cssi/SciSciGPT-SciSciNet huggingface dataset:
Microalgal assemblages in a poikilohaline pond.

Microalgal strains for algal biofuels production in outdoor ponds will need to have high net growth rates under diverse environmental conditions. A small, variable salinity pond in the San Elijo Lagoon estuary in southern California was chosen to serve as a model pond due to its routinely high chlorophyll content. Profiles of microalgal assemblages from water samples collected from April 2011 to January 2012 were obtained by constructing 18S rDNA environmental clone libraries. Pond assemblages were found to be dominated by green algae Picochlorum sp. and Picocystis sp. throughout the year. Pigment analysis suggested that the two species contributed most of the chlorophyll a of the pond, which ranged from 21.9 to 664.3 μg · L(-1) with the Picocystis contribution increasing at higher salinities. However, changes of temperature, salinity or irradiance may have enabled a bloom of the diatom Chaetoceros sp. in June 2011. Isolates of these microalgae were obtained and their growth rates characterized as a function of temperature and salinity. Chaetoceros sp. had the highest growth rate over the temperature test range while it showed the most sensitivity to high salinity. All three strains showed the presence of lipid bodies during nitrogen starvation, suggesting they have potential as future biofuels strains.
Root‐derived CO2 efflux via xylem stream rivals soil CO2 efflux

• Respiration consumes a large portion of annual gross primary productivity in forest ecosystems and is dominated by belowground metabolism. Here, we present evidence of a previously unaccounted for internal CO2 flux of large magnitude from tree roots through stems. If this pattern is shown to persist over time and in other forests, it suggests that belowground respiration has been grossly underestimated. • Using an experimental Populus deltoides plantation as a model system, we tested the hypothesis that a substantial portion of the CO2 released from belowground autotrophic respiration remains within tree root systems and is transported aboveground through the xylem stream rather than diffusing into the soil atmosphere. • On a daily basis, the amount of CO2 that moved upward from the root system into the stem via the xylem stream (0.26 mol CO2 m-2 d-1) rivalled that which diffused from the soil surface to the atmosphere (0.27 mol CO2 m-2 d-1). We estimated that twice the amount of CO2 derived from belowground autotrophic respiration entered the xylem stream as diffused into the soil environment. • Our observations indicate that belowground autotrophic respiration consumes substantially more carbohydrates than previously recognized and challenge the paradigm that all root-respired CO2 diffusesmore » into the soil atmosphere.« less
Pairwise registration of images with missing correspondences due to resection

Registration of images with missing correspondences, such as in the alignment of preoperative and postresection brain data, is a difficult task. To simplify this problem, we introduce an indicator map to segment valid correspondence regions from areas with missing data. The registration problem is posed in a marginalized maximum a posteriori (MAP) estimation framework in which the transformation and correspondence regions are simultaneously estimated using the expectation-maximization (EM) algorithm. The E-step calculates the weights of the possible indicator maps while the M-step updates the transformation. A spatial prior based on principal component analysis (PCA) is used to guide indicator map selection. We demonstrate the promise of our approach on synthetic and real data by comparing results using our algorithm to those from a standard non-rigid registration method.
P2Y11, a purinergic receptor acting via cAMP, mediates secretion by pancreatic duct epithelial cells

Pancreatic duct epithelial cells (PDEC) mediate the exocrine secretion of fluid and electrolytes. We previously reported that ATP and UTP interact with P2Y2 receptors on nontransformed canine PDEC ...
What’s the Name of the Game?

Abstract mathematics deals with the analysis of mathematical concepts and statements. Mathematics is unique among all disciplines in that its concepts have a precise and consistent meaning, and its results, once established, are not subject to opinions or experimental verification and remain valid independently of time, place, and culture—although their perceived importance might vary. In this chapter we discuss mathematical concepts; in Chap. 3 we study mathematical statements.
PP02.1 – 2612: The clinical value of neuromediators (brain derivated neurotrophic factor, galanin, neuropeptid Y) in neonatal encephalopathy

Objective To investigate the diagnostic and prognostic value of neuromediators (brain derivated neurotrophic factor-BDNF, galanin and neuropeptide Y-NPY) in pretem and term neonates with neonatal encephalopathy. Methods Fifty three neonates (preterm: 26, term: 27) who had lumbar puncture for the diagnostic investigation of neonatal encephalopathy in Ege University Children's Hospital NICU were enrolled to the study. Study group were divided in to 4 groups according to their gestational ages and based on whether they had seizures or not: Group 1: preterm neonates with seizures (n=13), Group 2: preterm neonates without seizures (n=13), Group 3: term neonates with seizures (n=13), Group 4: term neonates without seizures (n=14). Control group consisted of 32 healthy newborns (preterm: 13, term: 19) who were delivered in the same time frame at Ege University Hospital Maternity Ward. Only cord blood samples were obtained from these neonates. Amplitude integrated EEG (aEEG) and conventional EEG (cEEG) were simulataneously performed for neonates in NICU. All infants Infants were followed up prospectively and were evaluated with GMCD (Guide for Monitoring Child Development) and ADSI (Ankara Developmental Screening Inventory). Overal outcome at one-year-old was divided into two groups (favorable and unfavorable). Results There were no significant relationship between serum and CSF levels of BDNF, NPY, and galanin with gestational age. Serum BDNF, NPY, and galanin levels were suppressed in the neonates with neonatal encephalopathy in NICU compared to the healthy controls. Serum BDNF, serum NPY, CSF BDNF and CSF NPY levels were increased in neonates with clinical seizures. Conclusion Increased serum and CSF levels of BDNF and NPY in preterm and term neonates with clinical seizures might be indicators for early recognition of neonatal seizures. Supressed serum and CSF levels of neuromediators might be associated with unfavorable neurological outcome of neonates with neonatal encephalopathy in NICU.
Rheumatology Research Foundation Clinician Scholar Educator Award: Fifteen Years Promoting Rheumatology Educators and Education

