bluuebunny/crossref_metadata_2025 huggingface dataset:
Real-life assessment of the validity of patient global impression of change in fibromyalgia
Authors: Rampakakis Emmanouil , Ste-Marie Peter A , Sampalis John S , Karellis Angeliki , Shir Yoram , Fitzcharles Mary-Ann
Published: September 2015

Objectives

Patient Global Rating of Change (GRC) scales are commonly used in routine clinical care given their ease of use, availability and short completion time. This analysis aimed at assessing the validity of Patient Global Impression of Change (PGIC), a GRC scale commonly used in fibromyalgia, in a Canadian real-life setting.

Methods

167 fibromyalgia patients with available PGIC data were recruited in 2005–2013 from a Canadian tertiary-care multidisciplinary clinic. In addition to PGIC, disease severity was assessed with: pain visual analogue scale (VAS); Patient Global Assessment (PGA); Fibromyalgia Impact Questionnaire (FIQ); Health Assessment Questionnaire (HAQ); McGill Pain Questionnaire; body map. Multivariate linear regression assessed the PGIC relationship with disease parameter improvement while adjusting for follow-up duration and baseline parameter levels. The Spearman's rank coefficient assessed parameter correlation.

Results

Higher PGIC scores were significantly (p<0.001) associated with greater improvement in pain, PGA, FIQ, HAQ and the body map. A statistically significant moderate positive correlation was observed between PGIC and FIQ improvement (r=0.423; p<0.001); correlation with all remaining disease severity measures was weak. Regression analysis confirmed a significant (p<0.001) positive association between improvement in all disease severity measures and PGIC. Baseline disease severity and follow-up duration were identified as significant independent predictors of PGIC rating.

Conclusions

Despite that only a weak correlation was identified between PGIC and standard fibromyalgia outcomes improvement, in the absence of objective outcomes, PGIC remains a clinically relevant tool to assess perceived impact of disease management. However, our analysis suggests that outcome measures data should not be considered in isolation but, within the global clinical context.
Lifestyle factors may modify the effect of disease activity on radiographic progression in patients with ankylosing spondylitis: a longitudinal analysis
Authors: Ramiro Sofia , Landewé Robert , van Tubergen Astrid , Boonen Annelies , Stolwijk Carmen , Dougados Maxime , van den Bosch Filip , van der Heijde Désirée
Published: September 2015

Objectives

To investigate the complex relationship between inflammation, mechanical stress and radiographic progression in patients with ankylosing spondylitis (AS), using job type as a proxy for continuous mechanical stress.

Methods

Patients from the Outcome in Ankylosing Spondylitis International Study were followed up for 12 years, with 2-yearly assessments. Two readers independently scored the X-rays according to the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). Disease activity was assessed by the AS Disease Activity Score C reactive protein (ASDAS-CRP). The relationship between ASDAS and spinal radiographic progression was investigated with longitudinal analysis, with job type at baseline (physically demanding (‘blue-collar’) versus sedentary (‘white-collar’) labour) as a potential factor influencing this relationship. The effects of smoking status and socioeconomic factors were also investigated.

Results

In total, 184 patients were included in the analyses (70% males, 83% human leucocyte antigen-B27 positive, 39% smokers, 48% blue-collar workers (65/136 patients in whom data on job type were available)). The relationship between disease activity and radiographic progression was significantly and independently modified by job type: In ‘blue-collar’ workers versus ‘white-collar’ workers, every additional unit of ASDAS resulted in an increase of 1.2 versus 0.2 mSASSS-units/2-years (p=0.014 for the difference between blue-collar and white-collar workers). In smokers versus non-smokers, every additional unit of ASDAS resulted in an increase of 1.9 versus 0.4 mSASSS-units/2-years.

Conclusions

Physically demanding jobs may amplify the potentiating effects of inflammation on bone formation in AS. Smoking and socioeconomic factors most likely confound this relationship and may have separate effects on bone formation.
RNA polymerase II pausing as a context-dependent reader of the genome
Authors: Scheidegger Adam , Nechaev Sergei
Published: September 2015

The RNA polymerase II (Pol II) transcribes all mRNA genes in eukaryotes and is among the most highly regulated enzymes in the cell. The classic model of mRNA gene regulation involves recruitment of the RNA polymerase to gene promoters in response to environmental signals. Higher eukaryotes have an additional ability to generate multiple cell types. This extra level of regulation enables each cell to interpret the same genome by committing to one of the many possible transcription programs and executing it in a precise and robust manner. Whereas multiple mechanisms are implicated in cell type-specific transcriptional regulation, how one genome can give rise to distinct transcriptional programs and what mechanisms activate and maintain the appropriate program in each cell remains unclear. This review focuses on the process of promoter-proximal Pol II pausing during early transcription elongation as a key step in context-dependent interpretation of the metazoan genome. We highlight aspects of promoter-proximal Pol II pausing, including its interplay with epigenetic mechanisms, that may enable cell type-specific regulation, and emphasize some of the pertinent questions that remain unanswered and open for investigation.
Application of advanced bounding surface plasticity model in static and seismic analyses of Zipingpu Dam
Authors: Kan Mojtaba E. , Taiebat Hossein A.
Published: September 2015

