cssi/SciSciGPT-SciSciNet huggingface dataset:
Cheminformatics analysis of the AR agonist and antagonist datasets in PubChem.

As one of the largest publicly accessible databases for hosting chemical structures and biological activities, PubChem has been processing bioassay submissions from the community since 2004. With the increase in volume for the deposited data in PubChem, the diversity and wealth of information content also grows. Recently, the Tox21 program, has deposited a series of pairwise data in PubChem regarding to different mechanism of actions (MOA), such as androgen receptor (AR) agonist and antagonist datasets, to study cell toxicity. To the best of our knowledge, little work has been reported from cheminformatics study for these especially pairwise datasets, which may provide insight into the mechanism of actions of the compounds and relationship between chemical structures and functions, as well as guidance for lead compound selection and optimization. Thus, to fill the gap, we performed a comprehensive cheminformatics analysis, including scaffold analysis, matched molecular pair (MMP) analysis as well as activity cliff analysis to investigate the structural characteristics and discontinued structure–activity relationship of the individual dataset (i.e., AR agonist dataset or AR antagonist dataset) and the combined dataset (i.e., the common compounds between the AR agonist and antagonist datasets). Scaffolds associated only with potential agonists or antagonists were identified. MMP-based activity cliffs, as well as a small group of compounds with dual MOA reported were recognized and analyzed. Moreover, MOA-cliff, a novel concept, was proposed to indicate one pair of structurally similar molecules which exhibit opposite MOA. Cheminformatics methods were successfully applied to the pairwise AR datasets and the identified molecular scaffold characteristics, MMPs as well as activity cliffs might provide useful information when designing new lead compounds for the androgen receptor.
Modulation of Binge-like Ethanol Consumption by IL-10 Signaling in the Basolateral Amygdala

Excessive ethanol consumption alters the neuroimmune system and particularly impacts the cytokine milieu of the CNS. Cytokine dysregulation has been shown to underlie addictive-like behaviors including alcohol abuse; however, many studies focus primarily on the proinflammatory cytokine profile during alcohol dependence. The current study furthers this research by determining the impact of excessive ethanol consumption on interleukin-10 (IL-10) and interleukin-4 (IL-4) activity in a model of non-dependent binge consumption called the “drinking in the dark” (DID) paradigm. Furthermore, the ability of IL-10 to modulate ethanol consumption was tested using site-directed pharmacology. Immunohistochemistry analyses determined that ethanol decreased IL-10 by 50 % in the basolateral amygdala (BLA) but had no effect on IL-4. Neither IL-10 nor IL-4, however, were altered in the central amygdala (CEA). Enzyme linked immunosorbent assays confirmed that IL-10 was decreased in the amygdala but not in the serum, suggesting changes of this cytokine with the DID paradigm are restricted to the central nervous system. Finally, bilateral infusions of IL-10 into the BLA, but not CeA, reduced binge-like drinking and corresponding blood ethanol concentrations without impacting either locomotor activity or anxiety-like behavioral correlates. Together, these data support the idea that alcohol abuse dysregulates specific anti-inflammatory cytokines; however, ameliorating alcohol-induced effects on cytokines, like IL-10, may prove to be an effective therapy in curbing excessive consumption.
Scalp Rotation and Advancement Flap

Scalp defects occur secondary to acute trauma, tumor extirpation, burns, radiation necrosis, or excision of traumatic alopecia. Scalp rotational/advancement flaps are utilized in scalp defect reconstructions over 3 cm in diameter when exposed calvarium is devoid of periosteum (epicranium). The flap design is determined by the vascular pedicle based on one or two of the named scalp arteries that originate from their general vicinity. This chapter discusses the indications and intraoperative details for operative dictation. Pearls and pitfalls associated with the procedure and variants to the flaps are also discussed.
Porphyrin localizing phenomena.

The use of the porphyrin product HPD1 for tumor localization (1,2) and therapy (2–5) has been described. One report on an analysis of HPD appeared in 1980 (6) and other such reports are contained in this book. In order to characterize the events leading to tumor localization by HPD, it will be necessary to delineate active components in the product, the nature of any porphyrin transformations associated with the localization process and loci of binding of localized fluorescent porphyrins within the tumor cell.
Collisional Kinetic Models of Multispecies Plasmas in Nonuniform Magnetic Fields

It is generally the case in magnetic fusion devices that the magnetic field is nonuniform, but varies weakly on the scale of the gyro-motion, the fastest nearly recurrent motion of the charged particles comprising the plasma. However, motion along the direction of the field inexorably carries the particle through finite variations of the field, and the environment in which the charged particle is immersed as it executes its motion may vary significantly with these field variations. It is often necessary to consider this nonuniformity in order to involve salient features distinctive of a particular device in phenomena in which they play a significant role.
Uzbek re-modeled

This study investigates the relationship between Russian language use and language planning in the context of newly independent, post-soviet Uzbekistan (1991–1992). It is guided by the question: In what ways does the use of Russian loanwords in Uzbek language newspapers accomplish language planning in newly independent Uzbekistan? The main finding from this analysis is that post-independence use of Russian loanwords from particular semantic classes in particular contexts reinforce overtly stated ideologies about Russian and construct difference between soviet Uzbekistan and independent Uzbekistan. These findings demonstrate the need to reexamine the role of Russian language in post-soviet contexts, and they contribute a unique approach to analyzing links between lexical items and ideology in language planning
Atypical perceptual processing of faces in developmental dyslexia.

