cssi/SciSciGPT-SciSciNet huggingface dataset:
Golimumab for rheumatoid arthritis.

Background Golimumab is a humanized inhibitor of Tumor necrosis factor-alpha, recently approved by the Food and Drug Administration (FDA) for the treatment of Rheumatoid arthritis (RA). Objectives The objective of this systematic review was to compare the efficacy and safety of golimumab (alone or in combination with DMARDs or biologics) to placebo (alone or in combination with DMARDs or biologics) in randomized or quasi-randomized clinical trials in adults with RA. Search methods An expert librarian searched six databases for any clinical trials of golimumab in RA, including the Cochrane Central Register of Controlled Trials (CENTRAL), OVID MEDLINE, CINAHL, EMBASE, Science Citation Index (Web of Science) and Current Controlled Trials databases. Selection criteria Studies were included if they used golimumab in adults with RA, were randomized or quasi-randomized and provided clinical outcomes. Data collection and analysis Two review authors (JS, SN) independently reviewed all titles and abstracts, selected appropriate studies for full review and reviewed the full-text articles for the final selection of included studies. For each study, they independently abstracted study characteristics, safety and efficacy data and performed risk of bias assessment. Disagreements were resolved by consensus. For continuous measures, we calculated mean differences or standardized mean differences and for categorical measures, relative risks. 95% confidence intervals were calculated. Main results Four RCTs with 1,231 patients treated with golimumab and 483 patients treated with placebo were included. Of these, 436 were treated with the FDA-approved dose of golimumab 50 mg every four weeks. Compared to patients treated with placebo+methotrexate, patients treated with the FDA-approved dose of golimumab+methotrexate were 2.6 times more likely to reach ACR50 (95% confidence interval (CI) 1.3 to 4.9; P=0.005 and NNT= 5, 95% confidence interval 2 to 20), no more likely to have any adverse event (relative risk 1.1, 95% Cl 0.9 to 1.2; P=0.44), and 0.5 times as likely to have overall withdrawals (95% Cl 0.3 to 0.8; P=0.005). Golimumab-treated patients were significantly more likely to achieve remission, low disease activity and improvement in functional ability compared to placebo (all statistically significant). No significant differences were noted between golimumab and placebo regarding serious adverse events, infections, serious infections, lung infections, tuberculosis, cancer, withdrawals due to adverse events and inefficacy and deaths. No radiographic data were reported. Authors' conclusions With an overall high grade of evidence, at the FDA-approved dose, golimumab is significantly more efficacious than placebo in treatment of patients with active RA , when used in combination with methotrexate. The short-term safety profile, based on short-term RCTs, is reasonable with no differences in total adverse events, serious infections, cancer, tuberculosis or deaths. Long-term surveillance studies are needed for safety assessment.
A Rare Human Sequence Variant Reveals Myocardin Autoinhibition

Myocardin (MYOCD) is a transcriptional co-activator that promotes cardiac or smooth muscle gene programs through its interaction with myocyte-enhancing factor (MEF2) or serum-response factor (SRF). Isoforms of MYOCD with a truncated amino terminus show increased activity when compared with those with the full-length amino terminus, but how this is achieved remains unknown. We identified a rare human sequence variation in MYOCD in a patient with congenital heart disease that resulted in a missense mutation at codon 259 (K259R). This variation created a hypomorphic cardiac isoform with impaired SRF binding and transactivation capacity but did not impair the smooth muscle isoform of MYOCD, which lacks the amino terminus. Consistent with differential effects of the amino terminus on the K259R mutation, we found that the cardiac-specific amino terminus acted in an autoinhibitory fashion to bind MYOCD via specific negatively charged residues and thereby repressed SRF-dependent MYOCD activity. This effect was exaggerated in the MYOCD-K259R mutant. The amino terminus was sufficient to impair MYOCD-dependent fibroblast conversion into smooth muscle cells as well as cardiomyocyte hypertrophy. These findings identify a novel mechanism that regulates levels of MYOCD-dependent activation of the SRF genetic program differentially in cardiac and smooth muscle.
Delivery of Optimized Inpatient Anticoagulation Therapy: Consensus Statement from the Anticoagulation Forum

This is a copy of an article published in the Annals of Pharmacotherapy © 2013 SAGE Publications
Leaves and Fruits of Davidia (Cornales) from the Paleocene of North America

Abstract Davidia, a genus that is now endemic to China, played a prominent role in Paleocene vegetation of mid-latitude North America that previously was overlooked. Davidia antiqua (Newberry) comb. nov. is now known from co-occurring leaves and fruits at eight localities in the Fort Union Group of North Dakota, Montana, and Wyoming. The leaves, for more than a century called Viburnum antiquum (Newberry) Hollick, conform to extant Davidia in the long petiole, cordate base, pinnate venation, basal secondary veins with regular branches to the margin, typically blunt, large marginal dentations with medial vein insertion, and closely spaced percurrent tertiaries. Fruits are borne singly on otherwise staminate inflorescence heads. The peduncle bears two prominent scars, well below the head, interpreted as the attachment points of large bracts. The fruit stones are ellipsoidal, composed of fibers, with six to eight single-seeded locules, each with an elongate dorsal germination valve. Vascular bundles are not a...
Echocardiographic left ventricular end-diastolic pressure volume loop estimate predicts survival in congestive heart failure.