The strong ground motion of the Wenchuan earthquake that hit the Zipingpu Dam in China in 2008 has provided an excellent benchmark to study the behaviour of large modern rockfill dams subjected to seismic loading. The performance of the dam during construction and prior to and after the earthquake loading has been recorded with good accuracy, and provides a reliable database to examine the reliability of available constitutive models and numerical methods in predicting the static and dynamic behaviour of embankment dams. In this paper, an advanced bounding surface plasticity model has been used in a series of numerical analyses to study the static and dynamic behaviour of Zipingpu Dam. The model can take into account particle breakage that may occur in monotonic and cyclic loading of rockfill materials. The material parameters required for the model are calibrated based on the results of available monotonic and cyclic triaxial tests. In the numerical procedure, the staged construction of the dam and the subsequent impounding of the reservoir are simulated, followed by dynamic loading. At each stage, the results of the numerical analysis are compared with in situ monitoring records of the dam. The results of the numerical simulation and the displacements measured after the earthquake are also compared with those estimated by two simplified engineering procedures that are routinely used in practice. The effectiveness and applicability of the simplified procedures to such a large dam subjected to an earthquake with a long duration is also discussed.
Cone penetration tests in unsaturated silty sands
Authors: Yang Hongwei , Russell Adrian R.
Published: September 2015

Very little is known about how to interpret cone penetration tests (CPTs) when performed in unsaturated soils. The few published studies on CPTs in unsaturated soils have focused on either clean sands or silt. In this study, new results of laboratory-controlled CPTs in an unsaturated silty sand are presented. Silty sand exhibits hydraulic hysteresis and suction hardening. Suction is observed to have a pronounced effect on measured cone penetration resistance. For an isotropic net confining stress of 60 kPa, it is observed that higher suctions give rise to cone penetration resistances that are 50% larger than those for lower suctions. A semi-theoretical correlation is presented that links measured cone penetration resistances to initial relative density and mean effective stress. Suction has an influence on cone penetration resistances through suction hardening, as well as its contribution to effective stress. For this silty sand, it is shown that failing to account for suction may result in significant overestimations and unsafe predictions of soil properties from measured cone penetration resistances.
Body and organ mass dynamics during remigial moult in a wing–foot-propelled diving sea duck: the Common Eider (Atlantic) (Somateria mollissima dresseri)
Authors: Viain A. , Guillemette M. , Savard J.-P.L.
Published: September 2015

Body and organ dynamics, during remigial moult, have been mainly explored on geese, dabbling ducks, and foot-propelled diving ducks, but weakly on sea ducks. This study investigated the internal changes in a wing–foot-propelled sea duck to determine the adaptive strategies implemented. Forty-five male Common Eiders (Atlantic) (Somateria mollissima dresseri Sharpe, 1871), collected in the Gulf of St. Lawrence, were dissected; their body mass, muscle mass, and organ sizes were measured. We tested three hypotheses: (1) S. m. dresseri use a strategic reduction of body mass to reduce the flightlessness duration; (2) organs will exhibit changes consistent with a trade-off between function and maintenance to save and reallocate energy and proteins to feather growth; (3) S. m. dresseri would show lower flight muscle reduction than foot-propelled diving ducks. Somateria mollissima dresseri did not lose body mass, which does not support the first hypothesis. Atrophy of the heart followed by hypertrophy and opposite changes in leg muscle mass and gizzard mass are consistent with the second hypothesis. Flight muscle mass showed lower variations than in other ducks, validating the third hypothesis. We also suggest that the lipid depletion observed early in the moult could be a strategy to reduce foraging effort and minimize the risk of damaging the growing feathers.
Legendrian torus knots in S1 × S2
Authors: Chen Feifei , Ding Fan , Li Youlin
Published: September 2015

We classify Legendrian torus knots in S1 × S2 with its standard tight contact structure up to Legendrian isotopy.
Regional Performance of China's Banks: Evidence from Industrial and Commercial Bank of China
Authors: Yang Wen , Liu Yi-Cheng , Mai Shin-Ying , Mai Chao-Cheng
Published: September 2015

This paper investigates regional performances of China's and the world's largest commercial bank: the Industrial and Commercial Bank of China (ICBC), by its spatial patterns and geographical distribution of deposits. Moran I of Geoda software and the Local Indicators of Spatial Association (LISA) are applied. Empirical evidence shows that overall performances of ICBC depended consistently on Yangtze River Delta and Bohai Sea region while performances of other regions were relatively lower-performed during this period. Interestingly, branches performances in coastal provinces were not necessarily better than those in interior provinces because branches in Pearl River Delta were constantly under-performed. Furthermore, we identified that spatial effects and workers population have large, statistically significant impacts on branches' performances by employing spatial econometric tools. However, workers population have reverse effects on deposits performances. Evidences indicate that the bank branches performances of deposits rely on transferring deposits from less worker-concentrated areas or acquiring deposits through other sources: corporate, governmental accounts. It is the competitive advantage that ICBC becomes the most profitable bank from economies of scales and scopes in procuring deposit through various sources and making loans in worker-populated areas where funds are highly demanded. These also illuminate the future improvement and direction for bank management and government policy.
Biological transportation networks: Modeling and simulation
Authors: Albi Giacomo , Artina Marco , Foransier Massimo , Markowich Peter A.
Published: September 2015

We present a model for biological network formation originally introduced by Cai and Hu [Adaptation and optimization of biological transport networks, Phys. Rev. Lett. 111 (2013) 138701]. The modeling of fluid transportation (e.g., leaf venation and angiogenesis) and ion transportation networks (e.g., neural networks) is explained in detail and basic analytical features like the gradient flow structure of the fluid transportation network model and the impact of the model parameters on the geometry and topology of network formation are analyzed. We also present a numerical finite-element based discretization scheme and discuss sample cases of network formation simulations.
The Local Point Interpolation–Boundary Element Method: Application to 3D Stationary Thermo-Piezoelectricity
Authors: Njiwa Richard Kouitat
Published: September 2015

