cssi/SciSciGPT-SciSciNet huggingface dataset:
Abstract 3072: A clinical pharmacodynamic biomarker assay that distinguishes potentially repairable, cytotoxic drug-induced DNA double strand breaks (DSBs) from DSBs associated with apoptotic cell death

The effectiveness of certain classes of cytotoxic cancer therapeutics likely depends on whether drug-induced DNA damage is successfully repaired or not, with the latter situation leading to mutations and strand breaks. However, double strand breaks (DSBs) also occur independently of genotoxic insults during apoptotic cell death caused by many drug classes, as well as natural biological processes. We have developed an immunofluorescent confocal microscopy assay that uses a biomarker profile suitable for individual cell analysis designed to distinguish between DSBs caused by apoptosis and those caused by direct DNA damage from cytotoxic drug action. γ-H2AX is an established biomarker for DSBs and activated cleaved caspase 3 is an executioner caspase important for apoptosis, which leads to nuclear condensation, DNA fragmentation, plasma membrane blebbing, and subsequent cell death. Our assay defines the DSBs of apoptosis by co-localized γ-H2AX and cleaved caspase 3 in individual cells, while defining the DSBs from early drug effects of DNA damaging chemotherapeutics by γ-H2AX induction in the absence of cleaved caspase 3. Building on our published findings that topotecan strongly induces γ-H2AX and DSBs within 1-4 hours in vitro and in vivo, we observed exposure-dependent increases in γ-H2AX /cleaved caspase 3 double positive cells at later time points, both in an HT29 in vitro spheroid model and an MDA-MB-231 xenograft model. Fit-for-purpose studies in the MDA-MB-231 xenograft model treated with birinipant, a SMAC mimetic and IAP deregulator that does not directly produce lethal DSBs, demonstrated a dose-dependent increase in cellular co-localization of γ-H2AX/cleaved caspase 3 consistent with birinipant induced apoptosis and the established mechanism of action of this compound. Clinical feasibility was established in a canine clinical trial using formalin-fixed paraffin-embedded (FFPE) 18-gauge needle biopsies: two novel indenoisoquinolines, indotecan (LMP400) and indimitecan (LMP776), increased tumor cell co-localization of γ-H2AX/cleaved caspase 3 in tumor samples obtained on day 5 of qdx5 treatment. This PD biomarker assay of early and late DSB response to drug exposure could have important applications for elucidation of mechanisms of action of anticancer drugs and the development of investigational agents. Funded by NCI Contract No. HHSN261200800001E. Citation Format: Angie B. Dull, Deborah Wilsker, Robert J. Kinders, Ralph E. Parchment, David Evans, Beverly A. Teicher, James H. Doroshow. A clinical pharmacodynamic biomarker assay that distinguishes potentially repairable, cytotoxic drug-induced DNA double strand breaks (DSBs) from DSBs associated with apoptotic cell death [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3072. doi:10.1158/1538-7445.AM2017-3072
Shame is bad and guilt is good: An examination of the impaired control over drinking pathway to alcohol use and related problems.

Abstract Tension Reduction Theory (Kushner, Sher, Wood, & Wood, 1994) suggests alcohol is used as a means to alleviate negative affect (NA) such as shame and guilt. Shame is an internalized response in which blame is placed on the self, while guilt is not internalized and the blame is placed on the situation (Dearing, Stuewig, & Tangney, 2005). This study aims to investigate relationships of shame and guilt to alcohol use and problems through the mechanisms of multiple facets of impulsivity (i.e. UPPS) and impaired control over drinking (IC), which reflect behavioral control processes. The sample consisted of 419 college students (53% female). We examined direct and indirect relationships of shame and guilt on alcohol use and related problems through facets of impulsivity and IC. Shame and guilt were found to diverge (Woien, Ernst, Patock-Peckham, & Nagoshi, 2003). We found that those higher on shame-proneness used more alcohol and experienced more alcohol-related problems through increased negative urgency and IC. Conversely, guilt-prone individuals used less alcohol and experienced fewer alcohol-related problems through less negative urgency and IC. Our findings suggest that guilt is an adaptive form of negative affect, particularly when it comes to alcohol-related outcomes.
Using stakeholder marketing and social responsibility for new product development in higher education: a business Spanish model

ABSTRACTHigher education administrators are often faced with difficult choices in allocating limited resources for the creation of new programs. The purpose of this article is to explore the suitability of a new product, an integrated business Spanish major, by applying stakeholder marketing. In so doing, it provides a framework for the application of stakeholder marketing to other curricular decisions. The advantage of this approach is that it takes into account that US universities are accountable to multiple stakeholders. The research methods employed include secondary data analysis and a content analysis of the websites of universities that enroll over 5000 students, as well as a survey of students at a representative college in order to gain a better understanding of what motivates them in their academic choices. Our findings indicate that universities may be missing an important opportunity to better engage with the growing Hispanic population and with expanding Latin American markets abroad. Univer...
Social Vulnerability to Climate Change in Temperate Forest Areas: New Measures of Exposure, Sensitivity, and Adaptive Capacity

