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Endothelin-1 (ET-1) is elevated in patients with systemic lupus erythematosus (SLE), an autoimmune disease characterized by high rates of hypertension, renal injury, and cardiovascular disease. SLE is also associated with increased prevalence of obesity and insulin resistance compared to the general population. In the present study, we tested the hypothesis that elevated ET-1 in SLE is contributes to obesity and insulin resistance. For these studies, we used the NZBWF1 mouse model of SLE, which develops obesity and insulin resistance on a normal chow diet. To test this hypothesis, we treated control (NZW) and SLE (NZBWF1) mice with vehicle, atrasentan (ET

The fungal kingdom represents an extraordinary diversity of organisms with profound impacts across animal, plant, and ecosystem health. Fungi simultaneously support life, by forming beneficial symbioses with plants and producing life-saving medicines, and bring death, by causing devastating diseases in humans, plants, and animals. With climate change, increased antimicrobial resistance, global trade, environmental degradation, and novel viruses altering the impact of fungi on health and disease, developing new approaches is now more crucial than ever to combat the threats posed by fungi and to harness their extraordinary potential for applications in human health, food supply, and environmental remediation. To address this aim, the Canadian Institute for Advanced Research (CIFAR) and the Burroughs Wellcome Fund convened a workshop to unite leading experts on fungal biology from academia and industry to strategize innovative solutions to global challenges and fungal threats. This report provides recommendations to accelerate fungal research and highlights the major research advances and ideas discussed at the meeting pertaining to 5 major topics: (1) Connections between fungi and climate change and ways to avert climate catastrophe; (2) Fungal threats to humans and ways to mitigate them; (3) Fungal threats to agriculture and food security and approaches to ensure a robust global food supply; (4) Fungal threats to animals and approaches to avoid species collapse and extinction; and (5) Opportunities presented by the fungal kingdom, including novel medicines and enzymes.

The first meeting of the CIFAR Fungal Kingdom: Threats & Opportunities research program saw the congregation of experts on fungal biology to address the most pressing threats fungi pose to global health, agriculture, and biodiversity. This report covers the research discussed during the meeting and the advancements made toward mitigating the devastating impact of fungi on plants, animals, and humans.

Using the Parker Solar Probe FIELDS bandpass-filter data and SWEAP electron data from Encounters 1 through 9, we show statistical properties of narrowband whistlers from ∼16 R s to ∼130 R s, and compare wave occurrence to electron properties including beta, temperature anisotropy, and heat flux. Whistlers are very rarely observed inside ∼28 R s (∼0.13 au). Outside 28 R s, they occur within a narrow range of parallel electron beta from ∼1 to 10, and with a beta-heat flux occurrence consistent with the whistler heat flux fan instability. Because electron distributions inside ∼30 R s display signatures of the ambipolar electric field, the lack of whistlers suggests that the modification of the electron distribution function associated with the ambipolar electric field or changes in other plasma properties must result in lower instability limits for the other modes (including the observed solitary waves and ion acoustic waves) that are observed close to the Sun. The lack of narrowband whistler-mode waves close to the Sun and in regions of either low (10) beta is also significant for the understanding and modeling of the evolution of flare-accelerated electrons and the regulation of heat flux in astrophysical settings including other stellar winds, the interstellar medium, accretion disks, and the intragalaxy cluster medium.

SUMMARY Evasion of killing by immune cells is crucial for fungal survival in the host. For the human fungal pathogen Candida albicans, internalization by macrophages induces a transition from yeast to filaments that promotes macrophage death and fungal escape. Nutrient deprivation, alkaline pH, and oxidative stress have been implicated as triggers of intraphagosomal filamentation; however, the impact of other host-derived factors remained unknown. Here, we show that lysates prepared from macrophage-like cell lines and primary macrophages robustly induce C. albicans filamentation. Enzymatic treatment of lysate implicates a phosphorylated protein, and bioactivity-guided fractionation coupled to mass spectrometry identifies the immunomodulatory phosphoprotein PTMA as a candidate trigger of C. albicans filamentation. Immunoneutralization of PTMA within lysate abolishes its activity, strongly supporting PTMA as a filament-inducing component of macrophage lysate. Adding to the known repertoire of physical factors, this work implicates a host protein in the induction of C. albicans filamentation within immune cells., Graphical Abstract, In brief The human fungal pathogen Candida albicans filaments within host macrophages, enabling its escape. Case et al. demonstrate that lysates prepared from macrophage-like cell lines and primary macrophages induce C. albicans filamentation and implicate the immunomodulatory protein prothymosin alpha (PTMA) as a trigger of filamentation produced by host immune cells.