This paper presents a simple strategy allowing to adapt well-established isotropic BEM approach for the solution of multi-physics problems with anisotropic material parameters. The method is based on the partition of the primary kinematical fields into complementary and particular parts. The isotropic linear equations for the complementary fields are solved by the conventional boundary element method. The particular fields are obtained by a point collocation of a strong form differential equation. Adopting local radial point interpolation, the effectiveness of the approach is proved by considering various examples of stationary thermal conduction, thermos-elasticity and thermos-piezoelectricity.
General Relativity Search Algorithm: A Global Optimization Approach
Authors: Beiranvand Hamzeh , Rokrok Esmaeel
Published: September 2015

In this paper, a novel metaheuristic optimization algorithm inspired by General Relativity Theory (GRT) is presented. In this method that we named General Relativity Search Algorithm (GRSA), a population of particles is considered in a space free from all external non-gravitational fields and propel toward a position with least action. Based on GRT, particles have conserved masses and move along geodesic trajectories in a curved space. Step length and step direction for updating the particles are separately computed using particles velocity and geodesics, respectively. Velocity of particles is obtained by their energy–momentums. According to physical action principle, a population of particles goes to the position with minimum action. By inspiring this physical principle, GRSA will lead variables of an optimization problem move toward the optimal point. Performance of the proposed optimization algorithm is investigated by using several standard test functions and optimal Power System Stabilizers (PSSs) design in a multi-machine power system as a real-world application. Numerical simulations results demonstrate the efficiency, robustness and convergence speed of GRSA in solving various problems.
Effect of geometry on the pressure induced donor binding energy in semiconductor nanostructures
Authors: Kalpana P. , Jayakumar K. , Nithiananthi P.
Published: September 2015

The effect of geometry on an on-center hydrogenic donor impurity in a GaAs /( Ga,Al ) As quantum wire (QWW) and quantum dot (QD) under the influence of Γ–X band mixing due to an applied hydrostatic pressure is theoretically studied. Numerical calculations are performed in an effective mass approximation. The ground state impurity energy is obtained by variational procedure. Both the effects of pressure and geometry are to exert an additional confinement on the impurity inside the wire as well as dot. We found that the donor binding energy is modified by the geometrical effects as well as by the confining potential when it is subjected to external pressure. The results are presented and discussed.
Efficient Control and Communication Paradigms for Coarse-Grained Spatial Architectures
Authors: Pellauer Michael , Parashar Angshuman , Adler Michael , Ahsan Bushra , Allmon Randy , Crago Neal , Fleming Kermin , Gambhir Mohit , Jaleel Aamer , Krishna Tushar , Lustig Daniel , Maresh Stephen , Pavlov Vladimir , Rayess Rachid , Zhai Antonia , Emer Joel
Published: September 2015

There has been recent interest in exploring the acceleration of nonvectorizable workloads with spatially programmed architectures that are designed to efficiently exploit pipeline parallelism. Such an architecture faces two main problems: how to efficiently control each processing element (PE) in the system, and how to facilitate inter-PE communication without the overheads of traditional shared-memory coherent memory. In this article, we explore solving these problems using triggered instructions and latency-insensitive channels. Triggered instructions completely eliminate the program counter (PC) and allow programs to transition concisely between states without explicit branch instructions. Latency-insensitive channels allow efficient communication of inter-PE control information while simultaneously enabling flexible code placement and improving tolerance for variable events such as cache accesses. Together, these approaches provide a unified mechanism to avoid overserialized execution, essentially achieving the effect of techniques such as dynamic instruction reordering and multithreading.

Our analysis shows that a spatial accelerator using triggered instructions and latency-insensitive channels can achieve 8 × greater area-normalized performance than a traditional general-purpose processor. Further analysis shows that triggered control reduces the number of static and dynamic instructions in the critical paths by 62% and 64%, respectively, over a PC-style baseline, increasing the performance of the spatial programming approach by 2.0 ×.
Parameter Space Representation of Pareto Front to Explore Hardware-Software Dependencies
Authors: Catania Vincenzo , Araldo Andrea , Patti Davide
Published: September 2015

Embedded systems design requires conflicting objectives to be optimized with an appropriate choice of hardware-software parameters. A simulation campaign can guide the design in finding the best trade-offs, but due to the big number of possible configurations, it is often unfeasible to simulate them all. For these reasons, design space exploration algorithms aim at finding near-optimal system configurations by simulating only a subset of them.

