bluuebunny/crossref_metadata_2025 huggingface dataset:
Magnetoencephalography with a Cs-based high-sensitivity compact atomic magnetometer
Authors: Sheng Jingwei , Wan Shuangai , Sun Yifan , Dou Rongshe , Guo Yuhao , Wei Kequan , He Kaiyan , Qin Jie , Gao Jia-Hong
Published: September 2017

In recent years, substantial progress has been made in developing a new generation of magnetoencephalography (MEG) with a spin-exchange relaxation free (SERF)-based atomic magnetometer (AM). An AM employs alkali atoms to detect weak magnetic fields. A compact AM array with high sensitivity is crucial to the design; however, most proposed compact AMs are potassium (K)- or rubidium (Rb)-based with single beam configurations. In the present study, a pump-probe two beam configuration with a Cesium (Cs)-based AM (Cs-AM) is introduced to detect human neuronal magnetic fields. The length of the vapor cell is 4 mm, which can fully satisfy the need of designing a compact sensor array. Compared with state-of-the-art compact AMs, our new Cs-AM has two advantages. First, it can be operated in a SERF regime, requiring much lower heating temperature, which benefits the sensor with a closer distance to scalp due to ease of thermal insulation and less electric heating noise interference. Second, the two-beam configuration in the design can achieve higher sensitivity. It is free of magnetic modulation, which is necessary in one-beam AMs; however, such modulation may cause other interference in multi-channel circumstances. In the frequency band between 10 Hz and 30 Hz, the noise level of the proposed Cs-AM is approximately 10 f T/Hz1/2, which is comparable with state-of-the-art K- or Rb-based compact AMs. The performance of the Cs-AM was verified by measuring human auditory evoked fields (AEFs) in reference to commercial superconducting quantum interference device (SQUID) channels. By using a Cs-AM, we observed a clear peak in AEFs around 100 ms (M100) with a much larger amplitude compared with that of a SQUID, and the temporal profiles of the two devices were in good agreement. The results indicate the possibility of using the compact Cs-AM for MEG recordings, and the current Cs-AM has the potential to be designed for multi-sensor arrays and gradiometers for future neuroscience studies.
Optimization and control of electron beams from laser wakefield accelerations using asymmetric laser pulses
Authors: Gopal K. , Gupta D. N.
Published: September 2017

Optimization and control of electron beam quality in laser wakefield acceleration are explored by using a temporally asymmetric laser pulse of the sharp rising front portion. The temporally asymmetric laser pulse imparts stronger ponderomotive force on the ambient plasma electrons. The stronger ponderomotive force associated with the asymmetric pulse significantly affects the injection of electrons into the wakefield and consequently the quality of the injected bunch in terms of injected charge, mean energy, and emittance. Based on particle-in-cell simulations, we report to generate a monoenergetic electron beam with reduced emittance and enhanced charge in laser wakefield acceleration using an asymmetric pulse of duration 30 fs.
Excitation-wavelength scaling of terahertz radiation in alkali vapor plasmas
Authors: Zhang Shijing , Zhang Liangliang , Zhao Hang , Wu Tong , Zhang Cunlin , Zhao Yuejin
Published: September 2017

By using a wavelength-tunable near-infrared femtosecond laser, we demonstrate a wavelength scaling mechanism in which the efficiency of terahertz (THz) radiation production by Rb and Cs vapor plasmas increases with increasing excitation laser wavelength. Due to the low ionization energies of alkali metals, the THz radiation energy generated by Cs is an order of magnitude higher than that produced N2 at a wavelength of 1500 nm. The experimental results are well explained by the model of photocurrent as being induced by electron tunneling ionization.
Soil mechanical stresses in high wheel load agricultural field traffic: a case study
Authors: Lamandé Mathieu , Schjønning Per
Published: September 2017

Subsoil compaction is a serious long-term threat to soil functions. Only a few studies have quantified the mechanical stresses reaching deep subsoil layers for modern high wheel load machinery. In the present study we measured the vertical stresses in the tyre–soil contact area and at 0.3, 0.6 and 0.9 m depths of a sandy loam soil at field capacity water content. The soil was ploughed annually to a depth of 0.25 m and was tested in the spring following autumn ploughing but before secondary tillage. The machinery tested was a tractor–trailer system for slurry application with a total weight of 52 Mg. Wheel loads ranged from approximately 20 to 70 kN. The tyres were all radial ply with volumes ranging from 0.63 to 1.23 m3. The tyre inflation pressures were generally above those recommended by the manufacturer and ranged from 170 to 280 kPa. The stress distributions in the contact area were highly skewed. Across tyres, the maximum stress in the contact area correlated linearly with, but was much higher than, the mean ground pressure. For each of the three soil depths, the maximum stresses under the tyres were significantly correlated with the wheel load, but not with other loading characteristics. The data predict a 6.6-kPa increase in vertical stress at 0.9 m depth for each 1-Mg addition to the wheel load. The soil stress observations support a simple rule of thumb combining wheel load and inflation pressure in calculation of subsoil vertical stress. We measured vertical stresses up to 300, 100 and 45 kPa at soil depths of 0.3, 0.6 and 0.9 m respectively. Comparing these with the data in the literature regarding soil strength and measured compaction effects on the soil studied, we conclude that the traffic event investigated is likely to induce serious effects on soil properties and functions to a depth of at least 0.7 m.
Coupling of pollination services and coffee suitability under climate change
Authors: Imbach Pablo , Fung Emily , Hannah Lee , Navarro-Racines Carlos E. , Roubik David W. , Ricketts Taylor H. , Harvey Celia A. , Donatti Camila I. , Läderach Peter , Locatelli Bruno , Roehrdanz Patrick R.
Published: September 2017

