cssi/SciSciGPT-SciSciNet huggingface dataset:
Melatonin inhibits nitric oxide signaling by increasing PDE5 phosphorylation in coronary arteries.

Melatonin inhibits nitric oxide (NO)-induced relaxation of coronary arteries. We tested the hypothesis that melatonin increases the phosphorylation of phosphodiesterase 5 (PDE5), which increases the activity of the enzyme and thereby decreases intracellular cGMP accumulation in response to NO and inhibits NO-induced relaxation. Sodium nitroprusside (SNP) and 8-Br-cGMP caused concentration-dependent relaxation of isolated coronary arteries suspended in organ chambers for isometric tension recording. In the presence of melatonin, the concentration-response curve to SNP, but not 8-Br-cGMP, was shifted to the right. The effect of melatonin on SNP-induced relaxation was abolished in the presence of the PDE5 inhibitors zaprinast and sildenafil. Melatonin markedly inhibited the SNP-induced increase in intracellular cGMP in coronary arteries, an effect that was also abolished by zaprinast. Treatment of coronary arteries with melatonin caused a nearly fourfold increase in the phosphorylation of PDE5, which increased the catalytic activity of the enzyme and thereby increased the degradation of cGMP to inactive 5′-GMP. Melatonin-induced PDE5 phosphorylation was markedly attenuated in the presence of the PKG1 inhibitors DT-2 or Rp-8-Br-PET-cGMPS and in those arteries in which PKG1 expression was first downregulated by 24-h incubation with SNP before exposure to melatonin. The selective MT2 receptor antagonist 4-phenyl-2-propionamidotetralin completely blocked the stimulatory effect of melatonin on PDE5 phosphorylation as well as the inhibitory effect of melatonin on SNP-induced relaxation and intracellular cGMP. Thus, in coronary arteries, melatonin acts via MT2 receptors and PKG1 to increase PDE5 phosphorylation, resulting in decreased cGMP accumulation in response to NO and impaired NO-induced vasorelaxation.
What parents say about their child's surgeon: Parent-reported experiences with pediatric surgical physicians

Importance Reviews of patient and caregiver experience with health practitioners are increasingly important to consumers. Understanding physician qualities valued by patients and their families may facilitate more effective care and communication. Objective To identify physician qualities and care dimensions valued by parents during their child’s outpatient surgical care encounter. Design Mixed-methods analysis of comments from patient-satisfaction surveys. Setting Outpatient pediatric otolaryngology and surgical specialty clinics in an urban tertiary care center. Participants Parents of children seen in pediatric otolaryngology and surgical specialty clinics who completed the physician section of the patient satisfaction survey. Main Outcomes and Measures Free-text comments written in the physician section of the survey. Results A total of 195 survey comments from visits to 18 surgical specialty clinics were analyzed; 64 comments (33%) were global in nature, of which 58 (90%) were positive; 25 of 195 comments (13%) discussed recommendation of care. Of the 131 comments (67%) with specific content, 79 (60%) were positive. Major themes were physician interpersonal style (n = 78, 45%), physician technical skills/knowledge/preparation (n = 82, 47%), and systems issues (n = 14, 8%). The most commonly noted interpersonal subthemes were inclusion/interaction with the child (20%) and empathy/concern for the patient’s needs (29%). The most common skills themes related to whether the physician answered questions (16%) or explained treatment (23%). The most common negative subgroup was inadequate explanation of treatment (18%). The majority of comments related to systems were negative (13 of 14, 93%). Conclusions and Relevance Parents highly value physician interpersonal style and visit-specific skills (involving the child in discussion; showing empathy/concern for the patient/family; answering questions; explaining treatment). While most comments about surgeons were affirmative, clinical systems were more often negatively perceived. Attention to parent-reported experiences may help physicians improve communication and overall effectiveness of care provided.
Inflation, agency costs, and equity returns

Abstract The widely observed negative correlation between inflation and real equity returns is, in part, explained by the proxy hypothesis (Fama, 1981) according to which the negative correlation is simply induced by inflation and real equity returns reacting oppositely to news about future real output growth. However, controlling for output growth does not fully eliminate this negative correlation. I argue that agency costs increase with the relative price variability (RPV) that tends to accompany inflation, and find evidence that variations in RPV explain much of the negative relationship between inflation and real equity returns that persists after controlling for output growth. Keywords: Inflation; Relative price variability; Agency costs JEL classification: E31; E44; D82
Maximum-likelihood nonlinear transformation for acoustic adaptation