Abstract Background The left ventricular end-diastolic pressure-volume relationship (LV-EDPVR) is a measure of LV distensibility, conveying the size the LV will assume at a given LV end-diastolic pressure (LV-EDP). Measurement of LV-EDPVR requires invasive testing with specialized equipment. Echocardiography can be used to measure LV end-diastolic volume (EDV) and to grossly estimate LV-EDP noninvasively. We therefore hypothesized that categorization of patients based on these parameters to create an estimate of the end-diastolic pressure-volume loop position (EDPVE) could predict congestive heart failure (CHF) prognosis. Methods and Results Echocardiograms from 968 CHF clinic patients were reviewed. LV-EDP was considered to be elevated if mitral filling pattern was pseudo-normal or restrictive. EDPVE was categorized into 3 groups. EDPVE was considered to have evidence of rightward shift if the LV was severely dilated (>97 mL/m 2 ). EDPVE was considered to have evidence of leftward shift if the LV was normal size ( 2 ) and there was Doppler evidence of increased LV-EDP. Patients who did not meet criteria for leftward or rightward shift were classified as "intermediate." Using the intermediate group for comparison, those with evidence of leftward shift in EDPVE had increased mortality (hazard ratio [HR] 1.77; 95% confidence interval [CI]: 1.23-2.54). Rightward shift only correlated with increased mortality in those older than age 70 years. Leftward shift remained an independent predictor of mortality even after adjusting for LV ejection fraction, atrial fibrillation, mitral regurgitation, and Doppler indices of diastolic dysfunction. Conclusion EDPVE is a strong predictor of CHF survival which is independent of LV ejection fraction and traditional Doppler indices of LV diastolic function.
Hierarchical system architecture for multi-agent multi-modal systems

A hierarchical system architecture for multi-agent multi-modal systems is proposed. The design principle for the construction of the hierarchy is based on bisimulation and therefore a higher-level system and a lower-level system are bisimilar. The layered system is designed to promote proof obligations so that the system specification at one level of granularity conforms with system specification at another level and vice versa. Our approach is illustrated on designing a system architecture for executing a mission of controlling a group of autonomous agents in the pursuit of multiple evaders.
Sex differences in estrogen-induced progesterone and estrogen receptor mRNA in the ventromedial hypothalamus of hatchling whiptail lizards

The ventromedial hypothalamus (VMH) is an important neural locus for the control of female-typical sexual behavior in vertebrates, and exogenous estrogen stimulates a strong increase in progesterone receptor (PR) in the VMH of adult females. Estrogen also regulates its own receptor (ER), though the direction of the response varies from species to species. In rodents and whiptail lizards, males either lack estrogen regulation of PR and ER mRNA in the VMH or display a greatly attenuated response. We examined hatchlings of two closely related species of whiptail lizards, one of which is parthenogenetic. Though normally all female, the parthenogens can be made to develop as gonadal males by treating with aromatase inhibitor early in development. Thus, we were able to ask whether the brain sex of these 'created male' parthenogens corresponded to their gonadal sex or their genetic sex. We injected 1- and 30-day-old animals of both species and sexes with estradiol benzoate (EB) and assayed for PR and ER mRNA using in situ hybridization. All animals given EB responded with a strong increase in PR mRNA in the VMH. However, females of the sexual species had higher EB-induced PR mRNA levels than did conspecific males; there was no sex difference between the normal parthenogens and the created males of the parthenogenetic species. EB also stimulated an increase in ER mRNA in the VMH, but the pattern of response was more complex. Normal parthenogens did not increase ER mRNA in response to EB in either age group, in contrast to the strong response of 1-day-old males and females of the sexual species and 30-day-old created males. The results indicate that hatchling whiptails show striking species and sexual differences in the regulation of sex steroid receptor mRNAs in an area of the brain important for adult sexual behavior. This variation may play a role in the development of species and sexual differences in the adult neuroendocrine phenotype.
Theoretical Quality Assessment of Myocardial Elastography with In Vivo Validation

Myocardial elastography (ME), a radio frequency (RF)-based speckle tracking technique with one-dimensional (1-D) cross correlation and novel recorrelation methods in a 2-D search was proposed to estimate and fully image 2-1) transmural deformation field and to detect abnormal cardiac function. A theoretical framework was first developed in order to evaluate the performance of 2-D myocardial elastography based on a previously developed 3-D finite-element model of the canine left ventricle. A normal (control) and an ischemic (left-circumflex, LCx) model, which more completely represented myocardial deformation than a kinematic model, were considered. A 2-D convolu-tional image formation model was first used to generate RF signals for quality assessment of ME in the normal and ischemic cases. A 3-D image formation model was further developed to investigate the effect of the out-of-plane motion on the 2-D, in-plane motion estimation. Both orthogonal, in-plane displacement components (i.e., lateral and axial) between consecutive RF frames were iteratively estimated. All the estimated incremental 2-D displacements from end-diastole (ED) to end-systole (ES) were then accumulated to acquire the cumulative 2-D displacements, which were further used to calculate the cumulative 2-D systolic finite strains. Furthermore, the cumulative systolic radial and circumferential strains, which were angle-and frame-rate independent, were obtained from the 2-D finite-strain components and imaged in full view to detect the ischemic region. We also explored the theoretical understanding of the limitations of our technique for the accurate depiction of disease and validated it in vivo against tagged magnetic resonance imaging (tMRI) in the case of a normal human myocardium in a 2-D short-axis (SA) echocardiographic view. The theoretical framework succeeded in demonstrating that the 2-D myocardial elastography technique was a reliable tool for the complete estimation and depiction of the in-plane myocardial deformation field as well as for accurate identification of pathological mechanical function using established finite-element, left-ventricular canine models. In a preliminary study, the 2-D myocardial elastography was shown capable of imaging myocardial deformation comparable to equivalent tMRI estimates in a clinical setting.
Toward parameterization of the stable boundary layer

