bluuebunny/crossref_metadata_2025 huggingface dataset:
Sex as a biological variable in the pathology and pharmacology of neurodegenerative and neurovascular diseases
Authors: Honarpisheh Pedram , McCullough Louise D.
Published: April 2019

The incidence of dementia, most commonly caused by cerebrovascular and neurodegenerative diseases, continues to grow as our population ages. Alzheimer disease (AD) and vascular cognitive impairment (VCI) are responsible for more than 80% of all cases of dementia. There are few effective, long‐term treatments for AD and VCI‐related conditions (e.g., stroke and cerebral amyloid angiopathy (CAA)). This review focuses on AD (as the most common “neurodegenerative” cause of dementia), CAA (as an “emerging” cause of dementia), and stroke (as the most common cause of “vascular” dementia). We will discuss the available literature on the pharmacological therapies that demonstrate sex differences, which refer to any combination of structural, chromosomal, gonadal, or hormonal differences between males and females. We will emphasize the importance of considering sex as a biological variable in the design of preclinical and clinical studies that investigate underlying pathologies or response to pharmacological interventions in dementia.

LINKED ARTICLES

This article is part of a themed section on The Importance of Sex Differences in Pharmacology Research. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.21/issuetoc
A cross‐sectional study on intergenerational parenting and attachment patterns in adult children of parents with mental illness
Authors: Patrick Pamela M. , Reupert Andrea E. , McLean Louise A.
Published: April 2019

The present study adds to the existing knowledge about adult children of parents with mental illness. The aim was to explore differences between adult children of parents with mental illness and parents in the general population on a range of adult relationship and parenting variables. Utilizing a cross‐sectional design, 86 adults across Australia participated in this study (47 general population; 39 adult children of parents with mental illness). Data were analysed using descriptive statistics and parametric tests. Adult children of parents with mental illness were found to be more permissive in their parenting compared with parents in the general population. However, between‐group differences were not found on measures of parenting competence, adult attachment, and relationship satisfaction. These findings suggest that adult children of parents with mental illness are able to thrive just as well as individuals in the general population but may require some support in the form of parental skills training. The paper concludes by highlighting the role of mental health professionals in the empowerment and resilience building of adult children of parents with mental illness.
ESTIMATES OF THE PRICE ELASTICITY OF SWITCHING BETWEEN BRANDED AND GENERIC DRUGS
Authors: Terrizzi Sabrina , Meyerhoefer Chad
Published: April 2019

We estimate price elasticities of switching from branded to generic drugs for two widely used drugs: Prozac and Zocor. We find the price elasticity of switching varies by drug and is between 0.01 and 0.10. While elasticity estimates for Zocor are robust to the inclusion of controls for supply‐side factors, those for Prozac are not. Our results indicate consumers in managed care plans are most responsive to differences in out‐of‐pocket (OOP) cost, and we estimate that a 10% increase in the OOP cost difference between Zocor and generic Simvastatin increases an individual's probability of switching to the generic by approximately 0.3%. This would result in a modest total savings of $36,700 among our sample of 114,218 privately insured Zocor users. Our finding that individuals are relatively unresponsive to the lower prices caused by generic introduction implies that policies targeting supply‐side behavior are likely to have a larger effect on generic uptake than price‐based inducements. If generic‐uptake did occur immediately within the first 18 months after generic introduction, the total savings among individuals and insurance companies within our sample would be approximately $7 million for Zocor and $255,000 for Prozac. (JEL I11, I18)
Human enhancement: from disability to superability
Authors: Dan Bernard
Published: April 2019

Video Podcast: https://www.youtube.com/watch?v=GY9YmA2jkow&t=1s
Heineke–Mikulicz pyloroplasty for the treatment of pyloric stenosis secondary to gastro‐duodenal ulcer disease in three foals
Authors: Kent A. V. , Slone D. E. , Clark C. K. , Lynch T. M.
Published: April 2019

The objective of the study was to describe a modified Heineke–Mikulicz pyloroplasty for the treatment of pyloric stenosis in foals due to gastric ulceration and assess the short‐ and long‐term outcome of foals receiving the pyloroplasty. Medical records of foals undergoing a modified Heineke–Mikulicz pyloroplasty due to gastric outflow obstruction secondary to a pyloric stenosis were included in this retrospective case series. The pyloroplasty consisted of an oral to aboral full thickness longitudinal incision on the ventral aspect of the pylorus and proximal duodenum, which was sutured closed with 0 polydioxanone in a transverse orientation, thereby, enlarging the pyloric lumen diameter. Long‐term outcome was obtained from medical and race records. The pyloroplasty was successfully performed in three foals with a surgical time of 95–121 min, with immediate return to nursing and hospital stay of 4–14 days. Complications included a small intestinal volvulus and intra‐abdominal adhesions in a foal that did not survive. Another foal had an incisional infection. Two of the three foals went on to race. It was concluded that the pyloroplasty procedure is an acceptable option for the treatment of pyloric stenosis and secondary gastric outflow obstruction due to gastric ulceration. The limited amount of bowel manipulation with no change in intestinal flow, along with the successful outcomes achieved, make this another surgical option available for the correction of pyloric stenosis in foals.
Geographic Data Science
Authors: Singleton Alex , Arribas‐Bel Daniel
Published: April 2019

