bluuebunny/crossref_metadata_2025 huggingface dataset:
Optoacoustics—Advances in high-frequency optomechanics and Brillouin scattering
Authors: Stiller Birgit , Dainese Paulo , Verhagen Ewold
Published: November 2019

The fields of cavity optomechanics and Brillouin scattering, linked by common underlying physical mechanisms, involve the interaction of light waves with mechanical vibrations at the micro- and nanoscale. Exciting fundamental research in both classical and quantum regimes as well as opportunities for applications in microwave photonics, frequency conversion, narrow-linewidth lasers, optomechanical sensors, electro-optic transducers, coherent light storage, and Brillouin spectroscopy have stimulated significant interest in the last decade. This special issue brings contributions to fundamental aspects regarding the Brillouin interaction such as novel waveguide structures, novel guiding mechanisms, the interplay between Brillouin and other nonlinear phenomena, and applications in sensing and light storage, as well as an introductory tutorial to the research field. Here, we provide a brief introduction to the topics covered in the issue.
Phylogenetic relationships of the cuscuses (Diprotodontia : Phalangeridae) of island Southeast Asia and Melanesia based on the mitochondrial ND2 gene
Authors: Kealy Shimona , Donnellan Stephen C. , Mitchell Kieren J. , Herrera Michael , Aplin Ken , O'Connor Sue , Louys Julien
Published: November 2019

The species-level systematics of the marsupial family Phalangeridae, particularly Phalanger, are poorly understood, due partly to the family’s wide distribution across Australia, New Guinea, eastern Indonesia, and surrounding islands. In order to refine the species-level systematics of Phalangeridae, and improve our understanding of their evolution, we generated 36 mitochondrial ND2 DNA sequences from multiple species and sample localities. We combined our new data with available sequences and produced the most comprehensive molecular phylogeny for Phalangeridae to date. Our analyses (1) strongly support the monophyly of the three phalangerid subfamilies (Trichosurinae, Ailuropinae, Phalangerinae); (2) reveal the need to re-examine all specimens currently identified as ‘Phalanger orientalis’; and (3) suggest the elevation of the Solomon Island P. orientalis subspecies to species level (P. breviceps Thomas, 1888). In addition, samples of P. orientalis from Timor formed a clade, consistent with an introduction by humans from a single source population. However, further research on east Indonesian P. orientalis populations will be required to test this hypothesis, resolve inconsistencies in divergence time estimates, and locate the source population and taxonomic status of the Timor P. orientalis.
Relationship between turbidity and the benthic community in the preserved Montebello Lakes in Chiapas, Mexico
Authors: Sosa-Aranda Inari , Zambrano Luis
Published: November 2019

One of the consequences of increased turbidity in lakes is the modification of the structure of the benthic macroinvertebrate community. To understand this relationship, we evaluated 13 lakes in the Montebello Lakes National Park in Chiapas. The lakes have been affected by gradual eutrophication over decades, producing variable transparency values among lakes. Macroinvertebrates were sampled from each lake in the rainy and dry seasons, and species richness and abundance were calculated and related to Secchi disc transparency. Cluster analysis showed that community composition was similar in pristine and semitransparent lakes, in contrast with turbid lakes. Considering macroinvertebrate groups, hyalellids were dominant in pristine and semiturbid lakes, whereas chironomids were dominant in turbid lakes. A significant quadratic relationship between richness and Secchi disc depth values was found, which is consistent with the intermediate production hypothesis. This study shows how a gradual change in Secchi disc depth can markedly modify benthic communities.
Long-term in vivo microscopy of CAR T cell dynamics during eradication of CNS lymphoma in mice
Authors: Mulazzani Matthias , Fräßle Simon P. , von Mücke-Heim Iven , Langer Sigrid , Zhou Xiaolan , Ishikawa-Ankerhold Hellen , Leube Justin , Zhang Wenlong , Dötsch Sarah , Svec Mortimer , Rudelius Martina , Dreyling Martin , von Bergwelt-Baildon Michael , Straube Andreas , Buchholz Veit R. , Busch Dirk H. , von Baumgarten Louisa
Published: November 2019

Significance

Primary central nervous system lymphoma (PCNSL) is a highly malignant brain tumor with limited treatment options. Here, we show that genetically engineered T cells, expressing a chimeric antigen receptor, thoroughly infiltrate these tumors in mice. Combining intravital 2-photon microscopy with chronic cranial windows, we were able to visualize their intratumoral proliferation and intracerebral persistence for up to 159 d, leading to the eradication of large, established PCNSL and to long-term survival.
Distinct effects of orexin receptor antagonist and GABA
A
agonist on sleep and physical/cognitive functions after forced awakening
Authors: Seol Jaehoon , Fujii Yuya , Park Insung , Suzuki Yoko , Kawana Fusae , Yajima Katsuhiko , Fukusumi Shoji , Okura Tomohiro , Satoh Makoto , Tokuyama Kumpei , Kokubo Toshio , Yanagisawa Masashi
Published: November 2019