Objective The Rheumatology Research Foundation's Clinician Scholar Educator (CSE) award is a 3-year career development award supporting medical education research while providing opportunities for mentorship and collaboration. Our objective was to document the individual and institutional impact of the award since its inception, as well as its promise to strengthen the subspecialty of rheumatology. Methods All 60 CSE Award recipients were surveyed periodically. Fifty-six of those 60 awardees (90%) responded to requests for survey information that included post-award activities, promotions, and further funding. Data were also collected from yearly written progress reports for each grant. Results Of the total CSE recipients to date, 48 of 60 (80%) are adult rheumatologists, 11 of 60 (18%) are pediatric rheumatologists, and 1 is an adult and pediatric rheumatologist. Two-thirds of survey respondents spend up to 30% of their total time in educational activities, and one-third spend greater than 30%. Thirty-one of the 60 CSE recipients (52%) have published a total of 86 medical education papers. Twenty-six of 52 (50%) had received an academic promotion following the award. Eleven awardees earned advanced degrees. Conclusion We describe the creation and evolution of a grant program from a medical subspecialty society foundation and the impact on producing education research, individual identity formation, and ongoing support for educators. This community of rheumatology scholar educators now serves as an important resource at the national level for the American College of Rheumatology and its membership. We believe that this grant may serve as a model for other medical societies that want to promote education scholarship and leadership within their specialties.
Cap and Trade: Relative Gains Approach Towards Mitigating Climate Change

Climate change is undoubtedly one of the most salient concerns within environmental policy studies today. There are numerous outstanding points supported by increasing scientific evidence pointing to the urgency for climate change policy. This paper argues that policy approach of “Cap and Trade” is a reactive policy an at best offers modest gains in seeking to reduce carbon dioxide emissions. It also casts doubt regarding the viability of the United States meeting carbon emission reductions of 42% by 2030 and 83% by 2050 which were recently stated at the 2009 Copenhagen Conference on Climate Change.
Chevron's Demise: A Survey of Chevron from Infancy to Senescence

This article explores Chevron's role in statutory interpretation. In Chevron the Supreme Court resolved the question of how much deference courts must give to an agency's interpretation of a statute: first, determine whether Congress had decided the issue; if not, then defer to any reasonable agency interpretation. But Chevron has proved to be less clear, predictable, and simple than originally envisioned. For example, exactly how searching should the inquiry be at the first step? Should a court limit its search to the text of the statute at issue, or should a court look more broadly for Congressional intent? These are different questions. And, more importantly, the answer directly impacts the distribution of lawmaking power among the three branches of government. This article explores the Court's reformulation of Chevron's first step and ultimately concludes that Chevron's importance is fading: where Chevron's early application knew no bounds, today, Chevron applies less often and is cited by the Court far less frequently. In the end, the Court's reformulation of Chevron's first step has hastened Chevron's demise.
The chromosomal nature of LT-II enterotoxins solved: a lambdoid prophage encodes both LT-II and one of two novel pertussis-toxin-like toxin family members in type II enterotoxigenic Escherichia coli.

Heat-labile enterotoxins (LT) of enterotoxigenic Escherichia coli (ETEC) are structurally and functionally related to cholera toxin (CT). LT-I toxins are plasmid-encoded and flanked by IS elements, while LT-II toxins of type II ETEC are chromosomally encoded with flanking genes that appear phage-related. Here I determined the complete genomic sequence of the locus for the LT-IIa type strain SA53, and show that the LT-IIa genes are encoded by a 51,239 bp lambdoid prophage integrated at the rac locus, the site of a defective prophage in E. coli K12 strains. 46 of 50 LT-IIa and LT-IIc prophages also encode one member of two novel two-gene ADP-ribosyltransferase toxin families that are both related to pertussis toxin, which I named eplBA or ealAB respectively. The eplBA and ealAB genes are syntenic with the Shiga toxin loci in their lambdoid prophages of the enteric pathogen enterohemorrhagic E. coli . These novel AB5 toxins show pertussis-toxin-like activity on tissue culture cells, and like pertussis toxin bind to sialic acid containing glycoprotein ligands. Type II ETEC are the first mucosal pathogens known to simultaneously produce two ADP-ribosylating toxins predicted to act on and modulate activity of both stimulatory and inhibitory alpha subunits of host cell heterotrimeric G-proteins.
Carteretta Carteri Clavata, a New Subspecies from Nevada, and Notes on Synonymy (Siphonaptera)

Among the ectoparasites collected for identification during routine plague survey operations in Western United States there was found a pair of fleas closely related to, but not identical with, the species described by Fox in 1927 as Carteretta carteri . These specimens are here described as a new subspecies of C. carteri .
Relapsing Fever in California. I. The Experimental Disease.