It is widely acknowledged that the emergence of “Big Data” is having a profound and often controversial impact on the production of knowledge. In this context, Data Science has developed as an interdisciplinary approach that turns such “Big Data” into information. This article argues for the positive role that Geography can have on Data Science when being applied to spatially explicit problems; and inversely, makes the case that there is much that Geography and Geographical Analysis could learn from Data Science. We propose a deeper integration through an ambitious research agenda, including systems engineering, new methodological development, and work toward addressing some acute challenges around epistemology. We argue that such issues must be resolved in order to realize a Geographic Data Science, and that such goal would be a desirable one.
Nutritional quality evaluation of commercial protein supplements
Authors: Corgneau Magda , Gaiani Claire , Petit Jeremy , Nikolova Yoana , Banon Sylvie , Ritié‐Pertusa Léa , Le Doan Thanh Lam , Scher Joël
Published: April 2019

Protein supplements have received increasing attention by consumers over the last few decades. However, hundreds of them have recently exhibited irregularities including lower quantities of proteins than disclosed values. This study aimed to evaluate the nutritional quality of six commercial protein supplement powders (calcium caseinate, milk protein concentrate, egg white, pea protein isolate, whey protein concentrate and soy protein isolate). The chemical composition, amino acid content and in vitro digestibility were examined. Thus, calculate the amino acid scores corrected for amino acid and protein digestibility. In vitro digestion was also conducted and protein hydrolysis was monitored by SDS‐page. Calcium caseinate powder and whey protein concentrate were only composed of proteinogenic amino acids and exhibited the highest essential amino acid content. As regards in vitro digestibility, these two supplements perfectly meet the quality expectations of the Food and Agricultural Organization (FAO). Conversely, the other four supplements exhibited a lower quality than the FAO reference protein. This was due to low digestibility (for egg white and milk concentrate) and/or lack of a specific essential amino acid (for milk concentrate and pea isolate).
Active gelatin films incorporated with eugenol nanoemulsions: effect of emulsifier type on films properties
Authors: Dammak Ilyes , Sobral Paulo José do Amaral
Published: April 2019

The objective of this work was to study the impacts of the addition of eugenol nanoemulsions (NE) stabilised with two natural emulsifiers, soy lecithin (SL) or sodium caseinate (NaCas), on the properties of gelatin films for active packaging. All the films added with NE displayed higher tensile strength and elongation at break than control films. Films added with NaCas‐stabilised NE were more resistant to tension compared to films added with SL‐stabilised NE. Gelatin films added with both NE, showed significant differences in surface roughness compared to control film. Fourier‐transform infrared spectra showed that both NE achieved complete miscibility within the films. Differential scanning calorimetry analyses suggested compatibility among both NE embedded into the films. These films indicated great antioxidant activities monitored via ABTS radical scavenging activities. These findings are essential to better design active films incorporated with nanoemulsions, in order to optimise film formulation rationally towards their eventual application as food packaging.
Encounters with difference: Mental health nurses and Indigenous Australian users of mental health services
Authors: Molloy Luke , Walker Kim , Lakeman Richard , Lees David
Published: April 2019

This article presents findings from the multi‐sited ethnography of mental health nursing practice as it relates to the care of Indigenous users of public mental health services in Australia. It provides an analysis of mental health nurses beliefs and ideas about Aboriginal and Torres Strait Islander people encountered over the course of this research. The Indigenous service user was positioned as Other to the non‐Indigenous mental health nurse, and to non‐Indigenous service users. Cultural difference and the legacy of colonization, including its impact on the health of Aboriginal and Torres Strait Islander peoples, contributed to these beliefs of alterity. Despite emphasizing the differences with Aboriginal and Torres Strait Islander people in mental health services, nurses did not clearly relate this to Indigenous ways of understanding ill health. While cultural differences were recognized, what they meant for the nurses or their nursing practice was interpreted in different ways. In these circumstances, approaches towards care for Aboriginal and Torres Strait Islander people varied between nurses.
Effect of silicon on activity coefficients of Bi, Cd, Sn, and Ag in liquid Fe‐Si, and implications for differentiation and core formation
Authors: Righter K. , Pando K. , Ross D. K. , Righter M. , Lapen T. J.
Published: April 2019

The depletion of volatile siderophile elements (VSE) Sn, Ag, Bi, Cd, and P in mantles of differentiated planetary bodies can be attributed to volatile‐depleted precursor materials (building blocks), fractionation during core formation, fractionation into and retention in sulfide minerals, and/or volatile loss associated with magmatism. Quantitative models to constrain the fractionation due to core formation have not been possible due to the lack of activity and partitioning data. Interaction parameters in Fe‐Si liquids have been measured at 1 GPa, 1600 °C and increase in the order Cd (~6), Ag (~10), Sn (~28), Bi (~46), and P (~58). These large and positive values contrast with smaller and negative values in Fe‐S liquids indicating that any chalcophile behavior exhibited by these elements will be erased by dissolution of a small amount of Si in the metallic liquid. A newly updated activity model is applied to Earth, Mars, and Vesta. Five elements (P, Zn, Sn, Cd, and In) in Earth's primitive upper mantle can largely be explained by metal‐silicate equilibrium at high PT conditions where the core‐forming metal is a Fe‐Ni‐S‐Si‐C metallic liquid, but two other—Ag and Bi—become overabundant during core formation and require a removal mechanism such as late sulfide segregation. All of the VSE in the mantle of Mars are consistent with core formation in a volatile element depleted body, and do not require any additional processes. Only P and Ag in Vesta's mantle are consistent with combined core formation and volatile‐depleted precursors, whereas the rest require accretion of chondritic or volatile‐bearing material after core formation. The concentrations of Zn, Ag, and Cd modeled for Vesta's core are similar to the concentration range measured in magmatic iron meteorites indicating that these volatile elements were already depleted in Vesta's precursor materials.
An mHealth voice messaging intervention to improve infant and young child feeding practices in Senegal
Authors: Downs Shauna M. , Sackey Joachim , Kalaj Jozefina , Smith Stephen , Fanzo Jessica
Published: April 2019

