bluuebunny/crossref_metadata_2025 huggingface dataset:
Strategies for the Synthesis of the Halenaquinol and Xestoquinol Families of Natural Products
Authors: Schwarzwalder Gregg M. , Vanderwal Christopher D.
Published: February 2017

The halenaquinol family of naphthoquinol natural products includes a few closely related polycyclic compounds that each feature an activated, electrophilic furan ring. This motif is likely responsible for the rich biological activity attributed to these secondary metabolites. Their interesting structures – related through their electrophilic furan moieties to the biologically important furanosteroids – and their activities prompted significant efforts by organic chemists that resulted in many strategically compelling laboratory syntheses of these targets. These different strategies are compared and contrasted in this microreview, and the authors' recent work on the structurally different but biogenetically related natural product exiguaquinol is put into the context of the previous studies on halenaquinol‐type targets.
Synthesis of Steroidal D‐Ring‐Fused Pyrrolidines of Dehydroepiandrosterone
Authors: Blanco‐Ania Daniel , W. M. Aben René , van Berkom Leon W. A. , Scheeren Hans W. , Rutjes Floris P. J. T.
Published: February 2017

The commercially available steroid dehydroepiandrosterone 3‐acetate (DHEA) was converted into steroidal D‐ring‐fused pyrrolidines that combine two privileged structures: a steroid and a (2‐arylethyl)amine. The three‐step transformations proceeded through conversion of the C‐17 ketone into an enol ether, followed by high‐pressure‐mediated cascade [4+2]/[3+2] cycloadditions with two nitroalkenes ([4+2]) and five dipolarophiles ([3+2]) to yield azonite intermediates. Finally, reduction of these azonites formed the new azasteroids, which are suitable for further derivatization.
Age‐related changes in laser‐evoked potentials following trigeminal and hand stimulation in healthy subjects
Authors: de Tommaso M. , Ricci K. , Montemurno A. , Vecchio E.
Published: February 2017

Objective

This study aimed to evaluate age‐related changes in laser‐evoked potential (LEP) features, including habituation, via trigeminal and hand stimulation in a large group of healthy volunteers.

Methods

We recorded the LEPs by right‐hand stimulation in 237 healthy subjects and by stimulation of the right supraorbital zone in 170 cases. The subjects ranged in age from 7 to 72 years and were divided into six groups by age.

Results

At the trigeminal level, the N2 and P2 latencies were significantly shorter and the N2–P2 amplitude was significantly larger in the 7–17 age group than in the other groups. The N2–P2 amplitude of the responses evoked by hand stimulation was significantly larger in the 7–40 age range than in the older subjects. The N1 amplitude and latency were not significantly different among the groups. The N2–P2 habituation increased with age, but no significant changes among groups were revealed by the Bonferroni test.

Conclusions

Trigeminal vertex LEPs have greater amplitudes and appear earlier in children, while a progressive age‐related amplitude decrease characterizes the N2–P2 waves associated with hand stimulation. The N2–P2 habituation increases in older people. The N1 latency and amplitude seem to remain stable during ageing and are therefore potentially reliable and useful patterns for nociceptive system examination.

Significance

Standardization of age‐related changes in trigeminal and hand LEPs is possible and should improve their reliability in the objective assessment of pain pathways.
NTE/PNPLA6 is expressed in mature Schwann cells and is required for glial ensheathment of Remak fibers
Authors: McFerrin Janis , Patton Bruce L. , Sunderhaus Elizabeth R. , Kretzschmar Doris
Published: February 2017

Neuropathy target esterase (NTE) or patatin‐like phospholipase domain containing 6 (PNPLA6) was first linked with a neuropathy occurring after organophosphate poisoning and was later also found to cause complex syndromes when mutated, which can include mental retardation, spastic paraplegia, ataxia, and blindness. NTE/PNPLA6 is widely expressed in neurons but experiments with its Drosophila orthologue Swiss‐cheese (SWS) suggested that it may also have glial functions. Investigating whether NTE/PNPLA6 is expressed in glia, we found that NTE/PNPLA6 is expressed by Schwann cells in the sciatic nerve of adult mice with the most prominent expression in nonmyelinating Schwann cells. Within Schwann cells, NTE/PNPLA6 is enriched at the Schmidt‐Lanterman incisures and around the nucleus. When analyzing postnatal expression patterns, we did not detect NTE/PNPLA6 in promyelinating Schwann cells, while weak expression was detectable at postnatal day 5 in Schwann cells and increased with their maturation. Interestingly, NTE/PNPLA6 levels were upregulated after nerve crush and localized to ovoids forming along the nerve fibers. Using a GFAP‐based knock‐out of NTE/PNPLA6, we detected an incomplete ensheathment of Remak fibers whereas myelination did not appear to be affected. These results suggest that NTE/PNPLA6 is involved in the maturation of nonmyelinating Schwann cells during development and de‐/remyelination after neuronal injury. Since Schwann cells play an important role in maintaining axonal viability and function, it is therefore likely that changes in Schwann cells contribute to the locomotory deficits and neuropathy observed in patients carrying mutations in NTE.
Housing First for older homeless adults with mental illness: a subgroup analysis of the At Home/Chez Soi randomized controlled trial
Authors: Chung Timothy E. , Gozdzik Agnes , Palma Lazgare Luis I. , To Matthew J. , Aubry Tim , Frankish James , Hwang Stephen W. , Stergiopoulos Vicky
Published: February 2017

Objective

This study compares the effect of Housing First on older (≥50 years old) and younger (18–49 years old) homeless adults with mental illness participating in At Home/Chez Soi, a 24‐month multisite randomized controlled trial of Housing First.