I have made no attempt to review the incidence of relapsing fever in North America. This was done by Carlisle,1 who referred to the early epidemic form of the disease which occurred in the eastern states and in Alaska from 1844 to 1869. The last of these epidemics occurred in 1874, among Chinese in Oroville, Calif. During that period the disease was supposed to be contagious. Since the publication in 1873 of the report of the discovery, in 1868, of the causative organism, more exact knowledge of the etiology and epidemiology of the disease has been current. The first two authenticated cases occurred in North
Theory of Microwave Effects on Atomic Diffusion in Sintering: Basic Considerations of The Phenomenon of Thermal Runaway

We present the results of our recent studies of the possible origin of the reported increase in sintering efficiency brought about by the application of microwaves. We study the phenomenon of thermal runaway in ceramic materials undergoing microwave heating and present a theory on the basis of a simple temperature-time equation. The nonlinear evolution inherent in the equation arises naturally from physical considerations. The theory is applied to experimental observations reported on several different materials including silica, alumina, strontium titanate, zinc oxide and iron oxide, and shown to be in good agreement with the data.
‘You will always have to “out” yourself’: Reconsidering coming out through strategic outness

Increasingly, researchers casually use the concept of coming out. After tracing its conceptual inflation, this article shifts the lens from identity development to reconsider coming out as identity...
Limited Liability Company: Adherence and Improvement

The rational attitude to limited liability company in China' Company Act revision should follow the trend from appendix role to mainstream role, from the mixture of the character of personal joint and character of capital joint to the character of capital joint, and respect the fact that large majority and large-sized companies adopt this corporate form. Limited liability companies should be modified in accordance with private companies' character, increasing its capital character while decreasing its personal character. At the same time, ex ante regulation should be diminished to enhance the flexibility in corporate formation and administration. Company law rules should be devised as model rules and commercial contract doctrine and good faith principle should be introduced to resolve the disputes between the shareholders.
MRI diagnosis of solitary metastases

[Objective] To evaluate MRI manifestation and diagnostic value in solitary brain metastases. [Methods] MRI findings of 32 patients with solitary brain metastases were reviewed retrospectively. [Results] Among the 32 cases, 25 lesions were located in supratentorial cerebrum and 21 cases of them were situated in the cortex or subcortex, and 7 lesions were in infra-tentorium. The edema was slight in 9 cases, moderate in 5, serious in 18. The shapes of lesions in contrast-enhanced MRI were irregular ring(40%), nodule(18.7%), cysto-kernel type(40%) respectively. [Conclusion] Solitary brain metastases have some characteristic MRI features. MRI, including contrast-enhanced MRI is valuable in finding solitary brain metastases.
Study on Testing Technology for Merging Unit in Smart Substation

The merging unit is the foundation and guarantee of smart substation digital information transmission,and it is charged with the correct information communication between the state of high voltage equipment and bay level equipment. The merging unit indexes and requirements are pointed out in the standard of power industry,yet specific testing method are not available in it. On the basis of analysis of the merging unit indexes,this paper proposes the merging uint indexes in local test and verifies them. The effectiveness and the acuracy of the plan is proved.
Conclusions: Ethics for TechnoRebels—The Power of Embodied Vulnerability

Technosex pivots on a series of transformations that articulate bodies, desires, and technologies. These transformations reconfigure each element in the system in order to seamlessly imbricate them into the others. This is accomplished in three key ways: through reembodiment, turning bodies into digitized images; through de- and re-territorialization, where sexual mores are disseminated globally; and through incorporating sexualities into the power systems of technics, opening up avenues for rebellion and resistance as well as for violence and danger. Each technosexual encounter and event is embedded in a particular politics of embodiment and location, shot through with multiple crosscurrents of power. Thinking about power in relation to technosex offers the potential for advancing human rights and broadening the scope of sexual tolerance, but it also evinces the potential for brutality and repression. I argue for an “ethics of embodied technesis,” in which all these possibilities are acknowledged, and where progressive possibilities can be mobilized by recognizing the material dimensions of virtual sexuality and linking technosex with an ethics of care. I introduce the concept of embodied vulnerability as the lynchpin of technosexual ethics. In this chapter I develop an ethical framework that calls attention to the social, geopolitical, and material locations of bodies that render some of them more open to harm than others, moving us toward the interlinked goals of sexual dignity, safety, and justice.
The Fall Guy (I)

This case discusses the interaction of tamoxifen and metoclopramide. Tamoxifen is a cytochrome P450 2D6 prodrug and metoclopramide is a 2D6 inhibitor.
Utilizing the Cold Sintering Process for Flexible–Printable Electroceramic Device Fabrication

