bluuebunny/crossref_metadata_2025 huggingface dataset:
Bilateral blood pressure differential as a clinical marker for acute aortic dissection in the emergency department
Authors: Um Sung Wook , Ohle Robert , Perry Jeffrey J
Published: July 2018

Introduction

Interarm systolic BP differential is a classic sign of acute aortic dissection (AAD). All previous studies looking at the association of BP differential with AAD combine systolic BP differential >20 mm Hg with pulse deficit. Our aim was to assess the association of systolic BP differential with AAD, and its role in predicting AAD in the context of other signs and symptoms.

Methods

Historical matched case–control study using patient data collected between 2002 and 2014: participants were adults >18 years old with a bilateral BP measurement presenting to two tertiary care EDs or one regional cardiac referral centre in Canada. Cases were patients with diagnosed AAD; controls were those with a triage diagnosis of truncal pain (<14 days) and an absence of a clear diagnosis on basic investigation. Cases and controls were matched in a 1:1 ratio by sex and age. Bilateral BP differential and pulse deficit were compared between groups.

Results

A total of 222 patients (111 cases and 111 controls) were analysed. On univariate analysis systolic BP differential >20 mm Hg (OR 2.7, 95% CI 1.39 to 5.25) was significantly associated with AAD. Pulse deficit (diagnostic OR (DOR) 28.9) in isolation had better diagnostic accuracy than systolic BP differential >20 mm Hg in isolation (DOR 2.71) or combined with systolic BP differential >20 mm Hg (DOR 4.2).

Conclusion

Bilateral systolic BP differentials >20 mm Hg are associated with non-traumatic AAD. However, the poor diagnostic accuracy and potential variability in measurement limits its clinical usefulness.
2 Combat use of opioid analgesia and its complications: a retrospective review of data from OP herrick
Authors: Lewis P , Wright C , Hooper C
Published: July 2018

Background

On the battlefield, acute pain, particularly secondary to trauma, is a common condition which requires treatment in the pre-hospital, evacuation and hospital settings. The use of morphine to manage pain during combat has been well established since the 19th century. Despite this, there are relatively few papers reviewing analgesia use in a combat environment. This study aims to review the use and complications from morphine and other opioids during Op HERRICK.

Methods

A database search of the Joint Theatre Trauma Registry (JTTR) was carried out looking for all incidences of administration of either morphine, fentanyl or naloxone from January 2007 to September 2014. Microsoft Excel was then used to analyse the dataset and perform descriptive statistics on the data retrieved.

Results

Opioid analgesia was administered to 5801 casualties. Morphine was administered 6742 times to 3808 patients. Fentanyl was administered 9672 times to 4318 patients. Naloxone was used 18 times on 14 patients, giving a complication rate of 0.24%. Opioid doses prior to naloxone administration range from 0–72 mg of morphine and 0–100 mcg of fentanyl. 4 casualties (2 local civilian and 2 coalition forces) received naloxone despite no recorded opioids being administered. Opium abuse was prevalent amongst the local population in Afghanistan, and this could explain the rationale behind 2 local national casualties receiving naloxone without any documented opioids being given.

Conclusion

The use of opioids in a battlefield environment is extremely safe, with very few incidences of complications requiring the use of naloxone. Complication rates are comparable to previously published research. We are unable to comment on the effectiveness of opioids in relieving pain in this study, and further research is needed, particularly following the introduction of oral transmucosal fentanyl citrate (OTFC) and the availability of non-opioid analgesia.
What I learned from my illness. Listen to what a patient tells you about changes in their experience and function, not about their current state
Authors: Wade Derick T
Published: July 2018

I only realised how much my osteoarthritic hip had altered my life after the operation enabled me to return to activities I did not know I had stopped. Identifying need for and benefit from treatments should focus on relative changes in experience and function, not on a person’s absolute state at a particular time.
Prevalence and characteristics of secondhand smoke and secondhand vapour exposure among youth
Authors: Bayly Jennifer Ellen , Bernat Debra , Porter Lauren , O’Dare Kellie , Choi Kelvin
Published: July 2018

Background

It is well established that secondhand smoke (SHS) is harmful, and concern about the potential dangers associated with secondhand vapour (SHV) (ie, vapour from electronic vapour products, EVP) is growing. The present study examines the prevalence and characteristics associated with SHS and SHV exposure.

Methods

Data from youth aged 11–17 who completed the 2016 Florida Youth Tobacco Survey (n=58 616) were analysed. Demographics, past 30 day SHS and SHV exposure, environmental factors, cigarette and EVP use status, SHS and SHV harm perceptions, and tobacco susceptibility were assessed. Weighted multivariable logistic regressions were performed to examine characteristics associated with SHS and SHV exposure, and SHS and SHV exposure with tobacco susceptibility.

Results

Overall, 42% of Florida youth reported SHS exposure and 29% reported SHV exposure during the past 30 days. Living in a home where tobacco use was permitted (vs not permitted) was positively associated with SHS (adjusted OR (AOR) 2.57) and SHV exposure (AOR 1.56). Perceived SHS as harmful (vs not harmful) was positively associated with SHS (AOR 1.73) and SHV exposure (AOR 1.97), while perceived SHV as harmful was negatively associated with SHS (AOR 0.86) and SHV exposure (AOR 0.56). SHS and SHV exposure was significantly associated with susceptibility to cigarette and EVP use (AOR 1.40 and 2.08, respectively).

