bluuebunny/crossref_metadata_2025 huggingface dataset:
Separability of wave solutions in nonlinear brass instrument modelling
Authors: Harrison-Harsley R. L. , Bilbao S.
Published: June 2018

Travelling wave representations of wave propagation are commonly employed in brass instrument modeling and have been extended to the nonlinear regimes. For the case of a real brass instrument, the assumptions that lead to the travelling wave solutions no longer strictly hold. The validity of these assumptions is investigated here with regard to two typical parts of brass instrument geometry. The first example shows that there is a small interaction between forwards and backwards travelling waves in a cylindrical tube. The second example highlights nonlinear backscattering of a traveling wave caused by variations in the tube cross-sectional area.
Transcriptional Regulatory Circuits: Predicting Numbers from Alphabets
Authors: Kim Harold D. , Shay Tal , O’Shea Erin K. , Regev Aviv
Published: June 2018

Transcriptional regulatory circuits govern how cis and trans factors transform signals into messenger RNA (mRNA) expression levels. With advances in quantitative and high-throughput technologies that allow measurement of gene expression state in different conditions, data that can be used to build and test models of transcriptional regulation is being generated at a rapid pace. Here, we review experimental and computational methods used to derive detailed quantitative circuit models on a small scale and cruder, genome-wide models on a large scale. We discuss the potential of combining small- and large-scale approaches to understand the working and wiring of transcriptional regulatory circuits.
Hard feelings
The Neuroscience of Emotion: A New Synthesis
Ralph Adolphs and David J. Anderson
Princeton University Press, 2018. 372 pp.
Authors: Bauer Elizabeth
Published: June 2018

A pair of neuroscientists finds that investigating emotions is easier done than said
Rock-based 3-D reservoir characterization of a Silurian (Niagaran) reef—Ray gas storage field, Macomb County, Michigan
Authors: Wold Jessica L. , Grammer G. Michael
Published: June 2018

Silurian-age (Niagaran) reefs in the Michigan Basin have long been interpreted as relatively homogeneous units, despite production histories that strongly suggest the reefs are heterogeneous in both lateral and vertical dimensions. In an attempt to better illustrate reservoir heterogeneity in these reefs, a three-dimensional (3-D) sequence stratigraphic model was produced for the Ray Reef field. The resulting 3-D Petrel model incorporates 28 wells in the field using a combination of gamma-ray and neutron logs, porosity and permeability data from whole-core analysis, and facies descriptions from eight cores evenly distributed within the reef complex. Comparison of porosity and permeability values within the diverse depositional facies clearly shows trends related to the individual facies and positioning within the sequence hierarchy. Incorporation of the sequence stratigraphic framework into the 3-D model illustrates the episodic nature of reef growth as exhibited by the stacked nature of reef and capping grainstones, often separated by well-developed exposure horizons. The model also suggests a distinct difference between windward and leeward margins in both the geometry of the reef complex and the distribution of reservoir-prone facies. Windward margins are steeper due to higher rates of aggradational growth, and they typically contain higher percentages of reservoir-quality rock in both the reef core and forereef facies. Utilization of the sequence stratigraphic approach illustrates that the vertical reservoir heterogeneity often predicted from production in these reefs may be controlled in large part by the combination of vertical stacking patterns of facies within third- and fourth-order sequences.
Fifteen-minute consultation: Childhood burns: inflicted, neglect or accidental
Authors: Mullen Stephen , Begley Roisin , Roberts Zoe , Kemp Alison Mary
Published: June 2018

Burns are a relatively common injury in children accounting for over 50 000 emergency department attendances each year. An estimated 1 in 10 of these are due to maltreatment. These may present in the form of physical abuse or neglect with a reported ratio of 1:9. A burn associated with maltreatment may be a marker for future abuse or neglect and it is paramount that concerns are identified and addressed at the initial visit. Paediatricians need to be confident to identify safeguarding concerns specific to childhood burns and investigate accordingly. In this review, key variables that may aid in differentiating maltreatment from accidental burns are discussed in a case-based format, utilising up-to-date evidence to support the recommendations. Despite a proportion of burns resulting from physical abuse, the rate of child protection investigations in these patients are significantly lower than for children who present with other forms of physical injuries despite a similar proportion of positive findings. Our objective is to review the available evidence to support the safe assessment and management of children presenting with scalds or contact burns.
Cost-effective analysis of teaching pelvic examination skills using Gynaecology Teaching Associates (GTAs) compared with manikin models (The CEAT Study)
Authors: Janjua Aisha , Roberts Tracy , Okeahialam Nicola , Clark T Justin
Published: June 2018

Objective

To determine the cost-effectiveness of Gynaecology Teaching Associate (GTA) teaching versus conventional pelvic model (manikin) teaching of pelvic examination skills for final year medical students within a UK undergraduate obstetrics and gynaecology (O&G) curriculum.

Methods

An economic evaluation was carried out alongside a randomised controlled trial involving 492 final year medical students. 240 students received manikin teaching, and 241 GTA-led teaching. 418 (85%) students completed their assessment. Proficiency in gynaecological pelvic examination on GTAs was estimated by a senior clinical examiner, blinded to the method of teaching, using a standardised assessment tool. University of Birmingham Medical School thresholds were applied to determine proficiency levels; competence (pass) 50%, merit 60% and distinction 70%. Costs incurred in the delivery of both the educational pathways (control and intervention) were combined. All costs are reported in 2013–2014 prices and earlier costs adjusted using inflation indices.

Outcome measures

Cost per student competent in pelvic examination at completion of a 5-week clinical O&G placement.