Abstract Developmental Dyslexia (DD) is often attributed to phonological processing deficits. Recent evidence, however, indicates the need for a more general explanatory framework to account for DD’s range of deficits. The current study examined the specificity versus domain generality of DD by comparing the recognition and discrimination of three visual categories (faces and words with cars as control stimuli) in typical and dyslexic readers. Relative to controls, not only did dyslexic individuals perform more poorly on word recognition, but they also matched faces more slowly, especially when the faces differed in viewpoint, and discriminated between similar faces (but not cars) more poorly. Additionally, dyslexics showed reduced hemispheric lateralization for words and faces. These results reveal that DD affects both word and face, but not car, processing, implicating a partial domain general basis of DD. We offer a theoretical proposal to account for the multifaceted findings and suggestions for further, longitudinal studies.
The association of surgical versus natural menopause with future left ventricular structure and function: The Coronary Artery Risk Development in Young Adults (CARDIA) Study.

Objective To evaluate the association between surgical menopause (SM) versus natural menopause (NM) in relation to later left ventricular (LV) structure and function, while taking into account the LV parameters and other cardiovascular disease risk factor (CVDRF) levels that predate the menopausal transition. Methods We studied 825 premenopausal women from the Coronary Artery Risk Development in Young Adults study in 1990 to 1991 (baseline, mean age 32 years) who later reached menopause by 2010 to 2011 and had echocardiograms at these two time points. Results During 20 years of follow-up, 508 women reached NM, whereas 317 underwent SM (34% had bilateral oophorectomy). At baseline, women who later underwent SM were more likely to be black, younger, have greater parity, and higher mean values of systolic blood pressure, body mass index, and also lower mean high-density lipoprotein cholesterol and physical activity than women who reached NM. No significant differences in LV structure/function were found between groups. In 2010 to 2011, SM women had significantly higher LV mass, LV mass/volume ratio, E/e' ratio, and impaired longitudinal and circumferential strain than NM women. SM women with bilateral oophorectomy had adverse LV measures than women with hysterectomy with ovarian conservation. Controlling for baseline echocardiographic parameters and CVDRF in linear regression models eliminated these differences between groups. Further adjustment for age at menopause/surgery and hormone therapy use did not change these results. Conclusion In this study, the adverse LV structure and function observed among women with SM compared with NM were explained by their unfavorable presurgical CVDRF profiles, suggesting that premenopausal CVDRF rather than gynecologic surgery predispose SM women to elevated future cardiovascular disease risk.
Inhibition of phorbol ester-induced monocytic differentiation and c-fms gene expression by dexamethasone: potential involvement of arachidonic acid metabolites.

The treatment of human U-937 leukemia cells with 12-O- tetradecanoylphorbol-13-acetate (TPA) is associated with induction of monocytic differentiation. However, the signaling pathways responsible for induction of the differentiated monocytic phenotype remain unclear. The present studies demonstrate that dexamethasone blocks TPA-induced U- 937 cell growth inhibition, adherence, and alpha-naphthyl acetate esterase staining. The results also demonstrate that dexamethasone inhibits the appearance of c-fms transcripts associated with TPA treatment. Run-on transcription assays demonstrated that the c-fms gene is transcriptionally active in uninduced U-937 cells and that the rate of transcription is unchanged after dexamethasone and/or TPA treatment. These findings indicated that TPA increases c-fms expression by a dexamethasone-sensitive posttranscriptional mechanism. Treatment of U- 937 cells with TPA was also associated with stimulation of arachidonic acid metabolism. Furthermore, dexamethasone, an inhibitor of phospholipase A2 activity, blocked TPA-induced increases in arachidonic acid release. These findings suggested that TPA may regulate certain features of monocytic differentiation, such as c-fms gene expression, through the formation of arachidonic acid metabolites. Indomethacin, an inhibitor of cyclooxygenase, had no detectable effect on c-fms gene expression. However, the cyclooxygenase metabolite, prostaglandin E2, inhibited the TPA-induced increases in c-fms mRNA levels. Taken together, the results indicate that TPA regulates c-fms gene expression by a dexamethasone-sensitive mechanism and that c-fms mRNA levels are controlled by metabolites of the arachidonic acid pathway.
Safety and efficacy of ledipasvir/sofosbuvir on hepatitis C eradication in hepatitis C virus/human immunodeficiency virus co-infected patients

Safety and efficacy of ledipasvir/sofosbuvir on hepatitis C eradication in hepatitis C virus/human immunodeficiency virus co-infected patients
Multifunctional Silicon Metagratings

We design highly efficient multi-functional silicon metagratings based on adjoint-based optimization and experimentally demonstrate devices exhibiting negative refraction and wavelength sorting capabilities.
Patients with Fetal Alcohol Syndrome and Their Caretakers