Method

At Home/Chez Soi, participants (n = 2148) were randomized to receive rent supplements with intensive case management or assertive community treatment, based on their need level for mental health services, or usual care in their respective communities. A subgroup analysis compared older (n = 470) and younger (n = 1678) homeless participants across baseline characteristics and 24‐month outcomes including housing stability (primary outcome), generic and condition‐specific quality of life, community functioning, physical and mental health status, mental health symptom severity, psychological community integration, recovery, and substance use (secondary outcomes).

Results

At 24 months, Housing First significantly improved the percentage of days stably housed among older (+43.9%, 95% confidence interval [CI]: 38.4% to 49.5%) and younger homeless adults (+39.7%, 95% CI: 36.8% to 42.6%), compared with usual care, with no significant differences between age groups (difference of differences = +4.2%, 95% CI: −2.1% to 10.5%, p = 0.188). Improvements from baseline to 24 months in mental health and condition‐specific quality of life were significantly greater among older homeless adults than among younger homeless adults.

Conclusion

Housing First significantly improved housing stability among older and younger homeless adults with mental illness, resulting in superior mental health and quality of life outcomes in older homeless adults compared with younger homeless adults at 24 months. Copyright © 2017 John Wiley & Sons, Ltd.
Altered neural mechanisms of cognitive control in patients with primary progressive multiple sclerosis: An effective connectivity study
Authors: Dobryakova Ekaterina , Rocca Maria Assunta , Valsasina Paola , DeLuca John , Filippi Massimo
Published: February 2017

Primary progressive multiple sclerosis (PPMS) leads to physical and cognitive disability. Specifically, cognitive deficits in PPMS have been explained by both grey matter atrophy and white matter lesions. However, existing research still lacks in the understanding of how the brain of a patient with PPMS functions under cognitive control demands. Thus, the aim of the current study was to examine information integration in patients with PPMS using a search‐based effective connectivity method. Fourteen patients with PPMS and 22 age‐ and gender‐matched healthy controls (HC) performed the Stroop task, a cognitively demanding interference task that taxes neural resources required for cognitive control and response inhibition. Results showed that compared to HC, PPMS patients exhibited poor behavioral performance and alterations in information flow, manifested in the form of the loss of top‐down connections, reversal of connections, and hyperconnectivity. Significant correlations were observed between connection strengths and behavioral measures. The connection between the posterior parietal cortex (PCC) and left posterior parietal lobule, which was present in both groups, showed a negative correlation with performance accuracy on incongruent trials. The connection between the left dorsolateral prefrontal cortex and PCC showed a positive correlation with performance accuracy on incongruent trials. However, the adaptive nature of this connection was not significant on a behavioral level as the PPMS group performed significantly worse compared to the HC group during the Stroop task. Thus, the current study provides important evidence about effective connectivity patterns that can be characterized as maladaptive cerebral re‐organization in the PPMS brain. Hum Brain Mapp 38:2580–2588, 2017. © 2017 Wiley Periodicals, Inc.
Analysis of River Flow Regime Changes Related to Water Availability on the Kapuas River, Indonesia
Authors: Herawati Henny , Suripin S. , Suharyanto S. , Hetwisari Tia
Published: February 2017

Rivers are major sources of fresh water, which is a basic need in society. The availability of water is affected by river basin characteristics such as rainfall and land cover type. Along with population and economy growth, there has been a change in land use that leads to changes in land cover types, thereby changing the river flow regime and affecting the availability of water in the river. Thus it is necessary to analyse water flow regime changes in the river to determine water availability for proper action plans in the future. Studies on these aspects were conducted in the Kapuas River Basin with an area of about 100 000 km2, in West Kalimantan, Indonesia. The study was conducted by analysing the trend of annual rainfall and change of land cover during the last three decades, by analysing land cover types and comparing the availability of water in the Kapuas River from measurement results in 2002 and 2012. The results showed that the rainfall trend had increased 4.3% over the last 30 years. The changes in the hydrological aspects of the study area have altered the river flow regime of Kapuas River within the last 30 years and have influenced river water availability. Copyright © 2017 John Wiley & Sons, Ltd.
Lean six sigma methodologies improve clinical laboratory efficiency and reduce turnaround times
Authors: Inal Tamer C. , Goruroglu Ozturk Ozlem , Kibar Filiz , Cetiner Salih , Matyar Selcuk , Daglioglu Gulcin , Yaman Akgun
Published: February 2017

Background

Organizing work flow is a major task of laboratory management. Recently, clinical laboratories have started to adopt methodologies such as Lean Six Sigma and some successful implementations have been reported. This study used Lean Six Sigma to simplify the laboratory work process and decrease the turnaround time by eliminating non‐value‐adding steps.

Methods

The five‐stage Six Sigma system known as define, measure, analyze, improve, and control (DMAIC) is used to identify and solve problems. The laboratory turnaround time for individual tests, total delay time in the sample reception area, and percentage of steps involving risks of medical errors and biological hazards in the overall process are measured.