Significance

Coffee production supports the livelihoods of millions of smallholder farmers around the world, and bees provide coffee farms with pollination. Climate change will modify coffee and bee distributions, and thus coffee production. We modeled impacts for the largest coffee-growing region, Latin America, under global warming scenarios. Although we found reduced coffee suitability and bee species diversity for more than one-third of the future coffee-suitable areas, all future coffee-suitable areas will potentially host at least five bee species, indicating continued pollination services. Bee diversity also can be expected to offset farmers’ losses from reduced coffee suitability. In other areas, bee diversity losses offset increased coffee suitability. Our results highlight the need for responsive management strategies tailored to bee pollination, coffee suitability, and potential coupled effects.
Mechanisms for restraining cAMP-dependent protein kinase revealed by subunit quantitation and cross-linking approaches
Authors: Walker-Gray Ryan , Stengel Florian , Gold Matthew G.
Published: September 2017

Significance

Protein phosphorylation by cAMP-dependent protein kinase (PKA) triggers cellular changes, including fight-or-flight responses in heart cells, and synaptic potentiation in neurons. Uncontrolled activity of PKA catalytic subunits is pathological; however, the mechanism for directing PKA in cells is unclear. Using an approach for monitoring cellular PKA subunit interactions, we show that—contrary to recent proposals—catalytic subunits are released from regulatory subunits by cAMP. Instead, we identify mechanisms for rapid recapture of liberated catalytic subunits. Regulatory subunits are expressed much more highly than catalytic subunits to support rapid catalytic subunit reassociation. Furthermore, analysis of global PKA architecture reveals that type II regulatory subunit anchoring is compatible with catalytic subunit release and recapture within the cell membrane.
Exposure to unpredictable maternal sensory signals influences cognitive development across species
Authors: Davis Elysia Poggi , Stout Stephanie A. , Molet Jenny , Vegetabile Brian , Glynn Laura M. , Sandman Curt A. , Heins Kevin , Stern Hal , Baram Tallie Z.
Published: September 2017

Significance

The receipt of high-quality maternal care is an established promoter of optimal neurodevelopment, but the processes by which maternal care influences development remain unclear. Using a cross-species approach, we probe the possibility that predictability of sensory signals from the mother is a process by which maternal behavior influences cognitive circuits within the developing brain. This is in accord with established roles of patterns of sensory information in the organization of visual and auditory systems of the brain during sensitive periods. Our data support the argument that the degree of predictability of maternal sensory signals affects subsequent cognitive function in both rats and humans and suggest that these signals contribute to the shaping of the underlying neural circuits, including the hippocampus.
Evolution of flexibility and rigidity in retaliatory punishment
Authors: Morris Adam , MacGlashan James , Littman Michael L. , Cushman Fiery
Published: September 2017

Natural selection designs some social behaviors to depend on flexible learning processes, whereas others are relatively rigid or reflexive. What determines the balance between these two approaches? We offer a detailed case study in the context of a two-player game with antisocial behavior and retaliatory punishment. We show that each player in this game—a “thief” and a “victim”—must balance two competing strategic interests. Flexibility is valuable because it allows adaptive differentiation in the face of diverse opponents. However, it is also risky because, in competitive games, it can produce systematically suboptimal behaviors. Using a combination of evolutionary analysis, reinforcement learning simulations, and behavioral experimentation, we show that the resolution to this tension—and the adaptation of social behavior in this game—hinges on the game’s learning dynamics. Our findings clarify punishment’s adaptive basis, offer a case study of the evolution of social preferences, and highlight an important connection between natural selection and learning in the resolution of social conflicts.
Engineering a light-activated caspase-3 for precise ablation of neurons in vivo
Authors: Smart Ashley D. , Pache Roland A. , Thomsen Nathan D. , Kortemme Tanja , Davis Graeme W. , Wells James A.
Published: September 2017

Significance

We have engineered a light-activated caspase (Caspase-LOV) to better understand the roles of caspases in cells and to create a tool that would kill cells with temporal and spatial selectivity. This modified caspase is created based on the endogenous mechanism of caspase activation by adding a light-sensitive protein domain (LOV2) from oats into the intersubunit linker of the caspase. We tested variations of the Caspase-LOV construct in vitro and in
Drosophila
and found that it will kill many types of cells with light specificity. We were also able to use the Caspase-LOV to determine the time course of degeneration in two different neuronal cell types after caspase activation.
U-Th dating reveals regional-scale decline of branching
Acropora
corals on the Great Barrier Reef over the past century
Authors: Clark Tara R. , Roff George , Zhao Jian-xin , Feng Yue-xing , Done Terence J. , McCook Laurence J. , Pandolfi John M.
Published: September 2017

Significance

Branching
Acropora
corals are highly sensitive to environmental change and warrant close monitoring to avoid irreversible changes in ecosystem health. For the Great Barrier Reef, limited baseline information of ecological dynamics prior to ∼1980 makes it difficult to understand recent ecosystem trends. We demonstrate the use of high-resolution uranium–thorium dating, modern and palaeoecological techniques to improve our understanding of mortality and recovery dynamics over much broader scales. We found a loss of resilience in ecologically important branching
Acropora
corals at a regional scale. This work will prove valuable to reef managers by providing a reliable baseline for ongoing monitoring and identifying reefs at risk for deterioration, especially for those where modern observations are lacking.
Intestinal type 1 regulatory T cells migrate to periphery to suppress diabetogenic T cells and prevent diabetes development
Authors: Yu Hua , Gagliani Nicola , Ishigame Harumichi , Huber Samuel , Zhu Shu , Esplugues Enric , Herold Kevan C. , Wen Li , Flavell Richard A.
Published: September 2017