Patients with fetal alcohol syndrome typically have multiple handicaps and require special medical, educational, familial, and community assistance. Their caretakers need medical information, peer ...
Epidemiology of Carbapenem-Resistant Enterobacteriaceae at a Long-term Acute Care Hospital

Background Residents of long-term acute care hospitals (LTACHs) are considered important reservoirs of multidrug-resistant organisms, including Carbapenem-resistant Enterobacteriaceae (CRE). We conducted this study to define the characteristics of CRE-infected/colonized patients admitted to an LTACH and the molecular characteristics of the CRE isolates. Methods This retrospective study was conducted to collect information on demographic and comorbid conditions in CRE-colonized/infected patients admitted to a 77-bed LTACH in Detroit between January 2011 and July 2012. Data pertaining to hospital-related exposures were collected for 30 days before positive CRE culture. Polymerase chain reaction (PCR) gene amplification, repetitive sequence-based PCR, and multilocus sequence typing (MLST) were performed on 8 of the CRE isolates. Results The study cohort included 30 patients with CRE-positive cultures, 24 (80%) with infections, and 6 (20%) with colonization. The mean age of cohort was 69 ±12.41 years; 19 (63%) patients were ventilator-dependent, and 20 (67%) were treated with at least 1 antibiotic. Twenty-three (77%) patients had CRE detected following LTACH admission, and the median days from admission to CRE detection in these patients (interquartile range) was 25 (11-43). Seven more patients were already positive for CRE at the time of LTACH admission. Molecular genotyping and MLST of 8 CRE isolates demonstrated that all isolates belonged to the same strain type (ST258) and contained the bla KPC-3 sequence. Conclusions The majority of patients with CRE presented several days to weeks after LTACH admission, indicating possible organism acquisition in the LTACH itself. The genetic similarity of the CRE isolates tested could further indicate the occurrence of horizontal transmission in the LTACH or simply be representative of the regionally dominant strain.
Out-of-Sample Predictions of CPT and Geometric Dispersion Theory of Descriptive Choice Under Risk, Empirical Testbeds, Paradoxes, and Risk Triad

Out-of-sample prediction is the ultimate validity test of risk models for which theoretical appeal and justifications are irrelevant to the prediction results. Empirically, we show that all prominent risk models including Cumulative Prospect Theory (CPT), Expected Utility Theory (EUT), Rank Dependent expected Utility (RDU) and mean-variance have poor out-of-sample predictability. To accurately predict risk, we develop Geometric Dispersion Theory (GDT), which is based on two asymmetric simple dispersion functions, one for risk averse and the other for risk prone. Without using any parameters, they are convex functions of consequences and concave functions of probabilities. The linear tradeoffs of these two dispersion functions and the expected value (dubbed “risk triad”) explain all prominent risk paradoxes and offer excellent out-of-sample predictions using only two parameters. Furthermore, by using value and weights functions, GDT can generalize CPT, EUT, and RDU. While CPT and RDU are linear functions of weights and value functions, their one-parameter generalization by GDT is convex in weights and concave in value functions, denoted as meta-risk averse. For example, GDT, as a function of RDU, can be strict meta-risk averse while RDU can be strictly risk prone. We illustrate that the parametric GDT model can be easily assessed and validated. A three-parameter GDT model explains all risk paradoxes and is 200% superior to CPT in out-of-sample predictions. Finally, we show how different heterogeneous risk data can be decomposed into four types of predictable patterns of convex, concave, concave bowl, and convex bowl patterns.
Are We Innovative? Increasing Perceptions of Nonprofit Innovation Through Leadership, Inclusion, and Commitment:

Innovation is particularly important for the sustainability, functioning, and improvement of public and nonprofit organizations. Researchers have called for the examination of how leaders can foste...
Report on the Bronx 120 Mass 'Gang' Prosecution

In recent years, takedowns of gangs and crews in New York City have led to mass prosecutions of multiple defendants for conspiracy and RICO (Racketeering Influenced Corrupt Organization Act) conspiracy charges. While the takedowns are generally accompanied by intensive media coverage, information about the charges, process, and allegations against individuals caught up in these takedowns is not readily accessible. This report looks into the court records of the largest of the mass gang prosecutions — the takedown of the Bronx 120 in April of 2016. In the pre-dawn hours of April 27, 2016, nearly 700 officers in riot gear descended upon Eastchester Gardens and the adjoining neighborhood along White Plains Road. The officers were from the NYPD, ATF, DEA, and Homeland Security. Helicopters hovered overhead as armed SWAT teams used battering rams to execute no-knock warrants. They were arresting defendants charged in twin conspiracy indictments. The defendants and the raid have come to be known as the Bronx 120 for the 120 defendants named in the indictments. Preet Bharara, then-United States Attorney for the Southern District of New York, announced that the raid was believed to be the “largest gang takedown in New York City history.” The report concludes that nearly half of the 120 individuals targeted in these “gang” indictments were not alleged to be gang members by the prosecution, two-thirds of the defendants were not convicted based on violent conduct (including 35 for who were convicted based on marijuana sales), and two-thirds of defendants had no prior felony record, and nearly half were re-prosecuted for conduct previously adjudicated in state courts. Although many of the defendants were not violent gang members, the vast majority (101 of the 120) were held without the possibility of bail, and 15 of the 19 who were released were subject to house arrest. Further, these mass indictments fail to safeguard the public’s interest in transparency and speedy trial.
Oncology urgent care to decrease unnecessary emergency room visits.