Results

The pre‐analytical process in the reception area was improved by eliminating 3 h and 22.5 min of non‐value‐adding work. Turnaround time also improved for stat samples from 68 to 59 min after applying Lean. Steps prone to medical errors and posing potential biological hazards to receptionists were reduced from 30% to 3%.

Conclusion

Successful implementation of Lean Six Sigma significantly improved all of the selected performance metrics. This quality‐improvement methodology has the potential to significantly improve clinical laboratories.
A perspective on malignancy in the marrow
Authors: Reagan Michaela R. , Lian Jane B. , Rosen Clifford J. , Stein Gary S.
Published: February 2017

Malignancies that grow in the bone marrow cause a cascade of devastating consequences and are almost always fatal. For researchers to make significant headway in finding cures and treatments for these tumors and the subsequent devastation of cancer‐induced bone disease, novel strategies and creative solutions will have to be considered. Great progress has been made in treating hematologic and sold tumor malignancies that ultimately affect the bone marrow, although it is also obvious that multi‐disciplinary teams are required to ultimately win the war on cancers that affect the bone. In this perspective, we review recent advances in the identification of molecular and cellular targets in the bone marrow niche.
Potential of quantitative susceptibility mapping for detection of prostatic calcifications
Authors: Straub Sina , Laun Frederik B. , Emmerich Julian , Jobke Björn , Hauswald Henrik , Katayama Sonja , Herfarth Klaus , Schlemmer Heinz‐Peter , Ladd Mark E. , Ziener Christian H. , Bonekamp David , Röthke Matthias C.
Published: February 2017

Purpose

To evaluate whether quantitative susceptibility (QSM) may be used as an alternative to computed tomography (CT) to detect calcification in prostate cancer patients.

Materials and Methods

Susceptibility map calculation was performed using 3D gradient echo magnetic resonance imaging (MRI) data from 26 patients measured at 3T who previously received a planning CT of the prostate. Phase images were unwrapped using Laplacian‐based phase unwrapping, the background field was removed with the V‐SHARP method, and susceptibility maps were calculated with the iLSQR method. Two blinded readers were asked to identify peri‐ and intraprostatic calcifications.

Results

Average mean and minimum susceptibility values (referenced to iliopsoas muscle) of calcifications were −0.249 ± 0.179 ppm and –0.551 ± 0.323 ppm, and average mean and maximum intensities in CT images were 319 ± 164 HU and 679 ± 392 HU. Twenty‐one and 17 out of 22 prostatic calcifications were identified using susceptibility maps and magnitude images, respectively, as well as more than half of periprostatic phleboliths depicted by CT. Calcifications in the prostate and its periphery were quantitatively differentiable from noncalcified prostate tissue in CT (mean values for calcifications / for noncalcified tissue: 71 to 649 / –1 to 83 HU) and in QSM (mean values for calcifications / for noncalcified tissue: –0.641 to 0.063 / –0.046 to 0.181 ppm). Moreover, there was a significant correlation between susceptibility values and CT image intensities for calcifications (P < 0.004).

Conclusion

Prostatic calcifications could be well identified with QSM. Susceptibility maps can be easily obtained from clinical prostate MR protocols that include a 3D gradient echo sequence, rendering it a promising technique for detection and quantification of intraprostatic calcifications.

Level of Evidence: 1

J. Magn. Reson. Imaging 2017;45:889–898.
Bioprocessing of common beans in diets for tilapia: in vivo digestibility and antinutritional factors
Authors: Valdez‐González Francisco , Gutiérrez‐Dorado Roberto , Hernández‐Llamas Alfredo , García‐Ulloa Manuel , Sánchez‐Magaña Luís , Cuevas‐Rodríguez Breidy , Rodríguez‐González Hervey
Published: February 2017

BACKGROUND

Bioprocessing of ingredients by solid‐state fermentation is a low‐cost technique for preparing diets. It is performed by adding microorganisms such as Rhizopus oligosporus to bean grains, achieving minimal degradation of nutrients and a significant improvement in digestibility. In particular, fermentation induces favorable changes in beans by reducing enzyme inhibitors, such as phytates and tannins.

RESULTS

Fermentation significantly (P < 0.05) increased the protein content and digestibility of dry matter and protein compared with whole bean grains, and decreased the content of lipids, ash and phytic acid. Hardening did not have a significant (P > 0.05) effect on the chemical content of beans and digestibility of diets. The dehulled bean meal significantly (P < 0.05) increased protein and lipid content and digestibility of dry matter and protein of beans, and decreased fiber, ash and tannin content. The chemical content of beans and digestibility of ingredients compare favorably with those reported by other authors, indicating the benefits of fermentation and dehulling.