Wangara data is used to examine the depth of the nocturnal boundary layer (NBL) and the height to which surface-linked turbulence extends. It is noted that a linearity of virtual temperature profiles has been found to extend up to a significant portion of the NBL, and then diverge where the wind shear rides over the surface-induced turbulence. A series of Richardson numbers are examined for varying degrees of turbulence and the significant cooling region is observed to have greater depth than the depth of the linear relationship layer. A three-layer parameterization of the thermodynamic structure of the NBL is developed so that a system of five equations must be solved when the wind velocity profile and the temperature at the surface are known. A correlation between the bulk Richardson number and the depth of the linear layer was found to be 0.89.
Isn’t It Time to Establish Library-Related Social Media Best Practice Guidelines?

Most key legal populations are widely embracing social media. The positive uses can help students gain notoriety and followers and perhaps even land them a job. But, it’s often the negative uses we’re more likely to hear about. The author argues that law libraries need to take a stronger lead in teaching our users how to disseminate reliable, authentic, and private information. She concludes that social media is an information practice and librarians should take charge.
Cell cycle basis for the onset and progression of c-Myc-induced, TGFα-enhanced mouse mammary gland carcinogenesis

Using single and double transgenic mouse models, we investigated how c-Myc modulates the mammary epithelial cell cycle to induce cancer and how TGFα enhanced the process. In c-myc transgenic mice, c-myc expression was high in the hyperplastic mammary epithelium and in the majority of tumor areas. However, the tumors displayed focal areas of low expression of c-myc but high rates of proliferation. In contrast to E2F1 and cyclin A2, which were induced and co-localized with c-myc expression, induction of cyclins D1 and E occurred only in these tumor foci. Overexpression of cyclin D1 also occurred in the hyperplastic epithelium of tgfα-single and tgfα/c-myc-double transgenic mice. In tgfα/c-myc tumors, cells positive for cyclins D1 and E were randomly spread, without showing a reciprocal relationship to c-myc expression. In contrast to c-myc tumors, most tgfα/c-myc tumors showed undetectable levels of retinoblastoma protein (pRB), and the loss of pRB occurred in some cases at the mRNA level. These results suggest that E2F1 and cyclin A2 may be induced by c-Myc to mediate the onset of mammary cancer, whereas overexpression of cyclins D1 and E may occur later to facilitate tumor progression. TGFα may play its synergistic role, at least in part, by inducing cyclin D1 and facilitating the loss of pRB.
Role of BK Channels in Murine Carotid Body Neural Responses in vivo

The aim of this study was to explore the role of BK channels in the hypoxic sensitivity of the in vivo murine carotid body (CB). Four strains of mice (DBA/2J, A/J, BKα1 knockout and BKα1 wild type – FVB background) were used. The mice were anesthetized, paralyzed and mechanically ventilated (PaCO2 ~ 35 mmHg, PO2 > 300 mmHg). We measured carotid sinus nerve (CSN) activity during three gas challenges (FIO2: 0.21, 0.15 and 0.10). CSN activity was analyzed with time-variant spectral analysis with frequency domain conversion (Fast Fourier Transforms). Afferent CSN activity increased with lowering FIO2 in the DBA/2J, BKKO and BKWT mice with the most robust response in 600–800 frequencies. No substantial changes were observed in the A/J mice. Although maximal neural output was similar between the BKKO and BKWT mice, the BKWT had a higher early response compared to BKKO. Thus, BK channels may play a role in the initial response of the CB to hypoxia. The contribution of BKβ subunits or the importance of frequency specific responses was unable to be determined by the current study.
New Stream-reach Development: A Comprehensive Assessment of Hydropower Energy Potential in the United States