Human communities in forested areas that are expected to experience climate-related changes have received little attention in the scholarly literature on vulnerability assessment. Many communities rely on forest ecosystems to support their social and economic livelihoods. Climate change could alter these ecosystems. We developed a framework that measures social vulnerability to slow-onset climate-related changes in forest ecosystems. We focused on temperate forests because this biome is expected to experience dramatic change in the coming years, with adverse effects for humans. We advance climate change vulnerability science by making improvements to measures of exposure and sensitivity and by incorporating a measure of adaptive capacity. We improved on other methods of assessing exposure by incorporating climate change model projections and thus a temporal perspective. We improved on other methods of assessing sensitivity by incorporating a variable representing interdependency between human populations ...
Comparison of Causes and Associated Costs of 30-Day Readmission of Transcatheter Implantation Versus Surgical Aortic Valve Replacement in the United States (A National Readmission Database Study).

Our current knowledge about comparative differences in 30-day readmissions and the impact of readmissions on overall costs after transcatheter aortic valve implantation (TAVI) and surgical aortic valve replacement (SAVR) is largely derived from clinical trials. The objectives of this study were to compare readmissions and costs for TAVI and SAVR in a nationally representative population-based sample. The Healthcare Cost and Utilization Project's National Readmission Database was used for the study. Hierarchical multivariable regression analyses were used to examine differences in the propensity score 1:1 matched cohort. The matched cohort included 4,682 patients who survived index procedures done from January through November 2013. Compared with SAVR, the rate of 30-day readmission was not significantly different for endovascular TAVI (16% vs 18%; p = 0.19); and was higher for the transapical TAVI (22% vs 17%; p <0.01) group. The 30-day cumulative costs were higher for the 2 endovascular TAVI ($51,025 vs $46,228; p = 0.03) and transapical TAVI ($59,575 vs $45,792; p <0.01). In multivariable analyses, the risk of 30-day readmission was similar for endovascular TAVI (odds ratio [OR] 0.93; 95% confidence interval [CI] 0.78 to 1.12) and was 27% higher for transapical TAVI (OR 1.27; 95% CI 1.02 to 1.57). Cumulative costs (index plus readmission costs) were 13% (β 0.13; 95% CI 0.10 to 0.15) and 19% (β 0.19; 95% CI 0.16 to 0.23) higher for the endovascular TAVI and transapical TAVI, respectively. In conclusion, the rate of readmissions was similar for endovascular TAVI and SAVR but the costs were 26% higher for TAVI than for SAVR.
Application-driven device/circuit co-simulation framework for power MOSFET design and technology development

Physics-based device-circuit co-simulation turns out to be an extremely valuable tool to guide and optimize process technology development and device design for high-performance power MOSFETs. It is particularly well-suited to the need of emerging trend of integration of discrete power devices and analog ICs in the same package. In this article, we outline the key features and benefits of such an integrated design framework.
Open-Source Suite for Advanced Synchrophasor Analysis

The paper presents the results of the development of the open-source suite of applications for synchrophasor analysis. The suite includes several software tools for oscillation analysis, power plant model validation, and frequency response analysis using synchrophasor measurements. All tools are based on the common framework and data sources. The developed tools have been used by the Bonneville Power Administration and other utilities for synchrophasor analysis. The paper includes several use cases based on the actual system PMU data.
Biomechanics of the Upper Limbs: Mechanics, Modeling and Musculoskeletal Injuries, Second Edition

There is already a wealth of literature covering cumulative trauma disorders and medical management, as well as the biomechanics of manual material handling and lower back problems. However, despite a spike in the number of work-related musculoskeletal disorders (WRMSDs) in the upper limbs-due to a sharp increase in the amount of computer-related j
Outcome of phacoemulsification combined with excisional goniotomy using the Kahook Dual Blade in severe glaucoma patients at 6 months.

Purpose The aim of this study was to describe 6-month rates of achieving target IOP without requiring additional glaucoma surgery after excisional goniotomy using the Kahook Dual Blade combined with phacoemulsification (phaco-KDB) in patients with severe-stage glaucoma. Methods Retrospective review of 42 eyes from 36 patients with severe glaucoma who received phaco-KDB. Primary and secondary open-angle and combined-mechanism glaucoma were included. Preoperative, intraoperative, and postoperative data were collected through the 6-month follow-up period. The primary outcome was proportion of patients achieving IOP ≤15 mmHg without additional glaucoma procedures. Secondary outcomes were mean change in IOP, reduction of glaucoma medications, additional glaucoma procedures needed, and adverse events. Results Preoperative baseline mean IOP was 17.1±4.8 mmHg (mean ± SD) and number of medications was 2.4±1.3. At 6 months, 64.3% (27/42) of eyes had achieved IOP ≤15 mmHg without additional glaucoma procedures, 45.2% (19/42) reached this target IOP on fewer medications, and 31.0% (13/42) on no medications. Mean IOP reduction was 2.1±4.67 mmHg (P=0.022) and mean medication reduction was 1.2±1.4 (P≤0.001). Visually significant complications were experienced by 7.1% (3/42) of eyes, and 7.1% (3/42) required additional IOP-lowering procedures within 6 months of surgery. Conclusion Patients with severe-stage open-angle glaucoma achieved significant IOP and medication reductions following phaco-KDB. Notably, about two-thirds of eyes achieved an IOP of ≤15 mmHg at 6 months without additional glaucoma procedures. Complications and need for additional procedures were rare. Phaco-KDB may be an effective and safe alternative to more invasive filtering surgery in many patients with severe glaucoma.
Social Background: Fukuzawa Yukichi and the Transformation of Japan