Significance

Insomnia is a common symptom representing an important health burden. Widely prescribed hypnotic agents enhance the function of γ-aminobutyric acid (GABA), a major inhibitory neurotransmitter. The ability to arouse and respond to unexpected stimuli is a feature of normal sleep, and one of the concerns of this class of hypnotic agents is that patients may become physically and/or cognitively impaired while the drug is in effect. As a new approach for the treatment of insomnia, orexin receptor antagonists have been recently approved, which specifically inhibit the orexin-mediated wake-promoting system, supposedly without affecting the whole brain. We found that, compared with the GABA receptor agonist brotizolam, the orexin receptor antagonist suvorexant induced less impairment in body balance after taking the medicine.
On the energy efficiency of cell migration in diverse physical environments
Authors: Li Yizeng , Yao Lingxing , Mori Yoichiro , Sun Sean X.
Published: November 2019

In this work, we explore fundamental energy requirements during mammalian cell movement. Starting with the conservation of mass and momentum for the cell cytosol and the actin-network phase, we develop useful identities that compute dissipated energies during extensions of the cell boundary. We analyze 2 complementary mechanisms of cell movement: actin-driven and water-driven. The former mechanism occurs on 2-dimensional cell-culture substrate without appreciable external hydraulic resistance, while the latter mechanism is prominent in confined channels where external hydraulic resistance is high. By considering various forms of energy input and dissipation, we find that the water-driven cell-migration mechanism is inefficient and requires more energy. However, in environments with sufficiently high hydraulic resistance, the efficiency of actin-polymerization-driven cell migration decreases considerably, and the water-based mechanism becomes more efficient. Hence, the most efficient way for cells to move depends on the physical environment. This work can be extended to higher dimensions and has implication for understanding energetics of morphogenesis in early embryonic development and cancer-cell metastasis and provides a physical basis for understanding changing metabolic requirements for cell movement in different conditions.
Solvent fluctuations in the solvation shell determine the activation barrier for crystal growth rates
Authors: Dighe Anish V. , Singh Meenesh R.
Published: November 2019

Significance

Solution crystallization is a widely used technique to grow crystalline materials such as pharmaceuticals, agrochemicals, catalysts, semiconductors, and metal–organic frameworks. The highly probabilistic nature and complex molecular processes spanning multiple lengths and time scales have prevented full mechanistic understanding of crystallization processes for over a century. Here we show fluctuations in the solvation shell are key molecular events that explain and unify the empirical observations laid down since the inception of crystallization research. The activation barrier of the growth processes obtained from these molecular fluctuations can be used to estimate growth rates that show reasonable agreement with the experimental observations, hinting at the rise of additional and efficient strategies to control solution crystallization.
Multistable properties of human subthalamic nucleus neurons in Parkinson’s disease
Authors: Chopek Jeremy W. , Hultborn Hans , Brownstone Robert M.
Published: November 2019

Significance

Behaviors are realized through concerted activity in neural circuits. This activity results from a combination of neural connectivity and the properties of the involved neurons. By studying the activity of neurons in the human subthalamic nucleus during surgery for Parkinson’s disease, we report that these neurons have multiple stable states, and that brief electrical stimuli can lead to transitions between states. We thus suggest that these neurons function as finite state machines. The different states could influence the function of key motor circuits of the basal ganglia, and thus knowledge of these states in disease or in response to treatment could help to define new treatment strategies for people with movement disorders.
Elovanoids counteract oligomeric β-amyloid-induced gene expression and protect photoreceptors
Authors: Do Khanh V. , Kautzmann Marie-Audrey I. , Jun Bokkyoo , Gordon William C. , Nshimiyimana Robert , Yang Rong , Petasis Nicos A. , Bazan Nicolas G.
Published: November 2019

The onset of neurodegenerative diseases activates inflammation that leads to progressive neuronal cell death and impairments in cognition (Alzheimer’s disease) and sight (age-related macular degeneration [AMD]). How neuroinflammation can be counteracted is not known. In AMD, amyloid β-peptide (Aβ) accumulates in subretinal drusen. In the 5xFAD retina, we found early functional deficiencies (ERG) without photoreceptor cell (PRC) death and identified early insufficiency in biosynthetic pathways of prohomeostatic/neuroprotective mediators neuroprotectin D1 (NPD1) and elovanoids (ELVs). To mimic an inflammatory milieu in wild-type mouse, we triggered retinal pigment epithelium (RPE) damage/PRC death by subretinally injected oligomeric β-amyloid (OAβ) and observed that ELVs administration counteracted their effects, protecting these cells. In addition, ELVs prevented OAβ-induced changes in gene expression engaged in senescence, inflammation, autophagy, extracellular matrix remodeling, and AMD. Moreover, as OAβ targets the RPE, we used primary human RPE cell cultures and demonstrated that OAβ caused cell damage, while ELVs protected and restored gene expression as in mouse. Our data show OAβ activates senescence as reflected by enhanced expression of p16
INK4a
, MMP1, p53, p21, p27, and Il-6, and of senescence-associated phenotype secretome, followed by RPE and PRC demise, and that ELVs 32 and 34 blunt these events and elicit protection. In addition, ELVs counteracted OAβ-induced expression of genes engaged in AMD, autophagy, and extracellular matrix remodeling. Overall, our data uncovered that ELVs downplay OAβ-senescence program induction and inflammatory transcriptional events and protect RPE cells and PRC, and therefore have potential as a possible therapeutic avenue for AMD.
L2 Chinese learners’ pragmatic developmental patterns in data-driven instruction and computer-mediated communication (CMC)
Authors: Li Qiong
Published: November 2019