The rapid development of multiple national geospatial datasets related to topography, hydrology, and environmental characteristics in the past decade have provided new opportunities for the refinement of hydropower resource potential from undeveloped stream-reaches. Through 2011 to 2013, the Oak Ridge National Laboratory (ORNL) was tasked by the Department of Energy (DOE) Water Power Program to evaluate the new stream-reach development (NSD) resource potential for more than 3 million US streams. A methodology was designed that contains three main components: (1) identification of stream-reaches with high energy density, (2) topographical analysis of stream-reaches to estimate inundated surface area and reservoir storage, and (3) environmental attribution to spatially join information related to the natural ecological systems, social and cultural settings, policies, management, and legal constraints to stream-reaches of energy potential. An initial report on methodology (Hadjerioua et al., 2013) was later reviewed and revised based on the comments gathered from two peer review workshops. After implementing the assessment across the entire United States, major findings were summarized in this final report. The estimated NSD capacity and generation, including both higher-energy-density (>1 MW per reach) and lower-energy-density (<1 MW per reach) stream-reaches is 84.7 GW, around the same size as the existing USmore » conventional hydropower nameplate capacity (79.5 GW; NHAAP, 2013). In terms of energy, the total undeveloped NSD generation is estimated to be 460 TWh/year, around 169% of average 2002 2011 net annual generation from existing conventional hydropower plants (272 TWh/year; EIA, 2013). Given the run-of-river assumption, NSD stream-reaches have higher capacity factors (53 71%), especially compared with conventional larger-storage peaking-operation projects that usually have capacity factors of around 30%. The highest potential is identified in the Pacific Northwest Region (32%), followed by Missouri Region (15%) and California Region (9%). In terms of states, the highest potential is found in Oregon, Washington, and Idaho, the three states in the Pacific Northwest, followed by California, Alaska, Montana, and Colorado. In addition to the resource potential, abundant environmental attributes were also organized and attributed to the identified stream-reaches to support further hydropower market analysis. The prevalence of environmental variables and proportion of capacity from stream-reaches intersecting environmental variables varied according to hydrologic region. Detailed NSD findings are organized by hydrologic regions and presented in each chapter of this report.« less
Tucson: A History of the Old Pueblo from the 1854 Gadsden Purchase. By David Devine.

Tucson: A History of the Old Pueblo from the 1854 Gadsden Purchase . By David Devine. (Jefferson, NC: McFarland, 2015. vii + 298 pp. Illustrations, maps, charts, notes, bibliography, index. $39.95, paper.) As the old cliche admonishes, the devil is in the details. David Devine has taken that saying to heart as he meticulously details the history of Tucson, Arizona, since it became part of the United States in the mid-nineteenth century. Devine argues that boosters’ attempts to promote the city at the expense of the Old Pueblo’s “identity, history, traditions, and cultures” were misguided, but city officials succeeded in making Tucson the second-largest city in Arizona despite their ineptitude (p. 2). Most importantly, Devine contends that the ultimate result of this success is a city riven by inequality. The book, while interesting and well written, is at times …
Analysis and Suggestions of Land Use Patterns along Rail Transit Corridor—A Case Study of Beijing Metro Line 1

One of the urgent tasks of urban development is promoting dynamic integrative plan between rail transit and land use.The status of land use around Beijing Metro Line 1 stations are analyzed using GIS package.With passenger volume analysis of Beijing Metro Line 1,some existing problems are addressed.The interactive relationships between passenger volume land use are analyzed from the aspects of the potential impact on surrounding land use from rail transit construction,and the relationship between the land use plan and passenger volume of rail transit.Finally,some suggestions are proposed for land use along rail transit corridor.
Abstract A145: Radiation therapy induces tumor-promoting immune suppression in the microenvironment of pancreatic carcinoma

Radiation therapy (RT) has shown marginal efficacy in patients with pancreatic ductal adenocarcinoma (PDA). Two of the past three randomized controlled trials investigating the efficacy of RT for patients with locally advanced unresectable PDA have shown a statistically significant worse survival by 40% or more for patients receiving RT. We postulated that RT reprograms inflammatory cells within the tumor microenvironment to an immune suppressive phenotype limiting the efficacy of RT in invasive PDA and accelerating disease progression in surrounding pre-invasive foci. We found that RT markedly accelerates the progression of pre-invasive PDA in a dose-dependent manner and reduces animal survival by more than 6 months. In both invasive and pre-invasive PDA, RT reprograms immunogenic macrophages towards an immune-suppressive M2 phenotype resulting in CD8 T cell scarcity and Th2 and Treg differentiation of CD4 T cells. Moreover, adoptive transfer of T cells harvested from RT-treated tumors accelerates tumor growth in recipient hosts. We show that M-CSF blockade concurrent with RT prevents immune-suppressive macrophage and T cell reprogramming and markedly enhances the efficacy of RT in PDA. These data suggest that targeting macrophage reprogramming can unleash the utility of RT for PDA. Citation Format: Lena Tomkotter, Gregor Werba, Susanna Nguy, Sara Alothman, Dalia Alqunaibit, Shaun Tiwari, Nancy Ngoc Giao Ly, Donnele Daley, Atsuo Ochi, Rocky Barilla, Alejandro Torres-Hernandez, Ilenia Pellicciotta, Kevin Du, George Miller. Radiation therapy induces tumor-promoting immune suppression in the microenvironment of pancreatic carcinoma. [abstract]. In: Proceedings of the CRI-CIMT-EATI-AACR Inaugural International Cancer Immunotherapy Conference: Translating Science into Survival; September 16-19, 2015; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(1 Suppl):Abstract nr A145.
Optically Controlled Fast Reconfigurable Microwave Photonic Dual-Band Filter Based on Nonlinear Polarization Rotation