Fukuzawa famously said that he lived “two lives with one body,” and this reflected the character of Japan’s social transformation in his time. In addition to outlining how Japan transformed itself in Fukuzawa’s time, Hwang introduces the two primary enemies that Fukuzawa faced in his enlightenment project: first, Confucian scholars who promoted “Eastern Ethics, Western Practice,” and second, reactionary samurais who were willing to die for the “Japanese spirit” (yamato damashii). The former offered a conservative argument that accepted Western technologies but wanted to hold onto Confucianism and Japan’s class system, while the latter was a direct ideological predecessor of the Japanese totalitarianism that led to the Pacific War. Fukuzawa courageously criticized both as harmful to Japan’s modernization and the expansion of the freedom of the Japanese people.
Changes in the growth properties of CD34+, CD38- bone marrow progenitors during human fetal development.

We have previously described the isolation of separate populations of CD34+, CD38- stromal and hematopoietic progenitors cells within fetal bone marrow. The CD34+, CD38-, CD50+, HLA-DR+ population contained the majority of primitive hematopoietic progenitor cells, whereas stromal progenitors were contained within the CD34+, CD38-, CD50-, HLA-DR- population. In this study, we compared the frequencies and total numbers of clonogenic CD34+, CD38- stromal and hematopoietic cells as a function of fetal gestational age using single-cell fluorescent- activated cell sorting (FACS). At 14 weeks of gestation, 1/500 fetal bone marrow mononuclear cells were primitive hematopoietic CD34+, CD38- , HLA-DR+ progenitor cells, whereas 1/1,000 were stromal progenitors with the CD34+, CD38-, HLA-DR- phenotype. During fetal ontogeny there was a continuous, age-dependent decrease in the frequency of stromal progenitors, such that, at 24 weeks of gestation, only 1/100,000 of bone marrow cells had the CD34+, CD38-, HLA-DR- phenotype and were clonogenic stromal cells when isolated by FACS. In contrast, 1/250 bone marrow cells in a 24-week fetus had the CD34+, CD38-, HLA-DR+ phenotype and were clonogenic hematopoietic progenitors. The decrease in the frequency of stromal progenitors was a function of both a decreased frequency of cells with the CD34+, CD38-, HLA-DR- phenotype and a decrease in the growth potential of individual with this phenotype. The total numbers of mononuclear cells and the total numbers of hematopoietic progenitors in two fetal femurs increased in parallel, 100-fold, between 14 and 24 weeks of gestation. In contrast, the total numbers of clonogenic CD34+, CD38-, HLA-DR- stromal progenitor cells remained constant during this period. Although adult bone marrow samples contained stromal progenitor cells at a frequency of approximately 1/7,000 mononuclear cells, clonogenic stromal cells with the CD34+, CD38-, HLA-DR- phenotype could not be isolated by single- cell FACS from these samples. Thus, there are significant differences between the frequencies and biologic characteristics of stromal and hematopoietic stem cells during fetal and postnatal ontogeny.
Mating-System Evolution: All Roads Lead to Selfing

Fungi reproduce via both heterothallic outcrossing and homothallic selfing modes, and transitions between the two are common throughout the tree of life. A new study reports that the transition from heterothallism to homothallism is common and has repeatedly punctuated the evolutionary trajectory across a major lineage of the fungal kingdom.
Rapid identification of compounds with enhanced antimicrobial activity by using conformationally defined combinatorial libraries

We have combined the strength of our synthetic combinatorial library approach for the rapid identification of highly active compounds with prior knowledge of the relationship between the antimicrobial activities of individual peptides with specific induced conformations in order to identify new peptides with enhanced activity relative to a starting known antimicrobial sequence. In the current study, conformationally defined combinatorial libraries were generated based on an 18-mer antimicrobial peptide known to be induced into an alpha-helical conformation in a lipidic environment. Not only were novel sequences readily identified with 10-fold increases in activity, but detailed information about the structure-activity relationships of the peptides studied was also obtained during the deconvolution process. By using circular dichroism spectroscopy it was found that the individual 18-mer peptides could be induced into alpha-helical conformations on interaction with the cell lipid layer and/or sialic acids, which could result in bacterial cell lysis due to perturbation of the lipid packing of the cell wall.
Air occlusion in insulin pumps of children and adolescents with type 1 diabetes.