Mobile health (mHealth) interventions have the potential to improve infant and young child feeding (IYCF) practices; however, gaps in the literature remain regarding their design, implementation, and effectiveness. The aims of this study were to design an mHealth voice messaging intervention delivered to mothers and fathers targeting IYCF practices and examine its implementation and impact in households with children 6–23 months in three rural villages in Senegal. We conducted focus groups (n = 6) to inform the intervention development. We then conducted a pilot study (n = 47 households) to examine the impact of the intervention on IYCF practices of children 6–23 months. Voice messages were sent to the children's mothers and fathers over a period of 4 weeks (two messages per week; eight messages in total), and 24‐hr dietary recalls and food frequency questionnaires (FFQs) were conducted before and immediately after the implementation of the mHealth intervention to examine its impact on IYCF practices. Overall, three of the eight behaviours increased and one decreased. There was a significant increase in the number of children that consumed fish (60% vs. 94%; p = .008) as measured by the 24‐hr recall after the completion of the intervention. We also found significantly higher frequency of egg (p = .026), fish (p = .004), and thick porridge (p = .002) consumption in the previous 7 days measured by the FFQ. Our findings suggest that voice messaging IYCF interventions in Senegal have the potential to improve IYCF behaviours among young children in the short term. Future research should entail scaling‐up the intervention and examining its sustainability over the long‐term.
The Poor Lady Immured
Authors: Heath Eugene
Published: April 2019

This essay offers cautionary considerations on what has come to be called “public philosophy.” A conception of philosophy is set forth using Socrates as the paradigm of relentless philosophical questioning. The essay then outlines three types of public philosophy: a philosophy situated in a public setting, a philosophy whose content is modified for a varied public, and a philosophy that functions as normative consensus. The most important of these three is the philosophy modified for the public. The discussion notes examples of public philosophy from the history of philosophy, and examines the contribution of eighteenth‐century philosophers (such as David Hume) to a version of public philosophy. The risks of public philosophy are noted—in particular, that a modified philosophy may substitute the inculcation of belief over the modeling of philosophy. The essay concludes by noting that the university classroom remains an important but forgotten venue of public philosophy.
What is new and what is nationalist about Europe's new nationalism? Explaining the rise of the far right in Europe
Authors: Halikiopoulou Daphne , Vlandas Tim
Published: April 2019

Far‐right parties are on the rise across Europe. Their shared populist rhetoric, emphasis on sovereignty and policies that promote a ‘national preference’ has facilitated the term ‘the new nationalism’. According to an emerging consensus, this new nationalism is primarily a demand‐side phenomenon triggered by cultural grievances, i.e. a cultural backlash, driven by those on the wrong end of a new transnational cleavage. This explanation we argue tends to overlook important variations across countries and across time. As such, in this article, we contest the view that the ‘new nationalism’ is a linear and coherent phenomenon best understood as a cultural backlash. Specifically, our argument is threefold: (1) it is important to conceptually distinguish between populism, nationalism and the far right in order to draw meaningful conclusions about the extent to which this phenomenon is linear, coherent and comparable across cases; (2) voters' economic concerns remain pivotal within the context of the transnational cleavage, entailing that voting behaviour is structured by two dimensions of contestation; (3) the explanatory power of nationalism is in the supply, i.e. the ways in which parties use nationalism strategically in an attempt to broaden their appeal.
A Functional Protection Method for Availability and Cost Risk Management of Complex Research Facilities
Authors: Andersson R. , Bargalló E. , Nordt A.
Published: April 2019

While the area of functional safety for industry has evolved over the years by developing well-renowned standards and methods proven in use, such standards are not present in the field of equipment protection for complex research facilities. Research facilities in particular do typically not apply global, systematic approaches for functional equipment protection, but rather rely on system expert judgment for the individual systems, often leaving out the emergent properties of complex systems of systems. With the increasing demands on research facilities to be highly reliable and available, comparable to industrial facilities, a holistic and systematic method for equipment protection is, if not necessary, highly beneficial. This paper describes the development of a risk management method named functional protection, and benchmarks its lifecycle steps toward the IEC 61508 functional safety standard as well as the ISO 31000 risk management standard. The functional protection method is currently applied for the design and construction of the European Spallation Source in Lund, Sweden.
An Enhanced Axisymmetric Solid Element for Rotor Dynamic Model Improvement
Authors: Hu Lingnan , Palazzolo Alan
Published: April 2019