This study examined second language (L2) Chinese learners’ developmental patterns of pragmatic competence in two computer-mediated communication (CMC) conditions: (1) CMC with data-driven instruction embedded in the course of CMC and (2) CMC without data-driven instruction. Learners’ pragmatic competence was operationalized as their ability to use a Chinese sentence final particle (SFP)neduring CMC with a native speaker partner. The study investigated: (1) whether learners (as a group) developed their use ofneover time in the two CMC conditions, and (2) how individual learners changed their use ofne(if any) in the two conditions. The quantitative analysis (token and type frequency ofne) revealed that CMC itself did not promote learners’ use ofne. However, it promoted learners’ production ofnewhen data-driven instruction was incorporated into CMC. Supporting the quantitative findings, the qualitative analysis showed that one learner in the CMC with data-driven instruction outperformed his counterpart in the CMC without data-driven instruction group in the diverse use ofne.
The linguistic landscape of multilingual picturebooks
Authors: Daly Nicola
Published: November 2019

We often talk about ‘entering another world’ when we read a book. In this article it is argued that the way in which languages are presented in a picturebook can be seen as a linguistic landscape within the wider linguistic landscape of the world we are in. Previous studies of the linguistic landscape of bilingual picturebooks have shown that minority languages are afforded less space. In this article the linguistic landscape of 24 multilingual picturebooks from the Internationale Jugendbibliothek (Munich, Germany) are analysed. Findings show that languages given dominance in terms of order, size, and information mostly reflect the sociolinguistic setting in which these books are published, replicating power structures and potentially having negative implications for the ethnolinguistic vitality of minority language groups and their language maintenance or revitalisation. The potential effect on readers’ developing language attitudes is also explored.
Signs of resistance in the Asturian linguistic landscape
Authors: Sebastian Paul
Published: November 2019

A linguistic landscape analysis, grounded in the ideas of contestation and resistance (Blackwood, Lanza, & Woldemariam, 2016; Rubdy & Ben Said,
2015) and carried out using Scollon and Scollon’s (2003) concept of place
semiotics, was conducted in four cities located in the Asturias region of Northern Spain. The primary goals of the study were to
investigate and interpret the (in)visibility of Asturian, an endangered language spoken primarily in and around the capital city
of Oviedo. Distinct patterns on public signage involving font alterations, layering, and material selections indicate that the
linguistic landscape was being used as an asynchronous public forum between Asturian advocates and unseen actors. Drawing on
similar studies of deliberately modified linguistic landscapes (Gorter, Aiestaran, &
Cenoz, 2012; Tupas, 2015), this paper introduces the concept of the
asynchronously layered linguistic landscape in which evidence of contestation and resistance can be found in strategic
juxtapositions of sign materiality.
In-situ neutron diffraction measurement and numerical modelling of macro- and micro-strains in two porous synthetic graphites
Authors: Nakhodchi S. , Hayatian R. , Flewitt P. E. J.
Published: November 2019

In-situ neutron diffraction measurements have been performed on IMI-24 grade (20% porosity) and PG25 (48% porosity) graphite subjected to external uni-axial compression loading. The ‘pore free’ matrix properties such as modulus of elasticity of about 72 GPa and 46 GPa were measured for the IMI-24 and PG25, respectively, and were higher than those measured at the macro-length-scale. The elastic modulus of each crystal plane, hkl, is reported ranging from about 48–145 GPa and Poisson ratio ranging from 0.08–0.28 for IMI-24 graphite. With the proposed method, the pore morphology factor ‘m’ was independently evaluated to be 10.8 and 4.8 for IMI-24 and PG25, respectively. It has been demonstrated from that the micro-diffraction the Young modulus is not dependent on the pore morphology factor. We consider and discuss the experimental plus modelling approach to provide a new perspective on the micro-mechanics of porous graphites.
Strengthening mechanisms of Al wires processed by equal channel angular torsion drawing
Authors: Pourbashiri M. , Poletti C. , Sedighi M. , Sommitsch C.
Published: November 2019

This paper reports the microstructure evolution, mechanical properties and strengthening mechanisms of a commercial purity Al alloy (Al 1350) after severe plastic deformation by a novel continuous method called ‘Equal Channel Angular Torsion Drawing (ECATD)’. Electron backscatter diffraction (EBSD) results revealed an inhomogeneous grain refinement including a large fraction of low-angle grain boundaries. After four passes, the microhardness increases from the initial value of 35 HV up to 44 and 62 HV at the centre and near to wire surface, respectively. A combination of high strength and ductility can be achieved based on the results of a Taguchi design of experiment (DoE) for mechanical properties. The strengthening occurs due to increment of the dislocation density, and development of mainly new low-angle grain boundaries.
Chronic captivity stress in wild animals is highly species-specific
Authors: Fischer Clare Parker , Romero L Michael
Published: November 2019

Lay summary:

A review that compares changes in body mass, glucocorticoid and sympathetic responses, and reproductive and immune function, in wild animals recently introduced into captivity to their wild counterparts. Conclusion is that captivity can be a powerful chronic stressor that may be possible to mitigate, but the impact is highly species-specific.
Personalized monitoring of electrical remodelling during atrial fibrillation progression via remote transmissions from implantable devices
Authors: Lillo-Castellano José María , González-Ferrer Juan José , Marina-Breysse Manuel , Martínez-Ferrer José Bautista , Pérez-Álvarez Luisa , Alzueta Javier , Martínez Juan Gabriel , Rodríguez Aníbal , Rodríguez-Pérez Juan Carlos , Anguera Ignasi , Viñolas Xavier , García-Alberola Arcadio , Quintanilla Jorge G , Alfonso-Almazán José Manuel , García Javier , Borrego Luis , Cañadas-Godoy Victoria , Pérez-Castellano Nicasio , Pérez-Villacastín Julián , Jiménez-Díaz Javier , Jalife José , Filgueiras-Rama David
Published: November 2019

Aims

Atrial electrical remodelling (AER) is a transitional period associated with the progression and long-term maintenance of atrial fibrillation (AF). We aimed to study the progression of AER in individual patients with implantable devices and AF episodes.

Methods and results

Observational multicentre study (51 centres) including 4618 patients with implantable cardioverter-defibrillator +/−resynchronization therapy (ICD/CRT-D) and 352 patients (2 centres) with pacemakers (median follow-up: 3.4 years). Atrial activation rate (AAR) was quantified as the frequency of the dominant peak in the signal spectrum of AF episodes with atrial bipolar electrograms. Patients with complete progression of AER, from paroxysmal AF episodes to electrically remodelled persistent AF, were used to depict patient-specific AER slopes. A total of 34 712 AF tracings from 830 patients (87 with pacemakers) were suitable for the study. Complete progression of AER was documented in 216 patients (16 with pacemakers). Patients with persistent AF after completion of AER showed ∼30% faster AAR than patients with paroxysmal AF. The slope of AAR changes during AF progression revealed patient-specific patterns that correlated with the time-to-completion of AER (R2 = 0.85). Pacemaker patients were older than patients with ICD/CRT-Ds (78.3 vs. 67.2 year olds, respectively, P < 0.001) and had a shorter median time-to-completion of AER (24.9 vs. 93.5 days, respectively, P = 0.016). Remote transmissions in patients with ICD/CRT-D devices enabled the estimation of the time-to-completion of AER using the predicted slope of AAR changes from initiation to completion of electrical remodelling (R2 = 0.45).

Conclusion

The AF progression shows patient-specific patterns of AER, which can be estimated using available remote-monitoring technology.
Analysis of the genomic expression profile in trisomy 18: insight into possible genes involved in the associated phenotypes
Authors: Albizua Igor , Chopra Pankaj , Sherman Stephanie L , Gambello Michael J , Warren Stephen T
Published: November 2019

Trisomy 18, sometimes called Edwards syndrome, occurs in about 1 in 6000 live births and causes multiple birth defects in affected infants. The extra copy of chromosome 18 causes the altered expression of many genes and leads to severe skeletal, cardiovascular and neurological systems malformations as well as other medical problems. Due to the low rate of survival and the massive genetic imbalance, little research has been aimed at understanding the molecular consequences of trisomy 18 or considering potential therapeutic approaches. Our research is the first study to characterize whole-genome expression in fibroblast cells obtained from two patients with trisomy 18 and two matched controls, with follow-up expression confirmation studies on six independent controls. We show a detailed analysis of the most highly dysregulated genes on chromosome 18 and those genome-wide. The identified effector genes and the dysregulated downstream pathways provide hints of possible genotype–phenotype relationships to some of the most common symptoms observed in trisomy 18. We also provide a possible explanation for the sex-specific differences in survival, a unique characteristic of trisomy 18. Our analysis of genome-wide expression data moves us closer to understanding the molecular consequences of the second most common human autosomal trisomy of infants who survive to term. These insights might also translate to the understanding of the etiology of associated birth defects and medical conditions among those with trisomy 18.
The Disappeared Are Appearing: Murals that Recover Communal Memory
Authors: Bernardi Claudia
Published: November 2019

ABSTRACT∞

Relatives of the disappeared during the last civic–military dictatorship in Argentina who were able to recover the human remains of their family members through the work of the Argentine Forensic Anthropology Team (Equipo Argentino de Antropología Forense, or EAAF), painted a mural in March 2014. ‘The Disappeared Are Appearing’ is a collaborative and community-based mural project designed, rendered and completed by the relatives of victims of state terror in Argentina. The participating family members of the disappeared had recovered the human remains of their beloved relatives through the tenacious and constant work of the EAAF, a nongovernmental, not-for-profit, scientific organization. It was established in 1984 to investigate the cases of at least 9,000 disappeared people in Argentina under the military government that ruled from 1976 to 1983.
Ready Species One: Exploring the Use of Augmented Reality to Enhance Systematic Biology with a Revision of Fijian Strumigenys (Hymenoptera: Formicidae)
Authors: Sarnat Eli M , Hita Garcia Francisco , Dudley Kenneth , Liu Cong , Fischer Georg , Economo Evan P
Published: November 2019