Conclusions

Almost one-third of Florida youth reported SHV exposure. Factors associated with SHS and SHV exposure are somewhat similar, and exposure to SHS and SHV is associated with tobacco susceptibility in youth. Promoting tobacco-free homes is needed to protect youth from SHS and SHV exposure.
Little filtered cigars: US sales, flavours, package sizes and prices
Authors: Gammon Doris G , Rogers Todd , Coats Ellen M , Nonnemaker James M , Henriksen Lisa
Published: July 2018

Objective

At least four varieties of little filtered cigars (LFCs) violate the US prohibition on flavoured cigarettes other than menthol. This study characterises the sales of prohibited products and other LFCs by flavour category and pack size, as well as the price of LFCs relative to cigarettes.

Methods

Using retail sales data for 2016, we computed the sales volume in dollars and equivalent units and the percentage of total sales by flavour and pack size for the USA by region and state. Paired t-tests compared the prices for LFCs and cigarettes sold in same-sized packs and cartons.

Results

LFC sales totalled 24 033 equivalent units per 100 000 persons in 2016. Flavoured LFC varieties accounted for almost half (47.5%) of the total sales. LFCs were sold in 12 different pack sizes, but 79.7% of sales were packs of 20. The price of 20-packs averaged $2.41 (SD=$1.49), which was significantly less than cigarettes (M=$5.90, SD=$0.85). Regional differences suggest a greater proportion of menthol/mint LFCs and lower prices in the South than in other regions.

Conclusion

Classifying all LFCs as cigarettes would require that they be offered in a minimum package of 20, eliminate flavoured varieties other than menthol and increase prices through applicable state and local cigarette taxes.
Discrete Boltzmann model of shallow water equations with polynomial equilibria
Authors: Meng Jianping , Gu Xiao-Jun , Emerson David R. , Peng Yong , Zhang Jianmin
Published: July 2018

A type of discrete Boltzmann model for simulating shallow water flows is derived by using the Hermite expansion approach. Through analytical analysis, we study the impact of truncating distribution function and discretizing particle velocity space. It is found that the convergence behavior of expansion is nontrivial while the conservation laws are naturally satisfied. Moreover, the balance of source terms and flux terms for steady solutions is not sacrificed. Further numerical validations show that the capability of simulating supercritical flows is enhanced by employing higher-order expansion and quadrature.
An Efficient Match Search Approach Using Two-Dimensional Hash Function in Hardware-Based Dictionary Compression
Authors: Dong Qian , Li Bing
Published: July 2018

The hardware-based dictionary compression is widely adopted for high speed requirement of real-time data processing. Hash function helps to manage large dictionary to improve compression ratio but is prone to collisions, so some phrases in match search result are not true matches. This paper presents a novel match search approach called dual chaining hash refining, which can improve the efficiency of match search. From the experimental results, our method showed obvious advantage in compression speed compared with other approach that utilizes single hash function described in the previous publications.
Omni-Ensemble Learning (OEL): Utilizing Over-Bagging, Static and Dynamic Ensemble Selection Approaches for Software Defect Prediction
Authors: Mousavi Reza , Eftekhari Mahdi , Rahdari Farhad
Published: July 2018

Machine learning methods in software engineering are becoming increasingly important as they can improve quality and testing efficiency by constructing models to predict defects in software modules. The existing datasets for software defect prediction suffer from an imbalance of class distribution which makes the learning problem in such a task harder. In this paper, we propose a novel approach by integrating Over-Bagging, static and dynamic ensemble selection strategies. The proposed method utilizes most of ensemble learning approaches called Omni-Ensemble Learning (OEL). This approach exploits a new Over-Bagging method for class imbalance learning in which the effect of three different methods of assigning weight to training samples is investigated. The proposed method first specifies the best classifiers along with their combiner for all test samples through Genetic Algorithm as the static ensemble selection approach. Then, a subset of the selected classifiers is chosen for each test sample as the dynamic ensemble selection. Our experiments confirm that the proposed OEL can provide better overall performance (in terms of G-mean, balance, and AUC measures) comparing with other six related works and six multiple classifier systems over seven NASA datasets. We generally recommend OEL to improve the performance of software defect prediction and the similar problem based on these experimental results.
A Novel Hybrid-Based Ensemble for Class Imbalance Problem
Authors: Guo Huaping , Zhou Jun , Wu Chang-an , She Wei
Published: July 2018

Class-imbalance is very common in real world. However, conventional advanced methods do not work well on imbalanced data due to imbalanced class distribution. This paper proposes a simple but effective Hybrid-based Ensemble (HE) to deal with two-class imbalanced problem. HE learns a hybrid ensemble using the following two stages: (1) learning several projection matrixes from the rebalanced data obtained by under-sampling the original training set and constructing new training sets by projecting the original training set to different spaces defined by the matrixes, and (2) undersampling several subsets from each new training set and training a model on each subset. Here, feature projection aims to improve the diversity between ensemble members and under-sampling technique is to improve generalization ability of individual members on minority class. Experimental results show that, compared with other state-of-the-art methods, HE shows significantly better performance on measures of AUC, G-mean, F-measure and recall.
Origin of the magnetic momentum for regular electrically charged objects described by nonlinear electrodynamics coupled to gravity
Authors: Dymnikova Irina
Published: July 2018