212Background: In March 2019, Columbia University Irving Medical Center (CUIMC)/New York Presbyterian (NYP) piloted an oncology urgent care center, Oncology Care Initiation Unit (OCIU). Patients cu...
Sickle cell disease subjects and mouse models have elevated nitrite and cGMP levels in blood compartments

The hypothesis of decreased nitric oxide (NO) bioavailability in sickle cell disease (SCD) proposes that multiple factors leading to decreased NO production and increased consumption contributes to vaso-occlusion, pulmonary hypertension, and pain. The anion nitrite is central to NO physiology as it is an end product of NO metabolism and serves as a reservoir for NO formation. However, there is little data on nitrite levels in SCD patients and its relationship to pain phenotype. We measured nitrite in SCD subjects and examined its relationship to SCD pain. In SCD subjects, median whole blood, red blood cell and plasma nitrite levels were higher than in controls, and were not associated with pain burden. Similarly, Townes and BERK homozygous SCD mice had elevated blood nitrite. Additionally, in red blood cells and plasma from SCD subjects and in blood and kidney from Townes homozygous mice, levels of cyclic guanosine monophosphate (cGMP) were higher compared to controls. In vitro, hemoglobin concentration, rather than sickle hemoglobin, was responsible for nitrite metabolism rate. In vivo, inhibition of NO synthases and xanthine oxidoreductase decreased nitrite levels in homozygotes but not in control mice. Long-term nitrite treatment in SCD mice further elevated blood nitrite and cGMP, worsened anemia, decreased platelets, and did not change pain response. These data suggest that SCD in humans and animals is associated with increased nitrite/NO availability, which is unrelated to pain phenotype. These findings might explain why multiple clinical trials aimed at increasing NO availability in SCD patients failed to improve pain outcomes.
Release of Carbohydrate–Metal Adducts from Electrospray Droplets: Insight into Glycan Ionization by Electrospray

Glycans have an immense number of biological activities, necessitating increased efforts to characterize glycan structures. Mass spectrometry has been coupled to electrospray ionization (ESI) to ch...
Human zoonotic tuberculosis and livestock exposure in low- and middle-income countries: A systematic review identifying challenges in laboratory diagnosis

Background Zoonotic tuberculosis (zTB) accounts for 1.4% of the global tuberculosis burden, with the largest disease burden in low- and middle-income countries (LMICs). These populations have increased exposure to zTB due to livestock rearing practices and raw dairy consumption. This qualitative systematic literature review evaluates the quality of the literature that examines the association between human zTB in LMICs and frequent exposure to livestock and livestock products and summarizes current gaps in laboratory detection methods. Methods The Navigation Guide, a systematic review framework utilized to assess environmental health exposures, was used to conduct this literature review. Peer-reviewed research articles were selected and evaluated for risk of bias and quality of evidence. Only studies conducted in LMICs that mentioned livestock or livestock product exposure and had a confirmed diagnosis were eligible. Results Fifteen studies met the inclusion criteria. Reported prevalence of human zTB ranged from 0% to 28%, with cattle and raw dairy the primary exposures. All confirmed zTB cases were Mycobacterium bovis. Eight of the 15 studies included livestock sampling, predominantly cattle and reported prevalence of zTB between 0% and 23%. Laboratory methods used included nearly a dozen different culture methods and a variety of molecular methods, some of which are not appropriate for zTB. Conclusions This review revealed the need for appropriate and standardized laboratory diagnostic methods, and large prospective studies of at-risk populations to determine exposures that lead to an increased risk of tuberculosis conversion/infection to better understand the true burden of disease. Standardized, easy to implement laboratory diagnostics is an imperative focus for this scientific field to better identify the burden of zTB. Future studies pairing livestock and human subjects will allow better characterization of the high zTB transmission areas for targeted control and prevention programmes.
6 Self-Regulatory Perspectives on Personality

This chapter describes a set of ideas bearing on the self-regulation of action and emotion that has been identified with labels such as cybernetic and feedback control. The ideas have roots in many sources, including the concept of homeostasis. With respect to personality, these ideas yield a viewpoint in which goal-directed action reflects a hierarchy of feedback control processes and the creation and reduction of affect are seen as reflecting another set of feedback processes. The full hierarchy of a person's goals, then, is one manifestation of the person's personality. Also part of many self-regulatory models is the idea that people's continued efforts toward goal attainment depend on the confidence they have in their eventual success. This principle also leads to identification of several ways in which problems can develop. Recent interest in dual-process models, which distinguish between top-down goal pursuit and reflexive responses to cues of the moment, leads to reexamination of some prior assumptions, and raises the possibility that behavior is triggered in two distinct ways. The chapter closes with brief consideration of ideas from dynamic systems and catastrophe theories which may also be important to self-regulatory models in the future. Keywords: self-regulation; personality; goals; cybernetic; control; expectancy; affect
Analysis of the Block Segmentation Method of the Licklider Transmission Protocol