Advances in technology are rapidly changing the way people transmit, view, and interact with information. These advances offer new opportunities for researchers to share scientific discoveries with each other and the general public as never before. The field of revisionary biology has audiences confined to small groups of specialists, but the core task of systematic biology—documenting the endless forms of nature—is particularly well suited to capitalize on innovations in the realm of virtual, mixed and augmented reality. Interactive three-dimensional (3D) digital models of biological specimens can help bridge barriers across scientific disciplines by circumventing technical jargon, and also promise to open exciting new vistas for public engagement. Here, we explore the potential of augmented reality for communicating the discovery of new species. As a test case, we revise a radiation of Strumigenys Smith (Hymenoptera: Formicidae) miniature trap-jaw ants in Fiji. In addition to traditional revisionary elements, we present the augmented reality application ‘Insects3D’ built specifically for this study. The application runs on mobile devices and allows users to interact with X-ray microtomography-derived 3D specimen models and visualize 3D geographic distribution maps. We recognize 23 species in Fiji, including 6 new species: S. anorak n. sp., S. artemis n. sp., S. avatar n. sp., S. gunter n. sp., S. oasis n. sp., and S. parzival n. sp. This study demonstrates the potential of leveraging 3D data and technology for a more interactive systematic biology, and the need for research programs to develop robust and generalized tools to realize this potential.
Endogenous Gamma-Hydroxybutyrate in Postmortem Samples
Authors: Ha Helen H , Mata Dani C , Vargas Jay R
Published: November 2019

Gamma-hydroxybutyrate (GHB) is a naturally occurring molecule present in the human body as a catabolite of the neurotransmitter gamma-aminobutyrate (GABA). In the USA, GHB has a history of being manufactured illicitly and abused, with misguided proposed benefits for the body-building community and a persistent party drug with reported GHB overdoses occurring worldwide. The interpretation of GHB in postmortem biological fluids is complicated by the endogenous nature of the molecule. Analysis often requires more than one biological matrix to detect exogenous exposure, typically in urine. The analysis is further complicated by the endogenous de novo production of GHB in postmortem specimens. This work sought to examine the prevalence of endogenous GHB concentrations in postmortem toxicology samples from Orange County, CA, and to establish suitable in-house secondary matrices to confirm or rule out exogenous GHB exposure. A total of 348 postmortem heart blood samples were randomly selected and analyzed for GHB using liquid–liquid extraction followed by gas chromatography–mass spectrometry with selective ion monitoring and GHB-d6 as an internal standard. Of the 348 cases analyzed, 39 cases resulted in positive GHB detection with the median concentration of 22.45 mg/L (10.4–62.16 mg/L). None of the positive samples had suspected GHB ingestion or usage from the case report. GHB concentrations were then examined in secondary matrices collected at autopsy from the positive cases that included (when available) peripheral blood, urine, vitreous humor, liver homogenate and brain homogenate. Within the secondary matrices, GHB levels in peripheral blood compared to that of heart blood, while liver homogenate levels were variable. Quantifiable GHB levels were not identified in vitreous humor and brain homogenate samples. Our findings reaffirm the importance of multi-matrix analysis in postmortem toxicology and further confirm the utility of vitreous humor and brain tissue to distinguish exogenous GHB exposure from endogenous production.
Evaluating Endogenous GHB Variation in Hair with a Synthetic Hair Matrix
Authors: Lloyd Erin W , Thomas Jennifer L , Donnelly Christopher C , Montgomery Madeline A , Karas Roman P , LeBeau Marc A , Miller Mark L
Published: November 2019

The variation in drug concentrations in human head hair from 22 donors was measured using a synthetic hair matrix (SMx™ hair). This matrix is being reported for the first time as a calibrator for an endogenous substance. In comparison to authentic hair or melanin, the synthetic hair provided a reliable batch-to-batch source of liquid matrix similar in composition to authentic hair, but without detectable concentrations of endogenous gamma-hydroxybutyric acid (GHB). Using the synthetic matrix for calibrator samples, validation of a liquid chromatography–tandem mass spectrometry (LC-MS/MS) quantitative method for GHB in human head hair was completed. Validation included the evaluation of the following parameters: accuracy, precision, calibration model, carryover, interferences, limit of detection (LOD), limit of quantitation (LOQ) and processed sample stability. The method was valid over a range of 0.4–12 ng/mg, and its LOD and LOQ were both experimentally estimated to be 0.4 ng/mg. After validation, the variation in endogenous GHB concentrations across multiple donors and locations in the vertex posterior region of the human head were evaluated. Results for 11 non-GHB users showed minimal variability (average 3.0% RSD) across the vertex posterior for hair samples taken from three different areas. There was also low variability (average 1.8% RSD) in repeat samples taken from the same location for 11 other non-users. Endogenous GHB concentrations from the LOD/LOQ to 5.60 ng/mg were determined for the 22 donors using the synthetic hair as a calibrator. These results demonstrate the successful application of a synthetic hair matrix in the analysis of GHB in human hair.
Slope-to-optimal-solution-based evaluation of the hardness of travelling salesman problem instances
Authors: Cárdenas-Montes Miguel
Published: November 2019