In this paper, we describe an adaptation method for speech recognition systems that is based on a nonlinear transformation of the feature space. In contrast to most existing adaptation methods which assume some form of affine transformation of either the feature vectors or the acoustic models that model the feature vectors, our proposed method composes a general nonlinear transformation from two transformations, one of these being an affine transformation that combines the dimensions of the original feature space, and the other being a nonlinear transformation that is applied independently to each dimension of the previously transformed feature space leading to a general multidimensional nonlinear transformation of the original feature space. This method also differs from other affine techniques in the way the parameters of the transform are shared. In most previous methods, the parameters of the transformation are shared on the basis of the phonetic class, in our method, the parameters of the nonlinear transformation are shared not on the basis of the phonetic class, but rather on the location in the feature space. Experimental results show that the method outperforms affine methods providing up to a 25% relative improvement in the word error rate in an in-car speech recognition task.
Rapid and efficient glycoprotein identification through microwave-assisted enzymatic digestion

Identification of protein glycosylation sites is analytically challenging due to the diverse glycan structures associated with a glycoprotein. Mass spectrometry (MS)-based identification and characterization of glycoproteins has been achieved predominantly with the bottom-up approach, which typically involves the enzymatic cleavage of proteins to peptides prior to LC/MS or LC/MS/MS analysis. However, the process can be challenging due to the structural variations and steric hindrance imposed by the attached glycans. Alternatives to conventional heating protocols, that increase the rate of enzymatic cleavage of glycoproteins, may aid in addressing these challenges. An enzymatic digestion of a glycoprotein can be accelerated and made more efficient through microwave-assisted digestion. In this paper, a systematic study was conducted to explore the efficiency of microwave-assisted enzymatic (trypsin) digestion (MAED) of glycoproteins as compared with the conventional method. In addition, the optimum experimental parameters for the digestion such as temperature, reaction time, and microwave radiation power were investigated. It was determined that efficient tryptic digestion of glycoproteins was attained in 15 min, allowing comparable if not better sequence coverage through LC/MS/MS analysis. Optimum tryptic cleavage was achieved at 45°C irrespective of the size and complexity of the glycoprotein. Moreover, MAED allowed the detection and identification of more peptides and subsequently higher sequence coverage for all model glycoprotein. MAED also did not appear to prompt a loss or partial cleavage of the glycan moieties attached to the peptide backbones.
Can CATV availability reach that of the TELCOs? The road to 5NINES!

This paper discusses hardware, software, and human factors affecting cable television availability, and examines what can be done with each of these factors to enhance system availability. Factors are examined from a cost/benefit analysis standpoint. The paper notes that hardware redesign is expensive and yields only a one order of magnitude increase in availability. On the other hand, simple things like better training, education, and sparing of components-all of which are relatively cheap-can enhance availability by up to three orders of magnitude.
Extramacular Disciform Lesions Simulating Uveal Tumors

Purpose: The purpose of this study is to identify clinical, ultrasonographic, and fluorescein angiographic features of extramacular disciform lesions that allow differentiation from uveal tumors. Methods: This was a retrospective study of 19 patients referred to our ocular oncology unit with a possible malignancy who had a diagnosis of an extramacular disciform lesion made after complete evaluation. Results: The level of accuracy for each diagnostic technique alone was as follows: clinical (79%), ultrasonography (83%), and angiography (83%). Fluorescein angiography had limited utility because of severe media opacities in seven cases. No tumor developed an intraocular malignancy during the follow-up period. Conclusion: A combination of the above, noninvasive techniques can be used to correctly diagnose extramacular disciform lesions.
Relationships Between Short Fiber Content and HVI Fiber Length Uniformity

Fibrogram theory indicates that short fiber content (SF) should be negatively related to the uniformity index (UI), defined as the ratio of the mean length to the upper half mean length expressed a...
Linezolid for the Treatment of Resistant Gram-Positive Cocci

OBJECTIVE:To provide a comprehensive review of linezolid, the first of a new class of antibiotics, the oxazolidinones. Therapeutic issues regarding the emergence of multidrug-resistant bacteria and a brief history of the oxazolidinones are also discussed.DATA SOURCES:A MEDLINE search (1966–March 2001) was conducted to identify pertinent literature, including preclinical trials, clinical trials, and reviews. Unpublished clinical data, adverse effects, and dosing information were abstracted from product labeling.STUDY SELECTION:Clinical efficacy data were extracted from clinical trials, case reports, and abstracts that mentioned linezolid. Additional information concerning antibiotic resistance, the oxazolidinones, in vitro susceptibility, and the pharmacokinetic profile of linezolid also was reviewed.DATA SYNTHESIS:Linezolid exhibits activity against many gram-positive organisms, including vancomycin-resistant Enterococcus faecium, methicillin-resistant Staphylococcus aureus, and penicillin-resistant Strep...
Strain and violence: Testing a general strain theory model of community violence