Conventional thermal sintering of ceramics is generally accomplished at high temperatures in kilns or furnaces. We have recently developed a procedure where the sintering of a ceramic can take place at temperatures below 200°C, using aqueous solutions as transient solvents to control dissolution and precipitation and enable densification (i.e., sintering). We have named this approach as the “Cold Sintering Process” because of the drastic reduction in sintering temperature and time relative to the conventional thermal process. In this study, we fabricate basic monolithic capacitor array structures using a ceramic paste that is printed on nickel foils and polymer sheets, with silver electrodes. The sintered capacitors, using a dielectric Lithium Molybdenum Oxide ceramic, were then cold sintered and tested for capacitance, loss, and microstructural development. Simple structures demonstrate that this approach could provide a cost-effective strategy to print and densify different materials such as ceramics, polymers, and metals on the same substrate to obtain functional circuitry.
Statins Use Improves the Clinical Outcomes of Salvage Therapy in Relapsed/Refractory CLL

Abstract 3931 Introduction - Statins are a class of drugs used to lower cholesterol levels by inhibiting the enzyme HMG-CoA reductase. In addition, statins possess anti-inflammatory, immunomodulatory, antioxidant, and cell growth inhibitory properties. In B- CLL cells, statins induce in-vitro apoptosis (Daphne Chapman-Shimshon et-al), suggesting that statins might possess properties. We noticed a high prevalence of dyslipidemia in patients with chronic lymphocytic leukemia (CLL). However the impact of dyslipidemia and its modulation by statins on clinical outcomes of patients with CLL remains unclear. Therefore, we conducted a retrospective analysis to assess the effect of statins in patients with CLL who received salvage (fludarabine, cyclophosphamide and rituximab) FCR chemotherapy. Methods - We analyzed the clinical outcome of relapsed/refractory patients with CLL (n=284) who underwent FCR salvage therapy at our institution between 1999 and 2012. Patients who were uninterruptedly treated with statins at least one month prior to and during salvage therapy (n=35) were assigned to the statins arm, whereas the other arm consisted of 249 patients who were not treated with statins. The Cox proportional hazards regression model was used to assess the association between patient characteristics and progression-free survival (PFS) and overall survival (OS). Actual survival and PFS were estimated using the method of Kaplan-Meier, and OS and PFS were compared among two groups of patients using log-rank test. Results - All pretreatment characteristics of the patients with concurrent use of statins were similar to those who were not treated with statins except for their age. Patients in the statins arm were older: 21 patients (60%) were older than 65 compared to 74 patients of 249 (30%) in the other group (p The median OS and PFS of all 284 patients were 3.9 years (95% CI: 3.4–4.5) and 1.74 years (95% CI: 1.6–2.3), respectively. PFS was significantly longer in patients treated with statins. Fifteen of the 35 statin-treated patients (43%) as opposed to only 36 of 249 (14%) in the non-statins group experience no disease progression. Concurrent use of statins significantly prolonged PFS. The median PFS for statin-treated v/s. untreated was 4.6 and 1.7 years, respectively (p With the median follow-up of 5 years, the median overall survival was significantly longer in patients treated with statins, with 17 of 35 (49%) patients of the statins group and 59 (24%) of 249 in patients who were not treated with statins alive at the end of study. Concurrent use of statins significantly prolonged OS with an estimated median OS for the two groups of 6.9 years and 3.9 years, respectively (p Conclusions - In conclusion, concurrent use of statins significantly improved OS, PFS in relapsed/refractory CLL patients treated with salvage FCR therapy. Further studies to determine the role of statins and mechanism of action in patients with CLL are warranted. Disclosures: No relevant conflicts of interest to declare.
Resources and Economic Growth

Editor’s IntroductionOriginally published in Volume 22, Number 2, Fall 1978, pages 5-11. Robert Solow (born 1924) is one of the most honored economists of all time. In 1961 he received the John Bates Clark medal given by the American Economic Association for significant contributions to the field by an American economist under the age of forty. Several Clark medal recipients have gone on to win the Nobel Memorial Prize in Economic Sciences, including Professor Solow in 1987 for his work in economic growth. His work was again honored in 2014 when he was awarded the Presidential Medal of Freedom, the highest civilian award presented by the United States. The Solow Growth Model, originally developed in the 1950s, is one of the most widely applied theories in modern economics. In this paper, Professor Solow examines how future economic growth and development is constrained if the natural resource base narrows over time. Professor Solow then applies a variant of his eponymous growth model to analyze the relati...
Building an In-house Leadership and Management Development Program