Space communications are continuously challenged by extreme conditions that include large propagation delays, intermittent connectivity, and random losses. To combat these problems, the Licklider Transmission Protocol (LTP) splits data blocks into small segments that are radiated independently and retransmitted as needed, through a process that can be paused during long link disruptions. Given the extreme delays involved, the end performance of this protocol is driven by the number of transmission rounds needed to successfully deliver each block. LTP links are defined as overlays with one or more physical channels in the underlay, therefore with sections that may be on different administrative domains and experiencing different conditions. The question of how to select the length of the segments has received negligible attention and the use of improper values can easily lead to suboptimal performance. The segmentation process used by LTP is examined in this paper to determine the role that segmentation parameters and the conditions of the underlay have on the block delivery times. This goal is achieved through the definition of a basic model of LTP’s transmission process that allows deriving the optimal segmentation parameter. Simulation results provide additional evidence of LTP’s performance contrasting the results of the optimal segment length with fixed-length segments. The results provide a theoretical performance reference for practical parameter optimization methods.
On the Positivity of Weak Solutions to a Class of Cross Diffusion Systems

We establish the positivity of weak (and very weak) solutions to a class of cross diffusion systems which is inspired by models in mathematical biology/ecology, in particular the Shigesada-Kawasaki-Teramoto (SKT) model in population biology. Examples and counterexamples will be provided to show that our contions are near optimal.
Phosphorylated EGFR on tumor-associated endothelial cells in human renal cell carcinoma is a primary target for therapy by tyrosine kinase inhibitors.

5702 Our laboratory recently isolated a novel protein from lung carcinoma which has been found to inhibit tumor growth, metastasis, and angiogenesis in both in vitro and in vivo animal studies. This protein, termed Angiocidin, is over-expressed in a wide range of tumor tissue and is present at elevated levels in the blood of patients with advanced cancers. Subsequent to these initial studies, we have also obtained preliminary data indicating that Angiocidin may play a significant role in immune system modulation by functioning as a proinflammatory mediator. Activation of the acute monocytic leukemia cell line THP-1 with phorbol-12-myristate-13-acetate resulted in secretion of Angiocidin in the pg/mL range, as quantitated by an Angiocidin capture ELISA developed by our lab. This result was also observed with peripheral blood mononuclear cells (PBMCs), indicating potential cytokine-like activities for this molecule. MDA-MB-231 breast adenocarcinoma, Colo 357 pancreatic carcinoma, and DAOY medulloblastoma cell lines, as well as Human Umbilical Vein Endothelial Cells (HUVECs), have also been demonstrated to secrete Angiocidin. Flow cytometric analysis of PBMCs has demonstrated that Angiocidin also acts as a potent activator of both monocytes and lymphocytes. This activity has been titered to as little as 1 μg/mL Angiocidin. Flow cytometric analysis and human cytokine antibody arrays have shown various cytokines to be secreted from monocytes in response to Angiocidin treatment, including Monocyte Chemotactic Proteins 1 and 2, Interleukins 6, 10, and 12, and TNF-α. Using the THP-1 cell line, we have also demonstrated Angiocidin-induced monocyte activation immunocytochemically. Treated with 1 μg/mL Angiocidin for 24 hours causes cell-substratum adhesion. Cells morphologically resemble tissue macrophages, showing distinct focal adhesion and stress fiber formation. In addition to cytokine release, Angiocidin also stimulates secretion of several matrix-degrading enzymes, namely MMP-9 from THP-1 cells and PBMCs, and MMP-2 from HUVECs. Accordingly, conditioned media from Angiocidin-treated THPs has been shown to act as a potent inducer of monocyte invasion through Collagen Type I and gelatin. These data suggest a potential immunologic mechanism by which Angiocidin may exert its antitumor effect. We hypothesize that reduced tumor growth previously observed in Angiocidin-treated mice may be partly attributable to the specific cytokine profile found within the tumor microenvironment, as well as to enhanced leukocyte infiltration into the tumor bed. The focus of this project is to expand upon these data and elucidate the functional roles this molecule plays in modulating an immune response.
Localized cytokine responses to total knee arthroplasty and total knee revision complications

