a homogeneous (α,β)-metric is a Douglas metric if and only if either F is a Berwald metric or F is a Douglas metric of Randers type. In the second part, we prove that if F is a homogeneous (α,β)-metric which is neither a Riemannian metric nor a Minkowski metric,
then F is locally projectively flat if and only if F is a locally projectively flat left invariant Randers metric on the hyperbolic space

𝐇
n

${\mathbf {H}^n}$

as a solvable Lie group. We also give all the explicit forms of the metric F in the second case. This result also provides new examples of locally projectively flat metrics which have not been described before in the literature, presenting some new insight in the study of the Hilbert's fourth problem.
Application of Support Vector Machine Modeling on Phase Distribution in the Riser of an LSCFB Reactor
Authors: Razzak Shaikh A. , Hossain Muhammad I. , Rahman Syed M. , Hossain Mohammad M.
Published: February 2014

Support vector machine (SVM) modeling approach is applied to predict the solids holdups distribution of a liquid–solid circulating fluidized bed (LSCFB) riser. The SVM model is developed/trained using experimental data collected from a pilot-scale LSCFB reactor. Two different size glass bead particles (500 μm (GB-500) and 1,290 μm (GB-1290)) are used as solid phase, and water is used as liquid phase. The trained model successfully predicted the experimental solids holdups of the LSCFB riser under different operating parameters. It is observed that the model predicted cross-sectional average of solids holdups in the axial directions and radial flow structure are well agreement with the experimental values. The goodness of the model prediction is verified by using different statistical performance indicators. For the both sizes of particles, the mean absolute error is found to be less than 5%. The correlation coefficients (0.998 for GB-500 and 0.994 for GB-1290) also show favorable indications of the suitability of SVM approach in predicting the solids holdup of the LSCFB system.
Hypotensive property of Chenopodium ambrosioides in anesthetized normotensive rats
Authors: Assaidi Asmae , Legssyer Abdelkhaleq , Berrichi Abdelbasset , Aziz Mohammed , Mekhfi Hassane , Bnouham Mohammed , Ziyyat Abderrahim
Published: February 2014

Background: The leaves of Chenopodium ambrosioides L. (Chenopodiaceae) are widely used in Moroccan traditional medicine to treat diabetes and hypertension. The goal of the present work is to investigate the hypotensive properties of different extract and fractions of the plant in anesthetized normotensive rats and to elucidate the mechanism underlying this effect.Methods: The hypotensive effect of aqueous extract (AqE) of the leaves of C. ambrosioides L., methanolic (MF), ethyl acetate (AcF), and aqueous (AqF) Soxhlet fractions, administrated intravenously, was evaluated in anesthetized rats. The recorded signals of blood pressure and heart rate were visualized and analyzed by using an acquisition card “National Instrument” and software Labview 6.1.Results: Intravenous administration of AqE of the leaves of C. ambrosioides L. induces a dose-dependent hypotension. A similar effect was obtained with MF, AcF, and AqF. Atropine (1 mg/kg), used to block cholinergic system, significantly reduced the hypotensive response to MF and AcF suggesting the presence of the cholinomimetic–muscarinic components in these fractions. However, the blood pressure lowering effect of MF and AcF in rats pretreated with L-NAME 20 mg/kg was unchanged showing that the release of NO is not implicated in the hypotensive action of this plant.Conclusions: The present study demonstrates that extracts from leaves of C. ambrosioides induce hypotensive effect that may be partially associated with its cardiac effects. These results may partly explain the traditional use of leaves of C. ambrosioides L. for the treatment of disorders such as hypertension.
Advanced cervical dilatation and spontaneous preterm labor: a comparison between twin and singleton gestations
Authors: Dviri Michal , Simchen Michal J. , Kalter Anat , Tovi Shali Mazaki , Moran Orit , Schiff Eyal , Sivan Eyal , Hendler Israel
Published: February 2014

Objective: To determine the admission to delivery interval and the rate of immediate delivery in twin versus singleton gestation complicated by spontaneous preterm labor (SPTL).

Methods: A retrospective cohort study of pregnant women presenting with advanced cervical dilatation of 3–5 cm and frequent uterine contractions at 24–34 weeks of gestation was performed. The rate of progression to delivery within 12 h and 24 h, as well as rates of prolonged latency, were compared between twins and singletons gestations.