Dynamical equations of nonlinear electrodynamics minimally coupled to gravity (NED–GR), admit the class of regular solutions, asymptotically Kerr–Newman for a distant observer, which describe regular electrically charged rotating black holes and spinning electromagnetic solitons with the angular momentum [Formula: see text] and the gyromagnetic ratio [Formula: see text]. Their basic generic feature is the existence of the interior de Sitter equatorial disk of the radius [Formula: see text] with the equation-of-state [Formula: see text] in the co-rotating frame, with the properties of a perfect conductor and ideal diamagnetic, and with the superconducting ring current along the edge of the disk, which replaces the ring singularity of the Kerr–Newman geometry and provides the nondissipative source of electromagnetic fields and the origin of an intrinsic magnetic momentum for an electrically charged regular object described by NED–GR. Generic features of the electromagnetic soliton with the parameters of the electron, [Formula: see text], suggest that the intrinsic origin of the electron magnetic momentum can be a superconducting ring current evaluated as [Formula: see text] A.
3D Finite Element Simulation of Shot Peening Using a Sequential Model with Multiple-Shot Impacts
Authors: Wei Qin , Wu Wenxin , He Wei , Zhu Jianguo , Zhang Jian
Published: July 2018

A sequential model of multiple-shot impacts has been established to investigate the shot peening process. Shot groups are proposed and designed with different patterns to obtain full surface coverage in the impacted region and a satisfactory computational efficiency. The sequential model was applied for the prediction of residual stress on a GH4169 alloy specimen. The results showed that uniform and saturated states of residual stress along the surface and depth profile were obtained in the impacted region when the numerical order of shot patterns reached 4. Furthermore, the numerical results of compressive residual stress in the subsurface were compared with the experimental results obtained using the X-ray diffraction (XRD) analysis and the incremental hole drilling method. The maximum relative error between the numerical results and XRD measurement was 11.6%. Furthermore, the stress profile measured using the incremental hole drilling method was consistent with the numerical results. The established finite element model demonstrated its robustness and effectiveness for the evaluation of residual stress in the shot-peened GH4169 alloy, and it may be applied to other metallic materials with simple modifications.
Peristaltic transport of a Jeffrey fluid with double-diffusive convection in nanofluids in the presence of inclined magnetic field
Authors: Akram Safia , Zafar M. , Nadeem S.
Published: July 2018

In this paper, the effects of peristaltic transport with double-diffusive convection in nanofluids through an asymmetric channel with different waveforms is presented. Mathematical modeling for two-dimensional and two-directional flows of a Jeffery fluid model along with double-diffusive convection in nanofluids are given. Exact solutions are obtained for nanoparticle fraction field, concentration field, temperature field, stream functions, pressure gradient and pressure rise in terms of axial and transverse coordinates under the restrictions of long wavelength and low Reynolds number. With the help of computational and graphical results, the effects of Brownian motion, thermospheres, Dufour, Soret and Grashof numbers (thermal, concentration, nanoparticles) on peristaltic flow patterns with double-diffusive convection are discussed.
A history of the Asian monsoon and its interactions with solid Earth tectonics in Cenozoic South Asia
Authors: Clift Peter D. , Webb A. Alexander G.
Published: July 2018

Although there is some evidence for an Eocene monsoon, the most important intensification of rainfall appears to start at
c.
24 Ma in the Early Miocene. Many palaeoceanographical proxies for monsoon intensity are linked to wind and do not correlate well with humidity of the continental climate over tectonic timescales. Rainfall peaked in the middle Miocene (
c.
15 Ma) with strong drying after 8 Ma. This timing does not correlate well with either initial uplift of the Tibetan Plateau or with the retreat of shallow seas from central Asia. The
c.
24 Ma onset of strengthening rainfall is associated with the initiation of rapid erosion and cooling of Himalayan metamorphic rocks. The progressive detachment of the subducting Indian lithosphere from the eastern and western syntaxes at
c.
25 Ma to the east-central Himalaya at
c.
13–11 Ma would have produced corresponding propagation of rising Himalayan topography following release of the weight of the detached slab. Rapid uplift of the Himalayan barrier, blocking moisture-laden winds, is considered the most likely trigger for a stronger summer monsoon in South Asia, which in turn allowed faster erosion and exhumation of the Greater Himalaya after 24 Ma.
The Ethics and Aesthetics of Care
Authors: Black Steven P.
Published: July 2018