The authors present an improved formulation for the axisymmetric solid harmonic finite element (FE) modeling of a flexible, spinning rotor. A thorough comparison of beam-type FE and axisymmetric solid FE rotor models is presented, indicating the errors that result from beam FE usage for various nondimensional rotor topologies. The axisymmetric rotor is meshed in only two dimensions: axial and radial, with both displacement fields being represented with Fourier series expansions. Centrifugal stress-stiffening and spin-softening effects are included in all elements and most importantly in modeling flexible disks. Beam FE and axisymmetric FE natural frequencies, mode shapes, and critical speeds are compared to identify shaft geometries where the beam model yields a significant error. Finally, limitations of beam FE models and guidance for utilizing axisymmetric solid FE models in rotor dynamic simulations are provided.
Accurate Approximate Methods for the Fully Developed Flow of Shear-Thinning Fluids in Ducts of Noncircular Cross Section
Authors: Ruschak Kenneth J. , Weinstein Steven J.
Published: April 2019

The fully developed laminar flow of Non-Newtonian fluids in ducts has broad application in engineering. The power-law viscosity model is utilized most often in the engineering literature, but it is deficient for many fluids as it does not admit limiting Newtonian viscosities at low and high shear rates. The goal of this work is to demonstrate two approximate but accurate and efficient methods for computing the pressure gradient in ducts of noncircular cross section for shear-thinning fluids following a general viscosity curve. Both methods predict the pressure gradient to better than 1% as established by full numerical solutions for ten cross-sectional shapes, a result representing an order-of-magnitude improvement over previous approximate methods. In the first method, an approach recently proposed and demonstrated to be accurate for a circular duct is shown to be equally applicable to noncircular ducts. In the second method, a widely used approach for noncircular ducts based on a generalization of the Rabinowitsch–Mooney equation is improved through an alternate evaluation of its parameters. Both methods require one-time numerical solutions of the power-law viscosity model for a duct shape of interest, and the necessary results are tabulated for the ten cross-sectional shapes analyzed. It is additionally demonstrated that the pressure-gradient error of the second method is approximately halved by simply replacing the hydraulic diameter with a viscous diameter obtained from the Hagen–Poiseuille equation.
Wind Turbine Participation in Primary Frequency Control
Authors: Chu Cheong Matthew , Ma Zheren , Qian Haiya , Conger Julia , Du Pengwei , Chen Dongmei
Published: April 2019

Wind energy is a clean and desirable power source, but wind turbines can potentially operate to the detriment of grid stability. As wind turbine penetration increases, concerns grow regarding power intermittency and frequency regulation. These factors motivate a need for control methodologies that enable a wind turbine to support grid frequency regulation. In this paper, a control design is proposed for a wind turbine to operate in conjunction with a backup synchronous generator for primary frequency control in a microgrid. The proposed design capitalizes on the idea that the wind turbine has a significant amount of rotational inertia in its rotor, and so the power output of the wind turbine can be rapidly adjusted for frequency support via power electronic commands. A novel torque controller is proposed to quickly track the commanded power output without causing wind turbine instability, and an H2 gain-scheduled pitch controller has been developed to optimally track the commanded power output while avoiding turbine overspeeding. The proposed design may be used for either un-deloaded or deloaded wind turbine operation, depending on the available wind power. Simulation results show that the proposed wind turbine frequency control effectively enhances the grid frequency response by reducing the frequency deviation from its nominal value following a power imbalance event.
Hidden Markov Modeling-Based Decision-Making Using Short-Length Sensor Time Series
Authors: Ghalyan Najah F. , Mondal Sudeepta , Miller David J. , Ray Asok
Published: April 2019

Real-time decision-making (e.g., monitoring and active control of dynamical systems) often requires feature extraction and pattern classification from short-length time series of sensor data. An example is thermoacoustic instabilities (TAI) in combustion systems, caused by spontaneous excitation of one or more natural modes of acoustic waves. The TAI are typically manifested by large-amplitude self-sustained pressure oscillations in time scales of milliseconds, which need to be mitigated by fast actuation of the control signals, requiring early detection of the forthcoming TAI. This issue is addressed in this technical brief by hidden Markov modeling (HMM) and symbolic time series analysis (STSA) for near-real-time recognition of anomalous patterns from short-length time series of sensor data. An STSA technique is first proposed, which utilizes a novel HMM-based partitioning method to symbolize the time series by using the Viterbi algorithm. Given the observed time series and a hidden Markov model, the algorithm generates a symbol string with maximum posterior probability. This symbol string is optimal in the sense of minimizing string error rates in the HMM framework. Then, an HMM likelihood-based detection algorithm is formulated and its performance is evaluated by comparison with the proposed STSA-based algorithm as a benchmark. The algorithms have been validated on a laboratory-scale experimental apparatus. The following conclusions are drawn from the experimental results: (1) superiority of the proposed STSA method over standard methods in STSA for capturing the dynamical behavior of the underlying process, based on short-length time series and (2) superiority of the proposed HMM likelihood-based algorithm over the proposed STSA method for different lengths of sensor time series.
Optoelectronic control of single cells using organic photocapacitors
Authors: Jakešová Marie , Silverå Ejneby Malin , Đerek Vedran , Schmidt Tony , Gryszel Maciej , Brask Johan , Schindl Rainer , Simon Daniel T. , Berggren Magnus , Elinder Fredrik , Głowacki Eric Daniel
Published: April 2019