Results

GTA teaching was more effective compared with conventional teaching with 12 more students considered competent at pass level and 28 more students competent at merit and distinction levels, respectively. However, the average cost of GTA teaching was £45.06 per student compared with £7.40 per student for conventional teaching, with an increased cost of £37.66 per student. The incremental cost-effectiveness ratio demonstrated that it cost an additional £640.20 per competent student and £274.37 per student competent at merit level and £274.37 at distinction level compared with conventional manikin-based teaching.

Conclusions

GTA teaching of female pelvic examination at the start of undergraduate medical student O&G clinical placements is shown to cost more and be more effective. GTA teaching is likely to be considered cost-effective in the context of other tests, and over the lifespan of a competent doctor’s career.

Trial registration number

NCT01944592.
Association between acculturation and body weight status among migrant children in Guangzhou, China: a cross-sectional study
Authors: Huang Xiaoling , Chen Wen , Lin Yanwei , Zhang Qi , Ling Li
Published: June 2018

Objective

To assess the association between acculturation and body weight status among internal migrant children in China.

Design, setting and participants

A cross-sectional study was conducted among 1154 pairs of migrant children aged 11–17 years and their primary caregivers in Guangzhou, China, from April to May 2016.

Measures

Migrant children’s body weight status was measured by body mass index. Acculturation was measured by a questionnaire, developed and validated by the research team. The questionnaire had three dimensions with five factors, namely language, social interaction, custom, dressing and diet. Social anxiety was measured by Social Anxiety Scale for Children. Food intake was measured by the food frequency table that was developed from a previous study. Logistic regression was performed to examine the association between acculturation and overweight/obesity while controlling for migrant children’s and their caregivers’ demographic characteristics, children’s social anxiety and food intake.

Results

Seventy-six out of 1154 (6.6%) migrant children were overweight, and 36 (3.1%) were obese. The overall prevalence of overweight/obesity was 12.5% in boys, and 6.1% in girls (p<0.001), respectively. The mean scores of acculturation were 41.8 (SD=14.6). Migrant children had the highest level of acculturation in the aspect of dressing (mean=61.7, SD=16.6), followed by language (mean=47.9, SD=22.3), diet (mean=45.0, SD=18.5), social interaction (mean=42.4, SD=21.3) and custom (mean=27.6, SD=19.2). After controlling for confounding factors, the levels of acculturation was negatively associated with overweight/obesity (adjusted OR (aOR)=0.98, 95% CI 0.97 to 1.00, p=0.030). Furthermore, migrant children who had urban-to-urban migrant caregivers were more likely to be overweight/obese (aOR=2.07, 95% CI 1.16 to 3.69, p=0.014) than their counterparts living with rural-to-urban migrant caregivers.

Conclusions

The low levels of acculturation was associated with overweight/obesity among migrant children in Guangzhou, China. Promoting healthy acculturation and social campaign on healthy body weight may help prevent childhood overweight/obesity. Young migrant children, boys and children living with urban-to-urban migrant caregivers should be the target subgroups.
Risk of postneonatal mortality, hospitalisation and suboptimal breast feeding practices in low birthweight infants from rural Haryana, India: findings from a secondary data analysis
Authors: Upadhyay Ravi Prakash , Martines Jose Carlos , Taneja Sunita , Mazumder Sarmila , Bahl Rajiv , Bhandari Nita , Dalpath Suresh , Bhan Maharaj Kishan
Published: June 2018

Objectives

Low birth weight (LBW) is a risk factor for neonatal mortality and morbidity. It is important to examine whether this risk persists beyond neonatal period. The current secondary data analysis aimed to examine association of birth weight with mortality, hospitalisation and breast feeding practices during infancy.

Design

Data from a large randomised controlled trial of neonatal vitamin A supplementation (Neovita) trial were used. Log binomial model was applied to assess association between birth weight and mortality, hospitalisation and breast feeding practices.

Setting

Rural Haryana, North India.

Participants

Newborns recruited in the primary intervention trial that aimed to evaluate the effect of single-dose oral vitamin A supplementation on mortality in the first 6 months of life.

Results

We recruited a total of 44 984 infants, of which 10 658 (23.7%) were born LBW, that is, birth weight less than 2500 g. In the neonatal period, LBW babies had four times higher risk of mortality (relative risk (RR) 3.92; 95% CI 3.33 to 4.66) compared with normal birthweight babies. In the postneonatal period, the risk was two times higher (RR 1.92; 95% CI 1.71 to 2.15); even higher in those with birth weight <2000 g (RR 3.38; 95% CI 2.71 to 4.12). The risk of hospitalisation in the neonatal period and postneonatal period was (RR 1.86; 95% CI 1.64 to 2.11) and (RR 1.13; 95% CI 1.05 to 1.21), respectively. LBWs were at increased risk of breast feeding initiation 24 hours after birth (RR 1.64; 95% CI 1.45 to 1.81), no breast feeding at 6 months (RR 1.34; 95% CI 1.23 to 1.46) and at 12 months of age (RR 1.24; 95% CI 1.18 to 1.30).

Conclusions

LBW babies, especially those with birth weight of <2000 g, were at increased risk of mortality, hospitalisation and suboptimal breast feeding practices during entire infancy and therefore require additional care beyond the first 28 days of life.