This article is positioned at the intersection of linguistic, medical, and psychological anthropology and reviews scholarship on the communicative processes that constitute moral/ethical care. Varying notions of care have become a leitmotif in efforts to include the analysis of agency and creativity in discussions of the lived experience of marginalization. Understandings of care have in common an emphasis on relationality and activity: Communicative activities of care both constitute and are made relevant by morally/ethically framed relationships with others and oneself. Embodied communication is central in both care activities and the constitution of moral/ethical care. From a phenomenological standpoint, communicative activities of care are simultaneously social action and embodied experience. This article reviews three key themes: ( a) the embodied linguistic constitution of care, ( b) the performance of care, and ( c) exclusion from care. Together, these themes reveal common moral/ethical–aesthetic processes that are shared across diverse social and cultural contexts.
Debris Disks: Structure, Composition, and Variability
Authors: Hughes A. Meredith , Duchêne Gaspard , Matthews Brenda C.
Published: July 2018

Debris disks are tenuous, dust-dominated disks commonly observed around stars over a wide range of ages. Those around main sequence stars are analogous to the Solar System's Kuiper Belt and zodiacal light. The dust in debris disks is believed to be continuously regenerated, originating primarily with collisions of planetesimals. Observations of debris disks provide insight into the evolution of planetary systems; and the composition of dust, comets, and planetesimals outside the Solar System; as well as placing constraints on the orbital architecture and potentially the masses of exoplanets that are not otherwise detectable. This review highlights recent advances in multiwavelength, high-resolution scattered light and thermal imaging that have revealed a complex and intricate diversity of structures in debris disks and discusses how modeling methods are evolving with the breadth and depth of the available observations. Two rapidly advancing subfields highlighted in this review include observations of atomic and molecular gas around main sequence stars and variations in emission from debris disks on very short (days to years) timescales, providing evidence of non-steady-state collisional evolution particularly in young debris disks.
The Sharing Economy
Authors: Morgan Bronwen
Published: July 2018

The sharing economy is an emergent field of scholarship. This review explores two clusters of debate regarding the sharing economy and seeks to discern the lines of a productive dialogue between them. It suggests that the current state of scholarship on law in the sharing economy is a complex and asymmetrical mix of narrative articulation and empirical exploration. The first cluster focuses on an on-demand commercial vision of the sharing economy and is generating an exploding legal literature largely not grounded on empirical research. This coexists with an emergent social science literature focused on a solidarity-inflected version of the sharing economy, which, however, pays little or no explicit attention to law or legality. Each cluster of debate is first separately explored, after which three sites of détente are identified where these trajectories edge toward each other: urban governance, sociolegal accounts of the interplay between enterprise diversity and regulation, and reconfigurations of property law. Common to all three is an appreciation of collective economic agency as of equal importance to regulatory responses.
Unoccupied Aircraft Systems in Marine Science and Conservation
Authors: Johnston David W.
Published: July 2018

The use of unoccupied aircraft systems (UASs, also known as drones) in science is growing rapidly. Recent advances in microelectronics and battery technology have resulted in the rapid development of low-cost UASs that are transforming many industries. Drones are poised to revolutionize marine science and conservation, as they provide essentially on-demand remote sensing capabilities at low cost and with reduced human risk. A variety of multirotor, fixed-wing, and transitional UAS platforms are capable of carrying various optical and physical sampling payloads and are being employed in almost every subdiscipline of marine science and conservation. This article provides an overview of the UAS platforms and sensors used in marine science and conservation missions along with example physical, biological, and natural resource management applications and typical analytical workflows. It concludes with details on potential effects of UASs on marine wildlife and a look to the future of UASs in marine science and conservation.
Small System Collectivity in Relativistic Hadronic and Nuclear Collisions
Authors: Nagle James L. , Zajc William A.
Published: July 2018

The bulk motion of nuclear matter at the ultrahigh temperatures created in heavy ion collisions at the Relativistic Heavy Ion Collider and the Large Hadron Collider is well described in terms of nearly inviscid hydrodynamics, thereby establishing this system of quarks and gluons as the most perfect fluid in nature. A revolution in the field is under way, spearheaded by the discovery of similar collective, fluid-like phenomena in much smaller systems including p+ p, p+ A, d+Au, and3He+Au collisions. We review these exciting new observations and their profound implications for hydrodynamic descriptions of small and/or out-of-equilibrium systems.
Propionate-induced changes in cardiac metabolism, notably CoA trapping, are not altered byl-carnitine
Authors: Wang Yingxue , Christopher Bridgette A. , Wilson Kirkland A. , Muoio Deborah , McGarrah Robert W. , Brunengraber Henri , Zhang Guo-Fang
Published: July 2018

High concentrations of propionate and its metabolites are found in several diseases that are often associated with the development of cardiac dysfunction, such as obesity, diabetes, propionic acidemia, and methylmalonic acidemia. In the present work, we employed a stable isotope-based metabolic flux approach to understand propionate-mediated perturbation of cardiac energy metabolism. Propionate led to accumulation of propionyl-CoA (increased by ~101-fold) and methylmalonyl-CoA (increased by 36-fold). This accumulation caused significant mitochondrial CoA trapping and inhibited fatty acid oxidation. The reduced energy contribution from fatty acid oxidation was associated with increased glucose oxidation. The enhanced anaplerosis of propionate and CoA trapping altered the pool sizes of tricarboxylic acid cycle (TCA) metabolites. In addition to being an anaplerotic substrate, the accumulation of proprionate-derived malate increased the recycling of malate to pyruvate and acetyl-CoA, which can enter the TCA for energy production. Supplementation of 3 mM l-carnitine did not relieve CoA trapping and did not reverse the propionate-mediated fuel switch. This is due to new findings that the heart appears to lack the specific enzyme catalyzing the conversion of short-chain (C3and C4) dicarboxylyl-CoAs to dicarboxylylcarnitines. The discovery of this work warrants further investigation on the relevance of dicarboxylylcarnitines, especially C3and C4dicarboxylylcarnitines, in cardiac conditions such as heart failure.
High-intensity interval, but not endurance, training induces muscle fiber type-specific subsarcolemmal lipid droplet size reduction in type 2 diabetic patients
Authors: Koh Han-Chow E. , Ørtenblad Niels , Winding Kamilla M. , Hellsten Ylva , Mortensen Stefan P. , Nielsen Joachim
Published: July 2018