Observations of plasma waves by the Fields Suite and of electrons by the Solar Wind Electrons Alphas and Protons Investigation (SWEAP) on Parker Solar Probe provide strong evidence for pitch angle scattering of strahl-energy electrons by narrowband whistler-mode waves at radial distances less than ~0.3 AU. We present two example intervals of a few hours that include 8 waveform captures with whistler-mode waves and 26 representative electron distributions that are examined in detail. Two were narrow; 17 were clearly broadened, and 8 were very broad. The two with narrow strahl occurred when there were either no whistlers or very intermittent low amplitude waves. Six of the eight broadest distributions were associated with intense, long duration waves. Approximately half of the observed electron distributions have features consistent with an energy dependent scattering mechanism, as would be expected from interactions with narrowband waves. A comparison of the wave power in the whistler-mode frequency band to pitch angle width and a measure of anisotropy provides additional evidence for the electron scattering by whistler-mode waves. The pitch angle broadening occurs in over an energy range comparable to that obtained for the n=1 (co-streaming) resonance for the observed wave and plasma parameters. The additional observation that the heat flux is lower in the interval with multiple switchbacks may provide clues to the nature of switchbacks. These results provide strong evidence that the heat flux is reduced by narroweband whistler-mode waves scattering of strahl-energy electrons., 19 pages, 4 figures, 1 table

Aims.Large amplitude narrowband obliquely propagating whistler-mode waves at frequencies of ~0.2fce(electron cyclotron frequency) are commonly observed at 1 AU, and they are most consistent with the whistler heat flux fan instability. We want to determine whether similar whistler-mode waves occur inside 0.3 AU and how their properties compare to those at 1 AU.Methods.We utilized the waveform capture data from the Parker Solar Probe Fields instrument from Encounters 1 through 4 to develop a data base of narrowband whistler waves. The Solar Wind Electrons Alphas and Protons Investigation (SWEAP) instrument, in conjunction with the quasi-thermal noise measurement from Fields, provides the electron heat flux, beta, and other electron parameters.Results.Parker Solar Probe observations inside ~0.3 AU show that the waves are often more intermittent than at 1 AU, and they are interspersed with electrostatic whistler-Bernstein waves at higher-frequencies. This is likely due to the more variable solar wind observed closer to the Sun. The whistlers usually occur within regions when the magnetic field is more variable and often with small increases in the solar wind speed. The near-Sun whistler-mode waves are also narrowband and large amplitude, and they are associated with beta greater than 1. The association with heat flux and beta is generally consistent with the whistler fan instability. Strong scattering of strahl energy electrons is seen in association with the waves, providing evidence that the waves regulate the electron heat flux.

Display Omitted We introduce a semantic delta methodology for analyzing change in SNOMED CT.Two change analysis techniques are combined into one comprehensive methodology.Changes to sets of concepts are summarized and visualized.Changes in SNOMED CT's Bacterial infectious disease subhierarchy are analyzed. Thousands of changes are applied to SNOMED CTs concepts during each release cycle. These changes are the result of efforts to improve or expand the coverage of health domains in the terminology. Understanding which concepts changed, how they changed, and the overall impact of a set of changes is important for editors and end users. Each SNOMED CT release comes with delta files, which identify all of the individual additions and removals of concepts and relationships. These files typically contain tens of thousands of individual entries, overwhelming users. They also do not identify the editorial processes that were applied to individual concepts and they do not capture the overall impact of a set of changes on a subhierarchy of concepts.In this paper we introduce a methodology and accompanying software tool called a SNOMED CT Visual Semantic Delta (semantic delta for short) to enable a comprehensive review of changes in SNOMED CT. The semantic delta displays a graphical list of editing operations that provides semantics and context to the additions and removals in the delta files. However, there may still be thousands of editing operations applied to a set of concepts. To address this issue, a semantic delta includes a visual summary of changes that affected sets of structurally and semantically similar concepts. The software tool for creating semantic deltas offers views of various granularities, allowing a user to control how much change information they view. In this tool a user can select a set of structurally and semantically similar concepts and review the editing operations that affected their modeling. The semantic delta methodology is demonstrated on SNOMED CTs Bacterial infectious disease subhierarchy, which has undergone a significant remodeling effort over the last two years.