A high-speed optically controlled microwave photonic (MWP) reconfigurable dual-band filter is presented, which is achieved using a Lyot loop filter for spectrum slicing and ultrafast nonlinear polarization rotation (NPR) effect in a semiconductor optical amplifier for high-speed tuning. Through the control of optical pump power, the MWP filter is switchable between four different operation states-all-block state, dual-band state, and single-band state with two different passband frequencies. The use of NPR greatly increases the tuning speed of the MWP filter to gigahertz range, making it capable for high-speed tuning in dynamic multiband applications. The four operation states and high-speed adjustment significantly improve operation flexibility of the filter. Furthermore, good passband quality is also obtained that the sidelobe suppressions of both passbands are over 40 dB with clean and sharp passband profiles, providing good filter selectivity.
A 14-GHz, 22-dBm Series Doherty Power Amplifier in 45-nm CMOS SOI

This paper presents a new series Doherty power amplifier (SDPA) with a single-ended output that eliminates transformers in the output matching network. The series power combining architecture offers higher output power in scaled CMOS compared to conventional Doherty PAs and is amenable to integration at microwave and millimeter wave bands. The SDPA is implemented in 45-nm CMOS SOI and achieves a peak output power of 22-dBm and PAE of 24% and 20% at peak and 6 dB back-off powers, respectively.
PRUNE: A preserving run environment for reproducible scientific computing

Computing as a whole suffers from a crisis of reproducibility. Programs executed in one context are astonishingly hard to reproduce in another context, resulting in wasted effort by people and general distrust of results produced by computer. The root of the problem lies in the fact that every program has implicit dependencies on data and execution environment which are rarely understood by the end user. To address this problem, we present PRUNE, the Preserving Run Environment. In PRUNE, every task to be executed is wrapped in a functional interface and coupled with a strictly defined environment. The task is then executed by PRUNE rather than the user to ensure reproducibility. As a scientific workflow evolves in PRUNE, a growing but immutable tree of derived data is created. The provenance of every item in the system can be precisely described, facilitating sharing and modification between collaborating researchers, along with efficient management of limited storage space. We present the user interface and the initial prototype of PRUNE, and demonstrate its application in matching records and comparing surnames in U.S. Censuses.
Trouble on the far right. Contemporary right-wing strategies and practices in Europe

Motivated by an increased attention paid to the recent visibility and success of European far-right, the contributions included in the Trouble on the Far-Right aim to fill a void identified in past...
A Text Messaging Intervention (Txt4HappyKids) to Promote Fruit and Vegetable Intake Among Families With Young Children: Pilot Study

Background: Increasing fruit and vegetable intake among low-income populations, especially children, is a priority for United States federal food assistance programs. With over 49 million federal food assistance program recipients, cost-effective and efficient methods are needed to effectively deliver nutrition education to such a large population. Objective: The objective of our study was to examine the preliminary efficacy and acceptability of a text messaging intervention, Txt4HappyKids, to promote fruit and vegetable intake among families with young children. Methods: The intervention was evaluated using a pre-post study design. Parents (N=72) in Alaska were recruited from venues that serve a predominantly low-income population to participate in an 11-week intervention based on social cognitive theory. Parents received two texts per week promoting child fruit and vegetable intake. Behaviors, self-efficacy, and attitudes related to fruit and vegetable intake were measured at baseline and postintervention. Perceived changes in behaviors and open-ended feedback were also collected postintervention. Results: Of all participants, 67.3% (72/107) completed the intervention. We found no changes in behavior (P=.26), self-efficacy (P=.43), or attitudes (P=.35) related to fruit and vegetable intake from pre- to postintervention. Completers reported that since their participation in Txt4HappyKids, 92% (66/72) served more fruits and vegetables to their child because they thought fruits and vegetables were beneficial, 86% (62/72) tried to follow a healthier diet, 85% (61/72) tried different ways of preparing fruits and vegetables, and 81% (58/72) were more aware of the foods their child consumes. Additionally, 79% (57/72) of completers thought that Txt4HappyKids was credible, 71% (51/72) found texts useful, and 82% (59/72) would recommend it to a friend. Conclusions: A text messaging intervention was not sufficient to increase fruit and vegetable intake among families with young children. However, parents felt positively impacted by Txt4HappyKids and were receptive to nutrition information, despite the absence of face-to-face contact. High satisfaction among completers indicates that text messaging may be an acceptable complement to budget-constrained nutrition programs. These findings are an important first step in developing larger multi-level interventions utilizing mobile technology; however, a more rigorous evaluation of the Txt4HappyKids intervention is warranted.
Jackknife and Bootstrap

This chapter deals with statistical methods that, in some way, avoid mathematical difficulties that one would be facing using traditional approaches. The traditional approach of mathematical statistics is based on analytic expressions, or formulas, so avoiding these might seem itself a formidable task, especially in view of the chapters that so far have been covered. It should be pointed out that we have no objection of using mathematical formulas—in fact, some of these are pleasant to use. However, in many cases, such formulas are simply not available or too complicated to use.
Reoperation for Prosthetic Mitral Valve Endocarditis

Prosthetic valve endocarditis is a serious complication of mitral valve replacement with a reported incidence of 0.5% per patient-year (Current therapy in thoracic and cardiovascular surgery, 2004). Similar rates of infection are found with both biological and mechanical prostheses. Symptoms of infection are often variable with the diagnosis of prosthetic mitral valve endocarditis most often based upon blood culture data and echocardiographic evidence of vegetation or valve dysfunction. Despite advances in management of the condition, mortality associated with prosthetic mitral valve endocarditis remains high. As such, an aggressive surgical approach is required. This chapter will focus on the surgical management of the condition.
Microtexture in additively manufactured Ti-6Al-4V fabricated using directed energy deposition