Background Insulin pumps are a frequently used technology among youth with type 1 diabetes. Air bubbles within insulin pump tubing are common, preventing insulin delivery and increasing the risk of large glycemic excursions and diabetic ketoacidosis (DKA). We sought to determine the prevalence of air bubbles in insulin pump tubing and identify factors associated with clinically significant air bubbles. Methods Fifty-three subjects were recruited over 65 office visits. The insulin pump tubing was visualized, and any air bubbles were measured by length. The length of air bubbles was then converted to time without insulin at the lowest basal rate. Generalized linear model (GLM) was used to determine the associations between air bubble size and other variables. Results Of the 65 encounters, 45 had air bubbles in the tubing. Five (5/65 = 7.7%) encounters had a time without insulin of more than 60 min. Air bubble size was inversely correlated with time since infusion set change (p < 0.001), and directly correlated with age of the subject (p = 0.049). Conclusions Significantly more air bubbles were found in the tubing of insulin pumps soon after infusion set change and with older subjects, suggesting a relationship with the technique of filling the insulin cartridge and priming the tubing.
The OSI Upper Layers

Until now the concentration has been on the OSI layers responsible for building the network. The end–points of the data conversation are not responsible for the actual movement of messages but are responsible for the higher level functions to insure that the conversation meets the requirements of the final application. When the conversation is initiated, the details of the functioning of the upper levels are negotiated before data begins to flow.
A Matter of Trust: Parents’ Attitudes Toward Child Mental Health Information Sources

Mental health problems among children and adolescents are widespread. Parents seeking information about child mental health problems and treatments face numerous barriers, including fear of stigmatization and uncertainty about where to seek help. In this qualitative study, seven parents whose children had experienced a mental health, behavioral, or emotional problem were interviewed about their attitudes and beliefs about child mental health information sources. Analysis revealed that the concept of trust was an overarching theme in parents’ pursuit and evaluation of information. Related themes included a preference for information from other parents with experience parenting a child with a mental health problem; seeking information from knowledgeable professionals with whom the parents had personal relationships; concerns about confidentiality and protection of privacy; and involvement of school personnel when seeking mental health information and help. Findings support the need for improved mental health literacy among parents and suggest that social workers should play a more active role in educating families and service providers about child mental health.
BCL-6 Gene Mutations in Posttransplantation Lymphoproliferative Disorders Predict Response to Therapy and Clinical Outcome

Posttransplantation lymphoproliferative disorders (PT-LPDs) represent a heterogeneous group of Epstein-Barr virus-associated lymphoid proliferations that arise in immunosuppressed transplant recipients. Some of these lesions regress after a reduction in immunosuppressive therapy, whereas some progress despite aggressive therapy. Morphological, immunophenotypic, and immunogenotypic criteria have not been useful in predicting clinical outcome. Although structural alterations in oncogenes and/or tumor suppressor genes identified in some PT-LPDs correlate with a poor clinical outcome, the presence of these alterations has not been a consistently useful predictor of lesion regression after reduction of immunosuppression. We examined 57 PT-LPD lesions obtained from 36 solid organ transplant recipients for the presence of mutations in the BCL-6 proto-oncogene using single-strand conformation polymorphism and sequence analysis, followed by correlation with histopathologic classification and clinical outcome, which was known in 33 patients. BCL-6 gene mutations were identified in 44% of the specimens and in 44% of the patients; none were identified in the cases classified as plasmacytic hyperplasia. However, mutations were present in 43% of the polymorphic lesions and 90% of the PT-LPDs diagnosed as non-Hodgkin's lymphoma or multiple myeloma. BCL-6 gene mutations predicted shorter survival and refractoriness to reduced immunosuppression and/or surgical excision. Our results suggest that the BCL-6 gene structure is a reliable indicator for the division of PT-LPDs into the biological categories of hyperplasia and malignant lymphoma, of which only the former can regress on immune reconstitution. The presence of BCL-6 gene mutations may be a useful clinical marker to determine whether reduction in immunosuppression should be attempted or more aggressive therapy should be instituted.
The Role of Home Fungal Exposure in Allergic Fungal Rhinosinusitis.

BackgroundAllergic fungal rhinosinusitis (AFRS) is disproportionately identified in patients of low socioeconomic status living in warm, humid climates, and is thought to occur in response to envir...
Relative associations of body image avoidance constructs with eating disorder pathology in a large college student sample.

Abstract Models of eating disorder development point to the significant role body image avoidance plays in the development and perpetuation of eating disorder pathology (EDP), highlighting the importance of continued conceptual development. For example, approaches to assessing and conceptualizing body image avoidance vary in the extent to which they emphasize topography (i.e., common forms of avoidance), or their function (i.e., the conditions under which they occur). This study considered four body image avoidance constructs and their relative incremental contribution to predicting concurrent EDP in a college student population (N = 1228). Participants self-reported both the form and function of body image avoidance, including specific behaviors, appearance fixing and avoidant coping, and body image flexibility. A measure of the form of body image avoidance emerged as the best predictor of EDP, both in terms of consistently predicting aspects of disordered eating and in terms of accounting for the largest proportions of unique variance. Body image flexibility also contributed significantly to the prediction of cognitive and emotional aspects of concurrent EDP above and beyond self-report of common forms of avoidance only. Both form and function may be important when assessing and intervening on body image avoidance to prevent EDP.
Adaptive Multi-Hierarchical signSGD for Communication-Efficient Distributed Optimization