Significance

Past and current treatments for type 1 diabetes (T1D) have all suffered from adverse effects due to severe immune suppression or a lack of efficacy. A better understanding of the mechanisms and limitations of these therapies may help to maximize patient responses to treatment or elicit new ideas for a cure. Here, we discover a role for intestinal type 1 regulatory T (Tr1) cells in preventing autoimmune diabetes and provide mechanistic insight to explain the better efficacy of combination therapy in disease treatment. Our results also highlight the influence of dysbiotic gut microbiota on promotion of intestinal Tr1 cells and suggest that strategies targeting mucosal tissue to induce Tr1 in vivo might be used as a therapeutic approach for T1D.
Trichromacy increases fruit intake rates of wild capuchins (
Cebus capucinus imitator
)
Authors: Melin Amanda D. , Chiou Kenneth L. , Walco Emily R. , Bergstrom Mackenzie L. , Kawamura Shoji , Fedigan Linda M.
Published: September 2017

Significance

Color vision variation is prevalent among neotropical monkeys. Captive studies indicate that trichromacy should confer a fruit feeding advantage. This hypothesis, however, has yet to be supported by field studies. We collected behavioral and genetic data from 72 capuchins and analyzed ca. 20,000 fruit intake events across 27 plant species. Controlling for plant species and phenological condition, we find that trichromats eat reddish, conspicuous fruits more quickly than do dichromatic (red-green colorblind) groupmates. We demonstrate an advantage of trichromacy for consuming fruit among wild monkeys. Previous research has revealed dichromatic advantage for cryptic tasks; our results suggest fruit foraging plays an important role in the maintenance of primate opsin polymorphism via balancing selection.
N
-glycolyl groups of nonhuman chondroitin sulfates survive in ancient fossils
Authors: Bergfeld Anne K. , Lawrence Roger , Diaz Sandra L. , Pearce Oliver M. T. , Ghaderi Darius , Gagneux Pascal , Leakey Meave G. , Varki Ajit
Published: September 2017

Significance

We identified a glycan modification called
N
-glycolylated chondroitin sulfate (Gc-CS), derived from metabolic turnover of the nonhuman sialic acid
N
-glycolylneuraminic acid (Neu5Gc). The presence of Gc-CS could be demonstrated in species rich in Neu5Gc using chemically synthesized Gc-CS as a standard for mass spectrometry. Although humans cannot synthesize Neu5Gc due to a loss-of-function mutation, trace amounts of Gc-CS were found in humans, apparently derived from Neu5Gc-containing foods. Gc-CS was more easily detectable in animal fossils as old as 4 My, allowing indirect fossil evidence of Neu5Gc expression. These findings enable future studies to date the loss of Neu5Gc biosynthesis during human evolution and investigate this glycosaminoglycan modification in humans who consume Neu5Gc-rich foods (red meats).
Disassembly of theStaphylococcus aureushibernating 100S ribosome by an evolutionarily conserved GTPase
Authors: Basu Arnab , Yap Mee-Ngan F.
Published: September 2017

Significance

Bacterial protein synthesis requires the assembly of the 30S and 50S ribosomal subunits on mRNA to form the translationally competent 70S complex. Nontranslating 70S ribosomes homodimerize into a translationally inactive 100S ribosome to promote bacterial survival. The conversion between the 70S and 100S complexes is reversible, but the disassembly pathway of the 100S ribosome is unknown. We show that an evolutionarily conserved GTPase (HflX) splits theStaphylococcus aureus100S ribosome in a GTP-dependent fashion; the abundance of 100S is influenced by the opposing functions of the dimerizing factor (HPF) and HflX, whose actions are coregulated by the heat stress response and (p)ppGpp-mediated stringent control. These findings provide insights into the crosstalk between the 100S ribosome biogenesis and stress response.
Reexamining the origin of the directionality of myosin V
Authors: Alhadeff Raphael , Warshel Arieh
Published: September 2017

Significance

Myosin motors can convert chemical energy to motion. Myosin V is a processive motor that walks on actin filaments in one direction without detaching for a few dozen steps. Here we explore the nature of the directionality—namely, what is the microscopic mechanism that ensures the two myosin motor heads will coordinate to achieve unidirectional motion. With the help of Langevin Dynamics (LD) simulations, Monte Carlo (MC) simulations, and a technique we term SLiK (Segmental LD integrated Kinetics), we solve the kinetic equation and reach the conclusion that directionality is gained through selective ADP release. We find that ADP release has a higher barrier when the motor head is in the lever-up state (pre-power stroke) and support this through structure-based energy calculations.
Gut bacteria from multiple sclerosis patients modulate human T cells and exacerbate symptoms in mouse models
Authors: Cekanaviciute Egle , Yoo Bryan B. , Runia Tessel F. , Debelius Justine W. , Singh Sneha , Nelson Charlotte A. , Kanner Rachel , Bencosme Yadira , Lee Yun Kyung , Hauser Stephen L. , Crabtree-Hartman Elizabeth , Sand Ilana Katz , Gacias Mar , Zhu Yunjiao , Casaccia Patrizia , Cree Bruce A. C. , Knight Rob , Mazmanian Sarkis K. , Baranzini Sergio E.
Published: September 2017