Organic electronic materials enable a simple optoelectronic device for wireless electrical stimulation of single cells.
Slamming the brakes on lupus with CAR T cells
Authors: Clark Rachael A.
Published: April 2019

Sustained depletion of B cells with CAR T cells induces disease remission in lupus-prone mice.
Population Pharmacokinetics and Dosing Optimization of Imipenem in Children with Hematological Malignancies
Authors: Dong Lei , Zhai Xiao-Ying , Yang Yi-Lei , Wang Li , Zhou Yue , Shi Hai-Yan , Tang Bo-Hao , Wu Yue-E , Yang Fan , Wen Li , Kong Hong-Xiao , Zhi Li-Juan , Jacqz-Aigrain Evelyne , Zhao Wei
Published: April 2019

Imipenem is widely used for the treatment of children with serious infections. Currently, studies on the pharmacokinetics of imipenem in children with hematological malignancies are lacking.
Pharmacokinetics of Caspofungin in Critically Ill Patients in Relation to Liver Dysfunction: Differential Impact of Plasma Albumin and Bilirubin Levels
Authors: Kurland S. , Furebring M. , Löwdin E. , Eliasson E. , Nielsen E. I. , Sjölin J.
Published: April 2019

Caspofungin has a liver-dependent metabolism. Reduction of the dose is recommended based on Child-Pugh (C-P) score.
Methicillin-Resistant Staphylococcus aureus Harboring
mecC
Still Eludes Us in East London, United Kingdom
Authors: Ciesielczuk H. , Xenophontos M. , Lambourne J.
Published: April 2019

Reports of methicillin-resistant
Staphylococcus aureus
(MRSA) harboring the
mecC
gene have increased in the UK since first being described. To our diagnostic
S. aureus
multiplex PCR, a
mecC
primer set was designed and implemented, and then the prevalence in our patient population was investigated.
Understanding and Addressing CLSI Breakpoint Revisions: a Primer for Clinical Laboratories
Authors: Humphries Romney M. , Abbott April N. , Hindler Janet A.
Published: April 2019

The Clinical and Laboratory Standards Institute (CLSI) has revised several breakpoints since 2010 for bacteria that grow aerobically. In 2019, these revisions include changes to the ciprofloxacin and levofloxacin breakpoints for the
Enterobacteriaceae
and
Pseudomonas aeruginosa
, daptomycin breakpoints for
Enterococcus
spp., and ceftaroline breakpoints for
Staphylococcus aureus
.
Targeting NAMPT as a therapeutic strategy against stroke
Authors: Wang Shu-Na , Miao Chao-Yu
Published: April 2019

Stroke is the second and the leading most common cause of death in the world and China, respectively, but with few effective therapies. Nicotinamide phosphoribosyltransferase (NAMPT) is the rate-limiting enzyme for nicotinamide adenine dinucleotide (NAD) salvage synthesis in mammals, thereby influencing NAD-dependent enzymes and constituting a strong endogenous defence system against various stresses. Accumulating in-vitro and in-vivo studies have demonstrated the neuroprotective effect of NAMPT in stroke. Here, we review the direct evidence of NAMPT as a promising target against stroke from five potential therapeutic strategies, including NAMPT overexpression, recombinant NAMPT, NAMPT activators, NAMPT enzymatic product nicotinamide mononucleotide (NMN), and NMN precursors nicotinamide riboside and nicotinamide, and describe the relevant mechanisms and limitations, providing a promising choice for developing novel and effective therapeutic interventions against ischaemic and haemorrhagic stroke.
Do longer growing seasons give introduced plants an advantage over native plants in Interior Alaska?
Authors: Mulder Christa P.H. , Spellman Katie V.
Published: April 2019

In interior Alaska, increases in growing season length and rapid expansion of introduced species are altering the environment for native plants. We evaluated whether earlier springs, warmer summers, and extended autumns alter the phenology of leaves and flowers in native and introduced forbs and shrubs in the boreal understory and open-canopy habitats, and whether the responses provide an advantage to either group. We tracked the phenology of 29 native and 12 introduced species over three years with very different spring, summer, and autumn conditions. The native species produced flowers (but not leaves) earlier than the introduced species, and both groups advanced leaf-out and flowering in the early-snowmelt year. However, shifts in phenology between early and late years were similar for both groups. There was no increase in fruit development rate for either group in the warm summer. In contrast, in the year with the extended autumn, the introduced plants extended leaf production and time of senescence much more than native species. While growth form and leaf habit could explain the differences in phenology between native and introduced groups in spring and summer, these traits could not account for differences in autumn. We conclude that in boreal Alaska extended autumns may benefit introduced species more than native ones.
Spatiotemporal habitat use by a multitrophic Alaska alpine mammal community
Authors: Dertien Jeremy S. , Bagley Calvin F. , Haddix John A. , Brinkman Aleya R. , Neipert Elizabeth S. , Jochum Kim A. , Doherty Paul F.
Published: April 2019