In this work, we investigate a communication-efficient multi-hierarchical signSGD (MH-signSGD) algorithm with an adaptive learning rate. Under the symmetric assumption of the stochastic gradient distribution, we show that, without the need for learning rate tuning, our proposed MH-signSGD matches the state-of-art sublinear convergence rate O(1/ $\sqrt K $) in nonconvex settings, where K is the number of iterations. Our adaptive learning strategy is based on stochastically approximating the learning rate found by greedily minimizing an error upper bound between two successive iterations. Moreover, by leveraging a normal approximation technique to characterize stochastic gradient sign error, we are able to sharpen the convergence analysis of MH-sighSGD with a fixed learning rate 1/ $\sqrt K $ and establish a strong result in the large-system regime, which says that the MH-signSGD algorithm asymptotically converges to a stationary point at rate O(1/$\sqrt M $), where M is the number of workers. In comparison, most existing work on signSGD can only prove a weaker finite neighborhood convergence in the large system regime. We validate our theoretical results experimentally both on synthetic data and real-world datasets.
Stereolithography 3D Printing of Microcapsule Catalyst-Based Self-Healing Composites

Polymer-based components manufactured by stereolithography-based (SLA) three-dimensional (3D) printing tend to show relatively poor mechanical strength compared to polymer-based components fabricat...
Semaphorin 3A mediated brain tumor stem cell proliferation and invasion in EGFRviii mutant gliomas

Glioblastoma multiforme (GBM) is the most common primary brain tumor in adults, with a median survival of approximately 15 months. Semaphorin 3A (Sema3A), known for its axon guidance and antiangiogenic properties, has been implicated in GBM growth. We hypothesized that Sema3A directly inhibits brain tumor stem cell (BTSC) proliferation and drives invasion via Neuropilin 1 (Nrp1) and Plexin A1 (PlxnA1) receptors. GBM BTSC cell lines were assayed by immunostaining and PCR for levels of Semaphorin 3A (Sema3A) and its receptors Nrp1 and PlxnA1. Quantitative BrdU, cell cycle and propidium iodide labeling assays were performed following exogenous Sema3A treatment. Quantitative functional 2-D and 3-D invasion assays along with shRNA lentiviral knockdown of Nrp1 and PlxnA1 are also shown. In vivo flank studies comparing tumor growth of knockdown versus control BTSCs were performed. Statistics were performed using GraphPad Prism v7. Immunostaining and PCR analysis revealed that BTSCs highly express Sema3A and its receptors Nrp1 and PlxnA1, with expression of Nrp1 in the CD133 positive BTSCs, and absence in differentiated tumor cells. Treatment with exogenous Sema3A in quantitative BrdU, cell cycle, and propidium iodide labeling assays demonstrated that Sema3A significantly inhibited BTSC proliferation without inducing cell death. Quantitative functional 2-D and 3-D invasion assays showed that treatment with Sema3A resulted in increased invasion. Using shRNA lentiviruses, knockdown of either NRP1 or PlxnA1 receptors abrogated Sema3A antiproliferative and pro-invasive effects. Interestingly, loss of the receptors mimicked Sema3A effects, inhibiting BTSC proliferation and driving invasion. Furthermore, in vivo studies comparing tumor growth of knockdown and control infected BTSCs implanted into the flanks of nude mice confirmed the decrease in proliferation with receptor KD. These findings demonstrate the importance of Sema3A signaling in GBM BTSC proliferation and invasion, and its potential as a therapeutic target.
Using Multi-Arm Designs to Test Operating Welfare-to-Work Programs.

Background:In the early 1970s, most researchers thought that randomized controlled trials (RCTs) could not be used to measure the effectiveness of large-scale operating welfare reform and employmen...
Chemical biology of protein citrullination by the protein A arginine deiminases

Citrullination is a post-translational modification (PTM) that converts peptidyl-arginine into peptidyl-citrulline; citrullination is catalyzed by the protein arginine deiminases (PADs). This PTM is associated with several physiological processes, including the epigenetic regulation of gene expression, neutrophil extracellular trap formation, and DNA-damage induced apoptosis. Notably, aberrant protein citrullination is relevant to several autoimmune and neurodegenerative diseases and certain forms of cancer. As such, the PADs are promising therapeutic targets. In this review, we discuss recent advances in the development of PAD inhibitors and activity-based probes, the development and use of citrulline-specific probes in chemoproteomic applications, and methods to site-specifically incorporate citrulline into proteins.
Characteristics of infants or children presenting to outpatient bronchopulmonary dysplasia clinics in the United States.