Significance

We have experimentally investigated the immunoregulatory effects of human gut microbiota in multiple sclerosis (MS). We have identified specific bacteria that are associated with MS and demonstrated that these bacteria regulate T lymphocyte-mediated adaptive immune responses and contribute to the proinflammatory environment in vitro and in vivo. Thus, our results expand the knowledge of the microbial regulation of immunity and may provide a basis for the development of microbiome-based therapeutics in autoimmune diseases.
Varicose and cheerio collaborate with pebble to mediate semaphorin-1a reverse signaling in
Drosophila
Authors: Jeong Sangyun , Yang Da-som , Hong Young Gi , Mitchell Sarah P. , Brown Matthew P. , Kolodkin Alex L.
Published: September 2017

Significance

The transmembrane semaphorin Sema-1a functions as a ligand (forward signaling) and as a receptor (reverse signaling). Sema-1a reverse signaling plays a critical role in axon–axon repulsion during embryonic neural development. Pebble (Pbl), a Rho guanine nucleotide exchange factor, mediates Sema-1a reverse signaling through the regulation of the actin cytoskeleton by the small GTPase Rho1. Here, we find that two Sema-1a interacting proteins, varicose (Vari) and cheerio (Cher), are required for Pbl-mediated Sema-1a reverse signaling in
Drosophila
motor axon pathfinding. The Vari scaffolding function and Cher actin filament cross-linking properties suggest direct linkage between Sema-1a reverse signaling and the actin cytoskeleton. These results provide insight into mechanisms underlying semaphorin-induced localized changes in cytoskeletal organization.
Influence of Winter Conditions on the Age, Hatch Dates, and Growth of Juvenile Atlantic Menhaden in the Choptank River, Maryland
Authors: Atkinson Alexandra N. , Secor David H.
Published: September 2017

Since 1993, the Atlantic Menhaden Brevoortia tyrannus has experienced sustained low juvenile production (recruitment) in the Chesapeake Bay. We hypothesized that factors affecting wintertime larval growth in Atlantic Ocean shelf habitats carry over to juvenile growth and survival within the Chesapeake Bay. The effects of winter thermal conditions on the hatch dates and growth of larval and juvenile Atlantic Menhaden were examined using otolith increment analyses. During 2010–2013, truncated hatch date distributions for Atlantic Menhaden provided evidence of a winter recruitment bottleneck caused by cold temperatures. Hatch dates of surviving juveniles were skewed toward warmer months for years characterized by colder temperatures. Reduced larval growth rates, which were influenced by lower temperature and reduced food availability, carried over to juvenile growth rates for the same individuals. If larvae that are destined for ingress to the Chesapeake Bay predominately originate from early winter hatch, a recruitment bottleneck may occur, caused by either direct larval mortality or depressed larval growth rates owing to sublethal winter temperatures. Depressed larval growth rates, when not lethal, have the potential to carry over as reduced juvenile growth and survival after estuarine ingress.
Low-resistivity oxides in TixFeCoNi thin films after vacuum annealing
Authors: Yang Ya-Chu , Tsau Chun-Huei , Yeh Jien-Wei , Chen Swe-Kai
Published: September 2017

In this study, we investigated the electrical properties and microstructures of FeCoNi, Ti0.5FeCoNi, and TiFeCoNi thin films, with the aim of identifying new oxygen-deficient oxides with low resistivity. The resistivity values of as-deposited FeCoNi, Ti0.5FeCoNi, and TiFeCoNi films were 1089, 2883, and 5708 μΩ-cm, respectively. After vacuum annealing at 1000°C for 30 min, the resistivity values plummeted to 20.4, 32.1, and 45.4 μΩ-cm, respectively. Transmission electron microscope (TEM) analysis revealed that all of the as-annealed films were in the form of an oxygen-deficient oxide/metal composite with layered structure. The resistivity of these oxides is lower than that of indium tin oxide (ITO). They represent a new category of low-resistivity oxides.
B cell–derived IL-6 initiates spontaneous germinal center formation during systemic autoimmunity
Authors: Arkatkar Tanvi , Du Samuel W. , Jacobs Holly M. , Dam Elizabeth M. , Hou Baidong , Buckner Jane H. , Rawlings David J. , Jackson Shaun W.
Published: September 2017

Recent studies have identified critical roles for B cells in triggering autoimmune germinal centers (GCs) in systemic lupus erythematosus (SLE) and other disorders. The mechanisms whereby B cells facilitate loss of T cell tolerance, however, remain incompletely defined. Activated B cells produce interleukin 6 (IL-6), a proinflammatory cytokine that promotes T follicular helper (TFH) cell differentiation. Although B cell IL-6 production correlates with disease severity in humoral autoimmunity, whether B cell–derived IL-6 is required to trigger autoimmune GCs has not, to our knowledge, been addressed. Here, we report the unexpected finding that a lack of B cell–derived IL-6 abrogates spontaneous GC formation in mouse SLE, resulting in loss of class-switched autoantibodies and protection from systemic autoimmunity. Mechanistically, B cell IL-6 production was enhanced by IFN-γ, consistent with the critical roles for B cell–intrinsic IFN-γ receptor signals in driving autoimmune GC formation. Together, these findings identify a key mechanism whereby B cells drive autoimmunity via local IL-6 production required for TFH differentiation and autoimmune GC formation.
Differential Expression of Hypertensive Phenotypes in BXD Mouse Strains in Response to Angiotensin II
Authors: Zhao Wenyuan , Zhao Tieqiang , Chen Yuanjian , Bhattacharya Syamal K , Lu Lu , Sun Yao
Published: September 2017

BACKGROUND

Besides environmental risk factors, genetic factors play a crucial role in the pathogenesis of primary hypertension. The current study is to unravel whether hypertensive phenotypes vary in mice with different genetic background.