At a large public university in the U.S., managers within the Division of Information Technology (IT) were often promoted to managerial positions due to their excellence as individual contributors. Many of them, however, have not received any management education or training and are not prepared to take on supervisor roles. To support these managers to perform effectively and efficiently in their positions, an in-house leadership and management training program was established within the Division of IT. This in-house training program aims to meet the organization's leadership and management needs by identifying and preparing capable individuals through planned professional development. In this presentation, the presenter will introduce the organizational benefits of providing a leadership and management training program as well as factors that influence the decision of establishing an in-house training program versus using external vendors. Major program design processes used to create the in-house leadership and management training program, including determining the program purpose, conducting needs assessment, creating program goals and objectives, and establishing curriculum will be discussed. One training module will be demonstrated to show the various learning activities used in the hybrid training approach, which includes both online and face-to-face delivery. Feedback from a pilot study using one unit within the Division of IT will be shared. The presenter will also discuss plans for improvement and approaches for scaling-up the program to the whole Division of IT.
Psychopharmacology Utilization Among Children with Anxiety and Obsessive–Compulsive and Related Disorders Following Hurricane Katrina

This study aimed to examine the impact of Hurricane Katrina exposure on medication utilization among children with pre-existing anxiety and obsessive-compulsive and related disorders (OCRDs). Medicaid claims data from 2004 to 2006 were analyzed. Children with pre-existing anxiety/OCRDs were compared as a function of those living in a Louisiana disaster area, Louisiana non-disaster area, or Texas in terms of filled prescriptions and average days medication supply. This was further examined as a function of disorder/medication type. Prescriptions filled and average days medication supply were lower for those who resided in the disaster area of Louisiana relative to non-disaster zones in Texas (but not Louisiana). Children with OCD who lived in a disaster zone in Louisiana had 16.6 fewer days supply of antidepressants relative to youth in Texas. Similarly, children with PTSD who lived in a disaster zone in Louisiana had approximately 7 fewer days supply of stimulant medication relative to those who lived in Texas. Medication utilization was reduced for those youth directly exposed to Katrina relative to children in Texas, suggesting potential service disruption. Children with OCD and PTSD may be more likely to experience treatment disruption. Following disasters, particular attention should be given to ensuring continued treatment access for youth with pre-existing anxiety and OCRDs (as well as other conditions).
Abandoned not: media sociology as a networked transfield

The relationship between the disciplines of communication and sociology has been primarily described as being abandoned by sociologists. This article historicizes the alleged sociological abandonme...
Low concentrations of valproic acid increase invasiveness in non-metastatic osteosarcoma cell line SaOS2

3760 Introduction: Osteosarcoma is the most common bone cancer and the sixth most common cancer among children. Valproic acid is an anti-convulsant with HDAC inhibitory properties used in osteosarcoma treatment. A recent report indicates that valproic acid upregulates Notch signaling in carcinoid cells. Our recent studies indicate that Notch-mediated Hes1 expression induces invasion and metastasis in osteosarcoma. If valproic acid can induce Notch signaling in non-metastatic osteosarcoma, treatment of osteosarcoma patients with valproic acid might increase the invasiveness of their disease, countering the anti-tumor effects. Methods: This study was conducted using two osteosarcoma cell lines, SaOS2 and OS 187. SaOS2 is non-metastatic and has no endogenous Notch signaling. OS 187 is metastatic and has endogenous Notch signaling. Cells were treated with valproic acid at 0.3, 0.6, 1, 2, and 4 mM for 48 hours (Note: 0.3 mM = 50 µg/mL; therapeutic levels range from 50-100 µg/mL). Matrigel invasion was assayed in triplicate at 48 hours. RNA was isolated from cells treated with valproic acid for 48 hours. RT-PCR was used to assess expression of the Notch pathway genes DLL1, Notch1, Notch2 and Hes1. Results: After 48 hours of treatment, the cell morphology changed from round to spindle-shaped. At this time, OS 187 showed 79% cell loss at 1mM valproic acid (p value = 0.000025) and SaOS2 cell loss was 45% at 1 mM (p value = .088065). Significant cell loss in SaOS2 at 48 hours only occurred at 4mM valproic acid exposure (p value = .015512). In OS 187, PCR for Notch pathway expression showed no change of Notch 1, Notch 2, and Hes1 and a slight decrease in DLL1 with valproate exposure. In SaOS2, expression of Hes1 and DLL1 directly correlated with valproic acid concentration. Notch 1 induction was seen at 0.3 mM and remained expressed at a steady level. Notch 2 induction was not observed. Matrigel staining showed a 250-fold increase in invasion at 0.3 mM in SaOS2 (p value = .024938). After 0.3 mM, invasion decreased in a dose-dependent manner to non-invasiveness at 4 mM. Discussion: Valproic acid increases Notch-mediated invasion in non-metastatic osteosarcoma at therapeutic doses. The probable mechanism for this increased invasion is upregulation of the Notch pathway due to the HDAC inhibiting activity of valproic acid, seen by DLL1, Notch1, and Hes1 induction in SaOS2 with valproic acid. These data suggest caution should be used when treating non-metastatic osteosarcoma patients with valproic acid.
LEADING PRINCIPAL MINORS AND SEMIDEFINITENESS

Semidefinite matrices often arise in economic models, usually as Hessian matrices of convex or concave functions. Anytime the matrix can be semidefinite, rather than definite, the task of characterizing it is burdensome because extant results require that all principal minors be signed. A theorem is presented that shows it is sufficient to sign only selected principal minors when the matrix has a definite submatrix. This theorem is particularly useful in duality applications. The theorem also provides relatively easy proof of the standard relationship between semidefiniteness and principal minors. (JEL C02)
Probing Gating Mechanisms of Sodium Channels Using Pore Blockers