This study compared the effects of moderate-intensity endurance training and high-intensity interval training on fiber type-specific subcellular volumetric content and morphology of lipid droplets and mitochondria in skeletal muscles of type 2 diabetic patients. Sixteen sedentary type 2 diabetic patients (57 ± 7 yr old) were randomized to complete 11 wk of either 40-min cycling at 50% peak workload (Endurance, n = 8) or 10 1-min cycling intervals at 95% peak workload separated by 1 min of recovery (High-Intensity Interval, n = 8), three times per week. Assessments for cardiorespiratory fitness, body composition, glycemic control, together with muscle biopsies were performed before and after the intervention. Morphometric analyses of lipid droplets and mitochondria were conducted in the subcellular fractions of biopsied muscle fibers using quantitative electron microscopy. The training intervention increased cardiorespiratory fitness, lowered fat mass, and improved nonfasting glycemic control ( P < 0.05), with no difference between training modalities. In the subsarcolemmal space, training decreased lipid droplet volume ( P = 0.003), and high-intensity interval, but not endurance, training reduced the size of lipid droplets, specifically in type 2 fibers ( P < 0.001). No training-induced change in intermyofibrillar lipid droplets was observed in both fiber types. Subsarcolemmal mitochondrial volume was increased by high-intensity interval ( P = 0.02), but not endurance, training ( P = 0.79). Along with improvement in glycemic control, low-volume high-intensity interval training is an alternative time-saving training modality that affects subcellular morphology and volumetric content of lipid droplets in skeletal muscle of type 2 diabetic patients.
Cells of NG2 lineage increase in glomeruli of mice following podocyte depletion
Authors: Suzuki Taihei , Eng Diana G. , McClelland Aaron D. , Pippin Jeffrey W. , Shankland Stuart J.
Published: July 2018

Under certain circumstances, podocytes can be partially replaced following their loss in disease. The inability of podocytes to proliferate suggests that replacement derives from other cell types. Because neural/glial antigen 2 (NG2)-expressing cells can serve as progenitors in other organs and because herein we showed increased NG2 staining in podocytes following their loss in experimental focal segmental glomerulosclerosis, we used lineage tracing in NG2-CreER tdTomato mice to test the hypothesis that partial podocyte replacement might derive from this cell population. The percentage of glomeruli with red fluorescence protein (RFP)-labeled NG2 cells increased following podocyte depletion, which was augmented by enalapril. However, BrdU was not detected in RFP-labeled cells, consistent with the migration of these cells to the glomerulus. Within glomeruli, RFP-labeled cells did not coexpress podocyte proteins (p57, synaptopodin, nephrin, or podocin) but did coexpress markers for mesangial (α8 integrin, PDGFβ receptor) and parietal epithelial cells (PAX8, src-suppressed C-kinase substrate). These results suggest that following podocyte depletion, cells of NG2 lineage do not serve as adult podocyte progenitors but have the ability to transdifferentiate to mesangial and parietal epithelial cell fates.
Prospective relation of adolescent citrate excretion and net acid excretion capacity with blood pressure in young adulthood
Authors: Krupp Danika , Westhoff Timm H. , Esche Jonas , Remer Thomas
Published: July 2018

Experimental data and observational studies in adults suggest that even subtle changes in acid-base balance, indicative of a higher systemic proton load, are related to higher blood pressure (BP) levels and an increased hypertension risk. However, these associations have not been investigated during growth. The kidney is the central organ in regulating excretion of nonvolatile acids, and renal citrate excretion has been shown to be a sensitive, noninvasive marker of changes in systemic acid balance. We thus analyzed the prospective relation of 24-h citrate excretion, as well as net acid excretion capacity (NAEC; a noninvasive indicator of the renal ability to excrete protons), during adolescence (boys: 10–15 yr; girls: 9–14 yr) with BP levels in young adulthood (18–30 yr) in 374 healthy participants of the Dortmund Nutritional and Anthropometric Longitudinally Designed (DONALD) Study. In linear-regression analyses adjusted for age, sex, 24-h urinary excretions of sodium and potassium, as well as further relevant confounders, a 1-mmol/1.73 m2/day higher adolescent citrate excretion was related to 1.2 mmHg lower systolic BP ( P = 0.02) but not to diastolic BP ( P = 0.6). A 10-mEq higher NAEC during adolescence was related to 1.7 mmHg lower systolic BP in young men, but this association was statistically nonsignificant ( P = 0.07) after multivariable adjustment. Additional adjustment for adult body mass index did not alter these findings. To conclude, subtle changes in systemic acid-base balance during adolescence are already indicative for later BP. Potential sex differences in these associations should be investigated in further studies.
Reduced bladder responses to capsaicin and GSK-1016790A in retired-breeder female rats with diminished volume sensitivity
Authors: Wen Jiliang , Zu Shulu , Chen Zhenghao , Daugherty Stephanie L. , de Groat William C. , Liu Yuqiang , Yuan Mingzhen , Cheng Guanghui , Zhang Xiulin
Published: July 2018