METHODS

Hypertension was induced in C57BL/6J (B6), DBA/2J (D2), and 25 BXD strains by administrating angiotensin (Ang)II (2.5 mg/kg/day infused by osmotic minipump) for 4 weeks. Systolic blood pressure was monitored before (baseline) and after 4 weeks of AngII treatment by tail cuff. Cardiac and renal fibrosis was evaluated by picrosirius red staining and collagen volume fraction (CVF) was quantitated using imaging analyzing system; cardiac transforming growth factor (TGF)-β gene expression was monitored by RT-PCR, and inflammatory response was detected by immunohistochemical ED-1 staining.

RESULTS

AngII infusion caused hypertension in all strains. However, blood pressure elevation was more evident in the D2 strain than the B6 group, while it was widely variable among BXD strains. Furthermore, chronic AngII treatment lead to development of hypertensive cardiac and renal diseases. Cardiac and renal CVF levels in the D2 strain was significantly higher than the B6 cohort, whereas these varied vastly across BXD strains. Moreover, cardiac TGF-β mRNA levels were markedly diverse among various mouse strains.

CONCLUSION

Our study unequivocally demonstrates that in response to AngII, BXDs with different genetic background expressed hypertension phenotypes with varied degree in severity. It implicates that genomics contribute to pathogenesis of primary hypertension. Building upon the genotype and hypertensive phenotypes, the BXD cohort can be further exploited experimentally to identify genes that influence blood pressure.
Augmented Association Between Blood Pressure and Proteinuria in Hyperuricemic Patients With Nonnephrotic Chronic Kidney Disease
Authors: Kohagura Kentaro , Kochi Masako , Miyagi Tsuyoshi , Zamami Ryo , Nagahama Kazufumi , Yonemoto Koji , Ohya Yusuke
Published: September 2017

BACKGROUND

Hyperuricemia (HU) may enhance susceptibility to hypertensive renal damage via disrupted autoregulation of glomerular hemodynamics. The effect of HU on the association between blood pressure (BP) and proteinuria remains unknown in patients with chronic kidney disease (CKD).

METHODS

In total, 109 patients with nonnephrotic CKD (55 men and 54 females) who underwent renal biopsy were recruited. Arteriolar hyalinosis was semiquantitatively assessed via arteriole grading. Correlation between BP and urine protein (UP) level was examined based on the presence of HU, which was defined as the use of urate-lowering drugs or serum uric acid levels of ≥7 and ≥5 mg/dl in males and females, respectively, which were associated with increased risks of hyalinosis in our previous study.

RESULTS

Median age, BP, estimated glomerular filtration rate, and UP level were 38 years, 124/74 mm Hg, 82 ml/min/1.73 m2, and 0.8 g/gCr, respectively. In patients with HU (n = 59), log-transformed systolic BP (SBP) was significantly correlated with log-transformed UP level (r = 0.49, P < 0.0001); this was not observed in patients without HU (n = 50). Multiple regression analysis (R2 = 0.21, P = 0.0001) revealed that the interaction between HU and log-transformed SBP with respect to proteinuria was significantly correlated with log-transformed UP level (β = 7.0, P = 0.03), independent of age, sex, and potential confounding factors; however, this statistical significance was completely eliminated after adjustment for the arteriolar hyalinosis index.

CONCLUSIONS

HU potentiates susceptibility to hypertensive glomerular damage via disrupted autoregulation in patients with nonnephrotic CKD.
Serotonin 2A Receptor Signaling Underlies LSD-induced Alteration of the Neural Response to Dynamic Changes in Music
Authors: Barrett Frederick S , Preller Katrin H , Herdener Marcus , Janata Petr , Vollenweider Franz X
Published: September 2017

Classic psychedelic drugs (serotonin 2A, or 5HT2A, receptor agonists) have notable effects on music listening. In the current report, blood oxygen level-dependent (BOLD) signal was collected during music listening in 25 healthy adults after administration of placebo, lysergic acid diethylamide (LSD), and LSD pretreated with the 5HT2A antagonist ketanserin, to investigate the role of 5HT2A receptor signaling in the neural response to the time-varying tonal structure of music. Tonality-tracking analysis of BOLD data revealed that 5HT2A receptor signaling alters the neural response to music in brain regions supporting basic and higher-level musical and auditory processing, and areas involved in memory, emotion, and self-referential processing. This suggests a critical role of 5HT2A receptor signaling in supporting the neural tracking of dynamic tonal structure in music, as well as in supporting the associated increases in emotionality, connectedness, and meaningfulness in response to music that are commonly observed after the administration of LSD and other psychedelics. Together, these findings inform the neuropsychopharmacology of music perception and cognition, meaningful music listening experiences, and altered perception of music during psychedelic experiences.
Top Questions in the Diagnosis and Treatment of Coccidioidomycosis
Authors: Donovan Fariba M , Zangeneh Tirdad T , Malo Joshua , Galgiani John N
Published: September 2017