CONCLUSION

We concluded that bean meal obtained from fermentation or dehulling represents a low‐cost alternative for diets for tilapia. © 2017 Society of Chemical Industry
Atheroprotective Effects and Molecular Targets of Tanshinones Derived From Herbal Medicine Danshen
Authors: Fang Jian , Little Peter J. , Xu Suowen
Published: February 2017

Medicinal plant‐derived bioactive compounds modulate multiple therapeutic targets in cardiovascular diseases (CVDs), rendering herb‐derived phytochemicals effective against one of the major CVDs‐atherosclerosis. Danshen (Salvia milthiorriza Bunge) is a Chinese medicine that has been used in cardio‐ and cerebro‐vascular therapeutic remedies in Asian countries for many years. Emerging evidence from cellular, animal, and clinical studies suggests that major lipophilic tanshinones from Danshen can treat atherosclerotic CVDs. In this review, we highlight recent advances in understanding the molecular mechanisms of tanshinones in treating atherosclerosis, ranging from endothelial dysfunction to chronic inflammation. We also overview new molecular targets of tanshinones, including endothelial nitric oxide synthase, AMP‐activated protein kinase, ABC transporter A1, heme oxygenase 1, soluble epoxide hydrolase, 11β‐hydroxysteroid dehydrogenase, estrogen receptor, and proprotein convertase subtilisin/kexin type 9. Thus, this review provides a new perspective for advancing our understanding of the “ancient” herb Danshen from “modern” biomedical perspectives, supporting the possibility of exploiting tanshinones and derivatives as effective therapeutics against atherosclerosis‐related cardiovascular and metabolic diseases.
Automatic segmentation of the right ventricle from cardiac MRI using a learning‐based approach
Authors: Avendi Michael R. , Kheradvar Arash , Jafarkhani Hamid
Published: February 2017

Purpose

This study aims to accurately segment the right ventricle (RV) from cardiac MRI using a fully automatic learning‐based method.

Methods

The proposed method uses deep learning algorithms, i.e., convolutional neural networks and stacked autoencoders, for automatic detection and initial segmentation of the RV chamber. The initial segmentation is then combined with the deformable models to improve the accuracy and robustness of the process. We trained our algorithm using 16 cardiac MRI datasets of the MICCAI 2012 RV Segmentation Challenge database and validated our technique using the rest of the dataset (32 subjects).

Results

An average Dice metric of 82.5% along with an average Hausdorff distance of 7.85 mm were achieved for all the studied subjects. Furthermore, a high correlation and level of agreement with the ground truth contours for end‐diastolic volume (0.98), end‐systolic volume (0.99), and ejection fraction (0.93) were observed.

Conclusion

Our results show that deep learning algorithms can be effectively used for automatic segmentation of the RV. Computed quantitative metrics of our method outperformed that of the existing techniques participated in the MICCAI 2012 challenge, as reported by the challenge organizers. Magn Reson Med 78:2439–2448, 2017. © 2017 International Society for Magnetic Resonance in Medicine.
Multishot echo‐planar MREIT for fast imaging of conductivity, current density, and electric field distributions
Authors: Chauhan Munish , Vidya Shankar Rohini , Ashok Kumar Neeta , Kodibagkar Vikram D. , Sadleir Rosalind
Published: February 2017

Purpose

Magnetic resonance electrical impedance tomography (MREIT) sequences typically use conventional spin or gradient echo–based acquisition methods for reconstruction of conductivity and current density maps. Use of MREIT in functional and electroporation studies requires higher temporal resolution and faster sequences. Here, single and multishot echo planar imaging (EPI) based MREIT sequences were evaluated to see whether high‐quality MREIT phase data could be obtained for rapid reconstruction of current density, conductivity, and electric fields.

Methods

A gel phantom with an insulating inclusion was used as a test object. Ghost artifact, geometric distortion, and MREIT correction algorithms were applied to the data. The EPI‐MREIT‐derived phase‐projected current density and conductivity images were compared with simulations and spin‐echo images as a function of EPI shot number.

Results

Good agreement among measures in simulated, spin echo, and EPI data was achieved. Current density errors were stable and below 9% as the shot number decreased from 64 to 2, but increased for single‐shot images. Conductivity reconstruction relative contrast ratios were stable as the shot number decreased. The derived electric fields also agreed with the simulated data.

Conclusions

The EPI methods can be combined successfully with MREIT reconstruction algorithms to achieve fast imaging of current density, conductivity, and electric field. Magn Reson Med 79:71–82, 2018. © 2017 International Society for Magnetic Resonance in Medicine.
Towards performance prediction of multicore software routers
Authors: Suksomboon Kalika , Matsumoto Nobutaka , Fukushima Masaki , Okamoto Shuichi , Hayashi Michiaki
Published: February 2017

Rapid advances in network function virtualization technologies have led to the emergence of flexible and scalable embedded data plane processing functions, eg, packet forwarding, on commodity hardware. However, performance prediction of softwarized network functions on such shared resources is challenging but very important for obtaining the full benefits of network function virtualization. This paper addresses the problem of performance prediction for multicore software routers and reveals a key technique to achieve high accuracy. Motivated by observations, we first analyze how many CPU cycles are spent for forwarding a packet in multicore processing systems. Our prediction model of the CPU usage based on cache contention can capture its nonlinear dilation scaled by the number of CPU cores–called dilated CPU consumption (DCC). We validate the accuracy of the DCC model with measured data. On the basis of the DCC model, we develop 2 performance prediction algorithms to predict the maximum throughput of the packet‐forwarding function corresponding to the assigned resources. The first algorithm includes CPU utilization statistics (called DCC‐u), while its simplified version (called sDCC) does not require CPU utilization statistics. We validate the proposed models through the exhaustive set of experiments under various amounts of assigned resources (ie, CPU speeds and the number of CPU cores) and different traffic loads (ie, a large and small number of traffic flows). The results show that DCC‐u and sDCC achieve high accuracy under various amounts of resources and traffic conditions. Remarkably, they improve the precision of estimation from that of the existing techniques by up to 105% to 163%.
Stabilized velocity and pressure mixed hybrid DGFEM for the stokes problem
Authors: Igreja Iury , Loula Abimael F. D.
Published: February 2017