INTRODUCTION Bronchopulmonary dysplasia (BPD) is a common respiratory sequelae of preterm birth, for which longitudinal outpatient data are limited. Our objective was to describe a geographically diverse outpatient cohort of former preterm infants followed in BPD-disease specific clinics. METHODS Seven BPD specialty clinics contributed data using standardized instruments to this retrospective cohort study. Inclusion criteria included preterm birth (<37 weeks) and respiratory symptoms or needs requiring outpatient follow-up. RESULTS A total of 413 preterm infants and children were recruited (mean age: 2.4 ± 2.7 years) with a mean gestational age of 27.0 ± 2.8 weeks and a mean birthweight of 951 ± 429 grams of whom 63.7% had severe BPD. Total, 51.1% of subjects were nonwhite. Severe BPD was not associated with greater utilization of acute care/therapies compared to non-severe counterparts. Of children with severe BPD, differences in percentage of those on any home respiratory support (p = .001), home positive pressure ventilation (p = .003), diuretics (p < .001), inhaled corticosteroids (p < .001), and pulmonary vasodilators (p < .001) were found between centers, however no differences in acute care use were observed. DISCUSSION This examination of a multicenter collaborative registry of children born prematurely with respiratory disease demonstrates a diversity of management strategies among geographically distinct tertiary care BPD centers in the United States. This study reveals that the majority of children followed in these clinics were nonwhite and that neither variation in management nor severity of BPD at 36 weeks influenced outpatient acute care utilization. These findings suggest that post-neonatal intensive care unit factors and follow-up may modify respiratory outcomes in BPD, possibly independently of severity.
3D Encapsulation and tethering of functionally engineered extracellular vesicles to hydrogels

Mesenchymal stem cell (MSC) derived extracellular vesicles (EVs) in their naive and engineered forms have emerged as potential alternatives to stem cell therapy. While they have a defined therapeutic potential, the spatial and temporal control of their activity in vivo remains a challenge. The objective of this study was to devise a methodology to encapsulate EVs in 3D hydrogels for prolonged delivery. To achieve this, we have leveraged the MSC EV interactions with ECM proteins and their derivative peptides. Using osteoinductive functionally engineered EVs (FEEs) derived from MSCs, we show that FEEs bind to mimetic peptides from collagen (DGEA, GFPGER) and fibronectin (RGD). In in vitro experiments, photocrosslinkable alginate hydrogels containing RGD were able to encapsulate, tether and retain the FEEs over a period of 7 days while maintaining the structural integrity and osteoinductive functionality of the EVs. When employed in a calvarial defect model in vivo, alginate-RGD hydrogels containing the FEEs enhanced bone regeneration by a factor of 4 compared to controls lacking FEEs and by a factor of 2 compared to controls lacking the tethering peptide. These results show that EVs can be tethered to biomaterials to promote bone repair and the importance of prolonged delivery in vivo. Results also provide a prelude to the possible use of this technology for controlled delivery of EVs for other regenerative medicine applications. STATEMENT OF SIGNIFICANCE: The beneficial effects of human MSC (HMSC) therapy are attributable to paracrine effects of the HMSC derived EVs. While EV engineering has the potential to impact several fields of regenerative medicine, targeted delivery of the engineered EVs with spatial and temporal control is necessary to prevent off-target effects and enhance tissue specificity. Here, we have leveraged the interactions of MSC EVs with ECM proteins to develop a tethering system that can be utilized to prolong EV delivery in vivo while maintaining the structural and functional integrity of the EVs. Our work has provided a tunable platform for EV delivery that we envision can be formulated as an injectable material or a bulk hydrogel suitable for regenerative medicine applications.
Trait-Based Variation in the Foraging Performance of Individuals

Although average, species-level interaction strength plays a key role in driving population dynamics and community structure, predator-prey interactions occur among individuals. As a result, individual (or intra-specific more generally) variation in foraging rates may play an important role in determining the effects of predator-prey interactions on communities. Such variation in foraging rates stems from individual variation in traits that influence the mechanistic components of the functional response, such as movements that determine encounters and behaviors such as decisions to attack. However, we still have little information about individual-level variation in functional responses or the traits that give rise to such variation. Here we combine a standard functional response experiment with wolf spiders foraging on fruit flies with a novel analysis to connect individual morphology, physiology, and movement to individual foraging performance. We found substantial variation in traits between males and females, but these were not clearly linked to the differences in the functional response between males and females. Contrary to expectations, we found no effect of body velocity, leg length, energetic state, or metabolic rate on foraging performance. Instead, we found that body mass interacted with body rotations (clockwise turns), such that larger spiders showed higher foraging performance when they turned more but the reverse was true for smaller spiders. Our results highlight the need to understand the apparent complexity of the links between the traits of individuals and the functional response.
A COMPARISON OF THE IMPACT OF TWO HOSPITALS’ PHYSICAL ENVIRONMENTS ON SOCIAL SUPPORT FOR CHILDREN WITH CANCER AND THEIR FAMILIES

Social support has been shown to positively influence coping and healthcare outcomes.1 Family-to-family support does not seek to replace professionally-mediated support, but rather is a unique resource that promotes individual and family strengths through shared experience. Objective To describe and compare the ways in which the physical aspects of a US hospital with a single patient room plan and a UK hospital with an open ward plan affect social support for children with cancer and their families Methods Participants included 22 hospitalized children ages 7–18 years receiving treatment for cancer in the US or UK. Quantitative and qualitative methods were used within a grounded theory approach, and included interview, observation, and three drawings (Person Picking an Apple from a Tree, Scariest Image, Closure). Results Children and parents at the US site received limited support from other children and parents. Children and families at the UK site received a high level of support from other children and families. Conclusion Hospital environments affect the opportunity for supportive relationships. Hospitals that provide spaces for children and families to interact with other children and families promote social interaction, which leads to a higher level of social support than hospital environments that do not or that provide them in less accessible areas.2
Law and the Private Sector in Tanzania