Revised and greatly expanded treatment guidelines for coccidioidomycosis were published last year by the Infectious Diseases Society of America. We have selected 4 questions that commonly arise in the management of patients suspected of this disease and for which there remain divided opinions.
Governance of Academic Medical Centers Is Indeed a Complex and Unique Operation
Authors: Guzick David S. , Wilson Donald E.
Published: September 2017

As academic medical centers (AMCs) have extended their operations into their communities, partnered with new organizations, and developed new modes of operation to achieve their missions, new governance approaches are required. Chari and colleagues, in this issue of Academic Medicine, describe the development and application of criteria to evaluate governance options for the University of California (UC), which has a number of public AMCs, almost all of which are components of individual UC universities. Although many of these criteria may also be applicable to smaller AMCs, a more individual approach to governance is required—that is, one must step back and first ask about the organization, structure, and goals of the entities to be governed. The major nonfederal and nonspecialty teaching hospitals in the United States are about evenly split between those that are university owned or controlled and those having an independent relationship with their associated medical school. However, the challenges, obstacles, and desired end points are similar. The development of a successful governance structure will require identifying and appreciating many factors.
Disruption of Hippocampal Multisynaptic Networks by General Anesthetics
Authors: Kuo Min-Ching , Leung L. Stan
Published: September 2017

Background

Previous studies showed that synaptic transmission is affected by general anesthetics, but an anesthetic dose response in freely moving animals has not been done. The hippocampus provides a neural network for the evaluation of isoflurane and pentobarbital on multisynaptic transmission that is relevant to memory function.

Methods

Male Long-Evans rats were implanted with multichannel and single electrodes in the hippocampus. Spontaneous local field potentials and evoked field potentials were recorded in freely behaving rats before (baseline) and after various doses of isoflurane (0.25 to 1.5%) and sodium pentobarbital (10 mg/kg intraperitoneal).

Results

Monosynaptic population excitatory postsynaptic potentials at the basal and apical dendrites of CA1 were significantly decreased at greater than or equal to 0.25% (n = 4) and greater than or equal to 1.0% (n = 6) isoflurane, respectively. The perforant path evoked multisynaptic response at CA1 was decreased by ~50% at greater than or equal to 0.25% isoflurane (n = 5). A decreased population excitatory postsynaptic potential was accompanied by increased paired-pulse facilitation. Population spike amplitude in relation to apical dendritic population excitatory postsynaptic potential was not significantly altered by isoflurane. Spontaneous hippocampal local field potential at 0.8 to 300 Hz was dose-dependently suppressed by isoflurane (n = 6), with local field potential power in the 50- to 150-Hz band showing the highest decrease with isoflurane dose, commensurate with the decrease in trisynaptic CA1 response. Low-dose pentobarbital (n = 7) administration decreased the perforant path evoked trisynaptic CA1 response and hippocampal local field potentials at 78 to 125 Hz.

Conclusions

Hippocampal networks are sensitive to low doses of isoflurane and pentobarbital, possibly through both glutamatergic and γ-aminobutyric acid–mediated transmission. Network disruption could help explain the impairment of hippocampal-dependent cognitive functions with low-dose anesthetic.
Malignant Hyperthermia in the Post-Genomics Era
Authors: Riazi Sheila , Kraeva Natalia , Hopkins Philip M.
Published: September 2017

This article reviews advancements in the genetics of malignant hyperthermia, new technologies and approaches for its diagnosis, and the existing limitations of genetic testing for malignant hyperthermia. It also reviews the various RYR1-related disorders and phenotypes, such as myopathies, exertional rhabdomyolysis, and bleeding disorders, and examines the connection between these disorders and malignant hyperthermia.
Racial Disparities in Sepsis-Related In-Hospital Mortality: Using a Broad Case Capture Method and Multivariate Controls for Clinical and Hospital Variables, 2004–2013
Authors: Jones Jenna M. , Fingar Kathryn R. , Miller Melissa A. , Coffey Rosanna , Barrett Marguerite , Flottemesch Thomas , Heslin Kevin C. , Gray Darryl T. , Moy Ernest
Published: September 2017

Objectives:

As sepsis hospitalizations have increased, in-hospital sepsis deaths have declined. However, reported rates may remain higher among racial/ethnic minorities. Most previous studies have adjusted primarily for age and sex. The effect of other patient and hospital characteristics on disparities in sepsis mortality is not yet well-known. Furthermore, coding practices in claims data may influence findings. The objective of this study was to use a broad method of capturing sepsis cases to estimate 2004–2013 trends in risk-adjusted in-hospital sepsis mortality rates by race/ethnicity to inform efforts to reduce disparities in sepsis deaths.

Design:

Retrospective, repeated cross-sectional study.

Setting:

Acute care hospitals in the Healthcare Cost and Utilization Project State Inpatient Databases for 18 states with consistent race/ethnicity reporting.

Patients:

Patients diagnosed with septicemia, sepsis, organ dysfunction plus infection, severe sepsis, or septic shock.

Measurements and Main Results:

In-hospital sepsis mortality rates adjusted for patient and hospital factors by race/ethnicity were calculated. From 2004 to 2013, sepsis hospitalizations for all racial/ethnic groups increased, and mortality rates decreased by 5–7% annually. Mortality rates adjusted for patient characteristics were higher for all minority groups than for white patients. After adjusting for hospital characteristics, sepsis mortality rates in 2013 were similar for white (92.0 per 1,000 sepsis hospitalizations), black (94.0), and Hispanic (93.5) patients but remained elevated for Asian/Pacific Islander (106.4) and “other” (104.7; p < 0.001) racial/ethnic patients.