Trial registration number

NCT01138449.
A Remark on Rainbow 6-Cycles in Hypercubes
Authors: Hao Chen , Yang Weihua
Published: June 2018

We call an edge-coloring of a graph [Formula: see text] a rainbow coloring if the edges of [Formula: see text] are colored with distinct colors. For every even positive integer [Formula: see text], let [Formula: see text] denote the minimum number of colors required to color the edges of the [Formula: see text]-dimensional cube [Formula: see text], so that every copy of [Formula: see text] is rainbow. Faudree et al. [6] proved that [Formula: see text] for [Formula: see text] or [Formula: see text]. Mubayi et al. [8] showed that [Formula: see text]. In this note, we show that [Formula: see text]. Moreover, we obtain the number of 6-cycles of [Formula: see text].
The effect of carbon element on optical properties of n-doped Ge on silicon substrate
Authors: Luong Thi Kim Phuong
Published: June 2018

Highly n-doped Ge on Si has been demonstrated to be a promising candidate for the compatible light source with silicon technology. In the in-situ n-doping process of Ge epilayers, the active concentration is limited below [Formula: see text] due to low solubility of dopant element in Ge matrix. Many dopant atoms are incorporated in the interstitial sites instead of substitution sites. We present a new approach to increase the electron concentration by adding carbon elements into P-doped Ge epilayers. A gain of PL intensity has been obtained with a factor of 2. The crystalline quality of the Ge film is also investigated owing to using a reflection high-energy electron diffraction (RHEED) apparatus and high-resolution transmission electron microscopy (HR-TEM). Phosphorus dopant is incorporated into Ge epilayers from specific GaP solid source.
Block Thickness Measurement of Using the Structured Light Vision
Authors: Lian Fenghui , Tan Qingchang , Liu Siyuan
Published: June 2018

A method for measuring block thicknesses is proposed by the machine vision measurement. Equations of the measuring base plane and the light plane are formed by calibration. Then, the equation of the light strip image, that is, the image of the intersection between the base plane and light one, is established by the projection relation. Equation of the image of the light strip on the measured plane can be determined by the fitting. Since the light strip on the measuring base plane is parallel to one on the measured plane, the thickness of the measuring block is measured by using the two equations. The experiment evaluates the measurement accuracy of the measurement method and analyzes the influence of some factors on the measurement results.
Bifurcation of Mixed Mode Reaction–Diffusion Patterns in Spherical Caps
Authors: Charette Laurent , Nagata Wayne
Published: June 2018

We study pattern formation in a chemical reaction–diffusion system of partial differential equations in spherical cap domains. For certain critical values of parameters corresponding to cap flatness, cap radius, and chemical precursor concentrations, the unpatterned solution is unstable to two different linear normal modes. We use center manifold and normal form reductions to analyze the existence and stability of pure and mixed modes of nonlinear patterned solutions of the reaction–diffusion system, for parameters with two cases of critical values. In one case, the system reduces to a well known example of mode interaction. In the other case, the mode interaction is new, due to very small quadratic terms in the normal form.
Analysis of Oscillatory Patterns of a Discrete-Time Rosenzweig–MacArthur Model
Authors: Wu Xiaoqin P. , Wang Liancheng
Published: June 2018

This article investigates the oscillatory patterns of the following discrete-time Rosenzweig–MacArthur model [Formula: see text] The system describes the evolution and interaction of the populations of two associated species (prey and predator) from generation to generation. We show that this system can exhibit co-dimension-1 bifurcations (flip and Neimark–Sacker bifurcations) as [Formula: see text] crosses some critical values and codimension-2 bifurcations (1:2, 1:3, and 1:4 resonances) for certain critical values of [Formula: see text] at the positive equilibrium point. The normal form theory and the center manifold theorem are used to obtain the normal forms. For codimension-2 bifurcations, the bifurcation diagrams are established by using these normal forms along the orbits of differential equations. Numerical simulations are presented to confirm the theoretical results.
Jℱ-Class Weighted Backward Shifts
Authors: He Shengnan , Huang Yu , Yin Zongbin
Published: June 2018

In this article [Formula: see text]-class operators are introduced and some basic properties of [Formula: see text]-vectors are given. The [Formula: see text]-class operators include the [Formula: see text]-class operators and [Formula: see text]-class operators introduced by Costakis and Manoussos in 2008. This class also includes the [Formula: see text]-class and [Formula: see text]-class operators defined by Zhang [2012]. Furthermore, for the unilateral weighted backward shifts on a Fréchet sequence space, we establish a criterion under which the shift operators belong to the [Formula: see text]-class. From the criterion it is easy to obtain the existing criteria of hypercyclic backward shifts and of the topological mixing backward shifts. The obtained criterion also reveals the characteristic of [Formula: see text]-class shift operators by the recurrence property. Meanwhile, we obtain infinite topological entropy when the shifts have stronger recurrence property, which generalizes the related results by Brian et al. in 2017.
Pattern Dynamics in a Spatial Predator–Prey Model with Nonmonotonic Response Function
Authors: Li Xiaoling , Hu Guangping , Feng Zhaosheng
Published: June 2018

In this paper, we study a diffusive predator–prey system with the nonmonotonic response function. The conditions on Hopf bifurcation and Turing instability of spatial systems are obtained. Near the Turing bifurcation point we apply the weakly nonlinear analysis to derive the amplitude equations of stationary pattern, to investigate the selection of spatiotemporal pattern. It shows that different types of patterns will occur in the model under various conditions. Numerical simulations agree well with our theoretical analysis when control parameters are in the Turing space. This study may provide some deep insights into the formation and selection of patterns for diffusive predator–prey systems.
A Forgetting Memristive Spiking Neural Network for Pavlov Experiment
Authors: Chen Ling , Li Chuandong , Chen Yiran
Published: June 2018

In this paper, we designed a memristive spiking neural network (MSNN) to perform a fully functional Pavlov experiment. A memristor with forgetting effect is adopted to implement synapses while Izhikevich neurons are used for generating tonic spiking and tonic bursting signals. An asymmetric linear spiking time dependent plasticity (STDP) is naturally formed by taking into account the activation time difference between pre-synaptic neurons. Our design realizes associative, correcting, and forgetting processes without learning rule control modules. Moreover, an association will be enhanced if the activation time of two neurons is close enough, otherwise, all conditioned reflex associations will be weakened.
Maintenance Practices in Poor Uptime of Operating Equipment Toward Dynamic of Business Issues
Authors: Kareem Jamal Ahmed Hama , Saeed Kadhim Faraj Arif , Faraj Omar Mustafa Muhammad
Published: June 2018