Policy makers and scholars increasingly have acknowledged the role that law and legal institutions play in the economic development process. Much of the recent literature on law reform in developing and transition countries focuses primarily on the supply of legal institutions by the state – the assumption is that, as long as the state supplies properly-designed laws and legal institutions, the desired results will automatically follow. This condition may be necessary, but it is not sufficient. The “law and development” literature largely ignores other factors that shape levels of social demand for reformed laws and legal institutions. For law to play a role in promoting economic development, and more generally for the rule of law to emerge in Africa, law and legal institutions must matter to social actors. If law is irrelevant to private sector actors, it is largely irrelevant to private sector development. Under what conditions will law become relevant and meaningful to social actors in Africa? Synthesizing theoretical insights from socio-legal studies and the new institutional economics, the paper hypothesizes that private sector demand for law is a function of both (1) the characteristics of transactional networks within business communities and (2) the perceived credibility of the state-provided legal system. Demand for law is shaped by the characteristics of both informal social institutions and formal state-supplied legal institutions. The paper examines this hypothesis by analyzing survey data collected from business firms in Dar es Salaam, Tanzania. Probit analysis of the data suggests that demand for law among private sector actors is very much shaped by informal market institutions – the characteristics of business networks developed and maintained by firms. The results suggest further that these “demand side” variables matter more than the perceived quality and credibility of the legal system in the eyes of private sector actors, a “supply side” variable emphasized in the social science literature. The paper concludes by considering the implications of these findings for law and development research.
Design and manufacturing considerations for 0.25-1.5 meter beryllium telescopes for current and future space missions

Recently there has been resurging interest in beryllium telescopes ranging in aperture from 0.25-1.5 meter for various NASA space missions. The central theme for this discussion is axially symmetric, all beryllium telescope design forms that are part of advanced LIDAR altimetry systems used to measure the topography and relative density of surface and atmospheric features on the earth and on other planetary bodies. Similar NASA LIDAR missions have previously been sent to Earth’s orbit, the Moon, Mars, and are under consideration for other surveys within the solar system. Design considerations include achieving minimized mass simultaneous with demanding structural, thermal, and optical requirements on orbit after sustaining the rigors of space launch. Modern analysis tools and modeling techniques enable simulation of telescope wavefront errors resulting from environmental effects and the influences of bi-metallic bending from platings. Manufacturing considerations include progressive machining, diamond point turning, coordinate measurement machine profilometry, computerized grinding and polishing, brazing of complex beryllium structures, very thin electroless nickel plating, and other advanced manufacturing technologies imperative to successful visible–infrared optical performance. Recent design and manufacturing efforts on 0.60, 0.80, and 1.0 meter beryllium telescopes are profiled to illustrate the confluence of applicable design and manufacturing technologies.
Chapter 8. Computer simulation of surface diffusion in adsorbed phases

Publisher Summary The basic idea behind computer simulation is to use the power of the computer to bypass the simplifying assumptions made in the past to pass from a molecular model of the adsorption system to the evaluation of its observable, macroscopic properties. In essence, one defines the solid adsorbent in terms of its interaction energies with gas molecules that come in contact with its surface. This model is completed by defining the interactions of the adsorbate molecules with each other. The simulation that can then be performed relies on one of the two general algorithms: Monte Carlo or molecular dynamics. For both, tricks are needed to make such systems mimic the macroscopic adsorption of a gas on (or in) a solid: the potential energies of interaction must be modeled accurately, but not so accurately as to prevent the computer from evaluating them in a reasonable time; and periodic boundary and minimum image conditions must be applied to allow one to associate the properties of a few hundred molecules with those of a macroscopic fluid.
Isolation of a yeast gene involved in species-specific pre-tRNA processing.

Abstract To identify genes involved in pre-tRNA processing, we searched for yeast DNA sequences that specifically enhanced the expression of the SUP4(G37) gene. The SUP4(G37) gene possesses a point mutation at position 37 of suppressor tRNA(Tyr). This lesion results in a reduced rate of pre-tRNA splicing and a decreased level of nonsense suppression. A SUP4(G37) strain was transformed with a yeast genomic library, and the transformants were screened for increased suppressor activity. One transformant contained a plasmid that encoded an unessential gene, STP1, that in multiple copies enhanced the suppression of SUP4(G37) and caused increased production of mature SUP4(G37) product. Disruption of the genomic copy of STP1 resulted in a reduced efficiency of SUP4-mediated suppression and the accumulation of pre-tRNAs. Not all intron-containing pre-tRNAs were affected by the stp1-disruption. At least five of the nine families of pre-tRNAs were affected. Two other species, pre-tRNA(Ile) and pre-tRNA(3Leu), were not. We propose that STP1 encodes a tRNA species-specific product that functions as a helper for pre-tRNA splicing. The STP1 product may interact with pre-tRNAs to generate a structure that is efficiently recognized by splicing machinery.
Stackelberg Solutions for Nonlinear Games with Symmetries

It is shown that a symmetry in a Stackelberg game problem induces a reduction of the differential equation, which must be solved to determine the open-loop Stackelberg equilibrium solution, to one of lower dimension. This indicates a possibly more efficient method for solving such problems.
Benzotriazole-1-carboxamidinium Tosylate: An Alternative Method for the Conversion of Amines to Guanidines

Abstract A novel, effective and convenient reagent for the conversion of amines to guanidines is presented. Various primary and secondary amines react with benzotriazole-1-carboxamidinium tosylate (1) to give the corresponding guanidines in good yields under mild conditions.
Domain specificity in social interactions, social thought, and social development.