Conclusions:

Our results indicate that hospital characteristics contribute to higher rates of sepsis mortality for blacks and Hispanics. These findings underscore the importance of ensuring that improved sepsis identification and management is implemented across all hospitals, especially those serving diverse populations.
Radiation and Immunotherapy in High-grade Gliomas
Authors: Reznik Elizabeth , Smith Andrew W. , Taube Shoshana , Mann Justin , Yondorf Menachem Z. , Parashar Bhupesh , Wernicke A. Gabriella
Published: September 2017

High-grade glioma is the most common primary brain tumor, with glioblastoma multiforme (GBM) accounting for 52% of all brain tumors. The current standard of care (SOC) of GBM involves surgery followed by adjuvant fractionated radiotherapy and chemotherapy. However, little progress has been made in extending overall survival, progression-free survival, and quality of life. Attempts to characterize and customize treatment of GBM have led to mitigating the deleterious effects of radiotherapy using hypofractionated radiotherapy, as well as various immunotherapies as a promising strategy for the incurable disease. A combination of radiotherapy and immunotherapy may prove to be even more effective than either alone, and preclinical evidence suggests that hypofractionated radiotherapy can actually prime the immune system to make immunotherapy more effective. This review addresses the complications of the current radiotherapy regimen, various methods of immunotherapy, and preclinical and clinical data from combined radioimmunotherapy trials.
Relationship of low doses of alcohol voluntarily consumed during adolescence and early adulthood with subsequent behavioral flexibility
Authors: Fisher Hayley , Bright Nicholas , Gallo Mark , Pajser Alisa , Pickens Charles L.
Published: September 2017

Previous alcohol use is associated with impaired decision-making and impulsivity in humans, but the relationship between alcohol use and decision-making/impulsivity is unclear. In two experiments, we determined whether chronic intermittent access to alcohol during adolescence and early adulthood would alter or be correlated with performance in a go/no-go reversal task, a devaluation task, or operant extinction. Rats received 6 weeks of chronic intermittent access to 20% alcohol or water from postnatal day 26 to 66 and then behavioral testing was initiated 1.5–2.5 weeks later. We found no evidence that voluntary alcohol consumption altered behavior in either task. However, we found that rats that consumed more alcohol made fewer commission errors in reversal learning compared with rats that drank less. There was no relationship between alcohol consumption and reversal learning omission errors. Alcohol consumption was not correlated with the magnitude of the devaluation effect, but rats that consumed more alcohol showed faster extinction during the devaluation test. Our results suggest that the relationships between behavioral flexibility and alcohol consumption may represent individual differences. Future work will determine the neurobiological and genetic bases of these behavioral differences.
Myoelectric and Body Power, Design Options for Upper-Limb Prostheses: Introduction to the State of the Science Conference Proceedings
Authors: Stevens Phil M. , Highsmith M. Jason
Published: September 2017

This editorial serves as the introduction to the American Academy of Orthotists and Prosthetists State-of-the-Science Conference Proceedings covering the subject of upper-limb prosthetic control strategies. The purpose of the introduction is to orient consumers of the Proceedings regarding the breadth of its contents. Specifically, the conference centered about a systematic literature review comparing benefits of myoelectric and body-powered upper-limb prosthetic control options. The introduction lists the various perspectives such as clinical, engineering, and end-users represented at the face-to-face conference. It then introduces larger topics discussed by the conference participants, such as the traditional manner in which upper-limb prosthetic control strategies are introduced as well as viewpoints regarding standard of care.
Flexible Bronchoscope Use by Pulmonologists in Collaboration With Gastroenterologists for Placement of Percutaneous Endoscopic Gastrostomy Via Transnasal Route in Patients With Head and Neck Cancer
Authors: Mota Paulo J.L. , Dionísio Jorge , Duro da Costa José , Faias Sandra
Published: September 2017

This study was conducted with the aim of evaluating a 10-year experience in the Pulmonology Department of a cancer center for percutaneous endoscopic gastrostomy through transnasal route (TN-PEG) in patients with head and neck cancer whose oral access is precluded. This study was a retrospective analysis of 40 consecutive head and neck cancer patients referred for PEG placement, between 2005 and 2014, using a transnasal route because of the impossibility of intubation through the oral cavity. Demographics, outcome of TN-PEG procedure, indications for bronchoscopic approach (prophylactic/palliative), clinical need for bronchoscopy (trismus, oropharyngeal obstruction), location of cancer, complications, and overall survival were reviewed. In 40 TN-PEG procedures, executed by 1 of 3 pulmonologists, 39 were successfully placed and there were no immediate complications. All except 1 complication were minor, but no surgery or PEG removal was required. There was a rapid learning curve among all operators. A combined TN-PEG placement by a gastroenterologist and a pulmonologist is a safe and useful option for these patients; the learning curve for successfully performing the procedure was short.
Accurate Identification of Colonoscopy Quality and Polyp Findings Using Natural Language Processing
Authors: Lee Jeffrey K. , Jensen Christopher D. , Levin Theodore R. , Zauber Ann G. , Doubeni Chyke A. , Zhao Wei K. , Corley Douglas A.
Published: September 2017

Objectives:

The aim of this study was to test the ability of a commercially available natural language processing (NLP) tool to accurately extract examination quality–related and large polyp information from colonoscopy reports with varying report formats.

Background:

Colonoscopy quality reporting often requires manual data abstraction. NLP is another option for extracting information; however, limited data exist on its ability to accurately extract examination quality and polyp findings from unstructured text in colonoscopy reports with different reporting formats.