Objective: Quality assurance of large ontological systems such as SNOMED CT is an indispensable part of the terminology management lifecycle. We introduce a hybrid structural-lexical method for scalable and systematic discovery of missing hierarchical relations and concepts in SNOMED CT. Material and Methods: All non-lattice subgraphs (the structural part) in SNOMED CT are exhaustively extracted using a scalable MapReduce algorithm. Four lexical patterns (the lexical part) are identified among the extracted non-lattice subgraphs. Non-lattice subgraphs exhibiting such lexical patterns are often indicative of missing hierarchical relations or concepts. Each lexical pattern is associated with a potential specific type of error. Results: Applying the structural-lexical method to SNOMED CT (September 2015 US edition), we found 6801 non-lattice subgraphs that matched these lexical patterns, of which 2046 were amenable to visual inspection. We evaluated a random sample of 100 small subgraphs, of which 59 were reviewed in detail by domain experts. All the subgraphs reviewed contained errors confirmed by the experts. The most frequent type of error was missing is-a relations due to incomplete or inconsistent modeling of the concepts. Conclusions: Our hybrid structural-lexical method is innovative and proved effective not only in detecting errors in SNOMED CT, but also in suggesting remediation for these errors.

A miniaturized antipodal Vivaldi antenna to operate from 1 to 30 GHz is designed for nondestructive testing and evaluation of construction materials, such as concrete, polymers, and dielectric composites. A step-by-step procedure has been employed to design and optimize performance of the proposed antenna. First, a conventional antipodal Vivaldi antenna (CAVA) is designed as a reference. Second, the CAVA is shortened to have a small size of the CAVA. Third, to extend the low end of frequency band, the inner edges of the top and bottom radiators of the shortened CAVA have been bent. To enhance gain at lower frequencies, regular slit edge technique is employed. Finally, a half elliptical-shaped dielectric lens as an extension of the antenna substrate is added to the antenna to feature high gain and front-to-back ratio. A prototype of the antenna is employed as a part of the microwave imaging system to detect voids inside concrete specimen. High-range resolution images of voids are achieved by applying synthetic aperture radar algorithm.

A small antipodal Vivaldi antenna with rectangular slits at sun-shaped configuration and a half elliptical-shaped dielectric lens is designed for microwave and millimeter-wave imaging applications. The slits are developed to extend low end of frequency band and increase antenna gain at lower frequencies, while the lens is applied to this antenna to feature high gain at higher frequencies, high front-to-back ratio, low sidelobe and cross-polarization levels, narrow half-power beamwidth, and modification on E-plane tilt of beam. A prototype of the antenna with small size of 30 × 55 × 0.508 mm3 is fabricated and employed as a part of microwave and millimeter-wave imaging system. Applicability of the proposed antenna for 3-D and 2-D images of targets such as rubber discs and metal rods at different depths inside construction materials including foam and plasterboard sheet-layered structures is demonstrated. High-range resolution images are achieved by applying synthetic aperture radar algorithm.

SNOMED CT is a large, complex and widely-used terminology. Auditing is part of the life cycle of terminologies. A review of terminologies’ content can identify two error categories: commission errors, such as an incorrect parent or attribute relationship, indicating errors in a concept’s modeling, and omission errors, such as missing a parent or attribute relationship, representing incomplete modeling of a concept. According to our experience, terminology curators are mostly interested in commission errors. In recent years, a long-term remodeling project has addressed modeling issues in SNOMED CT’s Infectious disease and Congenital disease subhierarchies. In this longitudinal study, we investigated a posteriori the efficacy of complex concepts, called overlapping concepts, to identify commission errors during intensive auditing periods and during maintenance periods over several releases. The algorithmic implication is that when auditing resources are scarce, a methodology of auditing first, or only, the overlapping concepts will obtain a higher auditing yield.