Nothing lasts forever and all the equipment in a plant has associated with it some predefined life expectancy or operational life. Maintenance practices are the works of keeping the equipment of the plant in good condition for operation. However, the equipment that does not receive adequate maintenance tends to deviate from optimal performance. This can lead to non-control of degraded processes and product volatility, affecting in turn the dynamics of many business issues in industrial organizations. Given the importance of the foregoing, the current study tried to investigate the role of the set of maintenance practices in the poor uptime of operating equipment toward the dynamics of business issues in industrial companies. To achieve this end, the study was performed by conducting a questionnaire survey within the firms of the Kurdistan region of Iraq that have at least 100 employees. The results of the study revealed that improper maintenance practices play a great role in the poor uptime of operating equipment toward the negative dynamic of many business issues such as low customer satisfaction due to production schedules absent from customer shipment commitments, increased safety risks quantitatively and the high cost health losses, especially with the occurrence of major malfunction in operating equipment.
ALL FOR THE MONEY? THE LIMITS OF MONETARY REWARDS IN INNOVATION CONTESTS WITH USERS
Authors: IHL CHRISTOPH , VOSSEN ALEXANDER , PILLER FRANK
Published: June 2018

Practitioners increasingly use innovation contests to harness the knowledge of external crowds for internal innovation purposes in exchange for prize money. While some innovation contests have the objective to attract professional experts from distant fields to obtain technical solutions, other innovation contests primarily target customers or users in order to generate new product and service ideas. Hence, external crowds differ substantially across, but also within, innovation contests in terms of personal needs in the innovation domain. Drawing upon the private-collective model of innovation, we argue that participants’ “userness” in terms of personal needs gives rise to non-monetary reward expectations and collectively oriented participation as opposed to the private pursuit of monetary rewards emphasised in innovation contests. Hence, the effectiveness of monetary rewards in innovation contests is bound to certain participants and behaviours. In particular, participants weigh non-monetary rewards more strongly against monetary rewards (1) when their personal need in the innovation domain is high, and (2) when choosing to engage collectively in evaluating and commenting on other contributions as opposed to submitting own contributions. We find support for these hypotheses in an empirical study where user participation in a real innovation contest is regressed on survey-based measures of expected rewards that users perceive prior to the contest. The observed effect sizes of the proposed shifts from monetary to non-monetary rewards are so pronounced that for a given level of personal need and a given type of participation behaviour only either reward type is effective and a compensational relation between both types of rewards does not exist. Monetary rewards are even detrimental and lower user participation if the two proposed boundary conditions are taken together.
Impact of acute exposure to cigarette smoke on airway gene expression
Authors: Billatos E. , Faiz A. , Gesthalter Y. , LeClerc A. , Alekseyev Y. O. , Xiao X. , Liu G. , ten Hacken N. H. T. , Heijink I. H. , Timens W. , Brandsma C. A. , Postma D. S. , van den Berge M. , Spira A. , Lenburg M. E.
Published: June 2018

Background: Understanding effects of acute smoke exposure (ASE) on airway epithelial gene expression and their relationship with the effects of chronic smoke exposure may provide biological insights into the development of smoking-related respiratory diseases. Methods: Bronchial airway epithelial cell brushings were collected from 63 individuals without recent cigarette smoke exposure and before and 24 h after smoking three cigarettes. RNA from these samples was profiled on Affymetrix Human Gene 1.0 ST microarrays. Results: We identified 91 genes differentially expressed 24 h after ASE (false discovery rate < 0.25). ASE induced genes involved in xenobiotic metabolism, oxidative stress, and inflammation and repressed genes related to cilium morphogenesis and cell cycle. While many genes altered by ASE are altered similarly in chronic smokers, metallothionein genes are induced by ASE and suppressed in chronic smokers. Metallothioneins are also suppressed in current and former smokers with lung cancer relative to those without lung cancer. Conclusions: Acute exposure to as little as three cigarettes and chronic smoking induce largely concordant changes in airway epithelial gene expression. Differences in short-term and long-term effects of smoking on metallothionein expression and their relationship to lung cancer requires further study given these enzymes’ role in the oxidative stress response.
Accuracy of a Novel Handheld Wireless Platform for Detection of Cardiac Dysfunction in Anthracycline-Exposed Survivors of Childhood Cancer
Authors: Armenian Saro H. , Rinderknecht Derek , Au Kaylene , Lindenfeld Lanie , Mills George , Siyahian Aida , Herrera Claudia , Wilson Karla , Venkataraman Kalyanasundaram , Mascarenhas Kristen , Tavallali Peyman , Razavi Marianne , Pahlevan Niema , Detterich Jon , Bhatia Smita , Gharib Morteza
Published: June 2018

Purpose: Childhood cancer survivors are at risk for anthracycline-related cardiac dysfunction, often developing at a time when they are least engaged in long-term survivorship care. New paradigms in survivorship care and chronic disease screening are needed in this population. We compared the accuracy of a novel handheld mHealth platform (Vivio) as well as echocardiography for assessment of cardiac function [left ventricular ejection fraction (EF)] in childhood cancer survivors with cardiac magnetic resonance (CMR) imaging (reference).

Experimental Design: Cross-sectional study design was used. Concurrent evaluation of EF was performed using Vivio, two-dimensional (2D) echocardiography, and CMR. Differences in mean EF (2D echocardiography vs. CMR; Vivio vs. CMR) were compared using Bland–Altman plots. Linear regression was used to evaluate proportional bias.