In this work, we present PS, a new multiobjective optimization algorithm, and evaluate it in the context of the embedded system design. The basic idea is to recognize
interesting
regions—that is, regions of the configuration space that provide better configurations with respect to other ones. PS evaluates more configurations in the interesting regions while less thoroughly exploring the rest of the configuration space. After a detailed formal description of the algorithm and the underlying concepts, we show a case study involving the hardware/software exploration of a VLIW architecture. Qualitative and quantitative comparisons of PS against a well-known multiobjective genetic approach demonstrate that while not outperforming it in terms of Pareto dominance, the proposed approach can balance the uniformity and granularity qualities of the solutions found, obtaining more extended Pareto fronts that provide a wider view of the potentiality of the designed device. Therefore, PS represents a further valid choice for the designer when objective constrains allow it.
OPLE
Authors: Kamal Mehdi , Afzali-Kusha Ali , Safari Saeed , Pedram Massoud
Published: September 2015

In this article, a heuristic custom instruction (CI) selection algorithm is presented. The proposed algorithm, which is called OPLE for “Optimization based on Partitioning and Local Exploration,” uses a combination of greedy and optimal optimization methods. It searches for the near-optimal solution by reducing the search space based on partitioning the identified CI set. The partitioning of the identified set guarantees the success of the algorithm independent of the size of the identified set. First, the algorithm finds the near-optimal CIs from the candidate CIs for each part. Next, the suggested CIs from different parts are combined to determine the final selected CI set. To improve the set of the selected CIs, the solution is evolved by calling the algorithm iteratively. The efficacy of the algorithm is assessed by comparing its performance to those of optimal and nonoptimal methods. A comparative study is performed for a number of benchmarks under different area budgets and I/O constraints. The results reveal higher speedups for the OPLE algorithm, especially for larger identified candidate sets and/or small area budgets compared to those of the nonoptimal solutions. Compared to the nonoptimal techniques, the proposed algorithm provides 30% higher speedup improvement on average. The maximum improvement is 117%. The results also demonstrate that in many cases OPLE is able to find the optimal solution.
Parametrised Modal Interface Automata
Authors: Siirtola Antti , Heljanko Keijo
Published: September 2015

Interface theories (ITs) enable us to analyse the compatibility interfaces and refine them while preserving their compatibility. However, most ITs are for finite state interfaces, whereas computing systems are often parametrised involving components, the number of which cannot be fixed. We present, to our knowledge, the first IT that allows us to specify a parametric number of interfaces. Moreover, we provide a fully algorithmic procedure, implemented in a tool, for checking the compatibility of and refinement between parametrised interfaces. Finally, we show that the restrictions of the technique are necessary; removing any of them renders the refinement checking problem undecidable.
Signature-Free Asynchronous Binary Byzantine Consensus with t < n/3, O(n2) Messages, and O(1) Expected Time
Authors: Mostéfaoui Achour , Moumen Hamouma , Raynal Michel
Published: September 2015

This article is on broadcast and agreement in asynchronous message-passing systems made up of
n
processes, and where up to
t
processes may have a Byzantine Behavior. Its first contribution is a powerful, yet simple, all-to-all broadcast communication abstraction suited to binary values. This abstraction, which copes with up to
t
<
n
/3 Byzantine processes, allows each process to broadcast a binary value, and obtain a set of values such that (1) no value broadcast only by Byzantine processes can belong to the set of a correct process, and (2) if the set obtained by a correct process contains a single value
v
, then the set obtained by any correct process contains
v
.

The second contribution of this article is a new round-based asynchronous consensus algorithm that copes with up to
t
<
n
/3 Byzantine processes. This algorithm is based on the previous binary broadcast abstraction and a weak common coin. In addition to being signature-free and optimal with respect to the value of
t
, this consensus algorithm has several noteworthy properties: the expected number of rounds to decide is constant; each round is composed of a constant number of communication steps and involves
O
(
n
2) messages; each message is composed of a round number plus a constant number of bits. Moreover, the algorithm tolerates message reordering by the adversary (i.e., the Byzantine processes).
Evidence that Viewers Prefer Higher Frame-Rate Film
Authors: Wilcox Laurie M. , Allison Robert S. , Helliker John , Dunk Bert , Anthony Roy C.
Published: September 2015

High frame-rate (HFR) movie-making refers to the capture and projection of movies at frame rates several times higher than the traditional 24 frames per second. This higher frame rate theoretically improves the quality of motion portrayed in movies, and helps avoid motion blur, judder, and other undesirable artifacts. However, there is considerable debate in the cinema industry regarding the acceptance of HFR content given anecdotal reports of hyper-realistic imagery that reveals too much set and costume detail. Despite the potential theoretical advantages, there has been little empirical investigation of the impact of high frame-rate techniques on the viewer experience. In this study, we use stereoscopic 3D content, filmed and projected at multiple frame rates (24, 48, and 60 fps), with shutter angles ranging from 180° to 358°, to evaluate viewer preferences. In a paired-comparison paradigm, we assessed preferences along a set of five attributes (realism, motion smoothness, blur/clarity, quality of depth, and overall preference). The resulting data show a clear preference for higher frame rates, particularly when contrasting 24 fps with 48 or 60 fps. We found little impact of shutter angle on viewers' choices, with the exception of one measure (motion smoothness) for one clip type. These data are the first empirical evidence of the advantages afforded by high frame-rate capture and presentation in a cinema context.
Minimizing Organizational User Requirement while Meeting Security Constraints
Authors: Roy Arindam , Sural Shamik , Majumdar Arun Kumar , Vaidya Jaideep , Atluri Vijayalakshmi
Published: September 2015

Large systems are complex and typically need automatic configuration to be managed effectively. In any organization, numerous tasks have to be carried out by employees. However, due to security needs, it is not feasible to directly assign any existing task to the first available employee. In order to meet many additional security requirements, constraints such as separation of duty, cardinality and binding have to be taken into consideration. Meeting these requirements imposes extra burden on organizations, which, however, is unavoidable in order to ensure security. While a trivial way of ensuring security is to assign each user to a single task, business organizations would typically like to minimize their costs and keep staffing requirements to a minimum. To meet these contradictory goals, we define the problem of Cardinality Constrained-Mutually Exclusive Task Minimum User Problem (CMUP), which aims to find the minimum users that can carry out a set of tasks while satisfying the given security constraints. We show that the CMUP problem is equivalent to a constrained version of the weak chromatic number problem in hypergraphs, which is NP-hard. We, therefore, propose a greedy solution. Our experimental evaluation shows that the proposed algorithm is both efficient and effective.
Resolving Ambiguities in Natural Language Software Requirements
Authors: Shah Unnati S. , Jinwala Devesh C.
Published: September 2015