Results: Sixty-nine women were included, of which 25 carried twins and 44 singletons. The overall rate of spontaneous delivery within 12 h and 24 h was 47.8% and 59.4%, respectively, and similar between twins and singletons. Nevertheless, prolonged latency of 10 days or more after presentation was more frequent among twins compared with singletons [10/25 (40%) vs. 7/44 (15.9%), respectively; P=0.026]. Moreover, women carrying twins presenting with advanced cervical dilatation had a better chance of completing a full 2-dose antenatal betamethasone course compared with singletons [19/25 (76%) of twins compared with 21/44 (47.7%) of singletons, odds ratio 3.5, 95% confidence interval 1.16–10.34; P=0.022].

Conclusion: Up to 60% of women presenting with advanced cervical dilatation prior to 34 weeks’ gestation give birth within 24 h. Nevertheless, women carrying twins have a better chance of completing a betamethasone course and having prolonged latency compared with singletons.
Penalized differential pathway analysis of integrative oncogenomics studies
Authors: van Wieringen Wessel N. , van de Wiel Mark A.
Published: February 2014

Through integration of genomic data from multiple sources, we may obtain a more accurate and complete picture of the molecular mechanisms underlying tumorigenesis. We discuss the integration of DNA copy number and mRNA gene expression data from an observational integrative genomics study involving cancer patients. The two molecular levels involved are linked through the central dogma of molecular biology. DNA copy number aberrations abound in the cancer cell. Here we investigate how these aberrations affect gene expression levels within a pathway using observational integrative genomics data of cancer patients. In particular, we aim to identify differential edges between regulatory networks of two groups involving these molecular levels. Motivated by the rate equations, the regulatory mechanism between DNA copy number aberrations and gene expression levels within a pathway is modeled by a simultaneous-equations model, for the one- and two-group case. The latter facilitates the identification of differential interactions between the two groups. Model parameters are estimated by penalized least squares using the lasso (
The Divinity and Humanity of Caesar in 1Peter 2,13
Authors: Williams Travis B.
Published: February 2014

Abstract: Auf der Grundlage der – in der neutestamentlichen Wissenschaft unhin terfragten – Voraussetzung, dass der Autor des 1Petr eine ontologische Unterscheidung zwischen Göttlichkeit und Menschlichkeit des Kaisers vornimmt, wird ἀνθρωπίνη κτίσις in 1Petr 2,13 häufig als subtile Kritik am römischen Kaiser und am Kaiserkult gelesen. Die angesprochene Deutung wird allerdings durch die aktuelle Forschung zur römischen Religion – mit ihrer veränderten Sicht der Zuschreibung von Göttlichkeit an den Kaiser und der Einsicht in die Vielfalt des römischen Reichskultes – in signifikanter Weise in Frage gestellt. Der folgende Beitrag sucht dieses Problem zu lösen, indem erörtert wird, ob ἀνθρωπίνη κτίσις eine ontologische Ausrichtung besitzt, und
dargelegt wird, wie sich dies zum Widerstand des Autors gegen den Kaiserkult verhält.
Effect of Instructions on Selected Jump Squat Variables
Authors: Talpey Scott W. , Young Warren B. , Beseler Bradley
Published: February 2014

Talpey, SW, Young, WB, and Beseler, B. Effect of instructions on selected jump squat variables. J Strength Cond Res 30(9): 2508–2513, 2016—The purpose of this study was to compare 2 instructions on the performance of selected variables in a jump squat (JS) exercise. The second purpose was to determine the relationships between JS variables and sprint performance. Eighteen male subjects with resistance training experience performed 2 sets of 4 JS with no extra load with the instructions to concentrate on (a) jumping for maximum height and (b) extending the legs as fast as possible to maximize explosive force. Sprint performance was assessed at 0- to 10-m and 10- to 20-m distances. From the JS jump height, peak power, relative peak power, peak force, peak velocity, and countermovement distance were measured from a force platform and position transducer system. The JS variables under the 2 instructions were compared with paired t-tests, and the relationships between these variables and sprint performance were determined with Pearson’s correlations. The jump height instruction produced greater mean jump height and peak velocity (p < 0.05), but the fast leg extension instruction produced greater (p < 0.05) peak force (3.7%). There was a trivial difference between the instructions for peak power output (p > 0.05). Jump height was the variable that correlated most strongly with 10-m time and 10- to 20-m time under both instructions. The height instruction produced a stronger correlation with 10-m time (r = −0.455), but the fast leg extension JS produced a greater correlation with 10–20 time (r = −0.545). The results indicate that instructions have a meaningful influence on JS variables and therefore need to be taken into consideration when assessing or training athletes.
Proteomic Survey Reveals Altered Energetic Patterns and Metabolic Failure Prior to Retinal Degeneration
Authors: Griciuc Ana , Roux Michel J. , Merl Juliane , Giangrande Angela , Hauck Stefanie M. , Aron Liviu , Ueffing Marius
Published: February 2014