The travelling salesman problem is one of the most popular problems in combinatorial optimization. It has been frequently used as a benchmark of the performance of evolutionary algorithms. For this reason, nowadays practitioners request new and more difficult instances of this problem. This leads to investigate how to evaluate the intrinsic difficulty of the instances and how to separate ease and difficult instances. By developing methodologies for separating easy- from difficult-to-solve instances, researchers can fairly test the performance of their combinatorial optimizers. In this work, a methodology for evaluating the difficulty of instances of the travelling salesman problem near the optimal solution is proposed. The question is if the fitness landscape near the optimal solution encodes enough information to separate instances in function of their intrinsic difficulty. This methodology is based on the use of a random walk to explore the closeness of the optimal solution. The optimal solution is modified by altering one connection between two cities at each step, at the same time that the fitness of the altered solution is evaluated. This permits evaluating the slope of the fitness landscape. Later, and using the previous information, the difficulty of the instance is evaluated with random forests and artificial neural networks. In this work, this methodology is confronted with a wide set of instances. As a consequence, a methodology to separate the instances of the travelling salesman problem by their degree of difficulty is proposed and evaluated.
Impact of Precision Medicine on Efficiencies of Novel Drug Development in Cancer
Authors: Sarvas Holly , Carlisle Benjamin , Dolter Samantha , Vinarov Esther , Kimmelman Jonathan
Published: November 2019

Precision medicine (PM) offers opportunities for reducing the costs, burdens, and time associated with drug development. We examined time, number of trials, indications tested, and patient burden needed to achieve first U.S. Food and Drug Administration license for all five novel anticancer PM drugs and all 10 novel non-PM drugs receiving U.S. Food and Drug Administration approval during 2010–2014. The 15 drug portfolios encompassed 242 trials: 87 for PM drugs and 155 for non-PM drugs. Embase and MEDLINE databases were searched for all prelicensure clinical trials, and data on time, patient numbers, indications tested, and total treatment-emergent grade 3–5 adverse events were measured from the first trial of each drug. We did not find patterns suggesting greater efficiencies in PM compared with non-PM. Gains in efficiency for PM drug development may be offset by challenges with recruitment.
Health Care Utilization Among Homeless Veterans in Chicago
Authors: Raad Jason H , Tarlov Elizabeth , Kho Abel N , French Dustin D
Published: November 2019

Introduction

The U.S. Department of Veterans Affairs (VA), the single largest health care system in the United States, provides comprehensive medical and behavioral health services to more than 9 million Veterans. The size and scope of the VA’s system of care allow health care providers, policymakers, and community stakeholders to conduct detailed analyses of health care utilization among Veterans; however, these analyses do not include health care encounters that occur outside VA. Although many Veterans obtain care in non-VA settings, understanding health care utilization among vulnerable populations of Veterans, including those who are homeless or at risk of becoming homeless, is needed to identify potential opportunities to enhance access and reduce fragmentation of care.

Materials and Methods

VA administrative data were merged with data from the Chicago HealthLNK Data Repository to identify Veterans eligible for VA services who were homeless, or at risk of becoming homeless, in the greater Chicago metropolitan area for the years 2010–2012.

Results

During the 3-year study period, about 208,554 Veterans were registered for care at two VA medical centers located in the City of Chicago and an adjacent suburb. Of those, 13,948 were identified as homeless or at risk of becoming homeless. Results suggest that 17% (n = 2,309) of Veterans in this sample received some or all of their care in the community. Much of the care these Veterans received was for chronic health conditions, substance use, and mental health disorders.

Conclusions

Veterans eligible for VA servicers who are homeless, or at risk of becoming homeless, frequently sought care in the community for a variety of chronic health conditions. Health information exchanges and partner-based registries may represent an important tool for identifying vulnerable Veteran populations while reducing duplication of care.
Estimating trajectories of meteors: an observational Monte Carlo approach – I. Theory
Authors: Vida Denis , Gural Peter S , Brown Peter G , Campbell-Brown Margaret , Wiegert Paul
Published: November 2019

It has recently been shown by Egal et al. that some types of existing meteor in-atmosphere trajectory estimation methods may be less accurate than others, particularly when applied to high-precision optical measurements. The comparative performance of trajectory solution methods has previously only been examined for a small number of cases. Besides the radiant, orbital accuracy depends on the estimation of pre-atmosphere velocities, which have both random and systematic biases. Thus, it is critical to understand the uncertainty in velocity measurement inherent to each trajectory estimation method. In this first of a series of two papers, we introduce a novel meteor trajectory estimation method that uses the observed dynamics of meteors across stations as a global optimization function and that does not require either a theoretical or an empirical flight model to solve for velocity. We also develop a 3D observational meteor trajectory simulator that uses a meteor ablation model to replicate the dynamics of meteoroid flight, as a means to validate different trajectory solvers. We both test this new method and compare it to other methods, using synthetic meteors from three major showers spanning a wide range of velocities and geometries (Draconids, Geminids, and Perseids). We determine which meteor trajectory solving algorithm performs better for all-sky, moderate field-of-view, and high-precision narrow-field optical meteor detection systems. The results are presented in the second paper in this series. Finally, we give detailed equations for estimating meteor trajectories and analytically computing meteoroid orbits, and provide the python code of the methodology as open-source software.
Thyroid Storm in the ICU: A Retrospective Multicenter Study
Authors: Bourcier Simon , Coutrot Maxime , Kimmoun Antoine , Sonneville Romain , de Montmollin Etienne , Persichini Romain , Schnell David , Charpentier Julien , Aubron Cécile , Morawiec Elise , Bigé Naïke , Nseir Saad , Terzi Nicolas , Razazi Keyvan , Azoulay Elie , Ferré Alexis , Tandjaoui-Lambiotte Yacine , Ellrodt Olivier , Hraiech Sami , Delmas Clément , Barbier François , Lautrette Alexandre , Aissaoui Nadia , Repessé Xavier , Pichereau Claire , Zerbib Yoann , Lascarrou Jean-Baptiste , Carreira Serge , Reuter Danielle , Frérou Aurélien , Peigne Vincent , Fillatre Pierre , Megarbane Bruno , Voiriot Guillaume , Combes Alain , Schmidt Matthieu
Published: November 2019