Requirements Engineering is one of the most vital activities in the entire Software Development Life Cycle. The success of the software is largely dependent on how well the users' requirements have been understood and converted into appropriate functionalities in the software. Typically, the users convey their requirements in natural language statements that initially appear easy to state. However, being stated in natural language, the statement of requirements often tends to suffer from misinterpretations and imprecise inferences. As a result, the requirements specified thus, may lead to ambiguities in the software specifications. One can indeed find numerous approaches that deal with ensuring precise requirement specifications. Naturally, an obvious approach to deal with ambiguities in natural language software specifications is to eliminate ambiguities altogether i.e. to use formal specifications. However, the formal methods have been observed to be cost-effective largely for the development of mission-critical software. Due to the technical sophistication required, these are yet to be accepted in the mainstream. Hence, the other alternative is to let the ambiguities exist in the natural language requirements but deal with the same using proven techniques viz. using approaches based on machine learning, knowledge and ontology to resolve them. One can indeed find numerous automated and semi-automated tools to resolve specific types of natural language software requirement ambiguities. However, to the best of our knowledge there is no published literature that attempts to compare and contrast the prevalent approaches to deal with ambiguities in natural language software requirements. Hence, in this paper, we attempt to survey and analyze the prevalent approaches that attempt to resolve ambiguities in natural language software requirements. We focus on presenting a state-of-the-art survey of the currently available tools for ambiguity resolution. The objective of this paper is to disseminate, dissect and analyze the research work published in the area, identify metrics for a comparative evaluation and eventually do the same. At the end, we identify open research issues with an aim to spark new interests and developments in this field.
RIFFA 2.1
Authors: Jacobsen Matthew , Richmond Dustin , Hogains Matthew , Kastner Ryan
Published: September 2015

We present RIFFA 2.1, a reusable integration framework for Field-Programmable Gate Array (FPGA) accelerators. RIFFA provides communication and synchronization for FPGA accelerated applications using simple interfaces for hardware and software. Our goal is to expand the use of FPGAs as an acceleration platform by releasing, as open source, a framework that easily integrates software running on commodity CPUs with FPGA cores. RIFFA uses PCI Express (PCIe) links to connect FPGAs to a CPU’s system bus. RIFFA 2.1 supports FPGAs from Xilinx and Altera, Linux and Windows operating systems, and allows multiple FPGAs to connect to a single host PC system. It has software bindings for C/C++, Java, Python, and Matlab. Tests show that data transfers between hardware and software can reach 97% of the achievable PCIe link bandwidth.
When two obese parents are worse than one! Impacts on embryo and fetal development
Authors: McPherson N. O. , Bell V. G. , Zander-Fox D. L. , Fullston T. , Wu L. L. , Robker R. L. , Lane M.
Published: September 2015

The prevalence of overweight and obesity in reproductive-age adults is increasing worldwide. While the effects of either paternal or maternal obesity on gamete health and subsequent fertility and pregnancy have been reported independently, the combination of having both parents overweight/obese on fecundity and offspring health has received minimal attention. Using a 2 × 2 study design in rodents we established the relative contributions of paternal and maternal obesity on fetal and embryo development and whether combined paternal and maternal obesity had an additive effect. Here, we show that parental obesity reduces fetal and placental weights without altering pregnancy establishment and is not dependent on an in utero exposure to a high-fat diet. Interestingly combined parental obesity seemed to accumulate both the negative influences of paternal and maternal obesity had alone on embryo and fetal health rather than an amplification, manifested as reduced embryo developmental competency, reduced blastocyst cell numbers, impaired mitochondrial function, and alterations to active and repressive embryonic chromatin marks, resulting in aberrant placental gene expression and reduced fetal liver mtDNA copy numbers. Further understanding both the maternal cytoplasmic and paternal genetic interactions during this early developmental time frame will be vital for understanding how developmental programming is regulated and for the proposition of interventions to mitigate their effects.
Dehydration accelerates reductions in cerebral blood flow during prolonged exercise in the heat without compromising brain metabolism
Authors: Trangmar Steven J. , Chiesa Scott T. , Llodio Iñaki , Garcia Benjamin , Kalsi Kameljit K. , Secher Niels H. , González-Alonso José
Published: September 2015