Abstract The additive manufacturing (AM) of α + β titanium alloys using electron beam (EB) and laser directed energy deposition (DED) processes has been widely characterized in both the as-deposited and post processed conditions. Fine basket weave α lath structures are commonly observed in both the as-deposited and post processed hot isostatically pressed (HIP) conditions for both laser and EB DED processes, but more in-depth knowledge of the crystallographic texturing and variant selection of the α laths growing from the primary β-grains across the height of EB DED Ti-6Al-4V structures is not well established. At locations near the substrate in both conditions, microtexturing is weak, but EB DED builds exhibit a strong microtexture and pronounced variant selection with increasing build height. On the other hand, the laser DED builds displayed weak texturing and no prominent variant selection across all heights. With the addition of HIP post processing, there was no change in microtexturing of the coarsened α laths for both the laser and EB structures, and the same variant selection observed in the as-deposited EB DED builds was present.
Gases Generated During the Low-Temperature Oxidation and Pyrolysis of Coal and the Effects on Methane-Air Flammable Limits

Abstract Gas production during the low-temperature oxidation and pyrolysis of coal and the effects on methane-air flammable limits are examined. An oil bath temperature-programmed system was used to study gas generation. The production rate of the most important gas indicating pyrolysis, carbon monoxide, was calculated using a mathematical model. Gas production rates as a function of temperature for different ranks of coal were obtained and analyzed, and gas generation mechanisms are proposed and discussed. Experimental results showed that the types and sequence of gases released during low-temperature oxidation are basically the same for different ranks of coal. Microstructures in the coal are responsible for the amount of gases released during oxidation. The effects of the gases released on methane-air flammable limits were experimentally studied using gas-propagation cylindrical equipment. Analysis of the parameters of flammability, namely, the upper flammable limit lower flammable limit and explosion risk value revealed that the release of C 2 H 6 , C 2 H 4 , CO, H 2 , and their mixture decrease the flammability of a CH 4 –air mixture but increase the risk of explosion.
Mercury accumulation, speciation, and temporal trends in Atlantic Stingrays (Hypanus sabinus)

Mercury (Hg) deposited into aquatic sediments can be converted into the more toxic methylmercury (MeHg) by microbial activity. Atlantic stingrays (Hypanus sabinus) are an estuarine and nearshore species found in coastal regions of the western North Atlantic, occurring in multiple habitat types, and feeding mainly on benthic invertebrates. Mercury dynamics and speciation in stingrays have not been well examined. This study quantified total Hg and Hg species (Hg (II) and MeHg) in Atlantic stingrays sampled from Florida’s Indian River Lagoon (IRL) from 2012 to 2013. Tissues (muscle and liver) collected from 29 stingrays were lyophilized and homogenized before being analyzed using a direct mercury analyzer. Concentrations of total Hg in muscle were positively related to stingray disk width, but concentrations in liver were not. Mean (±SD) total Hg in muscle (0.56 ± 0.30 mg/kg dw) was significantly higher than mean total Hg in liver (0.23 ± 0.19 mg/kg dw). Within liver tissue, percent MeHg (of total Hg) ranged from 31 to 99%. The ratio between total Hg in liver and total Hg in muscle was <1 for nearly all individuals, suggesting a lack of active hepatic demethylation and sequestration mechanisms. Concentrations of Hg in IRL Atlantic stingrays fall below concentrations known to result in direct toxicity to fishes; however, effects thresholds are not well understood for elasmobranchs. Comparisons of Hg concentrations in IRL Atlantic stingrays sampled previously (37 individuals in 1994) indicate that total Hg concentrations in muscle of Atlantic stingrays have decreased over the past two decades, suggesting a reduction in the bioavailable Hg in the IRL ecosystem.
"What you say, I buy!": Information Diagnosticity and the Impact of Electronic Word-of-Mouth (eWOM) Consumer Reviews on Purchase Intention

With the increase of online sales, the understanding of online purchase intention formation is of direct economic interest in a global economy. Identifying and predicting ecommerce diagnostic criteria gives further insight into consumer behavior. Information Diagnosticity accounts for the utilization of criteria differentiation within the decision formation process [1, 4]. In a cross-sectional study of 218 English-speaking Amazon.com customers, recruited on Amazon's MTurk, who were exposed to five online consumer reviews survey stimuli, this research explored the impact of information diagnosticity on consumer purchase intentions. The findings of this study reveal that constructs representing trust and valence in the new model improve fit in ecommerce applications and offer increased power in predicting factors influencing purchase intention behaviors, while taking into account exiting ecommerce use acceptance. The results from 218 survey participants examine the research model identifying diagnostic aspects in ecommerce influencing purchase intentions.
Identifying Common Pool Resources in the Archaeological Record: A Case Study of Water Commons from the North American Southwest