Objectives:

Thyroid storm represents a rare but life-threatening endocrine emergency. Only rare data are available on its management and the outcome of the most severe forms requiring ICU admission. We aimed to describe the clinical manifestations, management and in-ICU and 6-month survival rates of patients with those most severe thyroid storm forms requiring ICU admission.

Design:

Retrospective, multicenter, national study over an 18-year period (2000–2017).

Setting:

Thirty-one French ICUs.

Patients:

The local medical records of patients from each participating ICU were screened using the International Classification of Diseases, 10th Revision. Inclusion criteria were “definite thyroid storm,” as defined by the Japanese Thyroid Association criteria, and at least one thyroid storm-related organ failure.

Measurements and Main Results:

Ninety-two patients were included in the study. Amiodarone-associated thyrotoxicosis and Graves’ disease represented the main thyroid storm etiologies (30 [33%] and 24 [26%] patients, respectively), while hyperthyroidism was unknown in 29 patients (32%) before ICU admission. Amiodarone use (24 patients [26%]) and antithyroid-drug discontinuation (13 patients [14%]) were the main thyroid storm-triggering factors. No triggering factor was identified for 30 patients (33%). Thirty-five patients (38%) developed cardiogenic shock within the first 48 hours after ICU admission. In-ICU and 6-month postadmission mortality rates were 17% and 22%, respectively. ICU nonsurvivors more frequently required vasopressors, extracorporeal membrane of oxygenation, renal replacement therapy, mechanical ventilation, and/or therapeutic plasmapheresis. Multivariable analyses retained Sequential Organ Failure Assessment score without cardiovascular component (odds ratio, 1.22; 95% CI, 1.03–1.46; p = 0.025) and cardiogenic shock within 48 hours post-ICU admission (odds ratio, 9.43; 1.77–50.12; p = 0.008) as being independently associated with in-ICU mortality.

Conclusions:

Thyroid storm requiring ICU admission causes high in-ICU mortality. Multiple organ failure and early cardiogenic shock seem to markedly impact the prognosis, suggesting a prompt identification and an aggressive management.
Serum Protein Changes in Pediatric Sepsis Patients Identified With an Aptamer-Based Multiplexed Proteomic Approach
Authors: Shubin Nicholas J. , Navalkar Krupa , Sampson Dayle , Yager Thomas D. , Cermelli Silvia , Seldon Therese , Sullivan Erin , Zimmerman Jerry J. , Permut Lester C. , Piliponsky Adrian M.
Published: November 2019

Objectives:

Sepsis, a life-threatening organ dysfunction caused by a dysregulated host response to infection, is a leading cause of death and disability among children worldwide. Identifying sepsis in pediatric patients is difficult and can lead to treatment delay. Our objective was to assess the host proteomic response to infection utilizing an aptamer-based multiplexed proteomics approach to identify novel serum protein changes that might help distinguish between pediatric sepsis and infection-negative systemic inflammation and hence can potentially improve sensitivity and specificity of the diagnosis of sepsis over current clinical criteria approaches.

Design:

Retrospective, observational cohort study.

Setting:

PICU and cardiac ICU, Seattle Children’s Hospital, Seattle, WA.

Patients:

A cohort of 40 children with clinically overt sepsis and 30 children immediately postcardiopulmonary bypass surgery (infection-negative systemic inflammation control subjects) was recruited. Children with sepsis had a confirmed or suspected infection, two or more systemic inflammatory response syndrome criteria, and at least cardiovascular and/or pulmonary organ dysfunction.

Interventions:

None.

Measurements and Main Results:

Serum samples from 35 of the sepsis and 28 of the bypass surgery subjects were available for screening with an aptamer-based proteomic platform that measures 1,305 proteins to search for large-scale serum protein expression pattern changes in sepsis. A total of 111 proteins were significantly differentially expressed between the sepsis and control groups, using the linear models for microarray data (linear modeling) and Boruta (decision trees) R packages, with 55 being previously identified in sepsis patients. Weighted gene correlation network analysis helped identify 76 proteins that correlated highly with clinical sepsis traits, 27 of which had not been previously reported in sepsis.