Literature documents an age-related reduction of bladder sensory function. Transient receptor potential vanilloid (TRPV)1 or TRPV4 channels have been implicated in bladder mechanotransduction. To investigate contributions of TRPV1 or TRPV4 to the age-related reduction of bladder sensory function, bladder responses to capsaicin (CAP; TRPV1 agonist) and GSK-1016790A (GSK; TRPV4 agonist) in retired breeder (RB; 12–15 mo) and young adult (2–3 mo) female rats were compared using multiple methods. Metabolic cage and continuous infusion cystometry [cystometrogram (CMG)] recordings revealed that RB rats exhibit larger bladder capacity and lower voiding frequency. RB rats also have a greater intravesical pressure threshold for micturition; however, the voiding contraction strength was equivalent to that in young rats. CAP (1 μM) or GSK (20 nM) administered intravesically evoked smaller changes in all CMG parameters in RB rats. In vitro, CAP (1 μM) or GSK (20 nM) evoked smaller enhancement of bladder strip contractions, while the muscarinic receptor agonist carbachol (at 100, 300, and 1,000 nM) elicited greater amplitude contractions in RB rats. Patch-clamp recording revealed smaller CAP (100 nM) induced inward currents in bladder primary sensory neurons, and Ca2+ imaging revealed smaller GSK (20 nM) evoked increases in intracellular Ca2+ concentration in urothelial cells in RB rats. These results suggest that RB rats have a decreased bladder sensory function commonly observed in elderly women, and could be used as an animal model to study the underling mechanisms. Reduced functional expression of TRPV1 in bladder afferents or reduced functional expression of urothelial TRPV4 may be associated with the diminished sensory function.
Evaluation of renal and cardiovascular protection mechanisms of SGLT2 inhibitors: model-based analysis of clinical data
Authors: Hallow K. Melissa , Greasley Peter J. , Helmlinger Gabriel , Chu Lulu , Heerspink Hiddo J. , Boulton David W.
Published: July 2018

The mechanisms of cardiovascular and renal protection observed in clinical trials of sodium-glucose cotransporter 2 (SGLT2) inhibitors (SGLT2i) are incompletely understood and likely multifactorial, including natriuretic, diuretic, and antihypertensive effects, glomerular pressure reduction, and lowering of plasma and interstitial fluid volume. To quantitatively evaluate the contribution of proposed SGLT2i mechanisms of action on changes in renal hemodynamics and volume status, we coupled a mathematical model of renal function and volume homeostasis with clinical data in healthy subjects administered 10 mg of dapagliflozin once daily. The minimum set of mechanisms necessary to reproduce observed clinical responses (urinary sodium and water excretion, serum creatinine and sodium) was determined, and important unobserved physiological variables (glomerular pressure, blood and interstitial fluid volume) were then simulated. We further simulated the response to SGLT2i in diabetic virtual patients with and without renal impairment. Multiple mechanisms were required to explain the observed response: 1) direct inhibition of sodium and glucose reabsorption through SGLT2, 2) SGLT2-driven inhibition of Na+/H+ exchanger 3 sodium reabsorption, and 3) osmotic diuresis coupled with peripheral sodium storage. The model also showed that the consequences of these mechanisms include lowering of glomerular pressure, reduction of blood and interstitial fluid volume, and mild blood pressure reduction, in agreement with clinical observations. The simulations suggest that these effects are more significant in diabetic patients than healthy subjects and that while glucose excretion may diminish with renal impairment, improvements in glomerular pressure and blood volume are not diminished at lower glomerular filtration rate, suggesting that cardiorenal benefits of SGLT2i may be sustained in renally impaired patients.
Biophysical basis of subthalamic local field potentials recorded from deep brain stimulation electrodes
Authors: Maling Nicholas , Lempka Scott F. , Blumenfeld Zack , Bronte-Stewart Helen , McIntyre Cameron C.
Published: July 2018