Inherited mutations that lead to misfolding of the visual pigment rhodopsin (Rho) are a prominent cause of photoreceptor neuron (PN) degeneration and blindness. How Rho proteotoxic stress progressively impairs PN viability remains unknown. To identify the pathways that mediate Rho toxicity in PNs, we performed a comprehensive proteomic profiling of retinas fromDrosophilatransgenics expressing Rh1P37H, the equivalent of mammalian RhoP23H, the most common Rho mutation linked to blindness in humans. Profiling of young Rh1P37Hretinas revealed a coordinated upregulation of energy-producing pathways and attenuation of energy-consuming pathways involving target of rapamycin (TOR) signaling, which was reversed in older retinas at the onset of PN degeneration. We probed the relevance of these metabolic changes to PN survival by using a combination of pharmacological and genetic approaches. Chronic suppression of TOR signaling, using the inhibitor rapamycin, strongly mitigated PN degeneration, indicating that TOR signaling activation by chronic Rh1P37Hproteotoxic stress is deleterious for PNs. Genetic inactivation of the endoplasmic reticulum stress-induced JNK/TRAF1 axis as well as the APAF-1/caspase-9 axis, activated by damaged mitochondria, dramatically suppressed Rh1P37H-induced PN degeneration, identifying the mitochondria as novel mediators of Rh1P37Htoxicity. We thus propose that chronic Rh1P37Hproteotoxic stress distorts the energetic profile of PNs leading to metabolic imbalance, mitochondrial failure, and PN degeneration and therapies normalizing metabolic function might be used to alleviate Rh1P37Htoxicity in the retina. Our study offers a glimpse into the intricate higher order interactions that underlie PN dysfunction and provides a useful resource for identifying other molecular networks that mediate Rho toxicity in PNs.
Cholinergic Neurons Excite Cortically Projecting Basal Forebrain GABAergic Neurons
Authors: Yang Chun , McKenna James T. , Zant Janneke C. , Winston Stuart , Basheer Radhika , Brown Ritchie E.
Published: February 2014

The basal forebrain (BF) plays an important role in the control of cortical activation and attention. Understanding the modulation of BF neuronal activity is a prerequisite to treat disorders of cortical activation involving BF dysfunction, such as Alzheimer's disease. Here we reveal the interaction between cholinergic neurons and cortically projecting BF GABAergic neurons using immunohistochemistry and whole-cell recordingsin vitro. InGAD67-GFPknock-in mice, BF cholinergic (choline acetyltransferase-positive) neurons were intermingled with GABAergic (GFP+) neurons. Immunohistochemistry for the vesicular acetylcholine transporter showed that cholinergic fibers apposed putative cortically projecting GABAergic neurons containing parvalbumin (PV). In coronal BF slices fromGAD67-GFPknock-in orPV-tdTomatomice, pharmacological activation of cholinergic receptors with bath application of carbachol increased the firing rate of large (>20 μm diameter) BF GFP+and PV (tdTomato+) neurons, which exhibited the intrinsic membrane properties of cortically projecting neurons. The excitatory effect of carbachol was blocked by antagonists of M1and M3muscarinic receptors in two subpopulations of BF GABAergic neurons [large hyperpolarization-activated cation current (Ih) and smallIh, respectively]. Ion substitution experiments and reversal potential measurements suggested that the carbachol-induced inward current was mediated mainly by sodium-permeable cation channels. Carbachol also increased the frequency of spontaneous excitatory and inhibitory synaptic currents. Furthermore, optogenetic stimulation of cholinergic neurons/fibers caused a mecamylamine- and atropine-sensitive inward current in putative GABAergic neurons. Thus, cortically projecting, BF GABAergic/PV neurons are excited by neighboring BF and/or brainstem cholinergic neurons. Loss of cholinergic neurons in Alzheimer's disease may impair cortical activation, in part, through disfacilitation of BF cortically projecting GABAergic/PV neurons.
Premotor Spinal Network with Balanced Excitation and Inhibition during Motor Patterns Has High Resilience to Structural Division
Authors: Petersen Peter C. , Vestergaard Mikkel , Jensen Kristian H. R. , Berg Rune W.
Published: February 2014