J. E. Grusec and M. Davidov (this issue) have taken good steps in formulating a domain-specific view of parent–child interactions. This commentary supports the introduction of domain specificity to analyses of parenting. Their formulation is an advance over formulations that characterized parental practices globally. This commentary calls for inclusion of definitions of the classification system of domain-specific interactions and criteria for each domain. It is also maintained that Grusec and Davidov’s domains of social interaction imply that processes of development are involved, along with socialization; that bidirectionality in parent–child relations needs to be extended to include mutual influences and the construction of domains of social thought; and that conflicts and opposition within families coexist with compliance and social harmony.
Orthostatic stability with intravenous levodopa

Intravenous levodopa has been used in a multitude of research studies due to its more predictable pharmacokinetics compared to the oral form, which is used frequently as a treatment for Parkinson's disease (PD). Levodopa is the precursor for dopamine, and intravenous dopamine would strongly affect vascular tone, but peripheral decarboxylase inhibitors are intended to block such effects. Pulse and blood pressure, with orthostatic changes, were recorded before and after intravenous levodopa or placebo-after oral carbidopa-in 13 adults with a chronic tic disorder and 16 tic-free adult control subjects. Levodopa caused no statistically or clinically significant changes in blood pressure or pulse. These data add to previous data that support the safety of i.v. levodopa when given with adequate peripheral inhibition of DOPA decarboxylase.
2‐Chloroethyl Dichloromethyl Ether

[13930-34-7] C3H5Cl3O (MW 163.44) InChI = 1S/C3H5Cl3O/c4-1-2-7-3(5)6/h3H,1-2H2 InChIKey = YDZZMFTYJPHETL-UHFFFAOYSA-N (reagent for forming cyclopropanols from alkenes1) Alternate Name: dichloromethyl 2-chloroethyl ether. Physical Data: bp 106–110.5 °C/10 mmHg. Solubility: sol most organic solvents. Preparative Method: not commercially available. It can be prepared by the action of Phosphorus(V) Chloride on β-chloroethyl formate (eqs 1 and 2).2, 3 (1) (2)
Abstract 262: Association of Lipoprotein Subclasses with Arterial Stiffness in a High Risk Working Population: The Baptist Employee Healthy Heart Study (BEHHS)

Introduction: Arterial stiffness is an independent predictor of cardiovascular disease (CVD) morbidity and mortality, and has been shown to be of prognostic value in CVD. A risk factor independent association between arterial stiffness and traditional lipids has been described extensively but it is unclear whether an independent relationship exists with lipoprotein subclasses. Methods: The Baptist Employee Healthy Heart Study (BEHHS) is a lifestyle intervention study examining the effects of web-based programs on reducing CVD risk in high-risk persons. Participants had their brachial arterial augmentation index (AIx, a measure arterial stiffness) assessed using the EndoPAT 2000 device. The AIx is standardized to gender-matched non-selective populations. Cardio IQ™ Ion Mobility lipoprotein fractionation was utilized for advanced lipid subclass measurement. Results: The population consisted of 182 participants, (74% women, 49% Hispanic) with a mean age of 52 ± 9 years. There was a significant trend associat...
Utilization of blood and components in a tertiary care hospital.

Purpose Blood transfusion is an important part of patient management. Indications for blood use must be clear in the mind of ordering clinicians, to avoid its misuse and also to avoid unnecessary exposure of the patient to donor blood antigens, adverse reactions and transfusion transmissible diseases.
Feeding rate of slimy sculpin and burbot on young lake charr in laboratory reefs

Predation and contaminants are two possible factors in the poor recruitment of young lake charr Salvelinus namaycush in the Great Lakes. We measured the feeding rate of slimy sculpins Cottus cognatus and burbot Lota lota on young lake charr (uncontaminated young from eggs of a hatchery brood stock and contaminated young from eggs of Lake Michigan lake charr) in laboratory test chambers with a cobble substrate. The median daily consumption rate of sculpins for all tests was 2 lake charr eggs (N = 22 tests; 95% confidence interval, 0–13) and 2 lake charr free embryos (N = 31 tests; 95% confidence interval, 0–10). Feeding rate did not differ between hatchery and contaminated prey. Slimy sculpins continued to feed on lake charr when another prey organism, the deepwater amphipod Pontoporeia hoyi, was present. Feeding by burbot on free embryos (4–36 d−1) increased as the mobility of young increased, but burbot consumed about 10% of their body weight weekly in free-swimming young (140–380 d−1). Predation on lake charr eggs by sculpins could be considerable over the 100 to 140 d incubation period, and burbot could eat large numbers of free-swimming lake charr as the young fish left the reef. Predation pressure on young lake charr may inhibit rehabilitation of self-sustaining populations of lake charr on some reefs unless a critical egg density has been reached.