Dehydration hastens the decline in cerebral blood flow (CBF) during incremental exercise, whereas the cerebral metabolic rate for O2(CMRO2) is preserved. It remains unknown whether CMRO2is also maintained during prolonged exercise in the heat and whether an eventual decline in CBF is coupled to fatigue. Two studies were undertaken. In study 1, 10 male cyclists cycled in the heat for ∼2 h with (control) and without fluid replacement (dehydration) while internal and external carotid artery blood flow and core and blood temperature were obtained. Arterial and internal jugular venous blood samples were assessed with dehydration to evaluate CMRO2. In study 2, in 8 male subjects, middle cerebral artery blood velocity was measured during prolonged exercise to exhaustion in both dehydrated and euhydrated states. After a rise at the onset of exercise, internal carotid artery flow declined to baseline with progressive dehydration ( P < 0.05). However, cerebral metabolism remained stable through enhanced O2and glucose extraction ( P < 0.05). External carotid artery flow increased for 1 h but declined before exhaustion. Fluid ingestion maintained cerebral and extracranial perfusion throughout nonfatiguing exercise. During exhaustive exercise, however, euhydration delayed but did not prevent the decline in cerebral perfusion. In conclusion, during prolonged exercise in the heat, dehydration accelerates the decline in CBF without affecting CMRO2and also restricts extracranial perfusion. Thus, fatigue is related to a reduction in CBF and extracranial perfusion rather than CMRO2.
Central-peripheral neural network interactions evoked by vagus nerve stimulation: functional consequences on control of cardiac function
Authors: Ardell Jeffrey L. , Rajendran Pradeep S. , Nier Heath A. , KenKnight Bruce H. , Armour J. Andrew
Published: September 2015

Using vagus nerve stimulation (VNS), we sought to determine the contribution of vagal afferents to efferent control of cardiac function. In anesthetized dogs, the right and left cervical vagosympathetic trunks were stimulated in the intact state, following ipsilateral or contralateral vagus nerve transection (VNTx), and then following bilateral VNTx. Stimulations were performed at currents from 0.25 to 4.0 mA, frequencies from 2 to 30 Hz, and a 500-μs pulse width. Right or left VNS evoked significantly greater current- and frequency-dependent suppression of chronotropic, inotropic, and lusitropic function subsequent to sequential VNTx. Bradycardia threshold was defined as the current first required for a 5% decrease in heart rate. The threshold for the right vs. left vagus-induced bradycardia in the intact state (2.91 ± 0.18 and 3.47 ± 0.20 mA, respectively) decreased significantly with right VNTx (1.69 ± 0.17 mA for right and 3.04 ± 0.27 mA for left) and decreased further following bilateral VNTx (1.29 ± 0.16 mA for right and 1.74 ± 0.19 mA for left). Similar effects were observed following left VNTx. The thresholds for afferent-mediated effects on cardiac parameters were 0.62 ± 0.04 and 0.65 ± 0.06 mA with right and left VNS, respectively, and were reflected primarily as augmentation. Afferent-mediated tachycardias were maintained following β-blockade but were eliminated by VNTx. The increased effectiveness and decrease in bradycardia threshold with sequential VNTx suggest that 1) vagal afferents inhibit centrally mediated parasympathetic efferent outflow and 2) the ipsilateral and contralateral vagi exert a substantial buffering capacity. The intact threshold reflects the interaction between multiple levels of the cardiac neural hierarchy.
Persistent change in cardiac fibroblast physiology after transient ACE inhibition
Authors: D'Souza K. M. , Biwer L. A. , Madhavpeddi L. , Ramaiah P. , Shahid W. , Hale T. M.
Published: September 2015

Transient angiotensin-converting enzyme (ACE) inhibition induces persistent changes that protect against future nitric oxide synthase (NOS) inhibitor-induced cardiac fibrosis and inflammation. Given the role of fibroblasts in mediating these effects, the present study investigates whether prior ACE inhibition produced persistent changes in cardiac fibroblast physiology. Adult male spontaneously hypertensive rats (SHRs) were treated with vehicle (C+L) or the ACE inhibitor, enalapril (E+L) for 2 wk followed by a 2-wk washout period and a subsequent 7-day challenge with the NOS inhibitor Nω-nitro-l-arginine methyl ester. A third set of untreated SHRs served as controls. At the end of the study period, cardiac fibroblasts were isolated from control, C+L, and E+L left ventricles to assess proliferation rate, collagen expression, and chemokine release in vitro. After 7 days of NOS inhibition, there were areas of myocardial injury but no significant change in collagen deposition in E+L and C+L hearts in vivo. In vitro, cardiac fibroblasts isolated from C+L but not E+L hearts were hyperproliferative, demonstrated increased collagen type I gene expression, and an elevated secretion of the macrophage-recruiting chemokines monocyte chemoattractant protein-1 and granulocyte macrophage-colony stimulating factor. These findings demonstrate that in vivo Nω-nitro-l-arginine methyl ester treatment produces phenotypic changes in fibroblasts that persist in vitro. Moreover, this is the first demonstration that transient ACE inhibition can produce a persistent modification of the cardiac fibroblast phenotype to one that is less inflammatory and fibrogenic. It may be that the cardioprotective effects of ACE inhibition are related in part to beneficial changes in cardiac fibroblast physiology.
Pregnancy-induced remodeling of heart valves
Authors: Pierlot Caitlin M. , Moeller Andrew D. , Lee J. Michael , Wells Sarah M.
Published: September 2015