Results: A total of 191 consecutive survivors participated [50.7% female; median time from diagnosis: 15.8 years (2–44); median anthracycline dose: 225 mg/m2 (25–642)]. Echocardiography overestimated mean EF by 4.9% (P < 0.001); linear regression analysis confirmed a proportional bias, when compared with CMR (t = 3.1, P < 0.001). There was no difference between mean EF derived from Vivio and from CMR (–0.2%, P = 0.68). The detection of cardiac dysfunction via echocardiography was poor when compared with CMR [Echo EF < 45% (sensitivity 14.3%), Echo EF < 50% (sensitivity 28.6%)]. Sensitivity was substantially better for Vivio-based measurements [EF < 45% or EF < 50% (sensitivity 85.7%)].

Conclusions: This accessible technology has the potential to change the day-to-day practice of clinicians caring for the large number of patients diagnosed with cardiac dysfunction and heart failure each year, allowing real-time monitoring and management of their disease without the lag-time between imaging and interpretation of results. Clin Cancer Res; 24(13); 3119–25. ©2018 AACR.
Pityriasis Rosea during Pregnancy: Major and Minor Alarming Signs
Authors: Drago Francesco , Ciccarese Giulia , Herzum Astrid , Rebora Alfredo , Parodi Aurora
Published: June 2018

Background: Pityriasis rosea (PR) is a self-limiting exanthematous disease associated with human herpesvirus (HHV)-6 and/or HHV-7 reactivation. In pregnant women, PR may be associated with pregnancy complications. Objective: To determine relevant risk factors in the development of negative pregnancy outcome in PR. Methods: Between 2005 and 2017 at the Department of Dermatology, University of Genoa, we recruited 76 women who developed PR during pregnancy. In 60 patients without known risk factors for intrauterine fetal death (30 with pregnancy complications and 30 without) we analyzed the pregnancy week of PR onset, presence of enanthem and of constitutional symptoms, PR body surface area involvement, age, and in 50 patients (20 with pregnancy complications and 30 without), the viral load of HHV-6 and HHV-7 (copies/mL). Results: In logistic regression analysis, early onset of PR (p = 0.0017) and enanthem (p = 0.0392) proved to be significantly associated with pregnancy complications. HHV-6 viral load (copies/mL) (p < 0.0001), constitutional symptoms (p < 0.001), and PR body surface area involvement (p < 0.004) were also significantly associated with pregnancy complications. Conclusion: The onset of PR before week 15 and enanthem may be considered major risk factors that should alarm the dermatologist. Constitutional symptoms and involvement of > 50% of the body area may be considered minor risk factors.
СМОРОДИНИ ЧОРНОЇ ПЛОДИ – ПЕРСПЕКТИВНА СИРОВИНА ДЛЯ РОЗРОБКИ НАЦІОНАЛЬНОЇ МОНОГРАФІЇ В ДЕРЖАВНУ ФАРМАКОПЕЮ УКРАЇНИ
Authors: V. Kuznietsova V. Yu. , Kotov A. G. , Kyslychenko V. S. , Kotova E. E.
Published: June 2018

Мета роботи. Проведення порівняльного аналізу параметрів стандартизації плодів смородини чорної та визначення підходів до розробки національних монографій «Смородини чорної плоди сухі» і «Смородини чорної плоди свіжі».Матеріали і методи. Проведено аналіз підходів до стандартизації плодів смородин чорної за Британською фармакопеєю 2012 року, ДСТ 21450-75 «Плоди смородини чорної» та ДСТ 6829-89 «Смородина чорна свіжі». Аналіз проводили за наступними показниками: назва статті, визначення, вимоги до вмісту біологічно активних речовин, ідентифікація за макро- та мікроскопічними ознаками, показники якості, метод кількісного визначення.Результати й обговорення. При дослідженні критеріїв в стандартизації, наведених у зазначених вище документах, встановлено, що не зовсім коректно порівнювати критерії стандартів, один з яких розроблений для харчової промисловості, а інший для стандартизації лікарської рослинної сировини. Крім того, обидва стандарти не переглядали більше 25 років. Монографія в Британській фармакопеї 2012 року наводить лише декілька сучасних критеріїв (макроскопічні та мікроскопічні ознаки сировини) стандартизації свіжих плодів смородини чорної. Водночас в усіх документах відсутні методи ідентифікації та кількісного визначення біологічно активних речовин.Висновки. Аналіз літературних джерел свідчить про присутність у плодах смородини чорної великої кількості різноманітних біологічно активних речовин, що мають широкий спектр фармакологічної активності, але широкому застосуванню їх в офіцінальній медицині заважає відсутність сучасних методів стандартизації.Аналіз існуючих вимог до якості смородини чорної плодів показав відсутність сучасних методик контролю якості даної сировини, які б відповідали вимогам ДФУ та Європейської фармакопеї та гостру потребу в розробці національних монографій на «Смородин чорної плоди свіжі» та «Смородини плоди висушені».
ВИБІР КІЛЬКІСНОГО СКЛАДУ ДОПОМІЖНИХ РЕЧОВИН ПРИ СТВОРЕННІ ТАБЛЕТОК ЦЕОЛІТУ ПРИРОДНОГО (КЛІНОПТИЛОЛІТУ)
Authors: Rybachuk V. D. , Ruban O. A.
Published: June 2018