We propose mixed hybrid Discontinuous Galerkin Finite Element (DGFEM) formulations for the Stokes problem characterized by the introduction of Lagrange multipliers associated with the traces of the velocity and pressure fields on the edges of the elements to weakly impose the transmission conditions. Both velocity and pressure multipliers are stabilized and, as a consequence of these stabilizations, we prove existence and uniqueness of solution for the local problems. All velocity and pressure degrees‐of‐freedom can be eliminated at the element level by static condensation leading to a global problem in the multipliers only. The proposed methodology is able to recover stability of very convenient choices of finite element spaces, such as those adopting equal order polynomial approximations for all fields. Numerical experiments illustrate the flexibility and robustness of the proposed formulations and show optimal rates of convergence. Copyright © 2017 John Wiley & Sons, Ltd.
Robustness Indices in Multistage Problems
Authors: Moslemi Amir , Seyyed‐Esfahani Mirmehdi
Published: February 2017

The study of robustness in single‐stage manufacturing has been surveyed by many researchers, while modeling of robustness in multistage manufacturing using multivariate data is seldom explored. The aim of this paper is to develop a methodology to model process robustness in a multistage manufacturing system. This paper proposes a methodology to study the robustness of a multistage process that creates a component and process capability that acts as a surrogate measure of robustness. A powerful technique to facilitate the analysis of the mentioned problem, response surfaces express the behavior of responses considering the above controllable factors (quality characteristics). A common approach to estimating response surfaces using experimental data is the ordinary least squares method. Because this method is very sensitive to outliers and correlated responses, in this paper, a robust coefficient estimation method is proposed for multiresponse surfaces in multistage processes based on M‐estimators. The results show that considering the proposed robustness criteria based on a multivariate process capability index, the robust multistage process would perform better than the individual stage process. This paper adds to the body of knowledge on the robustness of multistage manufacturing processes, and also the relationship between robustness and capability is to be explored as surrogate robustness indices in the multistage process. The efficiency of the proposed approach is assessed by a small simulation study besides a real manufacturing case study. Copyright © 2017 John Wiley & Sons, Ltd.
Implicit Lyapunov‐based control strategy for closed quantum systems with dipole and polarizability coupling
Authors: Zhao Shouwei , Lin Hai , Sun Jitao , Zhou Lei
Published: February 2017

In this paper, the state transfer of finite dimensional closed quantum systems with dipole and polarizability coupling in non‐ideal cases is investigated. Two kinds of non‐ideal systems are considered, where the internal Hamiltonian of the system is not strongly regular and not all the eigenvectors of the internal Hamiltonian are directly coupled with the target state. Such systems often exist in practical quantum systems such as the one‐dimensional oscillator and coupled two‐spin system. An implicit Lyapunov‐based control strategy is proposed here with convergence analysis for quantum systems modeled by finite dimensional bilinear Schrödinger equations. Specifically, two kinds of Lyapunov functions are defined via implicit functions, and their existences are guaranteed with the help of a fixed point theorem. Then, the local convergence analysis is investigated with the explicit characterization of the largest invariant set by LaSalle invariance principle. Finally, the performance of the feedback design is illustrated by numerical simulations. Copyright © 2017 John Wiley & Sons, Ltd.
Regional Controls on Physical Habitat Structure of Amazon Streams
Authors: Benone N. L. , Esposito M. C. , Juen L. , Pompeu P. S. , Montag L. F. A.
Published: February 2017

Drainage basins are inherently hierarchical and are composed of a series of nested subsystems, in which the functions and structure of lower levels depend on the features of higher levels. For a comprehensive understanding of the functioning of river systems, it is necessary to identify which factors are important at different scales and how they interact. Considering the importance of assessing lotic systems in the Amazon, our aim was to answer the following question: how do regional features at catchment scale constrain local physical habitat of streams? We sampled 55 streams distributed among six protected river basins of the Amazon, examining the associations of 11 catchment metrics with 146 local variables describing physical habitat structure derived from field measurements. Multivariate analyses showed that basins were structured according to different factors at both scales; variables related to substrate, cover for aquatic organisms and fast channel habitats were explained by altitude, catchment slope and proportion of coarse fragments in soils. Altitude was the most important catchment variable, strongly affecting flow velocity and regulating channel morphology and sediment transport. Spatial differences in environmental heterogeneity indicate that different processes act at each scale; this emphasizes how difficult it is to choose the most relevant spatial scale in ecological studies. Our results highlight the importance of regional variables, especially altitude and slope, as drivers of local‐scale environmental heterogeneity. We hope these results will help in developing more efficient monitoring projects and restoration practices to better understand and conserve aquatic resources in the Amazon Basin. Copyright © 2017 John Wiley & Sons, Ltd.
Microfluidic Screening Reveals Heparan Sulfate Enhances Human Mesenchymal Stem Cell Growth by Modulating Fibroblast Growth Factor-2 Transport
Authors: Titmarsh Drew M. , Tan Clarissa L.L. , Glass Nick R. , Nurcombe Victor , Cooper-White Justin J. , Cool Simon M.
Published: February 2017