Common Pool Resources (CPRs) were defined by Elinor Ostrom as natural or human-made resources of a size or with inherent characteristics that makes it costly, but not impossible to exclude from use by potential beneficiaries. Researchers who study CPRs largely focus on extant, directly observable systems and not archaeological contexts. In order to expand the pool of case studies of CPRs, I present an archaeological case study of investigating water CPRs by Ancestral Pueblo communities in the Jemez Mountains of New Mexico in the North American Southwest. Geoarchaeological and chronological analyses of 15 water reservoir features at 9 Ancestral Pueblo village sites were undertaken. Independent chronologies of water infrastructure serve as proxies for the emergence of social institutions to govern public access and distribution of domestic water. By testing reservoirs across the Jemez and Pajarito Plateaus, two adjoining regions settled by dryland maize agriculturalists between AD 1100 and 1700, I show how long-term archaeological records can be used to examine concepts central to the study of the commons and sustainability, such as institutional governance and inherent tradeoffs at the nexus of mitigating food-water insecurities.
Late mortality after bone marrow transplant for chronic myelogenous leukemia in the context of prior tyrosine kinase inhibitor exposure: A Blood or Marrow Transplant Survivor Study (BMTSS) report

Background Late mortality was investigated in patients with chronic myelogenous leukemia (CML) who underwent blood or bone marrow transplant (BMT) with or without prior tyrosine kinase inhibitor (TKI) therapy. Methods By using data from the Blood or Marrow Transplant Survivor Study, the authors examined late mortality in 447 patients with CML who underwent BMT between 1974 and 2010, conditional on surviving ≥2 years post-BMT. For vital status information, the medical records, the National Death Index, and the Accurint database were used. Standardized mortality ratios (SMRs) were calculated using general population age-specific, sex-specific, and calendar-specific mortality rates. Kaplan-Meier techniques and Cox regression were used for all-cause mortality analyses. Cumulative incidence and proportional subdistribution hazards models for competing risks were used for cause-specific mortality analyses. Results The 10-year overall survival rate was 65.7% and 73% for those who underwent transplant with and without pre-BMT exposure to TKI therapy, respectively. Patients who underwent transplant with and without pre-BMT TKI experienced SMRs of 6.4 and 6.4, respectively (P = .8); and the SMRs were 11.6 and 8.1, respectively, for those with high-risk disease (P = .2). Independent predictors of non-CML-related mortality included chronic graft-versus-host disease (hazard ratio [HR], 2.8; 95% CI, 1.8-4.4) and busulfan/cyclophosphamide conditioning (HR, 0.5; 95% CI, 0.3-0.9; reference, total body irradiation/cyclophosphamide conditioning). The 20-year cumulative incidence of CML-related and non-CML-related mortality was 6% and 36%, respectively, for the entire cohort. Both CML-related mortality (HR, 1.0; 95% CI, 0.1-12.6) and non-CML-related mortality (HR, 1.3; 95% CI, 0.6-3.1) were comparable for those with and without pre-BMT TKI therapy. Conclusions The similar late mortality experienced by patients with CML who undergo transplantation with or without pre-BMT TKIs suggests that allogeneic BMT can be considered in the context of TKI intolerance or nonadherence. The prevention of post-BMT non-CML-related mortality could favorably affect long-term survival.
Lenalidomide Suppression of Multiple Myeloma Cell Proliferation Is Associated with Downregulation of LEF/TCF Activity

Abstract Abstract 5014 Lenalidomide (Rev) is frequently used to treat multiple myeloma (MM). We reported that Rev promotes Dkk expression in MM cells. A recent study reported that resistance to Rev was associated with induction of Wnt/β-catenin signaling by increased β-catenin transcription and its decreased destruction (Bjorklund, JBC 2011). In this study, we evaluated whether these reported effects represent selection of pre-existing cell by exposure to Rev or regulation of the canonical Wnt signaling pathway by Rev, and whether the Wnt signaling pathway is associated with Rev’s direct effect on MM cell survival. To test the effect on Rev on proliferation of MM cells lines, the six MM cell lines H929, INA6, MM144, OPM-1, RPMI 8226, and U266 were cultured in growth media containing serial concentrations (0 to 1000 μM) of the drug for 24, 48 and 72 hours, and effect on proliferation measured by MTT assay. Rev diminished proliferation of these cell lines at concentrations between 50 to 1000 μM at 24 hours, and maximal inhibition occurred at 72 hours. Rev had little effect on the proliferation of the five MM cell lines at levels lower than 50 μM. Treatment with ≥5 μM Rev for 24, 48 and 72 hours resulted in increased DKK1 mRNA and Dkk1 protein levels as determined by qRT-PCR and by ELISA, respectively, in a dose dependent fashion, even at concentration that did not inhibit cell proliferation. These data suggest that Rev diminish MM proliferation is independent of its effects on Dkk1. We next examined the effect of Rev on β-catenin protein in cells treated with serial concentrations (0 to 1000 μM) of Rev for 6 hours. Immunoblotting analysis showed increased total β-catenin protein in 8226, OPM-2, H929, MM144 and U266 exposed to ≤100 μM, and no further increase in β-catenin levels when these cells were exposed to Rev concentrations higher than 100 μM. Rev did not affect changes in β-catenin levels in INA6. To determine the effects on Rev concentrations on TCF transcriptional activity, we infected cell lines with lentiviral particles containing the TCF reporter or with empty vector. Rev increased TCF activity at lower concentrations (10–20 μM) in all cells. As Rev concentration increased, TCF transcriptional activity gradually decreased, and was strongly inhibited (over 80%) at concentrations from 125 μM to 1000 μM, depending on the cell line; in this range, Rev suppressed MM proliferation. These results suggest that at cytotoxic concentrations, Rev regulation of TCF transcriptional activity is independent of its effect on total β-catenin levels. It remains to be determined if Rev-mediated inhibition of TCF activity is the cause of the drug’s cytotoxic effect, and the mechanism of the concentration dependent effects of Rev on TCF activity. Disclosures: No relevant conflicts of interest to declare.
Modulation of polycystic kidney disease by non-coding RNAs.