High-quality microwave and millimetre wave imaging of construction materials and structures requires ultra-wideband (UWB) techniques to provide high-range resolution as well as a reasonable penetration depth. A modified compact microwave and millimetre wave UWB antipodal Vivaldi antenna is designed and presented in this study. First, the conventional antipodal Vivaldi antenna is designed as a reference antenna. Then, to provide the desired frequency range (3.4-40 GHz) with increased gain at its lower frequencies, the slit edge technique is applied, thus creating a periodic slit edge antipodal Vivaldi antenna (PSEAVA). Finally, a trapezoid-shaped dielectric lens (TDL) as an extension of the substrate is added and optimised to increase gain and directivity at higher frequencies of the frequency range, creating PSEAVA with a TDL (PSEAVA-TDL). The results show that the PSEAVA-TDL has the highest gain (up to 16 dB) and front-to-back ratio (up to 37.5 dB), and the narrowest half power beamwidth (down to 11.7°). A prototype of the proposed PSEAVA-TDL with compact size of 40 × 90 × 0.508 mm 3 is fabricated and applied for the imaging of samples made of construction materials. High-range resolution images of the samples are obtained with this antenna by using synthetic aperture radar algorithm.

The biocultural effects of European contact varied considerably throughout the Americas. Some populations were decimated by colonialism, while others benefited from trade relationships and access to new technologies. It has been suggested that initial contact with European fur traders and explorers was economically favourable for Plains village populations, thereby facilitating a period of cultural florescence. In this study, we evaluate the hypothesis that Plains groups were better off than their predecessors during the initial contact period by comparing frequencies of enamel hypoplasia, cribra orbitalia, and porotic hyperostosis in pre- and post-contact Arikara skeletal assemblages. We included both juveniles and adults in our sample to capture variation in the stress experience of different segments of the population. Our analysis revealed similarly low frequencies of cribra orbitalia in the pre- and post-contact groups and no observed cases of porotic hyperostosis. Enamel hypoplasia, however, was significantly more prevalent among post-contact Arikara villagers when compared to their pre-contact counterparts, which suggests that stress levels were higher after European contact. Additionally, enamel hypoplasia was most common among post-contact juveniles. The elevated frequency of enamel hypoplasia in the post-contact sample combined with the low frequencies of cribra orbitalia and porotic hyperostosis suggests that disease stress, rather than nutritional deficiencies, was likely responsible for the decline in overall health following European contact. These results also suggest that juveniles are sensitive indicators of systemic stress within a population and should be included in bioarchaeological analyses of prehistoric health when available. Copyright © 2015 John Wiley & Sons, Ltd.

An ultra-wideband elliptically tapered antipodal Vivaldi antenna designed for civil engineering applications is presented. It is based on design of a conventional antipodal Vivaldi antenna (CAVA) which impedance bandwidth is limited at low end of frequency band. To extend impedance bandwidth, inner edges of top and bottom radiators of the CAVA have been properly bent; however, its gain and front-to-back (F-to-B) ratio is low at the low frequencies. To enhance gain and F-to-B ratio, the comb-shaped slits on edges of the radiators of CAVA are applied. The obtained results exhibit the impedance bandwidth of 1.65-18 GHz, gain of 6.7 dB at 1.65 GHz, and F-to-B ratio of 42 dB at 13.5 GHz that are higher than those parameters of the CAVA. Applicability of the proposed antenna for detection of void inside concrete beam is demonstrated. First, models of the proposed antenna and concrete beam possessing void are created in computer simulation technology and numerical study is performed. Then, a prototype of the antenna is fabricated and employed as part of microwave imaging system to verify simulation results and to detect voids inside concrete beam.

Cholinergic neurons in the basal forebrain project heavily to the main olfactory bulb, the first processing station in the olfactory pathway. The projections innervate multiple layers of the main olfactory bulb and strongly influence odor discrimination, detection, and learning. The precise underlying circuitry of this cholinergic input to the main olfactory bulb remains unclear, however. Here, we identify a specific basal forebrain cholinergic projection that innervates select neurons concentrated in the internal plexiform layer of the main olfactory bulb. Optogenetic activation of this projection elicits monosynaptic nicotinic and GABAergic currents in glomerular layer-projecting interneurons. Additionally, we show that the projection co-expresses markers for GABAergic neurotransmission. The data thus implicate neurotransmitter co-transmission in the basal forebrain regulation of this inhibitory olfactory microcircuit., Cholinergic neurons innervate multiple layers in the main olfactory bulb but the precise circuitry of this input is not known. Here the authors show that VGLUT3+ cholinergic neurons selectively innervate deep short axon cells in specific layers and elicit robust monosynaptic GABAergic and nicotinic postsynaptic currents.