Direct measurements of synaptic inhibition (I) and excitation (E) to spinal motoneurons can provide an important insight into the organization of premotor networks. Such measurements of flexor motoneurons participating in motor patterns in turtles have recently demonstrated strong concurrent E and I as well as stochastic membrane potentials and irregular spiking in the adult turtle spinal cord. These findings represent a departure from the widespread acceptance of feedforward reciprocal rate models for spinal motor function. The apparent discrepancy has been reviewed as an experimental artifact caused by the distortion of local networks in the transected turtle spinal cord. We tested this assumption in the current study by performing experiments to assess the integrity of motor functions in the intact spinal cord and the cord transected at segments D9/D10. Excitatory and inhibitory synaptic inputs to motoneurons were estimated during rhythmic motor activity and demonstrated primarily intense inputs that consisted of qualitatively similar mixed E/I before and after the transection. To understand this high functional resilience, we used mathematical modeling of networks with recurrent connectivity that could potentially explain the balanced E/I. Both experimental and modeling data support the concept of a locally balanced premotor network consisting of recurrent E/I connectivity, in addition to the well known reciprocal network activity. The multifaceted synaptic connections provide spinal networks with a remarkable ability to remain functional after structural divisions.
Dual Effect of CTCF Loss on Neuroprogenitor Differentiation and Survival
Authors: Watson L. Ashley , Wang Xu , Elbert Adrienne , Kernohan Kristin D. , Galjart Niels , Bérubé Nathalie G.
Published: February 2014

An increasing number of proteins involved in genome organization have been implicated in neurodevelopmental disorders, highlighting the importance of chromatin architecture in the developing CNS. The CCCTC-binding factor (CTCF) is a zinc finger DNA binding protein involved in higher-order chromatin organization, and mutations in the humanCTCFgene cause an intellectual disability syndrome associated with microcephaly. However, information on CTCF functionin vivoin the developing brain is lacking. To address this gap, we conditionally inactivated theCtcfgene at early stages of mouse brain development. Cre-mediatedCtcfdeletion in the telencephalon and anterior retina at embryonic day 8.5 triggered upregulation of the p53 effector PUMA (p53 upregulated modulator of apoptosis), resulting in massive apoptosis and profound ablation of telencephalic structures. Inactivation ofCtcfseveral days later at E11 also resulted in PUMA upregulation and increased apoptotic cell death, and theCtcf-null forebrain was hypocellular and disorganized at birth. Although deletion of bothCtcfandPumain the embryonic brain efficiently rescuedCtcf-null progenitor cell apoptosis, it failed to improve neonatal hypocellularity due to decreased proliferative capacity of rescued apical and outer radial glia progenitor cells. This was exacerbated by an independent effect of CTCF loss that resulted in depletion of the progenitor pool due to premature neurogenesis earlier in development. Our findings demonstrate that CTCF activities are required for two distinct events in early cortex formation: first, to correctly regulate the balance between neuroprogenitor cell proliferation and differentiation, and second, for the survival of neuroprogenitor cells, providing new clues regarding the contributions of CTCF in microcephaly/intellectual disability syndrome pathologies.
Bre1a, a Histone H2B Ubiquitin Ligase, Regulates the Cell Cycle and Differentiation of Neural Precursor Cells
Authors: Ishino Yugo , Hayashi Yoshitaka , Naruse Masae , Tomita Koichi , Sanbo Makoto , Fuchigami Takahiro , Fujiki Ryoji , Hirose Kenzo , Toyooka Yayoi , Fujimori Toshihiko , Ikenaka Kazuhiro , Hitoshi Seiji
Published: February 2014

Cell cycle regulation is crucial for the maintenance of stem cell populations in adult mammalian tissues. During development, the cell cycle length in neural stem cells increases, which could be associated with their capabilities for self-renewal. However, the molecular mechanisms that regulate differentiation and cell cycle progression in embryonic neural stem cells remain largely unknown. Here, we investigated the function of Bre1a, a histone H2B ubiquitylation factor, which is expressed in most but not all of neural precursor cells (NPCs) in the developing mouse brain. We found that the knockdown of Bre1a in NPCs lengthened their cell cycle through the upregulation ofp57kip2and the downregulation ofCdk2. In addition, the knockdown ofBre1aincreased the expression ofHes5, an effector gene of Notch signaling, through the action ofFezf1andFezf2genes and suppressed the differentiation of NPCs. Our data suggest thatBre1acould be a bifunctional gene that regulates both the differentiation status and cell cycle length of NPCs. We propose a novel model that the Bre1a-negative cells in the ventricular zone of early embryonic brains remain undifferentiated and are selected as self-renewing neural stem cells, which increase their cell cycle time during development.