Cost-effective expansion of human mesenchymal stem/stromal cells (hMSCs) remains a key challenge for their widespread clinical deployment. Fibroblast growth factor-2 (FGF-2) is a key hMSC mitogen often supplemented to increase hMSC growth rates. However, hMSCs also produce endogenous FGF-2, which critically interacts with cell surface heparan sulfate (HS). We assessed the interplay of FGF-2 with a heparan sulfate variant (HS8) engineered to bind FGF-2 and potentiate its activity. Bone marrow-derived hMSCs were screened in perfused microbioreactor arrays (MBAs), showing that HS8 (50 μg/ml) increased hMSC proliferation and cell number after 3 days, with an effect equivalent to FGF-2 (50 ng/ml). In combination, the effects of HS8 and FGF-2 were additive. Differential cell responses, from upstream to downstream culture chambers under constant flow of media in the MBA, provided insights into modulation of FGF-2 transport by HS8. HS8 treatment induced proliferation mainly in the downstream chambers, suggesting a requirement for endogenous FGF-2 accumulation, whereas responses to FGF-2 occurred primarily in the upstream chambers. Adding HS8 along with FGF-2, however, maximized the range of FGF-2 effectiveness. Measurements of FGF-2 in static cultures then revealed that this was because HS8 caused increased endogenous FGF-2 production and liberated FGF-2 from the cell surface into the supernatant. HS8 also sustained levels of supplemented FGF-2 available over 3 days. These results suggest HS8 enhances hMSC proliferation and expansion by leveraging endogenous FGF-2 production and maximizing the effect of supplemented FGF-2. This is an exciting strategy for cost-effective expansion of hMSCs.
Integrated precision medicine: the role of electronic health records in delivering personalized treatment
Authors: Sitapati Amy , Kim Hyeoneui , Berkovich Barbara , Marmor Rebecca , Singh Siddharth , El‐Kareh Robert , Clay Brian , Ohno‐Machado Lucila
Published: February 2017

Precision Medicine involves the delivery of a targeted, personalized treatment for a given patient. By harnessing the power of electronic health records (EHRs), we are increasingly able to practice precision medicine to improve patient outcomes. In this article, we introduce the scientific community at large to important building blocks for personalized treatment, such as terminology standards that are the foundation of the EHR and allow for exchange of health information across systems. We briefly review different types of clinical decision support (CDS) and present the current state of CDS, which is already improving the care patients receive with genetic profile‐based tailored recommendations regarding diagnostic and treatment plans. We also report on limitations of current systems, which are slowly beginning to integrate new genomic data into patient records but still present many challenges. Finally, we discuss future directions and how the EHR can evolve to increase the capacity of the healthcare system in delivering Precision Medicine at the point of care. WIREs Syst Biol Med 2017, 9:e1378. doi: 10.1002/wsbm.1378

This article is categorized under:

Translational, Genomic, and Systems Medicine > Translational Medicine
Phase 1b trial of proteasome inhibitor carfilzomib with irinotecan in lung cancer and other irinotecan-sensitive malignancies that have progressed on prior therapy (Onyx IST reference number: CAR-IST-553)
Authors: Arnold Susanne M. , Chansky Kari , Leggas Markos , Thompson Michael A. , Villano John L. , Hamm John , Sanborn Rachel E. , Weiss Glen J. , Chatta Gurkamal , Baggstrom Maria Q.
Published: February 2017

Introduction Proteasome inhibition is an established therapy for many malignancies. Carfilzomib, a novel proteasome inhibitor, was combined with irinotecan to provide a synergistic approach in relapsed, irinotecan-sensitive cancers. Materials and Methods Patients with relapsed irinotecan-sensitive cancers received carfilzomib (Day 1, 2, 8, 9, 15, and 16) at three dose levels (20/27 mg/m2, 20/36 mg/m2 and 20/45 mg/m2/day) in combination with irinotecan (Days 1, 8 and 15) at 125 mg/m2/day. Key eligibility criteria included measurable disease, a Zubrod PS of 0 or 1, and acceptable organ function. Patients with stable asymptomatic brain metastases were eligible. Dose escalation utilized a standard 3 + 3 design. Results Overall, 16 patients were enrolled to three dose levels, with four patients replaced. Three patients experienced dose limiting toxicity (DLT) and the maximum tolerated dose (MTD) was exceeded in Cohort 3. The RP2 dose was carfilzomib 20/36 mg/m2 (given on Days 1, 2, 8, 9, 15, and 16) and irinotecan 125 mg/m2 (Days 1, 8 and 15). Common Grade (Gr) 3 and 4 toxicities included fatigue (19%), thrombocytopenia (19%), and diarrhea (13%). Conclusions Irinotecan and carfilzomib were well tolerated, with common toxicities of fatigue, thrombocytopenia and neutropenic fever. Objective clinical response was 19% (one confirmed partial response (PR) in small cell lung cancer (SCLC) and two unconfirmed); stable disease (SD) was 6% for a disease control rate (DCR) of 25%. The recommended phase II dose was carfilzomib 20/36 mg/m2 and irinotecan125 mg/m2. The phase II evaluation is ongoing in relapsed small cell lung cancer.
« Ne nous engageons point dans les querelles »: un projet de guerre perpétuelle ?
Authors: Tunstall Kate E.
Published: February 2017