Evaluating sympatric habitat use of a mammal community can help determine intra- and inter-guild interactions and identify important habitats, potentially improving the management of these communities with a changing climate. Increasingly variable climatic patterns in Alaska, USA, are raising concerns of mismatched phenologies and altered ecosystem structures. We studied the occupancy of 10 mammal species over 15 months, via camera traps, occupying alpine areas of the Alaska Range in interior Alaska, from 2013 to 2014. We tested hypotheses about how habitat use of these species within and between groups varied by spatial and temporal covariates. Furthermore, we modeled two-species occupancy of brown bears (Ursus arctos Linnaeus, 1758) and gray wolves (Canis lupus Linnaeus, 1758) against different potential prey species. Our results suggest that medium-sized and large herbivore use was positively correlated with fine-scale covariates including rock, forb, and graminoid coverage. Large herbivore habitat use was also correlated with abiotic landscape covariates. Detection probabilities of predators and Dall’s sheep (Ovis dalli dalli Nelson, 1884) was improved by camera traps on wildlife trails. Two-species models suggested co-occurrence of habitat use between brown bear – caribou (Rangifer tarandus (Linnaeus, 1758)) and gray wolf – caribou. Results demonstrate the sympatric habitat use by multiple groups of mammals within Alaskan alpine ecosystems and the importance of incorporating multiple groups and spatial scales when making management decisions.
Zitterbewegung in noncommutative geometry
Authors: Zahiri Abyaneh Mehran , Farhoudi Mehrdad
Published: April 2019

We have considered the effects of space and momentum noncommutativity separately on the zitterbewegung (ZBW) phenomenon. In the space noncommutativity scenario, it has been expressed that, due to the conservation of momentum, the Fourier decomposition of the expectation value of position does not change. However, the noncommutative (NC) space corrections to the magnetic dipole moment of electron, that was traditionally perceived to come into play only in the first-order of perturbation theory, appear in the leading-order calculations with the similar structure and numerically the same order, but with an opposite sign. This result may explain why for large lumps of masses, the Zeeman effect due to the noncommutativity remains undetectable. Moreover, we have shown that the x- and y-components of the electron magnetic dipole moment, contrary to the commutative (usual) version, are nonzero and with the same structure as the z-component. In the momentum noncommutativity case, we have indicated that, due to the relevant external uniform magnetic field, the energy spectrum and also the solutions of the Dirac equation are changed in 3[Formula: see text]+[Formula: see text]1 dimensions. In addition, our analysis shows that in 2[Formula: see text]+[Formula: see text]1 dimensions, the resulted NC field makes electrons in the zero Landau level rotate not only via a cyclotron motion, but also through the ZBW motion with a frequency proportional to the field which doubles the amplitude of the rotation. In fact, this is a hallmark of the ZBW in graphene that provides a promising way to be tested experimentally.
Smooth Transition HYGARCH Model: Stability and Testing
Authors: Basatini Ferdous Mohammadi , Rezakhah Saeid
Published: April 2019

HYGARCH process is commonly used for modeling long memory volatility. Many financial time series are characterized by transition between different levels of volatilities. Smooth transition HYGARCH (ST-HYGARCH) model is proposed to model smooth transition between components of HYGARCH process. The behavior of the conditional variance in the ST-HYGARCH are allowed to change smoothly over time. The asymptotic finiteness of the second moment is studied. A score test is developed to check the smooth transition property. The performance of the new proposed model and the score test are examined by some simulations. Applying the log returns of some part of S&P500 and Dow Jones industrial average indexes, we show the competing performance of the ST-HYGARCH model in comparison to HYGARCH and ST-GARCH models in forecasting volatility and value-at-risk.
Regulation of Transmembrane Signaling by Phase Separation
Authors: Case Lindsay B. , Ditlev Jonathon A. , Rosen Michael K.
Published: April 2019

Cell surface transmembrane receptors often form nanometer- to micrometer-scale clusters to initiate signal transduction in response to environmental cues. Extracellular ligand oligomerization, domain-domain interactions, and binding to multivalent proteins all contribute to cluster formation. Here we review the current understanding of mechanisms driving cluster formation in a series of representative receptor systems: glycosylated receptors, immune receptors, cell adhesion receptors, Wnt receptors, and receptor tyrosine kinases. We suggest that these clusters share properties of systems that undergo liquid–liquid phase separation and could be investigated in this light.
Colloidal Materials for 3D Printing
Authors: Zhu Cheng , Pascall Andrew J. , Dudukovic Nikola , Worsley Marcus A. , Kuntz Joshua D. , Duoss Eric B. , Spadaccini Christopher M.
Published: April 2019

In recent years, 3D printing has led to a disruptive manufacturing revolution that allows complex architected materials and structures to be created by directly joining sequential layers into designed 3D components. However, customized feedstocks for specific 3D printing techniques and applications are limited or nonexistent, which greatly impedes the production of desired structural or functional materials. Colloids, with their stable biphasic nature, have tremendous potential to satisfy the requirements of various 3D printing methods owing to their tunable electrical, optical, mechanical, and rheological properties. This enables materials delivery and assembly across the multiple length scales required for multifunctionality. Here, a state-of-the-art review on advanced colloidal processing strategies for 3D printing of organic, ceramic, metallic, and carbonaceous materials is provided. It is believed that the concomitant innovations in colloid design and 3D printing will provide numerous possibilities for the fabrication of new constructs unobtainable using traditional methods, which will significantly broaden their applications.
Exercise in Glucose-6-Phosphate Dehydrogenase Deficiency: Harmful or Harmless? A Narrative Review
Authors: Georgakouli Kalliopi , Fatouros Ioannis G. , Draganidis Dimitrios , Papanikolaou Konstantinos , Tsimeas Panagiotis , Deli Chariklia K. , Jamurtas Athanasios Z.
Published: April 2019