A NASA effort is underway to develop a nondestructive inspection method to evaluate the bonding condition for heat shield blocks that are bonded to a composite substrate. The initial effort is reported in this paper. The goal is to demonstrate a proof of concept for a reliable detection method using a single-sided scan capability applied from the outside of the heat shield blocks. Two representative samples with known defects are made available for the initial proof of concept; the results of one sample are reported here. The two specimens had been scanned using various nondestructive testing methods including immersion ultrasound, handheld ultrasound, air-coupled ultrasound, microwave, Terahertz, computed radiography, and shearography. These efforts were performed by industry experts and academia. All were limited in their detectability of the known flawed regions in the specimens and suffered high levels of uncertainty in the good regions. Most nondestructive evaluation methods are sensitive to detecting changes in the material property. This means that an air pocket is easy to detect in an unbounded interface but when the air pocket is absent and the two surfaces are in intimate contact (kissing bond) most methods fails to detect the difference. Electromagnetic methods (radiography, thermography, microwave, Terahertz) will not detect a change in material property. Shearography is not successful in attempting to detect changes in stiffness through the highly damping thick heat shield layer. As a mechanical wave, ultrasound is the primary method that may be able to detect a kissing bond. However, it was quickly recognized that ultrasound has to overcome a number of difficult challenges related to the nonhomogeneous and highly damping nature of the thermal shield material. Inhomogeneity causes pronounced changes in signal strength that make the distinction between good and bad areas very difficult. At the same time, scatter and attenuation become detrimental to high frequency ultrasonic signals, which are necessary to resolve echoes returning from the bond line. Conversely, low frequency sound waves provide poor spatial and temporal resolution due to the broader wavelengths associated with the signal.

The striatum is essential for many aspects of mammalian behavior, including motivation and movement, and is dysfunctional in motor disorders such as Parkinson's disease. The vesicular glutamate transporter 3 (VGLUT3) is expressed by striatal cholinergic interneurons (CINs) and is thus well positioned to regulate dopamine (DA) signaling and locomotor activity, a canonical measure of basal ganglia output. We now report that VGLUT3 knock-out (KO) mice show circadian-dependent hyperlocomotor activity that is restricted to the waking cycle and is due to an increase in striatal DA synthesis, packaging, and release. Using a conditional VGLUT3 KO mouse, we show that deletion of the transporter from CINs, surprisingly, does not alter evoked DA release in the dorsal striatum or baseline locomotor activity. The mice do, however, display changes in rearing behavior and sensorimotor gating. Elevation of DA release in the global KO raised the possibility that motor deficits in a Parkinson's disease model would be reduced. Remarkably, after a partial 6-hydroxydopamine (6-OHDA)-mediated DA depletion (∼70% in dorsal striatum), KO mice, in contrast to WT mice, showed normal motor behavior across the entire circadian cycle.l-3,4-dihydroxyphenylalanine-mediated dyskinesias were also significantly attenuated. These findings thus point to new mechanisms to regulate basal ganglia function and potentially treat Parkinson's disease and related disorders.SIGNIFICANCE STATEMENTDopaminergic signaling is critical for both motor and cognitive functions in the mammalian nervous system. Impairments, such as those found in Parkinson's disease patients, can lead to severe motor deficits. Vesicular glutamate transporter 3 (VGLUT3) loads glutamate into secretory vesicles for neurotransmission and is expressed by discrete neuron populations throughout the nervous system. Here, we report that the absence of VGLUT3 in mice leads to an upregulation of the midbrain dopamine system. Remarkably, in a Parkinson's disease model, the mice show normal motor behavior. They also show fewer abnormal motor behaviors (dyskinesias) in response tol-3,4-dihydroxyphenylalanine, the principal treatment for Parkinson's disease. The work thus suggests new avenues for the development of novel treatment strategies for Parkinson's disease and potentially other basal-ganglia-related disorders.