Cet article aborde la querelle comme un élément de la stratégie d'un philosophe vis-à-vis de la postérité. On pourrait évidemment penser à des querelleurs invétérés comme Pascal, Voltaire ou Rousseau, mais il sera question ici du cas plus complexe de Diderot et du dernier ouvrage publié de son vivant, I 'Essai sur les règnes de Claude et de Néron et sur les moeurs et les écrits de Sénèque pour servir à l 'introduction de la lecture de ce philosophe (1782). L'article démontre que celui-ci constitue un cas de « texte-querelle», c'est-à-dire un texte qui met en scène la querelle menée à son propre sujet et qui ainsi la fait redémarrer; il analyse la posture qu'adopte le philosophe-querelleur, surtout dans l'énoncé paradoxal « ne nous engageons point dans les querelles», dont il examine les qualités performatives.
Deep Neck Flexor Endurance in the Adolescent and Young Adult: Normative Data and Associated Attributes
Authors: Jarman Nathan F. , Brooks Toby , James C. Roger , Hooper Troy , Wilhelm Mark , Brismée Jean‐Michel , Domenech Manuel A. , Kotara Stanley J. , Sizer Phillip S.
Published: February 2017

Background

Deep neck flexor (DNF) muscles stabilize the neck and contribute to head acceleration control. The function of DNF in cervical spine dynamic stabilization has not been examined in athletes of any age group, including adolescents. This investigation was necessary prior to studying the DNF muscles' role in cervical spine injury patterns.

Objectives

The objectives of this study were (1) to determine average Deep Neck Flexor Endurance Test (DNFET) time scores in high school−aged and university‐aged subjects (aged 14‐22 years); and (2) to establish the relationship between gender and age for adolescent DNFET time scores.

Design

Cross‐sectional design.

Setting

Public high school and private university.

Participants

A total of 81 (40 male, 41 female) healthy high school and collegiate athletes.

Intervention

DNFET time scores (in seconds) were collected and means values were calculated. Interrater reliability was established using the first 15 university‐aged subjects enrolled in the study.

Main Outcomes

Mean DNFET time (seconds) scores.

Results

The DNF muscle endurance interrater reliability coefficient of reproducibility for 4 allied health clinicians was intraclass correlation coefficient (2,4) 0.712 (confidence interval, 0.24‐0.85). The mean (± standard deviation) DNFET time score for females was 31.86 (±8.53) seconds versus 35.57 (±10.43) seconds for males. The DNFET performance demonstrated a significant but fair correlation with age (r = 0.401, P = .0001). No significant performance differences were found between male and female subjects in the 14‐ to 17‐year‐old group (U = 187.0, P = .285), the 18‐ to 22‐year‐old group (U = 145.0, P = .215), or the total male versus female subject groups (U = 653.0, P = .083).

Conclusion

Our study establishes a normative data set available for the DNFET in the adolescent population. The fair correlation between DNFET time scores and age is consistent with other studies. These findings serve as a basis for clinician testing, objectifying, and monitoring DNF dysfunction in an adolescent athletic population.

Level of Evidence

II
Demonstrating Construct Validity of the American Board of Physical Medicine and Rehabilitation Part I Examination: An Analysis of Dimensionality
Authors: Raddatz Mikaela M. , Robinson Lawrence R.
Published: February 2017

Background

Ideally, high‐stakes examinations assess 1 dimension of medical knowledge to produce precise estimates of a candidate's performance. It has not been reported whether the American Board of Physical Medicine and Rehabilitation Part 1 Certification Examination (ABPMR‐CE‐1) is unidimensional or not.

Objective

To examine the ABPMR‐CE‐1 to measure how many dimensions it assesses.

Design

Retrospective observational study.

Setting

We assessed examination results from the 2015 ABPMR‐CE‐1.

Participants

A total of 489 deidentified candidates taking the 2015 ABPMR‐CE‐1.

Methods

A 1‐parameter Item Response Theory (IRT) measurement model was utilized. A Principal Components Analysis (PCA) of standardized residual correlations was used to detect multidimensionality.

Main Outcome Measure

Number of primary dimensions reflected in the 325 test questions.

Results

The results of the dimensionality analysis indicated that the ABPMR‐CE‐1 examination is highly unidimensional from a psychometric perspective. Expert content review of the substantive content of small contrasting clusters of questions provided additional assurance of the unidimensional nature of the examination.

Conclusions

The ABPMR‐CE‐1 appears indeed to measure a single construct, which suggests a sound structure of the examination. It closely approximates the assumption of statistical unidimensionality.