Several classes of small molecules and peptides bind at the central pore of voltage-gated sodium channels either from the extracellular or intracellular side of the membrane and block ion conduction through the pore. Biophysical studies that shed light on the chemical nature, accessibility, and kinetics of binding of these naturally occurring and synthetic compounds reveal a wealth of information about how these channels gate. Here, we discuss insights into the structural underpinnings of gating of the channel pore and its coupling to the voltage sensors obtained from pore blockers including site 1 neurotoxins and local anesthetics.
Frequency-sum beamforming for passive cavitation imaging

Beamforming includes a variety of spatial filtering techniques that may be used for determining sound source locations from near-field sensor array recordings. For this scenario, beamforming resolution depends on the acoustic frequency, array geometry, and target location. Random scattering in the medium between the source and the array may degrade beamforming resolution with higher frequencies being more susceptible to degradation. The performance of frequency-sum (FS) beamforming for reducing such sensitivity to mild scattering while increasing resolution is reported here. FS beamforming was used with a data-dependent [minimum variance (MV)] or data-independent (delay-and-sum, DAS) weight vector to produce higher frequency information from lower frequency signal components via a quadratic product of complex signal amplitudes. The current findings and comparisons are based on simulations and passive cavitation imaging experiments using 3 MHz and 6 MHz emissions recorded by a 128-element linear array. FS beamforming results are compared to conventional DAS and MV beamforming using four metrics: point spread function (PSF) size, axial and lateral contrast, and computation time. FS beamforming produces a smaller PSF than conventional DAS beamforming with less computation time than MV beamforming in free space and mild scattering environments. However, it may fail when multiple unknown sound sources are present.
Clinical Pharmacology of Brain Tumor Chemotherapy

Abstract Chemotherapy is a common adjunctive treatment for most patients with malignant brain tumors and for selected patients with lower-grade neoplasms. In general, the most effective chemotherapeutic drugs are alkylating agents, such as the nitrosoureas, procarbazine, temozolomide, cisplatin, carboplatin, and cyclophosphamide. Other pharmacological agents that have been applied to brain tumors include methotrexate, vincristine, etoposide, irinotecan, and hydroxyurea. Promising treatment strategies that may be combined with chemotherapeutics include targeted therapies, personalized genomic or epigenomic therapeutics, or the application of electromagnetic tumor treatment fields. This Chapter reviews the pharmacology and clinical application of chemotherapy and complimentary supportive agents for brain tumor patients.
Recombinant human erythropoietin therapy for anemic cancer patients receiving cisplatin chemotherapy.

PURPOSE To assess whether the administration of recombinant human erythropoietin (r-HuEPO) would increase the hematocrit, reduce the requirement for transfusion, and improve the quality of life in anemic cancer patients receiving myelosuppressive, cisplatin-based chemotherapy. PATIENTS AND METHODS One hundred thirty-two anemic cancer patients receiving cyclic, cisplatin-containing, myelosuppressive chemotherapy were evaluated. Patients received either r-HuEPO (150 U/kg) or placebo, subcutaneously, three times a week for 3 months. Responses were assessed by measuring changes in hemoglobin/hematocrit, transfusion requirement, and quality of life. RESULTS The mean hematocrit increased by 6.0 percentage points in the r-HuEPO group versus 1.3 in the placebo group. A decrease in transfusion requirement did not reach significance over all 3 months, but there was a significant reduction in the percentage of patients transfused in the second and third months (27% r-HuEPO vs. 56% placebo) and a trend toward reduction in the mean total number of units transfused (1.20 units r-HuEPO vs. 2.02 units placebo), suggesting a lag of 1 month before r-HuEPO can affect the transfusion requirement. Pretreatment serum erythropoietin levels were lower in responders than in nonresponders (73.5 IU/L and 86.3 IU/L means, respectively). However, the magnitude of this difference was not helpful in defining which patients were likely to respond. There was a significant improvement in overall quality of life between the two treatment arms in favor of the r-HuEPO-treated group. There were no significant adverse effects associated with r-HuEPO. CONCLUSIONS r-HuEPO is safe and can cause a significant improvement in the hematocrit and quality of life of anemic cancer patients receiving myelosuppressive, cisplatin-based chemotherapy. After 1 month of r-HuEPO, there is also a reduction in transfusion requirement.
DEFEAT - Heart Failure: a guide to management of geriatric heart failure by generalist physicians.