Objectives. Glucose-6-phosphate dehydrogenase (G6PD) deficiency, theoretically, renders red blood cells (RBC) susceptible to oxidative stress. G6PD deficiency has also been found in other types of cells than RBC, such as leukocytes and myocytes, where an inefficient protection against oxidative stress may occur too. Glutathione (GSH), a significant antioxidant molecule, levels are lower in G6PD individuals, and theoretically, the probability of oxidative stress and haemolysis due to exercise in individuals with G6PD deficiency is increased, whereas dietary supplementation with antioxidants may have beneficial effects on various aspects of this enzymopathy.Methods. A search of the available literature was conducted using the keywords glucose-6-phosphate dehydrogenase (G6PD), deficiency, disease, exercise, muscle, antioxidant, vitamin, supplement, and supplementation. The search was limited to publications in English, conducted on humans, and published until August 2018. After screening, only relevant articles were included.Results. There is little evidence indicating that G6PD deficiency can cause perturbations in redox status, haemolysis, and clinical symptoms such as fatigability and myoglobinuria, especially after intense exercise, compared to individuals with normal enzyme levels.Conclusions. Exercise could be used by G6PD-deficient individuals as a tool to improve their quality of life. However, there is a lack of training studies, and assessment of the effects of regular and systematic exercise in G6PD-deficient individuals is warranted. Finally, since GSH levels are lower in G6PD deficiency, it would be interesting to examine the effects of antioxidant or cysteine donor supplements on redox status after exercise in these individuals.
Long Noncoding RNA ELIT-1 Acts as a Smad3 Cofactor to Facilitate TGFβ/Smad Signaling and Promote Epithelial–Mesenchymal Transition
Authors: Sakai Satoshi , Ohhata Tatsuya , Kitagawa Kyoko , Uchida Chiharu , Aoshima Takuya , Niida Hiroyuki , Suzuki Tetsuro , Inoue Yasumichi , Miyazawa Keiji , Kitagawa Masatoshi
Published: April 2019

TGFβ is involved in various biological processes, including development, differentiation, growth regulation, and epithelial–mesenchymal transition (EMT). In TGFβ/Smad signaling, receptor-activated Smad complexes activate or repress their target gene promoters. Smad cofactors are a group of Smad-binding proteins that promote recruitment of Smad complexes to these promoters. Long noncoding RNAs (lncRNA), which behave as Smad cofactors, have thus far not been identified. Here, we characterize a novel lncRNA EMT-associated lncRNA induced by TGFβ1 (ELIT-1). ELIT-1 was induced by TGFβ stimulation via the TGFβ/Smad pathway in TGFβ-responsive cell lines. ELIT-1 depletion abrogated TGFβ-mediated EMT progression and expression of TGFβ target genes including Snail, a transcription factor critical for EMT. A positive correlation between high expression of ELIT-1 and poor prognosis in patients with lung adenocarcinoma and gastric cancer suggests that ELIT-1 may be useful as a prognostic and therapeutic target. RIP assays revealed that ELIT-1 bound to Smad3, but not Smad2. In conjunction with Smad3, ELIT-1 enhanced Smad-responsive promoter activities by recruiting Smad3 to the promoters of its target genes including Snail, other TGFβ target genes, and ELIT-1 itself. Collectively, these data show that ELIT-1 is a novel trans-acting lncRNA that forms a positive feedback loop to enhance TGFβ/Smad3 signaling and promote EMT progression.

Significance:

This study identifies a novel lncRNA ELIT-1 and characterizes its role as a positive regulator of TGFβ/Smad3 signaling and EMT.
Targeting High Mobility Group Box-1 (HMGB1) Promotes Cell Death in Myelodysplastic Syndrome
Authors: Kam Angel Y.F. , Piryani Sadhna O. , McCall Chad M. , Park Hee Su , Rizzieri David A. , Doan Phuong L.
Published: April 2019

Purpose:

Myelodysplastic syndrome (MDS) is associated with a dysregulated innate immune system. The purpose of this study was to determine whether modulation of the innate immune system via high mobility group box-1 (HMGB1) could reduce cell viability in MDS.

Experimental Design:

We quantified HMGB1 in an MDS cell line MDS-L and in primary MDS cells compared with nonmalignant hematopoietic cells. We performed loss-of-function studies of HMGB1 using pooled siRNAs and a small-molecule inhibitor sivelestat compared with standard chemotherapy. We measured levels of engraftment of MDS-L cells in NOD-scidIL2Rgnull (NSG) mice following treatment with sivelestat. Mechanistically, we interrogated cell survival pathways and 45 targets within the NFκB pathway using both protein analysis and a proteome profiler array.

Results:

We discovered that HMGB1 had increased expression in both MDS-L cells and in primary CD34+ MDS cells compared with healthy CD34+ hematopoietic cells. Sivelestat impaired MDS cell expansion, increased cellular death, and spared healthy hematopoietic cells. MDS-L marrow engraftment is reduced significantly at 17 weeks following treatment with sivelestat compared with control mice. Treatment of CD34+ MDS cells with sivelestat and azacitidine or decitabine was additive to increase apoptotic cell death compared with chemotherapy alone. Sivelestat promoted apoptosis with increased expression of PUMA, activated caspase 3, and increased DNA double-strand breaks. Inhibition of HMGB1 reduced levels of Toll-like receptors (TLR) and suppressed activation of NFκB in MDS-L cells.