The study of localized immune-related factors has proven beneficial for a variety of conditions, and one area of interest in the field of orthopaedics is the impact of implants and localized infections on immune response. Several cytokines have shown increased systemic concentrations (in serum/plasma) in response to implants and infection, but tissue-level cytokines have not been investigated as thoroughly. This exploratory study investigated tissue-level cytokines in a cohort of patients (N = 17) in response to total knee arthroplasty and total knee revision to better understand the immune response to implants and localized infection (e.g., prosthetic joint infection). The overall goal of this study was to provide insight into the localized cytokine response of tissues and identify tissue-level markers specific to inflammation caused by implants vs. inflammation caused by infection. Tissues were collected across several anatomical locations and assayed with a panel of 20 human inflammatory cytokines to understand spatial differences in cytokine levels. In this study, six cytokines were elevated in implanted joints, as compared to native joints: IL-10, IL-12p70, IL-13, IL-17A, IL-4, and TNF-α (p < 0.05). Seven cytokines showed infection-dependent increases in localized tissues: IL-1α, IL-1β, IL-6, IL-8, MCP-1, MIP-1α, and MIP-1β (p < 0.05). This study demonstrated that differences exist in tissue-level cytokines in response to presence of implant, and some cytokines were specifically elevated for infection; these responses may be informative of overall tissue health. These results highlight the utility of investigating localized cytokine concentrations to offer novel insights for total knee arthroplasty and total knee revision procedures, as well as their complications. Ultimately, this information could provide additional, quantitative measurements of tissue to aid clinical decision making and patient treatment options.
Comparative Adherence Trajectories of Oral Fingolimod and Injectable Disease Modifying Agents in Multiple Sclerosis

Background Oral fingolimod is convenient to use than injectable disease modifying agents (DMAs) in patients with multiple sclerosis (MS). However, the existing literature regarding the comparative adherence trajectories between oral fingolimod and injectable DMAs is limited. Objective To compare the adherence trajectories between oral DMA, fingolimod, and injectable DMAs in patients with MS. Methods A retrospective longitudinal study was conducted using adults (≥18 years) with MS (ICD-9-CM: 340 and a DMA prescription) from the IBM MarketScan Commercial Claims and Encounters Database between 2010 and 2012. Patients were grouped into oral fingolimod or injectable DMA users based on the index DMA among patients with MS. The annual DMA adherence trajectories, based on the proportion of days covered (PDC), were examined using group-based trajectory modeling (GBTM) during the one-year follow-up period after treatment initiation. Multivariable multinomial logistic regression using stabilized inverse probability treatment weights (IPTW) was performed to assess the association between the DMA route of administration (Oral vs Injectable) and the adherence trajectory groups. The balance of covariates between oral and injectable DMAs before and after IPTW was checked against a standardized difference threshold of 0.25. Results The study cohort consisted of 1,700 MS patients who were initiated with oral (15.8%) or injectable (84.2%) DMAs between 2010 and 2012. The adherence rates (PDC≥0.8) in oral fingolimod and injectable DMA users were found to be 64.7% and 50.8%, respectively. The GBTM grouped individuals in the study cohort into three adherence trajectories - rapid discontinuers (23.5%), complete adherers (49.9%), and slow decliners (26.6%). The multinomial logistic regression model with stabilized IPTW revealed that oral fingolimod users had higher odds to be a complete adherer (adjusted odds ratio [AOR]: 2.78, 95% CI: 1.85-4.16) or a slow discontinuer (AOR: 2.62, 95% CI: 1.70-4.05) than injectable DMA users. Conclusions Oral DMA fingolimod was associated with better adherence than injectable DMAs across group-based trajectories. Further research is warranted to evaluate the adherence trajectories with newer oral DMAs introduced in the last decade for MS.
Distribution of rare earth elements in fly ash derived from the combustion of Illinois Basin coals

Abstract This study examined rare earth element (REE) trends for Illinois Basin coal-sourced fly ashes, with the goal of understanding the elemental composition and resource potential for various fly ash fractions. Illinois Basin coals have a high volatile C through A bituminous rank with a moderate ash content (slightly>12% ash (dry basis)), about 3% sulfur, and, in general, lower concentrations of hazardous and other trace elements than many Central Appalachian coals. Fly ash from the combustion of Illinois Basin coals tends to have a high Fe2O3 content owing to the amount of pyrite in the feed coals. The rare earth element (REE) concentrations in Illinois Basin coal-sourced fly ashes are less than that for fly ashes from the combustion of Central Appalachian coals. The Upper continental crust-corrected fly ashes show an H-type enrichment, a positive EuN/EuN*, and, in some cases, a sharp Gd peak. For comparison, a suite of fly ashes from the combustion of a blend of eastern Kentucky coals had an H-type enrichment, a positive EuN/EuN*, but only a minimal Gd peak. In contrast, fly ash from the combustion of the Fire Clay coal, a REE-rich coal, had a negative EuN/EuN* and a sharp Gd peak. These results highlight the importance of feed coal composition on trace element contents of respective combustion fly ash fractions and also the unique REE enrichment patterns of the Illinois Basin fly ashes relative to the better studied fly ashes of eastern Kentucky and Central Appalachia.
ShareDNA: a smartphone app to facilitate family communication of genetic results