Heart failure is a geriatric syndrome as most heart failure patients are older adults. Heart failure is also a cardiac syndrome with complex and rapidly evolving pathogenesis and treatment. However, heart failure is ultimately a syndrome, as most heart failure patients are managed by generalist physicians and it is also a leading cause of hospitalization among older adults. Further, unlike other cardiovascular disorders, heart failure is a clinical diagnosis that can be made at bedside and the established evidence-based therapy for heart failure can be easily implemented by generalist physicians. The diagnosis and management of heart failure in the elderly can be complicated by multiple co-morbidities and polypharmacy.1 The management of heart failure in a 75-year-old elderly woman with normal left ventricular ejection fraction may be complicated by lack of evidence to guide therapy, comorbidities such as hypertension, atrial fibrillation, diabetes mellitus, osteoarthritis, chronic kidney disease, and depression, and polypharmacy related to these conditions. The management of heart failure in the elderly is further made difficult by atypical presentation of heart failure in older adults.2 Heterogeneity is another name of aging, and geriatric heart failure is no exception. Geriatric heart failure patients may present with a wide range of phenotypic heterogeneity, as can be seen from the cases presented.
A functional method for generating individualized spine models from motion-capture data

A representative model is necessary for the analysis of spine kinematics and dynamics during motion. Existing models, based on stationary imaging or cadaveric data, may not be accurate through the full range of spinal motion or for clinical populations. In this paper, we propose a functional method for estimating subject-specific spinal joint centers, generating a one-joint or two-joint kinematic model of the spine. These models are driven by the motion of the thorax and pelvis as observed by eight surface landmarks. We apply this method to experimental data from ten subjects performing flexion/extension and sit-to-stand motions. The recovered functional models are assessed against an allometric model though the analysis of marker residuals. We found that the functional models provide lower residuals than the allometric methods. Between the functional models, the two-joint model provided lower residuals with less sensitivity to the training action, while the one-joint model should be trained on the motion of interest.
Augmenting Compositional Models for Knowledge Base Completion Using Gradient Representations.

Neural models of Knowledge Base data have typically employed compositional representations of graph objects: entity and relation embeddings are systematically combined to evaluate the truth of a candidate Knowedge Base entry. Using a model inspired by Harmonic Grammar, we propose to tokenize triplet embeddings by subjecting them to a process of optimization with respect to learned well-formedness conditions on Knowledge Base triplets. The resulting model, known as Gradient Graphs, leads to sizable improvements when implemented as a companion to compositional models. Also, we show that the "supracompositional" triplet token embeddings it produces have interpretable properties that prove helpful in performing inference on the resulting triplet representations.
A history of meta‐regression: Technical, conceptual, and practical developments between 1974 and 2018

At the beginning of the development of meta-analysis, understanding the role of moderators was given the highest priority, with meta-regression provided as a method for achieving this goal. Yet in current practice, meta-regression is not as commonly used as anticipated. This paper seeks to understand this mismatch by reviewing the history of meta-regression methods over the past 40 years. We divide this time span into four periods and examine three types of methodological developments within each period: technical, conceptual, and practical. Our focus is broad and includes development of methods in the fields of education, psychology, and medicine. We conclude the paper with a discussion of five consensus points, as well as open questions and areas of research for the future.
MSK30: a validated tool to assess clinical musculoskeletal knowledge

Background Musculoskeletal (MSK) complaints comprise a large proportion of outpatient visits. However, multiple studies show that medical school curriculum often fails to adequately prepare graduates to diagnose and manage common MSK problems. Current standardised exams inadequately assess trainees’ MSK knowledge and other MSK-specific exams such as Freedman and Bernstein’s (1998) exam have limitations in implementation. We propose a new 30-question multiple choice exam for graduating medical students and primary care residents. Results highlight individual deficiencies and identify areas for curriculum improvement. Methods/Results We developed a bank of multiple choice questions based on 10 critical topics in MSK medicine. The questions were validated with subject-matter experts (SMEs) using a modified Delphi method to obtain consensus on the importance of each question. Based on the SME input, we compiled 30 questions in the assessment. Results of the large-scale pilot test (167 post-clerkship medical students) were an average score of 74 % (range 53% – 90 %, SD 7.8%). In addition, the tool contains detailed explanations and references were created for each question to allow an individual or group to review and enhance learning. Summary The proposed MSK30 exam evaluates clinically important topics and offers an assessment tool for clinical MSK knowledge of medical students and residents. It fills a gap in current curriculum and improves on previous MSK-specific assessments through better clinical relevance and consistent grading. Educators can use the results of the exam to guide curriculum development and individual education.
Identifying the Transcriptome Signatures of Calcium Channel Blockers in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes.

Rationale: Calcium channel blockers (CCBs) are an important class of drugs in managing cardiovascular diseases. Patients usually rely on these medications for the remainder of their lives after dia...
A Binder Jet Printed, Stainless Steel Preconcentrator as an In-Line Injector of Volatile Organic Compounds