Recent studies have demonstrated remodeling of aortic and mitral valves leaflets under the volume loading and cardiac expansion of pregnancy. Those valves' leaflets enlarge with altered collagen fiber architecture, content, and cross-linking and biphasic changes (decreases, then increases) in extensibility during gestation. This study extends our analyses to right-sided valves, with additional compositional measurements for all valves. Valve leaflets were harvested from nonpregnant heifers and pregnant cows. Leaflet structure was characterized by leaflet dimensions, and ECM composition was determined using standard biochemical assays. Histological studies assessed changes in cellular and ECM components. Leaflet mechanical properties were assessed using equibiaxial mechanical testing. Collagen thermal stability and cross-linking were assessed using denaturation and hydrothermal isometric tension tests. Pulmonary and tricuspid leaflet areas increased during pregnancy by 35 and 55%, respectively. Leaflet thickness increased by 20% only in the pulmonary valve and largely in the fibrosa (30% thickening). Collagen crimp length was reduced in both the tricuspid (61%) and pulmonary (42%) valves, with loss of crimped area in the pulmonary valve. Thermomechanics showed decreased collagen thermal stability with surprisingly maintained cross-link maturity. The pulmonary leaflet exhibited the biphasic change in extensibility seen in left side valves, whereas the tricuspid leaflet mechanics remained largely unchanged throughout pregnancy. The tricuspid valve exhibits a remodeling response during pregnancy that is significantly diminished from the other three valves. All valves of the heart remodel in pregnancy in a manner distinct from cardiac pathology, with much similarity valve to valve, but with interesting valve-specific responses in the aortic and tricuspid valves.
FDA Approval: Blinatumomab
Authors: Przepiorka Donna , Ko Chia-Wen , Deisseroth Albert , Yancey Carolyn L. , Candau-Chacon Reyes , Chiu Haw-Jyh , Gehrke Brenda J. , Gomez-Broughton Candace , Kane Robert C. , Kirshner Susan , Mehrotra Nitin , Ricks Tiffany K. , Schmiel Deborah , Song Pengfei , Zhao Ping , Zhou Qing , Farrell Ann T. , Pazdur Richard
Published: September 2015

On December 3, 2014, the FDA granted accelerated approval of blinatumomab (Blincyto; Amgen, Inc.) for treatment of Philadelphia chromosome–negative relapsed or refractory precursor B-cell acute lymphoblastic leukemia (R/R ALL). Blinatumomab is a recombinant murine protein that acts as a bispecific CD19-directed CD3 T-cell engager. The basis for the approval was a single-arm trial with 185 evaluable adults with R/R ALL. The complete remission (CR) rate was 32% [95% confidence interval (CI), 26%–40%], and the median duration of response was 6.7 months. A minimal residual disease response was achieved by 31% (95% CI, 25%–39%) of all patients. Cytokine release syndrome and neurologic events were serious toxicities that occurred. Other common (>20%) adverse reactions were pyrexia, headache, edema, febrile neutropenia, nausea, tremor, and rash. Neutropenia, thrombocytopenia, and elevated transaminases were the most common (>10%) laboratory abnormalities related to blinatumomab. A randomized trial is required in order to confirm clinical benefit. Clin Cancer Res; 21(18); 4035–9. ©2015 AACR.
RICTOR Amplification Defines a Novel Subset of Patients with Lung Cancer Who May Benefit from Treatment with mTORC1/2 Inhibitors
Authors: Cheng Haiying , Zou Yiyu , Ross Jeffrey S. , Wang Kai , Liu Xuewen , Halmos Balazs , Ali Siraj M. , Liu Huijie , Verma Amit , Montagna Cristina , Chachoua Abraham , Goel Sanjay , Schwartz Edward L. , Zhu Changcheng , Shan Jidong , Yu Yiting , Gritsman Kira , Yelensky Roman , Lipson Doron , Otto Geoff , Hawryluk Matthew , Stephens Philip J. , Miller Vincent A. , Piperdi Bilal , Perez-Soler Roman
Published: September 2015

We identified amplification of RICTOR, a key component of the mTOR complex 2 (mTORC2), as the sole actionable genomic alteration in an 18-year-old never-smoker with lung adenocarcinoma. Amplification of RICTOR occurs in 13% of lung cancers (1,016 cases) in The Cancer Genome Atlas and at a similar frequency in an independent cohort of 1,070 patients identified by genomic profiling. In the latter series, 11% of cases harbored RICTOR amplification as the only relevant genomic alteration. Its oncogenic roles were suggested by decreased lung cancer cell growth both in vitro and in vivo with RICTOR ablation, and the transforming capacity of RICTOR in a Ba/F3-cell system. The mTORC1/2 inhibitors were significantly more active against RICTOR-amplified lung cancer cells as compared with other agents targeting the PI3K–AKT–mTOR pathway. Moreover, an association between RICTOR amplification and sensitivities to mTORC1/2 inhibitors was observed. The index patient has been treated with mTORC1/2 inhibitors that led to tumor stabilization for more than 18 months.

Significance: RICTOR amplification may define a novel and unique molecular subset of patients with lung cancer who may benefit from treatment with mTORC1/2 inhibitors. Cancer Discov; 5(12); 1262–70. ©2015 AACR.

This article is highlighted in the In This Issue feature, p. 1225
ЕПІДЕМІОЛОГІЧНИХ ПОКАЗНИКІВ І ПРОГНОЗ РОЗВИТКУ ЕПІДЕМІЇ ВІЛ-ІНФЕКЦІЇ В ЗАПОРІЗЬКІЙ ОБЛАСТІ ДО 2018 РОКУ
Authors: Живиця Д.Г.
Published: September 2015