Мета роботи. Вивчити вплив кількостей допоміжних речовин на фармако-технологічні властивості таблеток цеоліту природного (кліноптилоліту) та оптимізувати склад готової лікарської форми.Матеріали і методи. Об’єкти досліджень – таблетки цеоліту природного середньої маси 0,55 г та діаметром 10 мм, отримані пресуванням із попередньою вологою грануляцією. У дослідженнях використовували цеоліт природний (кліноптилоліт) Сокирницького родовища (Закарпатська область, Україна). Для вибору фармацевтичних факторів, які суттєво впливають на об’єкт дослідження, використовували дробний факторний експеримент 23 з рівним дублюванням дослідів. Вивчено 3 кількісні фактори, взаємозв’язок між факторами та фармако-технологічними показниками таблеток виражали та інтерпретували за допомогою рівнянь регресії. У дослідах використовували сучасне обладнання. Для тестів користувалися методиками Державної фармакопеї України.Результати й обговорення. За отриманими даними встановлено, що на однорідність маси таблеток найбільшою мірою впливає концентрація зволожувача, на механічну стійкість до роздавлювання – концентрація наповнювача, на стійкість до стирання – вміст суміші лактози моногідрату з МКЦ-101 та крохмалю картопляного, а на час розпадання – вміст крохмалю картопляного. За допомогою регресійного аналізу та додаткових досліджень за схемою «крутого сходження» встановлено оптимальний склад таблеток цеоліту природного (кліноптилоліту): цеоліту природного (кліноптилоліту) –0,4 г; суміші лактози моногідрату  з МКЦ-101 (1:1) –0,085 г; крохмалю картопляного –0,047 г; 7 % клейстеру крохмального картопляного –0,1 г (0,007 г сухого); кальцію стеарату –0,003 г.Висновок. Проведено дослідження з підбору кількісного вмісту допоміжних речовин для отримання таблеток цеоліту природного пресуванням із попередньою вологою грануляцією та запропоновано оптимальний склад таблеток, властивості яких відповідають діючим вимогам ДФУ.
ЕКСПЕРТНА ОЦІНКА ПРОСТАТОПРОТЕКТОРІВ ДЛЯ ФАРМАКОТЕРАПІЇ ХРОНІЧНОГО ПРОСТАТИТУ (на прикладі Івано-Франківської області)
Authors: Hromovyk B. P. , Gadyak I. V. , Trishch V. I.
Published: June 2018

Мета роботи. Проведення експертної оцінки простатопротекторів (ПП) як  лікарських засобів, що впливають на запальне ураження передміхурової залози.Матеріали і методи. Матеріалом дослідження була інформація експертної оцінки фармакотерапії (ФТ) простатиту, отримана за допомогою анкетування, яке здійснювалося за методикою О. Р. Левицької. Було проаналізовано 55 анкет від лікарів-урологів Івано-Франківської області, з них для подальшого дослідження за рівнем компетентності експертів відібрано 34 анкети (61,8 %).Результати й обговорення. Виявлено, що всі експерти повністю володіють інформацією щодо ПП. Для понад чотирьох п’ятих основним джерелом інформації є Державний формуляр лікарських засобів, для близько чотирьох п’ятих – мережа Internet, для понад половини – інструкції для медичного застосування ПП. Майже дві третини лікарів-урологів при призначенні ПП не зважають на платоспроможність хворого, понад дві п’яті з них призначають ПП після ретельного аналізу його клінічного застосування, майже всі експерти обирають ПП відповідно до стандартів лікування, майже половина з них не надає значення походженню ПП, але віддає перевагу оригінальним ПП. Усі експерти ПП торгові назви тамсулозину, силодозину, теразозину, тамсулозину і дудастериду, фінастериду віднесли до класу V і Е, тобто життєво важливих і необхідних. Омнік капс. одностайно визнаний як найбільш важливим для ФТ, ефективним, безпечним та часто призначуваним ПП. Інші два ПП із сильною узгодженістю думок експертів щодо групи V (Фокусин капс. 0,4, Омнік Окас таб.) характеризуються таким же рівнем узгодженості щодо високої ефективності, безпечності та частоти призначення. Встановлено, що необхідно звернути увагу на Простатилен-Біофарма ліофілізат  10 мг та Простатилен суп.0,03 г, які характеризуються високою узгодженістю думок експертів щодо групи D, високої ефективності і безпечності та помітною узгодженістю щодо частоти призначення.Висновки. Шляхом анкетного опитування лікарів-урологів Івано-Франківської області вивчено доступність для них інформації про сучасні ПП, особливості сприйняття ними нових ПП та рівень впливу окремих чинників  на призначення ПП. Здійснено, з урахуванням компетентності експертів, оцінку важливості для ФТ ХП, ефективності, безпечності та частоти призначення ПП. Отримані результати будуть використані для оптимізації локальних та регіонального формулярів лікарських засобів в частині ФТ ХП.
МАРКЕТИНГОВІ ДОСЛІДЖЕННЯ ФАРМАЦЕВТИЧНОГО РИНКУ ЛІКАРСЬКИХ ЗАСОБІВ ДЛЯ ЛІКУВАННЯ СЕРЦЕВО-СУДИННИХ ЗАХВОРЮВАНЬ
Authors: Nemchenko A. S. , Kurylenko Yu. Ye.
Published: June 2018

Мета роботи. Проведення маркетингових досліджень фармацевтичного ринку (ФР) лікарських засобів (ЛЗ), рекомендованих для лікування серцево-судинних захворювань (ССЗ).Матеріали і методи. У дослідженні використано ЛЗ з уніфікованих клінічних протоколів лікування ССЗ за міжнародною непатентованою назвою (МНН) та данні реєстрів ліків за торговими назвами (ТН). Застосовані методи маркетингового аналізу, аналітичний, порівняльний та узагальнення інформації.Результати й обговорення. Наведені результати маркетингового дослідження ФР ЛЗ для лікування ССЗ за 2013–2017 рр. Розраховані середні показники індексу цін ЛЗ, ліквідності ціни та доступності препаратів, які застосовують для фармакотерапії ССЗ.Висновки. Встановлено значне превалювання на ФР препаратів іноземного виробництва над вітчизняними – 70,05 % до 29,95 %. Спостерігається зростання цін на препарати іноземних виробників у 1,09 раза та для вітчизняних у 1,06 раза, які використовуються у лікуванні ССЗ у 2017 р. порівняно з 2013 р. Це вплинуло на зниження доступності даної категорії ліків для хворих. У зв’язку з цим все більшої соціально-економічної значущості набуває потреба в розвитку вітчизняного виробництва та впровадження програм імпортозаміщення, а також розвитку Урядових програм із державного регулювання цін, зокрема референтного ціноутворення.
Algumas considerações sobre a Filosofia da história de Kant
Authors: Cassirer Ernst , Garcia Rafael Rodrigues
Published: June 2018