A conventional approach to making miniature or microscale gas chromatography (GC) components relies on silicon as a base material and MEMS fabrication as manufacturing processes. However, these devices often fail in medium-to-high temperature applications due to a lack of robust fluidic interconnects and a high-yield bonding process. This paper explores the feasibility of using metal additive manufacturing (AM), which is also known as metal 3D printing, as an alternative platform to produce small-scale microfluidic devices that can operate at a temperature higher than that which polymers can withstand. Binder jet printing (BJP), one of the metal AM processes, was utilized to make stainless steel (SS) preconcentrators (PCs) with submillimeter internal features. PCs can increase the concentration of gaseous analytes or serve as an inline injector for GC or gas sensor applications. Normally, parts printed by BJP are highly porous and thus often infiltrated with low melting point metal. By adding to SS316 powder sintering additives such as boron nitride (BN), which reduces the liquidus line temperature, we produce near full-density SS PCs at sintering temperatures much lower than the SS melting temperature, and importantly without any measurable shape distortion. Conversely, the SS PC without BN remains porous after the sintering process and unsuitable for fluidic applications. Since the SS parts, unlike Si, are compatible with machining, they can be modified to work with commercial compression fitting. The PC structures as well as the connection with the fitting are leak-free with relatively high operating pressures. A flexible membrane heater along with a resistance-temperature detector is integrated with the SS PCs for thermal desorption. The proof-of-concept experiment demonstrates that the SS PC can preconcentrate and inject 0.6% headspace toluene to enhance the detector's response.
Stress-Associated Neurobiological Pathway Linking Socioeconomic Disparities to Cardiovascular Disease.

Abstract Background Lower socioeconomic status (SES) associates with a higher risk of major adverse cardiac events (MACE) via mechanisms that are not well understood. Objectives Because psychosocial stress is more prevalent among those with low SES, this study tested the hypothesis that stress-associated neurobiological pathways involving up-regulated inflammation in part mediate the link between lower SES and MACE. Methods A total of 509 individuals, median age 55 years (interquartile range: 45 to 66 years), underwent clinically indicated whole-body 18 F-fluorodeoxyglucose positron emission tomography/computed tomography imaging and met pre-defined inclusion criteria, including absence of known cardiovascular disease or active cancer. Baseline hematopoietic tissue activity, arterial inflammation, and in a subset of 289, resting amygdalar metabolism (a measure of stress-associated neural activity) were quantified using validated 18 F-fluorodeoxyglucose positron emission tomography/computed tomography methods. SES was captured by neighborhood SES factors (e.g., median household income and crime). MACE within 5 years of imaging was adjudicated. Results Over a median 4.0 years, 40 individuals experienced MACE. Baseline income inversely associated with amygdalar activity (standardized β: −0.157 [95% confidence interval (CI): −0.266 to −0.041]; p = 0.007) and arterial inflammation (β: −0.10 [95% CI: −0.18 to −0.14]; p = 0.022). Further, income associated with subsequent MACE (standardized hazard ratio: 0.67 [95% CI: 0.47 to 0.96]; p = 0.029) after multivariable adjustments. Mediation analysis demonstrated that the path of: ↓ neighborhood income to ↑ amygdalar activity to ↑ bone marrow activity to ↑ arterial inflammation to ↑ MACE was significant (β: −0.01 [95% CI: −0.06 to −0.001]; p Conclusions Lower SES: 1) associates with higher amygdalar activity; and 2) independently predicts MACE via a serial pathway that includes higher amygdalar activity, bone marrow activity, and arterial inflammation. These findings illuminate a stress-associated neurobiological mechanism by which SES disparities may potentiate adverse health outcomes.
Invasive Intraductal Papillary Mucinous Neoplasms: CT Features of Colloid Carcinoma Versus Tubular Adenocarcinoma of the Pancreas

OBJECTIVE. The purpose of this study is to compare the CT features of colloid carcinoma and tubular adenocarcinoma of the pancreas arising in association with intraductal papillary mucinous neoplasms (IPMNs). MATERIALS AND METHODS. The preoperative CT images of 85 patients with histopathologically proven IPMNs and associated invasive adenocarcinoma located next to each other were retrospectively reviewed. Twenty-nine patients (34.1%; 19 men and 10 women; mean [± SD] age, 68.0 ± 9.5 years) had invasive colloid carcinoma, and 56 patients (65.9%; 31 men and 25 women; mean age, 70.8 ± 10.6 years) had invasive tubular adenocarcinoma. We compared the following CT features between the two groups: IPMN type, main pancreatic duct (MPD) and common bile duct diameters, diameter and characteristics of the largest cystic lesion for branch duct and mixed-type IPMNs, presence of an extracystic or extraductal solid mass next to the cystic lesion or MPD, morphologic features of the upstream MPD in relation to the cystic lesion or solid mass, and presence of a fistula to the adjacent organs. RESULTS. An MPD size of 9.5 mm or greater, a largest cystic lesion diameter of 28 mm or greater, location in the head or neck, septation, calcification, presence of a mural nodule(s) within a cystic lesion or MPD, and presence of a fistula were all more commonly associated with colloid carcinoma. In contrast, presence of an extracystic or extraductal solid mass and an abrupt change in the caliber of the dilated MPD were associated with tubular adenocarcinoma. The best CT feature for differentiating between the two groups was the morphologic features of the upstream MPD in relation to the cystic lesion or solid mass (sensitivity, 81.3%; specificity, 92.3%). CONCLUSION. Preoperative CT is helpful in differentiating two types of invasive carcinoma arising in association with IPMNs. These findings are clinically important because prognosis is better for colloid carcinoma than for tubular adenocarcinoma.