Micro Computed Tomography (micro-CT) of cores is an emerging technology that yields vital information about key rock and fluid properties at pore-scale resolution. Micro-CT imaging results presented to date are encouraging and indicate that this technology has the potential to revolutionize petrophysical analysis and reservoir engineering. The application of micro-CT in petroleum engineering requires reconstructed scan data to be of high and uniform image quality to enable reliable analysis during subsequent segmentation and numerical modeling. This is achievable in existing micro-CT systems using standard circular scan trajectories with non-exact filtered backprojection (FBP) reconstruction, but requires small cone angles to keep cone beam artifacts below detectable limits. We describe the implementation and results of adapting an exact helical FBP reconstruction algorithm (the so-called “Katsevich Algorithm” or KFBP) and data acquisition scheme on a high-performance micro-CT system normally running in circular scan trajectory mode. Side-by-side comparisons of stitched circular scan trajectories with continuous helical scan trajectories on simulated and real rock core data show the throughput advantage of this modality for applications relevant for the petroleum industry keeping equivalent image quality to low cone angle circular scans. The analytical exact helical reconstruction can be performed in quasi-real time leading to instantaneous results. Simulated and experimental results indicate that an imaging throughput improvement of 2-5 times can be achieved employing KFBP-based exact helical reconstruction compared to the standard circle scan trajectory when imaging whole rock cores/plugs that are significantly longer than their diameter.

Objective Standards terminologies may be large and complex, making their quality assurance challenging. Some terminology quality assurance (TQA) methodologies are based on abstraction networks (AbNs), compact terminology summaries. We have tested AbNs and the performance of related TQA methodologies on small terminology hierarchies. However, some standards terminologies, for example, SNOMED, are composed of very large hierarchies. Scaling AbN TQA techniques to such hierarchies poses a significant challenge. We present a scalable subject-based approach for AbN TQA. Methods An innovative technique is presented for scaling TQA by creating a new kind of subject-based AbN called a subtaxonomy for large hierarchies. New hypotheses about concentrations of erroneous concepts within the AbN are introduced to guide scalable TQA. Results We test the TQA methodology for a subject-based subtaxonomy for the Bleeding subhierarchy in SNOMED's large Clinical finding hierarchy. To test the error concentration hypotheses, three domain experts reviewed a sample of 300 concepts. A consensus-based evaluation identified 87 erroneous concepts. The subtaxonomy-based TQA methodology was shown to uncover statistically significantly more erroneous concepts when compared to a control sample. Discussion The scalability of TQA methodologies is a challenge for large standards systems like SNOMED. We demonstrated innovative subject-based TQA techniques by identifying groups of concepts with a higher likelihood of having errors within the subtaxonomy. Scalability is achieved by reviewing a large hierarchy by subject. Conclusions An innovative methodology for scaling the derivation of AbNs and a TQA methodology was shown to perform successfully for the largest hierarchy of SNOMED.

Background: The rate \lambda_pp\mu\ characterizes the formation of pp\mu\ molecules in collisions of muonic p\mu\ atoms with hydrogen. In measurements of the basic weak muon capture reaction on the proton to determine the pseudoscalar coupling g_P, capture occurs from both atomic and molecular states. Thus knowledge of \lambda_pp\mu\ is required for a correct interpretation of these experiments. Purpose: Recently the MuCap experiment has measured the capture rate \Lambda_S from the singlet p\mu\ atom, employing a low density active target to suppress pp\mu\ formation (PRL 110, 12504 (2013)). Nevertheless, given the unprecedented precision of this experiment, the existing experimental knowledge in \lambda_pp\mu\ had to be improved. Method: The MuCap experiment derived the weak capture rate from the muon disappearance rate in ultra-pure hydrogen. By doping the hydrogen with 20 ppm of argon, a competing process to pp\mu\ formation was introduced, which allowed the extraction of \lambda_pp\mu\ from the observed time distribution of decay electrons. Results: The pp\mu\ formation rate was measured as \lambda_pp\mu = (2.01 +- 0.06(stat) +- 0.03(sys)) 10^6 s^-1. This result updates the \lambda_pp\mu\ value used in the above mentioned MuCap publication. Conclusions: The 2.5x higher precision compared to earlier experiments and the fact that the measurement was performed at nearly identical conditions to the main data taking, reduces the uncertainty induced by \lambda_pp\mu\ to a minor contribution to the overall uncertainty of \Lambda_S and g_P, as determined in MuCap. Our final value for \lambda_pp\mu\ shifts \Lambda_S and g_P by less than one tenth of their respective uncertainties compared to our results published earlier., Comment: 12 pages, 6 figures, to be submitted to Phys. Rev. C