Conclusions:

The serum protein changes identified with the aptamer-based multiplexed proteomics approach used in this study can be useful to distinguish between sepsis and noninfectious systemic inflammation.
The Physician's Guide to Platelet-Rich Plasma in Dermatologic Surgery Part I: Definitions, Mechanisms of Action, and Technical Specifications
Authors: Hausauer Amelia K. , Humphrey Shannon
Published: November 2019

BACKGROUND

Platelet-rich plasma (PRP) is an increasingly popular treatment modality for various dermatologic conditions, but there are limitations in both the published literature and clinician knowledge.

OBJECTIVE

To create a high-yield, in-depth analysis of PRP in procedural dermatology by reviewing available data on its role in hair restoration, soft-tissue remodeling, resurfacing, and rejuvenation; identifying practice gaps and controversies; and making suggestions for future research that will establish dermatologists as pioneers of regenerative medicine.

MATERIALS AND METHODS

A 2-part systematic review and expert analysis of publications before October 2018.

RESULTS AND CONCLUSION

Most studies on PRP report favorable outcomes with the strongest level of evidence existing for androgenetic alopecia followed by postprocedure wound healing, scar revision, striae, rejuvenation, and dermal filling. There is a dearth of large randomized controlled trials, considerable heterogeneity in the variables studied, and lack of specificity in the preparatory protocols, which may influence clinical outcomes. Future investigations should use consistent nomenclature, find ideal solution parameters for each cutaneous indication, determine significant outcome metrics, and follow double-blinded, randomized, controlled methodologies. Addressing these deficiencies will take sound scientific inquiry but ultimately has the potential to benefit the authors' specialty greatly.
Diagnostic Validity of Cardiopulmonary Exercise Testing for Screening Pulmonary Hypertension in Patients With Chronic Obstructive Pulmonary Disease
Authors: Kader Mohamed Nabhan , Moiz Jamal Ali , Bhati Pooja , Ali Mir Shad , Talwar Deepak
Published: November 2019

Purpose:

To determine diagnostic validity of cardiopulmonary exercise testing (CPX) parameters for detecting pulmonary hypertension (PH) in patients with chronic obstructive pulmonary disease (COPD) and to investigate association between CPX parameters and indices of PH.

Methods:

This cross-sectional study enrolled 48 moderate to very severe COPD patients in whom PH was confirmed by echocardiography. Symptom-limited CPX was performed using an incremental exercise protocol. Relevant CPX parameters were derived and were tested for their diagnostic ability for diagnosing PH. Logistic regression was applied to examine the effect of various clinical covariates on the diagnostic ability of exercise test variables for detecting PH.

Results:

Of the 48 patients, 29 were diagnosed with PH and 19 were negative for PH based on echocardiographic testing. CPX measures including peak oxygen uptake (% predicted

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2peak,

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2peak [mL/min],

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2/kg), oxygen pulse (

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2/HR % predicted,

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2/HR mL/beat), and peak minute ventilation (

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peak [L/m]) were inversely correlated with mean pulmonary arterial pressure (mPAP). Peak

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2/HR and

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2peak were found to be significant predictors of PH in univariate analysis.

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2peak (%),

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2/HR (mL/beat), and desaturation (%) were identified as independent predictors of PH adjusted for age, forced expiratory volume in 1 sec (%), and forced vital capacity (L).

Conclusion:

The present study validates the use of CPX parameters such as

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2peak and

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2/HR as a diagnostic tool for correctly identifying PH in COPD patients. Therefore, CPX may be used as an adjunct to echocardiographic measurement of PH where there is unavailability of equipment and expertise.
Pedometer Feedback Interventions Increase Daily Physical Activity in Phase III Cardiac Rehabilitation Participants
Authors: Ozemek Cemal , Strath Scott J. , Riggin Katrina , Harber Matthew P. , Imboden Mary T. , Kaminsky Leonard A.
Published: November 2019

Purpose:

To determine the effects of individually tailored interventions designed to increase physical activity (PA) in cardiac patients.

Methods:

A total of 99 (77 men and 22 women, 61.5 ± 10.7 yr) patients entering a phase III cardiac rehabilitation program completed a 12-wk PA intervention. Patients were randomized to usual care (UC, time-based recommendation), pedometer feedback (PF), newsletter-based motivational messaging (MM), or PF + MM. Both PF groups were given a goal of increasing steps/d by 10% of individual baseline value each week. If the goal for the week was not reached, the same goal was used for the next week. Physical activity was assessed for 7 d before beginning and after completing the program. The change in steps/d, moderate to vigorous intensity PA minutes, and sedentary time were compared among intervention groups.

Results:

Average change in steps/d was found to be significantly greater (P < .01) in the PF (2957 ± 3185) and the PF + MM (3150 ± 3007) compared with UC (264 ± 2065) and MM (718 ± 2415) groups. No group experienced changes in moderate to vigorous intensity PA time and only the PF intervention group decreased sedentary time (baseline 470.2 ± 77.1 to postintervention 447.8 ± 74.9 min/d, P = .01).

Conclusion:

The findings from this study demonstrate that using PF was superior to the usual time–based PA recommendations and to newsletter-based MM in patients starting a phase III CR program. Cardiac rehabilitation programs are encouraged to implement PA feedback with individualized PA goals in order to support the increase in PA.