Епідемія ВІЛ-інфекції в Україні є однією з найтяжчих серед країн Східної Європи. В рамках стратегії децентралізації медичної допомоги в Україні в цілому, в тому числі у відношенні до хворих на ВІЛ-інфекцію, та оптимізації матеріальних і кадрових ресурсів вкрай важливе значення має прогноз розвитку інфекційного процесу ВІЛ/СНІД на окремих територіях країни. Метою нашого дослідження була розробка прогнозу розвитку епідемії ВІЛ-інфекції у Запорізькій області до 2018 р. Згідно з розрахованим прогнозом, у 2018 р. захворюваність може зрости до показника 42,9 на 100 тисяч населення, кількість нових випадків ВІЛ-інфекції може досягти 729 осіб на рік, а приріст кількості вперше виявлених хворих складе у середньому 21 пацієнт щорічно. За даними прогнозу, щорічне збільшення кількості ВІЛ-інфікованих пацієнтів на обліку в Запорізькій області складе 235 пацієнтів і у 2018 р. чисельність пацієнтів, які перебувають на обліку, досягне 4738.
А.П. Подаваленко, Т.Є. Петренко, Л.О. Клещар, О.В. Подаваленко ОЦІНКА ЕФЕКТИВНОСТІ КОМП’ЮТЕРНОЇ ПРОГРАМИ ПРОГНОЗУВАННЯ РІВНЯ ЗАХВОРЮВАНОСТІ НА КІР, КРАСНУХУ ТА ЕПІДЕМІЧНИЙ ПАРОТИТ
Authors: Подаваленко А.П. , Петренко Т.Є. , Клещар Л.О. , Подаваленко О.В.
Published: September 2015

Комп’ютерна програма з використанням методу експонентного згладжування (математична модель Брауна) розроблена та успішно впроваджена в роботу санітарно-епідеміологічного закладу м. Харкова. Встановлено хорошу її чутливість (86,4 %) та специфічність (70,8 %). Застосування програми прогнозування рівня інфекційної захворюваності сприяло удосконаленню епідеміологічного нагляду за кором, краснухою та епідемічним паротитом, що підтверджено зниженням захворюваності на ці інфекції. Прогнозується ускладнення епідемічної ситуації через низький рівень охоплення щепленнями та активізацію міграційних процесів.
ПОШИРЕНІСТЬ ДЕЯКИХ ГЕЛЬМІНТОЗІВ У ЧЕРНІВЕЦЬКІЙ ОБЛАСТІ
Authors: Захарчук О.І. , Пішак В.П. , Кривчанська М.І. , Миронюк М.Б.
Published: September 2015

Досліджено екологічні та епідеміологічні особливості аскаридозу, ентеробіозу та трихоцефальозу в різних регіонах Чернівецької області за 2013 рік та перше півріччя 2014 року. Висока захворюваність на гельмінтози зумовлюється низькою дегельмінтизацією населення та тварин, збільшенням кількості домашніх тварин, забрудненням навколишнього середовища стічними водами, які містять яйця глистів, відсутністю цілеспрямованої пропаганди щодо дотримання гігієнічних норм, міграцією населення та поширенням туризму у Чернівецькій області, вкрай низькою інформованістю про сучасні методи діагностики гельмінтозів (послуги місцевих лабораторій), не завжди своєчасним та адекватним лікуванням. 
РЕЗУЛЬТАТИ ЕПІДРОЗСЛІДУВАННЯ СПАЛАХУ САЛЬМОНЕЛЬОЗУ У ТЕРНОПІЛЬСЬКІЙ ОБЛАСТІ
Authors: Паничев В.О. , Цяпа Н.В. , Павельєва М.М. , Кулачковська І.В. , Маціпура С.В. , Годована Н.І. , Білинська О.Я. , Дементьєв Ю.Г. , Барна Т.Б. , Ясіновська С.Є.
Published: September 2015

Масштаби спалаху сальмонельозу залежать від оперативності дій фахівців у напрямку встановлення спільного фактора передачі інфекції, а час існування осередку – від якості проведених протиепідемічних заходів.
КРИПТОКОКОВИЙ МЕНІНГІТ ОСОБЛИВОСТІ ЛІКУВАННЯ (частина I)*
Authors: Бондаренко А.М.
Published: September 2015

Проведений ретельний аналіз етіотропної терапії криптококового менінгіту. Показана необхідність повного перегляду старого вітчизняного клінічного протоколу з лікування криптококового менінгіту та внесення до нього істотних коректив відповідно до даних сучасних і перспективних досліджень. Етіотропна терапія криптококового менінгіту вимагає сьогодні забезпечення максимальної ефективності та безпеки. Показано, що вирішення цього завдання можливо досягти при: динамічному визначенні рівня антимікотику в лікворі та сироватці крові хворого; динамічному визначенні чутливості криптококів до антимікотиків; ретельному доборі антимікотиків, їхніх комбінацій, доз та режимів введення; врахуванні можливих лікарських взаємодій при комбінуванні антимікотиків, а також їх взаємодії з іншими, особливо антиретровірусними, препаратами.
РЕТРОСПЕКТИВНИЙ АНАЛІЗ ЕПІДСИТУАЦІЇ ЩОДО ТУБЕРКУЛЬОЗУ НА ТЕРИТОРІЇ ТЕРНОПІЛЬСЬКОЇ ОБЛАСТІ ЗА 2010-2014 РОКИ
Authors: Паничев В.О. , Павельєва М.М. , Кулачковська І.В. , Маціпура С.В. , Годована Н.І.
Published: September 2015

Протягом останніх років епідемічна ситуація щодо туберкульозу на території області, незважаючи на зниження показників захворюваності та смертності, залишається напруженою. Домогтися зниження розповсюдження туберкульозу на території області можна за умови активного реагування на проблему, покращення фінансування, впровадження сучасних методів діагностики та лікування, організації ефективних профілактичних і протиепідемічних заходів в осередках.