Socioeconomic status (SES) impacts educational opportunities and outcomes which explains, in part, why the majority of medical students come from the upper two quintiles of family income. A two-factor SES indicator based on parental education (E) and occupation (O) has recently been established by the Association of American Medical Colleges (AAMC). This study validates this two-factor indicator as applicable to the national pool of medical school applicants.The AAMC SES EO indicator classifies applicants into five ordered groups (EO-1 through EO-5) based on four aggregated categories of parental education and two aggregated categories of occupation. The EO indicator was applied to the 2012 American Medical College Application Service applicant pool. The authors examined the associations that the EO category had with six additional and independent indicators of socioeconomic (dis)advantage, as well as with demographic and educational characteristics and life experiences.The EO indicator could be applied to 89% of the 2012 applicants. The lower the EO category, the stronger the association with each of the six indicators of socioeconomic disadvantage. Other notable, but weaker, associations with the EO indicator were differences by age, race/ethnicity, performance on the Medical College Admission Test, community college attendance, and certain self-reported life experiences.The EO indicator provides a simple, intuitive, widely applicable, and valid means for identifying applicants from socioeconomically disadvantaged backgrounds. This affords admissions committees an additional factor to consider during the holistic review of applicants in order to further diversify the medical school class.

The vesicular glutamate transporter 3 (VGLUT3) is expressed at several locations not normally associated with glutamate release. Although the function of this protein has been generally elusive, when expressed in non-glutamatergic synaptic terminals, VGLUT3 can not only allow glutamate co-transmission but also synergize the action of non-glutamate vesicular transporters. Interestingly, in the immature glycinergic projection between the medial nucleus of the trapezoid body (MNTB) and the lateral superior olive (LSO) of auditory brainstem, the transient early expression of VGLUT3 is required for normal developmental refinement. It has however been unknown whether the primary function of VGLUT3 in development of these inhibitory synapses is to enable glutamate release or to promote loading of inhibitory neurotransmitter through vesicular synergy. Using tissue from young mice in which Vglut3 had been genetically deleted, we evaluated inhibitory neurotransmission in the MNTB-LSO pathway. Our results show, in contrast to what has been seen at adult synapses, that VGLUT3 expression has little or no effect on vesicular synergy at the immature glycinergic synapse of brainstem. This finding supports the model that the primary function of increased VGLUT3 expression in the immature auditory brainstem is to enable glutamate release in a developing inhibitory circuit.

Objective Large and complex terminologies, such as Systematized Nomenclature of Medicine–Clinical Terms (SNOMED CT), are prone to errors and inconsistencies. Abstraction networks are compact summarizations of the content and structure of a terminology. Abstraction networks have been shown to support terminology quality assurance. In this paper, we introduce an abstraction network derivation methodology which can be applied to SNOMED CT target hierarchies whose classes are defined using only hierarchical relationships (ie, without attribute relationships) and similar description-logic-based terminologies. Methods We introduce the tribal abstraction network (TAN), based on the notion of a tribe—a subhierarchy rooted at a child of a hierarchy root, assuming only the existence of concepts with multiple parents. The TAN summarizes a hierarchy that does not have attribute relationships using sets of concepts, called tribal units that belong to exactly the same multiple tribes. Tribal units are further divided into refined tribal units which contain closely related concepts. A quality assurance methodology that utilizes TAN summarizations is introduced. Results A TAN is derived for the Observable entity hierarchy of SNOMED CT, summarizing its content. A TAN-based quality assurance review of the concepts of the hierarchy is performed, and erroneous concepts are shown to appear more frequently in large refined tribal units than in small refined tribal units. Furthermore, more erroneous concepts appear in large refined tribal units of more tribes than of fewer tribes. Conclusions In this paper we introduce the TAN for summarizing SNOMED CT target hierarchies. A TAN was derived for the Observable entity hierarchy of SNOMED CT. A quality assurance methodology utilizing the TAN was introduced and demonstrated.