Study Design:

NLP strategies were developed using 500 colonoscopy reports from Kaiser Permanente Northern California and then tested using 300 separate colonoscopy reports that underwent manual chart review. Using findings from manual review as the reference standard, we evaluated the NLP tool’s sensitivity, specificity, positive predictive value (PPV), and accuracy for identifying colonoscopy examination indication, cecal intubation, bowel preparation adequacy, and polyps ≥10 mm.

Results:

The NLP tool was highly accurate in identifying examination quality–related variables from colonoscopy reports. Compared with manual review, sensitivity for screening indication was 100% (95% confidence interval: 95.3%–100%), PPV was 90.6% (82.3%–95.8%), and accuracy was 98.2% (97.0%–99.4%). For cecal intubation, sensitivity was 99.6% (98.0%–100%), PPV was 100% (98.5%–100%), and accuracy was 99.8% (99.5%–100%). For bowel preparation adequacy, sensitivity was 100% (98.5%–100%), PPV was 100% (98.5%–100%), and accuracy was 100% (100%–100%). For polyp(s) ≥10 mm, sensitivity was 90.5% (69.6%–98.8%), PPV was 100% (82.4%–100%), and accuracy was 95.2% (88.8%–100%).

Conclusion:

NLP yielded a high degree of accuracy for identifying examination quality–related and large polyp information from diverse types of colonoscopy reports.
Effectiveness of a post-emergency department discharge multidisciplinary bundle in reducing acute hospital admissions for the elderly
Authors: Ong Colin E.C. , Asinas-Tan Marxengel , Quek Lit-Sin , de Dios Michael , Cai Xue-Ting , Lim Beng-Leong
Published: September 2017

Objective

We evaluated the effectiveness of the Subacute Ambulatory care for the Functionally challenged and Elderly (SAFE) programme, a post-emergency department (ED) discharge intervention for elderly and functionally challenged patients, in reducing acute hospital admissions.

Methods

This study was a 32-month retrospective quasi-experimental study comparing patients with at least one of six diagnostic classifications who underwent SAFE intervention with those who were eligible but declined and received usual ED care (control). The primary outcomes were rates of first acute hospital admission at 30 and 60 days post-ED discharge. Secondary outcomes were 20-day withdrawal rate and 60-day mortality. The difference in primary outcome between the two groups was compared using a Cox proportional hazards model. We reported adjusted hazard ratios (HRs) with their 95% confidence intervals (CIs) adjusting for predefined factors of age, sex, triage risk assessment tool scores and baseline ED utilization and acute hospital admission rates in the past year.

Results

There were 438 and 209 patients in the intervention and control groups, respectively. The intervention group had reduced risk of first acute hospital admission at 30 days (10 vs. 27%, HR=0.34, 95% CI: 0.22–0.52) and 60 days (18 vs. 33%, HR=0.48, 95% CI: 0.34–0.69) compared with the control. The 20-day withdrawal rate was 3.2%. Both groups did not differ in 60-day mortality rates.

Conclusion

The SAFE programme was effective in reducing first acute hospital admissions in selected elderly and functionally challenged patients after ED discharge at 30 and 60 days compared with usual ED discharge care.
The neurophysiology of paediatric movement disorders
Authors: McClelland Verity M.
Published: September 2017

Purpose of review

To demonstrate how neurophysiological tools have advanced our understanding of the pathophysiology of paediatric movement disorders, and of neuroplasticity in the developing brain.

Recent findings

Delineation of corticospinal tract connectivity using transcranial magnetic stimulation (TMS) is being investigated as a potential biomarker for response to therapy. TMS measures of cortical excitability and neuroplasticity are also being used to investigate the effects of therapy, demonstrating neuroplastic changes that relate to functional improvements. Analyses of evoked potentials and event-related changes in the electroencephalogaphy spectral activity provide growing evidence for the important role of aberrant sensory processing in the pathophysiology of many different movement disorders. Neurophysiological findings demonstrate that children with clinically similar phenotypes may have differing underlying pathophysiology, which in turn may explain differential response to therapy. Neurophysiological parameters can act as biomarkers, providing a means to stratify individuals, and are well suited to provide biofeedback. They therefore have enormous potential to facilitate improvements to therapy.

Although currently a small field, the role of neurophysiology in paediatric movement disorders is poised to expand, both fuelled by and contributing to the rapidly growing fields of neuro-rehabilitation and neuromodulation and the move towards a more individualized therapeutic approach.
Deep brain stimulation for monogenic dystonia
Authors: Aravamuthan Bhooma R. , Waugh Jeff L. , Stone Scellig S.
Published: September 2017

Purpose of review

Deep brain stimulation (DBS) has recently emerged as an important management option in children with medically refractory dystonia. DBS is most commonly used, best studied, and thought to be most efficacious for a select group of childhood or adolescent onset monogenic dystonias (designated with a standard ’DYT’ prefix). We review how to clinically recognize these types of dystonia and the relative efficacy of DBS for key monogenic dystonias.

Recent findings

Though used for dystonia in adults for several years, DBS has only lately been used in children. Recent evidence shows that patients with shorter duration of dystonia often experience greater benefit following DBS. This suggests that early recognition of the appropriate dystonic phenotypes and consideration of DBS in these patients may improve the management of dystonia.

DBS should be considered early in patients who have medically refractory dystonia, especially for the monogenic dystonias that have a high response rate to DBS. It is important to differentiate between these monogenic dystonias and dystonias of other causes to properly prognosticate for these patients and to determine whether DBS is an appropriate management option.