Genetic testing allows patients and clinicians to understand the risk of hereditary diseases. By testing early, individuals can make informed medical decisions about management which may minimize the risk of developing certain diseases. Importantly, genetic test results may also be applicable to patients’ biological relatives; thus, these results could also lead to minimizing their risk of disease. However, sharing genetic test results between patients and their relatives is scarce. The most frequently reported problems are that patients cannot clearly explain this information and relatives misinterpret the results. Smartphone apps in the healthcare field are a possible solution as they allow patients to accurately share sensitive information to others, while providing educational material to support understanding the information. However, these apps may not provide security to protect patients’ identifiable information. We developed ShareDNA, a smartphone app that (1) allows patients to securely share their genetic test results with others, (2) provides information on how to interpret these results, and (3) minimizes the amount of patient information needed to use the service. We recruited thirteen participants to test the usability of our app and provide feedback. We found overall that participants were comfortable with using this app and could easily learn each app function when filling out our questionnaire. Additionally, based on vocalized impressions of the usefulness of the app, participants indicated that the user-interface could be more intuitive and that we needed to add more text within the app to explain why ShareDNA is a secure service. ShareDNA is a free smartphone app that allows patients to share their genetic test results with others, including their biological relatives. Sharing these results along with educational material will enable relatives to share accurate information and discuss their possible risk for disease with their clinical providers. As a result, appropriate testing in relatives could be improved.
Ventricular assist devices in a contemporary pediatric cohort: Morbidity, functional recovery, and survival.

Background Limited availability of donor organs has led to the use of ventricular assist devices (VADs) to treat heart failure in pediatric patients, primarily as bridge to transplantation. How effective VAD therapy is in promoting functional recovery in children is currently not known. Methods We report morbidity and mortality as defined by the Interagency Registry for Mechanically Assisted Circulatory Support Modified for Pediatrics (PediMACS) and the use of the Treatment Intensity Score to assess functional status for 50 VAD patients supported at a single pediatric program from 2004 to 2013. Results In this cohort, 30-day survival on VAD was 98%, and 180-day survival was 83%. Stroke occurred in 11 patients (22%), with 8 (16%) resulting in persistent neurologic deficit or death. The adverse event rate was 2-fold to 3-fold higher in the first 7 days of support compared with the subsequent support period. Functional status, as measured by the Treatment Intensity Score, improved with duration of support. Successful bridge to transplantation was associated with fewer adverse events during support and greater improvement in the Treatment Intensity Score during the period of support. Conclusions Overall survival in this cohort is excellent. The risk of serious adverse events decreases over the first month of support. However, a clinically significant risk of morbidity and mortality persists for the duration of pediatric VAD support. Measures of functional status improve with duration of support and are associated with survival to transplantation.
A Process Evaluation of the Alaska Native Colorectal Cancer Family Outreach Program

This article presents the results of a process evaluation of the Alaska Native (AN) Colorectal Cancer (CRC) Family Outreach Program, which encourages CRC screening among AN first-degree relatives (i.e., parents, siblings, adult children; hereafter referred to as relatives) of CRC patients. Among AN people incidence and death rates from CRC are the highest of any ethnic/racial group in the United States. Relatives of CRC patients are at increased risk; however, CRC can be prevented and detected early through screening. The evaluation included key informant interviews (August to November 2012) with AN and non-AN stakeholders and program document review. Five key process evaluation components were identified: program formation, evolution, outreach responses, strengths, and barriers and challenges. Key themes included an incremental approach that led to a fully formed program and the need for dedicated, culturally competent patient navigation. Challenges included differing relatives’ responses to screening outreach, health system data access and coordination, and the program impact of reliance on grant funding. This program evaluation indicated a need for more research into motivating patient screening behaviors, electronic medical records systems quality improvement projects, improved data-sharing protocols, and program sustainability planning to continue the dedicated efforts to promote screening in this increased risk population.
Constrained reconstruction of sparse cardiac MR DTI data

Magnetic resonance diffusion tensor imaging (DTI) has emerged as a convenient and reliable alternative to conventional histology for characterizing the fiber structure of the myocardium. The acquisition of full data for different diffusion directions for a large number of slices often takes a long time and results in trade-offs in the number of slices and signal to noise ratios. We propose a constrained reconstruction technique based on a regularization framework to jointly reconstruct sparse sets of cardiac DTI data. Constraints on spatial variation and directional variation were used in the reconstruction. The method was tested on sparse data undersampled in both rectilinear and (simulated) radial fashions and compared to reconstructions from full data. The method provided reasonable reconstructions with half of the data for rectilinear undersampling and similar quality images with a quarter of the data if radial undersampling was used.
In Brief: Protecting Louisiana's coasts

With numerous wetlands restoration and protection projects slated for Louisiana, a well-developed implementation strategy that can address a number of uncertainties is important for the success of these projects, according to a 14 December report by the U.S. Government Accountability Office (GAO). GAO specifically urged maintaining the collaborative process that is used by Coastal Wetlands Planning, Protection and Restoration Act (CWPPRA) program agencies, with scientists, engineers, and others working together to plan and design restoration projects. The report also noted the need to address such other issues as having an integrated monitoring system to determine whether goals and objectives are met as well as to understand that projects can encounter significant setbacks due to storms and hurricanes, landscape and structural causes, and spiraling project costs. Louisiana state officials anticipate the state could receive about $8.5 billion over the next 10 years for coastal restoration and protection.
Deoxyribokinase from Salmonella typhimurium. Purification and properties.