Tradução de Rafael Rodrigues Garcia
Mudança de significado do parlamentarismo
Authors: Kirchheimer Otto , Tavolari Bianca
Published: June 2018

Tradução de Bianca Tavolari
O dinheiro do espírito: idealismo e crítica da economia política no jovem Marx
Authors: Serrano Bruno Klein
Published: June 2018

O objetivo do artigo é apresentar uma interpretação do estatuto teórico da crítica da economia política nos escritos de juventude de Marx. Para isso, privilegia os assim chamados Manuscritos econômico-filosóficos e os Excertos do livro de James Mill “Éléments d’économie politique”. Nesse contexto, o artigo procura esclarecer a relação mutuamente constitutiva que Marx via entre a economia política, o idealismo de Hegel e a sociedade capitalista. Sustenta-se a ideia de que essa relação define o sentido teórico geral de seu projeto de crítica da economia, bem como precisa as noções de crítica e dialética nela empregadas.
Diabetic Vascular Calcification Mediated by the Collagen Receptor Discoidin Domain Receptor 1 via the Phosphoinositide 3-Kinase/Akt/Runt-Related Transcription Factor 2 Signaling Axis
Authors: Lino Marsel , Wan Mark H. , Rocca Antonio S. , Ngai David , Shobeiri Navid , Hou Guangpei , Ge Chunxi , Franceschi Renny T. , Bendeck Michelle P.
Published: June 2018

Objective—

Vascular calcification is a common and severe complication in patients with atherosclerosis which is exacerbated by type 2 diabetes mellitus. Our laboratory recently reported that the collagen receptor discoidin domain receptor 1 (DDR1) mediates vascular calcification in atherosclerosis; however, the underlying mechanisms are unknown. During calcification, vascular smooth muscle cells transdifferentiate into osteoblast-like cells, in a process driven by the transcription factor RUNX2 (runt-related transcription factor 2). DDR1 signals via the phosphoinositide 3-kinase/Akt pathway, which is also central to insulin signaling, and upstream of RUNX2, and this led us to investigate whether DDR1 promotes vascular calcification in diabetes mellitus via this pathway.

Approach and Results—

Ddr1
+/+
; Ldlr
−/−
(single knock-out) and
Ddr1
−/−
; Ldlr
−/−
(double knock-out) mice were placed on high-fat diet for 12 weeks to induce atherosclerosis and type 2 diabetes mellitus. Von Kossa staining revealed reduced vascular calcification in the aortic arch of double knock-out compared with single knock-out mice. Immunofluorescent staining for RUNX2 was present in calcified plaques of single knock-out but not double knock-out mice. Primary vascular smooth muscle cells obtained from
Ddr1
+/+
and
Ddr1
−/−
mice were cultured in calcifying media. DDR1 deletion resulted in reduced calcification, a 74% reduction in p-Akt levels, and an 88% reduction in RUNX2 activity. Subcellular fractionation revealed a 77% reduction in nuclear RUNX2 levels in
Ddr1
−/−
vascular smooth muscle cells. DDR1 associated with phosphoinositide 3-kinase, and treatment with the inhibitor wortmannin attenuated calcification. Finally, we show that DDR1 is important to maintain the microtubule cytoskeleton which is required for the nuclear localization of RUNX2.

Conclusions—

These novel findings demonstrate that DDR1 promotes RUNX2 activity and atherosclerotic vascular calcification in diabetes mellitus via phosphoinositide 3-kinase/Akt signaling.
The Transcription Factor ETV1 Induces Atrial Remodeling and Arrhythmia
Authors: Rommel Carolin , Rösner Stephan , Lother Achim , Barg Margareta , Schwaderer Martin , Gilsbach Ralf , Bömicke Timo , Schnick Tilman , Mayer Sandra , Doll Sophia , Hesse Michael , Kretz Oliver , Stiller Brigitte , Neumann Franz-Josef , Mann Matthias , Krane Markus , Fleischmann Bernd K. , Ravens Ursula , Hein Lutz
Published: June 2018

Rationale:

Structural and electrophysiological remodeling of the atria are recognized consequences of sustained atrial arrhythmias, such as atrial fibrillation. The identification of underlying key molecules and signaling pathways has been challenging because of the changing cell type composition during structural remodeling of the atria.

Objective:

Thus, the aims of our study were (1) to search for transcription factors and downstream target genes, which are involved in atrial structural remodeling, (2) to characterize the significance of the transcription factor ETV1 (E twenty-six variant 1) in atrial remodeling and arrhythmia, and (3) to identify ETV1-dependent gene regulatory networks in atrial cardiac myocytes.