Conclusions:

Inhibition of HMGB1 could promote MDS cell death and alter innate immune responses via suppression of NFκB pathways.
The Role of Staging Laparoscopy in Resectable and Borderline Resectable Pancreatic Cancer: A Systematic Review and Meta-Analysis
Authors: Ta Robert , O’Connor Donal B. , Sulistijo Andrew , Chung Benjamin , Conlon Kevin C.
Published: April 2019

Aim: The study aimed to determine the additional value of staging laparoscopy in patients with pancreatic cancer deemed potentially resectable based on computed tomography imaging. Methods: A systematic literature search was performed using MEDLINE and the Cochrane Register of Controlled Trials (January 1995 to June 2017). Primary outcome measures were the overall yield and sensitivity to detect non-resectable disease. Quality of studies was assessed with the Newcastle-Ottawa Scale. Results: From 156 records, 15 studies including 2,776 patients met the inclusion criteria. In 12 studies, reporting outcomes on 1,756 patients with resectable disease after standard imaging, 350 (20%, range 14–38%) cases of non-resectable cancer were detected with staging laparoscopy. In 3 studies on 242 patients with locally advanced disease after standard imaging, staging laparoscopy detected metastases in 86 patients (36%). The failure rate of staging laparoscopy to detect non-resectable disease was 5% (64 of 1,406). Conclusion: Staging laparoscopy reduces the non-therapeutic laparotomy rate, and in locally advanced or borderline resectable disease, staging laparoscopy could more accurately select patients for neoadjuvant protocols.
Interleukin 10-Mediated Response and Correlated Anemia in a Patient with Advanced Non-Small Cell Lung Carcinoma
Authors: Choucair Khalil , Kelso Jesse D. , Duff Joseph R. , Cassidy Christine S. , Albrethsen Mary T. , Ashraf Mushtaq , Verghese Cherian , Oft Martin , Brunicardi F. Charles , Dworkin Lance , Nemunaitis John
Published: April 2019

Anemia in cancer patients is associated with poor quality of life, reduced response to therapy, and decreased overall survival. We describe a case of a 56-year old woman with advanced metastatic non-small cell lung carcinoma who demonstrated marked response to a novel combinational immunotherapy approach involving a long-acting PEGylated construct of recombinant human Interleukin-10 with Nivolumab, an anti-PD-L1 checkpoint inhibitor. While on treatment, the patient developed severe anemia and hyper-ferritinemia requiring RBC transfusion support. Here we discuss a possible novel immune mechanism of IL10-mediated anemia in correlation with tumor response.
Racial, Ethnic, and Socioeconomic Inequities in the Prescription of Direct Oral Anticoagulants in Patients With Venous Thromboembolism in the United States
Authors: Nathan Ashwin S. , Geng Zhi , Dayoub Elias J. , Khatana Sameed Ahmed M. , Eberly Lauren A. , Kobayashi Taisei , Pugliese Steven C. , Adusumalli Srinath , Giri Jay , Groeneveld Peter W.
Published: April 2019

Background:

Beginning in 2012, direct oral anticoagulants (DOACs) were approved for treatment and prevention of venous thromboembolism. Prior investigations have demonstrated slow rates of adoption of novel therapeutics for black patients. We assessed the association of racial/ethnic and socioeconomic factors with DOAC use among commercially insured venous thromboembolism patients.

Methods and Results:

We performed a retrospective cohort analysis of adult patients with an incident diagnosis of venous thromboembolism between January 2010 and December 2016 using OptumInsight’s Clinformatics Data Mart. We identified the first filled oral anticoagulant prescription within 30 days of discharge of an inpatient admission. We performed a multivariable logistic regression, adjusting for age, sex, race/ethnicity, region, zip code–linked household income, and clinical covariates to identify factors associated with the use of DOACs. Race and ethnicity were determined in this database through a combination of public records, self-report, and proprietary ethnicity code tables. There were 14 140 patients included in the analysis. Treatment with DOACs increased from <0.1% in 2010 to 65.6% in 2016. In multivariable analyses, black patients were less likely to receive a DOAC compared with white patients (odds ratio, 0.86; 95% CI, 0.77–0.97;
P
=0.02). There were no differences in DOAC utilization among Asian (odds ratio, 1.06; 95% CI, 0.75–1.49;
P
=0.74) or Hispanic patients (odds ratio, 1.04; 95% CI, 0.88–1.22;
P
=0.66) compared with whites. Patients with a household income over $100 000 per year were more likely to receive DOAC therapy compared with patients with a household income of <$40 000 per year (odds ratio, 1.50; 95% CI, 1.33–1.69;
P
<0.0001).

Conclusions:

Although DOAC adoption has increased steadily since 2012, among a commercially insured population, black race and low household income were associated with lower use of DOACs for incident venous thromboembolism despite controlling for other clinical and socioeconomic factors. These findings suggest the possibility of both racial and socioeconomic inequity in access to this novel pharmacotherapy.