Abstract Deoxyribokinase, which catalyzes the ATP-dependent phosphorylation of 2-deoxy- d -ribose to 2-deoxy- d -ribose-5- P as the first step in the inducible fermentation pathway for this sugar in Salmonella typhimurium , was purified approximately 600-fold from deoxyribose-grown cells. Apparent K m ′s for 2-deoxy- d -ribose and ATP were 0.1 and 0.5 m m , respectively. The enzyme had an absolute requirement for divalent cations which was best satisfied by Mg 2+ . Optimal activity was obtained in the presence of 0.5 m NH 4 + or Cs + . Rb + and K + also stimulated enzyme activity whereas Na + and Li + inhibited. d -Ribose and 2-deoxy- d -ribitol could replace 2-deoxy- d -ribose as phosphoryl acceptor, and several ribo- and deoxyribonucleotides could replace ATP as phosphoryl donor. Molecular weight determinations gave values of 67,800 for the native enzyme and 33,500 for the dissociated enzyme, suggesting the probable existence of two subunits of similar size.
Longitudinal cortical thinning in adolescents with autism: good or bad?

t is a fairly well-established fact that autism is associated with a general increase in total brain volume based on I increased gray matter and white matter proliferation during infancy and toddlerhood. Despite the clear assumption that there are likely large deviations in specific areas of brain development, there are conflicting findings and much to be learned about the neural circuitry of autism. For example, several previous studies have demonstrated that in very early childhood, there are clear deviations in patterns of regional brain development in autism that persist and evolve during infancy, early childhood, and adolescence. Recent work has begun to more clearly identify specific neural networks that might be more significantly involved in the early development of autism spectrum disorder (ASD). However, it is only recently that the importance of specific cortical characterization, including the assessment of components that make up cortical structure, has been obtainable and advocated for in the neuroimaging research community. Previous studies would look at regional volumes or regional cortical thickness (CT) in association with specific characteristics or disease; however, recent evidence has repeatedly demonstrated that there is more biological validity and sensitivity when assessing the components of regional volume by quantifying more specific cortical parameters, including CT, quantification of cortical gyrification (the extent and degree of cortical folding patterns), and cortical surface area (CSA). This is supported by evidence from several lines of research, including recent studies demonstrating that when parameters of CSA are included in addition to regional volume and CT, there is improved sensitivity in relation to illness and a clear significant relation with higher indices of heritability. In this issue of the Journal, Wallace et al. adopted these principles of deconstructing components of cortical structure in a new investigation characterizing longitudinal cortical developmental changes associated with autism in late adolescence. They present findings related to developmental patterns of cortical characteristics during late adolescence in a small longitudinal study of participants with ASD (n 1⁄4 17) in contrast to typical healthy controls (n 1⁄4 18). The findings support that ASD is associated with more dramatic cortical thinning in several regions compared with healthy controls during the late adolescent to early adulthood period. Although there has been a handful of previous investigations looking at CSA and CT in ASD during childhood and adolescence, none of these publications were based on longitudinal data. This interesting study covers an important topic in a somewhat new and novel way. These investigators
Abstract 17790: Can 3D Echocardiography Play a Role in Left Ventricular Assist Device Optimization?

Introduction: Left ventricular (LV) assist device (LVAD) has emerged as a valuable option for patients with severe congestive heart failure both as bridge to transplantation or destination therapy. Speed optimization of LVAD is currently based on the position of the inter-ventricular septum, mitral regurgitation severity and aortic valve opening. Hypothesis: We hypothesized that 3D transthoracic echocardiography (3DE) would provide additional information on left and right ventricular (RV) volumes and shape, which could be valuable in determining optimal LVAD speed. Our aim was to assess the feasibility of combined 3D LV and RV analysis during an incremental RAMP study. Methods: Six consecutive patients undergoing a RAMP test were studied. Device speed was increased from 8000 to 12000 rpm in 400-rpm increments for axial-flow pumps (n=2) and from 2300 to 3200 rpm in 100 rpm increments for centrifugal-flow pumps (n=4). Transthoracic 3DE apical full-volume datasets of the LV and the RV were acquired (Philips) at every other step. RV and LV endocardial surfaces were reconstructed using commercial software (TomTec) and used to calculate ventricular volumes. Custom software was used to calculate LV shape indices of sphericity and conicity (a perfectly spherical/conical ventricle would result in 1.0 value). Results: Data acquisition and post-processing was feasible in 5/6 patients. In axial pumps (Figure), increments in LVAD speed were associated with gradually decreasing LV volume, while RV volume initially decreased to a minimum and then increased at higher speeds. These volumetric changes were associated with alterations in LV shape, with the LV becoming less spherical and more conical at higher speeds. With centrifugal pumps, increased speed was associated with similar changes in LV shape but with minimal changes in volumes. Conclusions: Acquisition of 3D datasets during RAMP studies is feasible and could become a valuable aid in optimizing LVAD pump speed. ![][1] [1]: /embed/graphic-1.gif