Clinical deep brain stimulation (DBS) technology is evolving to enable chronic recording of local field potentials (LFPs) that represent electrophysiological biomarkers of the underlying disease state. However, little is known about the biophysical basis of LFPs, or how the patient’s unique brain anatomy and electrode placement impact the recordings. Therefore, we developed a patient-specific computational framework to analyze LFP recordings within a clinical DBS context. We selected a subject with Parkinson’s disease implanted with a Medtronic Activa PC+S DBS system and reconstructed their subthalamic nucleus (STN) and DBS electrode location using medical imaging data. The patient-specific STN volume was populated with 235,280 multicompartment STN neuron models, providing a neuron density consistent with histological measurements. Each neuron received time-varying synaptic inputs and generated transmembrane currents that gave rise to the LFP signal recorded at DBS electrode contacts residing in a finite element volume conductor model. We then used the model to study the role of synchronous beta-band inputs to the STN neurons on the recorded power spectrum. Three bipolar pairs of simultaneous clinical LFP recordings were used in combination with an optimization algorithm to customize the neural activity parameters in the model to the patient. The optimized model predicted a 2.4-mm radius of beta-synchronous neurons located in the dorsolateral STN. These theoretical results enable biophysical dissection of the LFP signal at the cellular level with direct comparison to the clinical recordings, and the model system provides a scientific platform to help guide the design of DBS technology focused on the use of subthalamic beta activity in closed-loop algorithms.

NEW & NOTEWORTHY The analysis of deep brain stimulation of local field potential (LFP) data is rapidly expanding from scientific curiosity to the basis for clinical biomarkers capable of improving the therapeutic efficacy of stimulation. With this growing clinical importance comes a growing need to understand the underlying electrophysiological fundamentals of the signals and the factors contributing to their modulation. Our model reconstructs the clinical LFP from first principles and highlights the importance of patient-specific factors in dictating the signals recorded.
Chronic recording and electrochemical performance of Utah microelectrode arrays implanted in rat motor cortex
Authors: Black Bryan J. , Kanneganti Aswini , Joshi-Imre Alexandra , Rihani Rashed , Chakraborty Bitan , Abbott Justin , Pancrazio Joseph J. , Cogan Stuart F.
Published: July 2018

Multisite implantable electrode arrays serve as a tool to understand cortical network connectivity and plasticity. Furthermore, they enable electrical stimulation to drive plasticity, study motor/sensory mapping, or provide network input for controlling brain-computer interfaces. Neurobehavioral rodent models are prevalent in studies of motor cortex injury and recovery as well as restoration of auditory/visual cues due to their relatively low cost and ease of training. Therefore, it is important to understand the chronic performance of relevant electrode arrays in rodent models. In this report, we evaluate the chronic recording and electrochemical performance of 16-channel Utah electrode arrays, the current state-of-the-art in pre-/clinical cortical recording and stimulation, in rat motor cortex over a period of 6 mo. The single-unit active electrode yield decreased from 52.8 ± 10.0 ( week 1) to 13.4 ± 5.1% ( week 24). Similarly, the total number of single units recorded on all electrodes across all arrays decreased from 106 to 15 over the same time period. Parallel measurements of electrochemical impedance spectra and cathodic charge storage capacity exhibited significant changes in electrochemical characteristics consistent with development of electrolyte leakage pathways over time. Additionally, measurements of maximum cathodal potential excursion indicated that only a relatively small fraction of electrodes (10–35% at 1 and 24 wk postimplantation) were capable of delivering relevant currents (20 µA at 4 nC/ph) without exceeding negative or positive electrochemical potential limits. In total, our findings suggest mainly abiotic failure modes, including mechanical wire breakage as well as degradation of conducting and insulating substrates.

NEW & NOTEWORTHY Multisite implantable electrode arrays serve as a tool to record cortical network activity and enable electrical stimulation to drive plasticity or provide network feedback. The use of rodent models in these fields is prevalent. We evaluated chronic recording and electrochemical performance of 16-channel Utah electrode arrays in rat motor cortex over a period of 6 mo. We primarily observed abiotic failure modes suggestive of mechanical wire breakage and/or degradation of insulation.
To look or not to look? Reward, selection history, and oculomotor guidance
Authors: Preciado Daniel , Theeuwes Jan
Published: July 2018

The current eye-tracking study examined the influence of reward on oculomotor performance, and the extent to which learned stimulus-reward associations interacted with voluntary oculomotor control with a modified paradigm based on the classical antisaccade task. Participants were shown two equally salient stimuli simultaneously: a gray and a colored circle, and they were instructed to make a fast saccade to one of them. During the first phase of the experiment, participants made a fast saccade toward the colored stimulus, and their performance determined a (cash) bonus. During the second, participants made a saccade toward the gray stimulus, with no rewards available. On each trial, one of three colors was presented, each associated with high, low or no reward during the first phase. Results from the first phase showed improved accuracy and shorter saccade latencies on high-reward trials, while those from the second replicated well-known effects typical of the antisaccade task, namely, decreased accuracy and increased latency during phase II, even despite the absence of abrupt asymmetric onsets. Crucially, performance differences between phases revealed longer latencies and less accurate saccades during the second phase for high-reward trials, compared with the low- and no-reward trials. Further analyses indicated that oculomotor capture by reward signals is mainly found for saccades with short latencies, while this automatic capture can be overridden through voluntary control with longer ones. These results highlight the natural flexibility and adaptability of the attentional system, and the role of reward in modulating this plasticity.