Level of Evidence

Not applicable.
Grounds for Learning: Schoolyard Activities as Provocations, Scaffolds and Mediators for Childhood Learning
Authors: Johnson Paul
Published: February 2017

Compelling evidence links childhood experiences in quasi-natural settings with learning and wellbeing, but, as cities grow, children's activities have been increasingly restricted to de-natured spaces that are designed or controlled by adults. In recent years, academics and education practitioners have campaigned to reverse this trend, and one result is that Australian early childhood centres and schools increasingly provide environments that enhance opportunities for children to engage with nature. These moves are also underpinned by higher-level policy initiatives. For example, the National Quality Standard, Element 3.2.1, requires that early childhood outdoor spaces are designed so that children experience natural environments (ACECQA, 2013). Similarly, the South Australian Department for Education and Child Development (2016, p. 5) Outdoor Learning Environments Standard mandates ‘balanced environments which instil a sense of wonder, generate curiosity and spark the imagination of children and young people’. However, despite recent interest and policy initiatives, the processes by which environments influence learning remain ‘under-researched’ (Engelen et al., 2013, p. 324) and constitute a ‘significant blind spot’ (Rickinson et al., 2004, p. 8) in the literature.
Kalyani cohort – the first platform in Eastern India for longitudinal studies on health and disease parameters in peri-urban setting
Authors: Chatterjee S. , Majumder P. P.
Published: February 2017

The Kalyani cohort created in 2010 by the National Institute of Biomedical Genomics, West Bengal, India, is designed to serve as a platform for conducting prospective basic and translational studies on epidemiology and genomics of health and disease-related parameters, particularly of non-communicable diseases (NCDs). The overall goal is to assess behavioural, biological, genetic, social and environmental factors and obtain necessary evidence for effective health improvement. Collected baseline data comprise 15727 individuals, >14 years of age from seven municipal wards in the Kalyani and Gayeshpur regions. Data are being collected on demographics, current health status, medical history and health-related behaviours. Blood samples were also collected from a subset of individuals (n = 5132) and analysed for estimation of known markers of NCDs. DNA has been extracted from blood samples and stored for future use. Important baseline findings include a high prevalence of diabetes, dyslipidemias and hypothyroidism. Prevalence estimates for these disorders obtained from self-reported data are significantly lower, indicating that participants are unaware of their health problems. The identification of ‘at risk’ individuals will allow formation of sub-cohorts for further investigations of epidemiological and genetic risk factors for NCDs. Access to the resource, including data and blood samples, created by this study will be provided to other researchers.
Disability Adjusted Life Year (DALY) of Central-Line Bloodstream Infection (CLABSI) in a University Hospital in a Developing Country, Brazil
Authors: da Rocha Jaqueline Abel , do Valle Fernanda Moreth , da Silva Natalia Chilinque Zambão , Nunes Silva Ana Sheila Duarte , Vaz Suzana dos Santos , de Araújo Wildo Navegantes , Martins Ianick Souto
Published: February 2017

Central-line bloodstream infection (CLABSI) increases hospital mortality. A cohort study was conducted in a Brazilian hospital to estimate the disability-adjusted life year (DALY) of CLABSI using modified World Health Organization (WHO) methodology. CLABSI DALY was 20.44 per 1,000 inpatients, most were the result of premature death (20.42 per 1,000 inpatients). DALY can be useful to guide and measure the impact of healthcare infection prevention.

Infect Control Hosp Epidemiol 2017;38:606–609
Immigration Policies and Group Identity: How Immigrant Laws Affect Linked Fate among U.S. Latino Populations
Authors: Vargas Edward D. , Sanchez Gabriel R. , Valdez Juan A.
Published: February 2017

Immigrant sentiment, measured by the number of state laws enacted to curb the flow of undocumented immigration or expand rights to immigrants, have been on a steady incline since September 11, 2001. Despite the increased attention to unauthorized immigration, little research has examined how immigrant policies are affecting group identity (i.e., linked fate). Linked fate is a form of collective group identity that develops when a group of people experience discrimination and marginalization. Using a unique database that merges the 2012 Collaborative Multiracial Post-Election Survey (n= 934 Latinos) with the sum of state-level immigration policies enacted from 2005 to 2012, this study is the first to examine the direct relationship between immigrant climate and linked fate. Results from our multinomial logistic regressions indicate that the linked fate among Latinos increases as the number of punitive immigration laws in a state increases, controlling for a vector of control variables. Consistent with our theory regarding differential impact, our findings also suggest that immigration laws have a more pronounced influence on the linked fate of foreign-born Latinos.
Impact of routine Bacillus thuringiensis israelensis (Bti) treatment on the availability of flying insects as prey for aerial feeding predators
Authors: Timmermann Ute , Becker Norbert
Published: February 2017

Since 1980, mosquito breeding habitats in the Upper Rhine Valley were routinely treated with Bacillus thuringiensis var. israelensis (Bti). Bti is considered to significantly reduce the number of mosquitoes, and – especially when used in higher dosages – to be toxic to other Nematocera species, e.g. Chironomidae, which could be food sources for aerial feeding predators. To investigate direct and indirect effects of routine Bti treatment on food sources for aerial feeding predators, the availability of flying insects in treated and untreated areas was compared. A car trap was used for insect collection, which allowed their exact spatiotemporal assignment. The statistical analysis revealed that insect taxa abundance was influenced differently by the factors season, temperature and time of day. Nematocera (Diptera) were the most frequently collected insects in all areas. Chironomidae were the predominant aquatic Nematocera. The comparison of treated and untreated sites did not show significant differences that would indicate any direct or indirect effect of routine Bti treatment on the availability of flying insects. Additional to food availability, food selection must be considered when investigating food resources for aerial feeding predators. In this study, food selection of Delichon urbicum (House Martin) as an example was investigated with the help of neck ring samples. The preferred prey of the investigated D. urbicum colony consisted of diurnal insects with terrestrial larvae (Aphidina, Brachycera, Coleoptera). Chironomidae were consumed, but not preferred.