Methods and Results:

The transcription factor ETV1 was significantly upregulated in atrial tissue from patients with permanent atrial fibrillation. Mice with cardiac myocyte-specific overexpression of ETV1 under control of the myosin heavy chain promoter developed atrial dilatation, fibrosis, thrombosis, and arrhythmia. Cardiac myocyte-specific ablation of ETV1 in mice did not alter cardiac structure and function at baseline. Treatment with Ang II (angiotensin II) for 2 weeks elicited atrial remodeling and fibrosis in control, but not in ETV1-deficient mice. To identify ETV1-regulated genes, cardiac myocytes were isolated and purified from mouse atrial tissue. Active
cis
-regulatory elements in mouse atrial cardiac myocytes were identified by chromatin accessibility (assay for transposase-accessible chromatin sequencing) and the active chromatin modification H3K27ac (chromatin immunoprecipitation sequencing). One hundred seventy-eight genes regulated by Ang II in an ETV1-dependent manner were associated with active
cis
-regulatory elements containing ETV1-binding sites. Various genes involved in Ca
2+
handling or gap junction formation (
Ryr2, Jph2, Gja5
), potassium channels (
Kcnh2, Kcnk3
), and genes implicated in atrial fibrillation (
Tbx5
) were part of this ETV1-driven gene regulatory network. The atrial ETV1-dependent transcriptome in mice showed a significant overlap with the human atrial proteome of patients with permanent atrial fibrillation.

Conclusions:

This study identifies ETV1 as an important component in the pathophysiology of atrial remodeling associated with atrial arrhythmias.
Circulating Progenitor Cells and Racial Differences
Authors: Samman Tahhan Ayman , Hammadah Muhammad , Kelli Heval Mohamed , Kim Jeong Hwan , Sandesara Pratik B. , Alkhoder Ayman , Kaseer Belal , Gafeer Mohamad Mazen , Topel Matthew , Hayek Salim S. , O’Neal Wesley T. , Obideen Malik , Ko Yi-An , Liu Chang , Hesaroieh Iraj , Mahar Ernestine , Vaccarino Viola , Waller Edmund K. , Quyyumi Arshed A.
Published: June 2018

Rationale:

Blacks compared with whites have a greater risk of adverse cardiovascular outcomes. Impaired regenerative capacity, measured as lower levels of circulating progenitor cells (CPCs), is a novel determinant of adverse outcomes; however, little is known about racial differences in CPCs.

Objective:

To investigate the number of CPCs, PC-mobilizing factors, PC mobilization during acute myocardial infarction and the predictive value of CPC counts in blacks compared with whites.

Methods and Results:

CPCs were enumerated by flow cytometry as CD45med
+
blood mononuclear cells expressing CD34+, CD133+, VEGF2R+, and CXCR4+ epitopes in 1747 subjects, mean age 58.4±13, 55% male, and 26% self-reported black. Patients presenting with acute myocardial infarction (n=91) were analyzed separately. Models were adjusted for relevant clinical variables. SDF-1α (stromal cell-derived factor-1α), VEGF (vascular endothelial growth factor), and MMP-9 (matrix metallopeptidase-9) levels were measured (n=561), and 623 patients were followed for median of 2.2 years for survival analysis. Blacks were younger, more often female, with a higher burden of cardiovascular risk, and lower CPC counts. Blacks had fewer CD34+ cells (−17.6%; [95% confidence interval (CI), −23.5% to −11.3%];
P
<0.001), CD34+/CD133+ cells (−15.5%; [95% CI, −22.4% to −8.1%];
P
<0.001), CD34+/CXCR4+ cells (−17.3%; [95% CI, −23.9% to −10.2%];
P
<0.001), and CD34+/VEGF2R+ cells (−27.9%; [95% CI, −46.9% to −2.0%];
P
=0.04) compared with whites. The association between lower CPC counts and black race was not affected by risk factors or cardiovascular disease. Results were validated in a separate cohort of 411 patients. Blacks with acute myocardial infarction had significantly fewer CPCs compared with whites (
P
=0.02). Blacks had significantly lower plasma MMP-9 levels (
P
<0.001) which attenuated the association between low CD34+ and black race by 19% (95% CI, 13%–33%). However, VEGF and SDF-1α levels were not significantly different between the races. Lower CD34+ counts were similarly predictive of mortality in blacks (hazard ratio, 2.83; [95% CI, 1.12–7.20];
P
=0.03) and whites (hazard ratio, 1.79; [95% CI, 1.09–2.94];
P
=0.02) without significant interaction.

Conclusions:

Black subjects have lower levels of CPCs compared with whites which is partially dependent on lower circulating MMP-9 levels. Impaired regenerative capacity is predictive of adverse outcomes in blacks and may partly account for their increased risk of cardiovascular events.
Size Matters: Ryanodine Receptor Cluster Size Affects Arrhythmogenic Sarcoplasmic Reticulum Calcium Release
Authors: Galice Samuel , Xie Yuanfang , Yang Yi , Sato Daisuke , Bers Donald M.
Published: June 2018

Background

Ryanodine receptors (RyR) mediate sarcoplasmic reticulum calcium (Ca
2+
) release and influence myocyte Ca
2+
homeostasis and arrhythmias. In cardiac myocytes, RyRs are found in clusters of various sizes and shapes, and RyR cluster size may critically influence normal and arrhythmogenic Ca
2+
spark and wave formation. However, the actual RyR cluster sizes at specific Ca
2+
spark sites have never been measured in the physiological setting.

Methods and Results

Here we measured RyR cluster size and Ca
2+
sparks simultaneously to assess how RyR cluster size influences Ca
2+
sparks and sarcoplasmic reticulum Ca
2+
leak. For small RyR cluster sizes (<50), Ca
2+
spark frequency is very low but then increases dramatically at larger cluster sizes. In contrast, Ca
2+
spark amplitude is nearly maximal even at relatively small RyR cluster size (≈10) and changes little at larger cluster size. These properties agreed with computational simulations of RyR gating within clusters.

Conclusions

Our study explains how this combination of properties may limit arrhythmogenic Ca
2+
sparks and wave propagation (at many junctions) while preserving the efficacy and spatial synchronization of Ca
2+
‐induced Ca
2+
‐release during normal excitation‐contraction coupling. However, variations in RyR cluster size among individual junctions and RyR sensitivity could exacerbate heterogeneity of local sarcoplasmic reticulum Ca
2+
release and arrhythmogenesis under pathological conditions.