NEW & NOTEWORTHY Typically, in the antisaccade task, participants need to suppress an automatic orienting reflex toward a suddenly appearing peripheral stimulus. Here, we introduce an alternative antisaccade task without such abrupt onsets. We replicate well-known antisaccade effects (more errors and longer latencies), demonstrating the role of reward in developing selective oculomotor biases. Results highlight how reward and selection history facilitate developing automatic biases from goal-driven behavior, and they suggest that this process responds to individual differences in impulsivity.
Specificity in the interaction of high-voltage-activated Ca2+ channel types with Ca2+-dependent afterhyperpolarizations in magnocellular supraoptic neurons
Authors: Kirchner Matthew K. , Foehring Robert C. , Callaway Joseph , Armstrong William E.
Published: July 2018

Magnocellular oxytocin (OT) and vasopressin (VP) neurons express an afterhyperpolarization (AHP) following spike trains that attenuates firing rate and contributes to burst patterning. This AHP includes contributions from an apamin-sensitive, medium-duration AHP (mAHP) and from an apamin-insensitive, slow-duration AHP (sAHP). These AHPs are Ca2+ dependent and activated by Ca2+ influx through voltage-gated Ca2+ channels. Across central nervous system neurons that generate Ca2+-dependent AHPs, the Ca2+ channels that couple to the mAHP and sAHP differ greatly, but for magnocellular neurosecretory cells this relationship is unknown. Using simultaneous whole cell recording and Ca2+ imaging, we evaluated the effect of specific high-voltage-activated (HVA) Ca2+ channel blockers on the mAHP and sAHP. Block of all HVA channels via 400 μM Cd2+ inhibited almost the entire AHP. We tested nifedipine, conotoxin GVIA, agatoxin IVA, and SNX-482, specific blockers of L-, N-, P/Q-, and R-type channels, respectively. The N-type channel blocker conotoxin GVIA (1 μM) was the only toxin that inhibited the mAHP in either OT or VP neurons although the effect on VP neurons was weaker by comparison. The sAHP was significantly inhibited by N-type block in OT neurons and by R-type block in VP neurons although neither accounted for the entirety of the sAHP. Thus the mAHP appears to be elicited by Ca2+ from mostly N-type channels in both OT and VP neurons, but the contributions of specific Ca2+ channel types to the sAHP in each cell type are different. Alternative sources to HVA channels may contribute Ca2+ for the sAHP.

NEW & NOTEWORTHY Despite the importance of afterhyperpolarization (AHP) mechanisms for regulating firing behavior of oxytocin (OT) and vasopressin (VP) neurons of supraoptic nucleus, which types of high-voltage-activated Ca2+ channels elicit AHPs in these cells was unknown. We found that N-type channels couple to the medium AHP in both cell types. For the slow AHP, N-type channels contribute in OT neurons, whereas R-type contribute in VP neurons. No single Ca2+ channel blocker abolished the entire AHP, suggesting that additional Ca2+ sources are involved.
Force dynamics and synergist muscle activation in stick insects: the effects of using joint torques as mechanical stimuli
Authors: Zill Sasha N. , Dallmann Chris J. , Büschges Ansgar , Chaudhry Sumaiya , Schmitz Josef
Published: July 2018

Many sensory systems are tuned to specific parameters of behaviors and have effects that are task-specific. We have studied how force feedback contributes to activation of synergist muscles in serially homologous legs of stick insects. Forces were applied using conventional half-sine or ramp and hold functions. We also utilized waveforms of joint torques calculated from experiments in freely walking animals. In all legs, forces applied to either the tarsus (foot) or proximal leg segment (trochanter) activated synergist muscles that generate substrate grip and support, but coupling of the depressor muscle to tarsal forces was weak in the front legs. Activation of trochanteral receptors using ramp and hold functions generated positive feedback to the depressor muscle in all legs when animals were induced to seek substrate grip. However, discharges of the synergist flexor muscle showed adaptation at moderate force levels. In contrast, application of forces using torque waveforms, which do not have a static hold phase, produced sustained discharges in muscle synergies with little adaptation. Firing frequencies reflected the magnitude of ground reaction forces, were graded to changes in force amplitude, and could also be modulated by transient force perturbations added to the waveforms. Comparison of synergist activation by torques and ramp and hold functions revealed a strong influence of force dynamics (dF/d t). These studies support the idea that force receptors can act to tune muscle synergies synchronously to the range of force magnitudes and dynamics that occur in each leg according to their specific use in behavior.

NEW & NOTEWORTHY The effects of force receptors (campaniform sensilla) on leg muscles and synergies were characterized in stick insects using both ramp and hold functions and waveforms of joint torques calculated by inverse dynamics. Motor responses were sustained and showed reduced adaptation to the more “natural” and nonlinear torque stimuli. Calculation of the first derivative (dF/d t) of the torque waveforms demonstrated that this difference was correlated with the dynamic sensitivities of the system.
Herz-Type Hardy Spaces Associated with Operators
Authors: Chai Yan , Han Yaoyao , Zhao Kai
Published: July 2018

Suppose L is a nonnegative, self-adjoint differential operator. In this paper, we introduce the Herz-type Hardy spaces associated with operator L. Then, similar to the atomic and molecular decompositions of classical Herz-type Hardy spaces and the Hardy space associated with operators, we prove the atomic and molecular decompositions of the Herz-type Hardy spaces associated with operator L. As applications, the boundedness of some singular integral operators on Herz-type Hardy spaces associated with operators is obtained.