Abstract Purpose of review microRNAs (miRNAs) are a class of small, evolutionarily conserved, non-coding RNAs (ncRNAs) that function as inhibitors of post-transcriptional mRNA expression. They are implicated in the pathogenesis of numerous diseases, including many common kidney conditions. In this review, we focus on how miRNAs impact autosomal dominant polycystic kidney disease (ADPKD) progression. We also discuss the feasibility of the emerging novel antisense oligonucleotides (ASOs) drug class, which includes anti-miRNA drugs, for the treatment of ADPKD. Recent findings Aberrant miRNA expression is observed in multiple PKD murine models and human ADPKD samples. Gain and loss-of-function studies have directly linked dysregulated miRNA activity to kidney cyst growth. The most comprehensively studied miRNA in PKD is the miR-17 family, which promotes PKD progression through the rewiring of cyst metabolism and by directly inhibiting PKD1 and PKD2 expression. This discovery has led to the development of an anti-miR-17 drug for ADPKD treatment. Other miRNAs such as miR-21, miR-193, and miR-214 are also known to regulate cyst growth by modulating cyst epithelial apoptosis, proliferation, and interstitial inflammation. Summary miRNAs have emerged as novel pathogenic regulators of ADPKD progression. Anti-miR-based drugs represent a new therapeutic modality to treat ADPKD patients.
Predictors of Augmented Renal Clearance in a Heterogeneous ICU Population as Defined by Creatinine and Cystatin C.

Introduction The incidence of augmented renal clearance (ARC) in the intensive care unit (ICU) is highly variable, and identification of these patients remains challenging. Objective The objective of this study was to define the incidence of ARC in a cohort of critically ill adults, using serum Cr and cystatin C, and to identify factors associated with its development. Methods This is a retrospective cohort study of critically ill patients without stage 2 or 3 acute kidney injury with both serum Cr and cystatin C available. The incidence of ARC was defined as a Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)Cr-cystatin C-estimated glomerular filtration rate >130 mL/min. A multivariable logistic regression model using a penalized Lasso method was fit to identify independent predictors of ARC. Results Among the 368 patients included in the study, indication for ICU admission was nonoperative in 55% of patients, and 9% of patients were admitted for major trauma. The overall incidence of ARC was low at 4.1%. In a multivariable logistic regression model, Charlson comorbidity index, major trauma, intracerebral hemorrhage, age, and Sequential Organ Failure Assessment score were found to predict ARC. Conclusion The incidence of ARC in this study was low, but prediction models identified several factors for early identification of patients with risk factors for or who develop ARC, particularly in a cohort with a low baseline risk of ARC. These factors could be used to help identify patients who may develop ARC.
Polycystic kidney disease and other genetic kidney disorders

Abstract Cystic kidney diseases encompass a range of genetic disorders in which the primary cilia of the cells are affected and thereby cysts form as a result. There are an increasing range of cystic renal diseases recognized due to the advances in genomics. The most common genetic kidney condition is autosomal dominant polycystic kidney disease (ADPKD). ADPKD leads to renal failure in adulthood. In children, hypertension is common and if treated, may slow down renal decline. The most common cystic kidney disease causing renal failure in children is autosomal recessive polycystic kidney disease (ARPKD). ARPKD also affects the liver. These conditions often have extra-renal features which also need to be addressed. Until recently, treatments were mainly supportive but now it is possible to slow down development of cyst formation and renal decline in ADPKD. This raises hope for treatment for other cystic renal conditions as more genes are identified and underlying mechanisms defined.
Inland Damage from Hurricanes

Coch, N.K., 2020. Inland damage from hurricanes. Journal of Coastal Research, 36(5), 1093–1105. Coconut Creek (Florida), ISSN 0749-0208.Hurricanes result in severe wind and flooding along the coast. In general, their effects decrease in intensity inland. A less well-known feature is that some tropical storms can penetrate deep into the interior and cause severe freshwater flooding and wind destruction far from the coast. Exceptional inland damage can result from a number of meteorological and topographical scenarios. A deteriorating hurricane may merge with a moist extratropical low-pressure system, causing massive rainfall and river flooding (Tropical Storm Agnes in Pennsylvania, 1969). Winds can be channeled through passes on mountainous islands, like Kauai, to cause massive destruction on the lee side (Hurricane Iniki, 1992). Mountains can induce orographic precipitation that can result in massive debris flows (Hurricane Camille in Nelson County, Virginia, 1969). A decaying hurricane can have high convective centers inland that result in localized damage more typical of the hurricane at landfall (Hurricane Hugo, 1989). Finally, northern hurricanes can encounter polar air masses on their left sides as they move inland in the early fall (the New England Hurricane of 1938). While inland intensification is not common, it can occur under certain conditions as outlined in this paper. It is important to consider the possibility of inland intensification in every hurricane. Although the frequency is low, the consequences can be very high.