Agnew's General Strain Theory (GST) has come to be recognized as an increasingly important explanation for violence at the individual level. Drawing on this individual level theory, Agnew [Journal of Research in Crime and Delinquency 36 (1999) 123] recently suggested that GST might also be applicable to explaining variations in community crime rates. This macro level General Strain Theory (MST) has, however, rarely been empirically examined. This article provides an examination of some of the central ideas in Agnew's MST using data from sixty-six neighborhoods in a southern state. The findings presented here suggest that neighborhood disadvantage and stability significantly affect neighborhood levels of strain. In turn, strain significantly affects levels of violence. The extent to which the effects of strain on violence are conditioned by levels of informal social control and social support/capital are also examined in this article. The results are partially supportive of MST.
A 26-Year-Old Woman With Systemic Lupus Erythematosus Presenting With Orthopnea and Restrictive Lung Impairment

A 26-year-old white woman diagnosed with systemic lupus erythematosus (SLE) presented with left shoulder pain and a three-pillow orthopnea. Lupus was diagnosed at age 21 years when she developed arthritis, and she has been maintained on prednisone (2.5 mg) and mycophenolate (500 mg bid). In the course of evaluating her new symptoms, imaging revealed a small left pleural effusion with exudative characteristics on a diagnostic thoracentesis, but there was no evidence of infection. Her immunosuppression treatment was increased to 1,000 mg bid of mycophenolate and 20 mg of prednisone. Three months later, she presented to our clinic with worsening six-pillow orthopnea, such that she usually slept with 45° truncal elevation on a recliner at night. She was unable to lie flat. Her dyspnea was worse in the mornings, and she described having to "gasp" for air.
C4 EM and CPI Reliability Benefits and Process Challenges of FBEOL Integration Changes Implemented in Lead-free C4 Products

The introduction of low-k & ultra-low-k dielectrics, lead-free (Pb-free) solder interconnects or C4's, and organic flip-chip laminates for integrated circuits have led to some major reliability challenges for the semiconductor industry. These include C4 electromigration (EM) and mechanical failures induced with-in the Si chip due to chip-package interactions (CPI). In 32nm technology, certain novel design changes were evaluated in the last Cu wiring level and the Far Back End of Line levels (FBEOL) to strategically re-distribute the current more uniformly through the Pb-free C4 bumps and therefore improve the C4 EM capabilities of the technology. FBEOL process integration changes, such as increasing the thickness of the hard dielectric (SiNx & SiOx) and reducing the final via diameter, were also evaluated for reducing the mechanical stresses in the weaker BEOL levels and mitigating potential risks for mechanical failures within the Si chip. The supporting white-bump, C4 EM and electrical/mechanical modeli...
Cdc45-induced alterations in replication fork stability enhance cell sensitivity to camptothecin

AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA 3209 Topoisomerase I (Top1) functions in DNA replication and transcription by catalyzing changes in DNA topology through a mechanism of transient DNA strand breakage and rejoining. Top1 is also the target of camptothecin (CPT), FDA approved analogs of which are effective new agents in the treatment of human cancers. CPT poisons Top1 by reversibly stabilizing a covalent enzyme-DNA complex. During S-phase, the collision of replication forks with CPT-Top1-DNA adducts produces DNA lesions that signal cell cycle arrest and cell death. Yet, little is known of the interactions with the replication machinery required for the formation of Top1-DNA damage. In yeast genetic screens, we isolated temperature sensitive mutants with enhanced sensitivity to Top1-DNA damage. Our characterization of yeast cdc45-10 and dpb11-10 mutants revealed functional links between the initiation of DNA replication and replication fork progression in mediating cell sensitivity to CPT. Cdc45 and Dpb11 are essential proteins, with well-defined human orthologs, CDC45 and TOPBP1, respectively. Cdc45 functions in pre-replicative complex (pre-RC) formation at origins of replication in G1 phase, and, in concert with Mcm2-7, forms the replicative helicase as forks progress along the DNA in S-phase. Here we show that a decrease in active Cdc45 enhanced yeast and human cell sensitivity to CPT-induced Top1 damage. 2-D gel analyses of origin firing and fork progression in cdc45-10 mutant cells determined that when pre-RCs, formed at 26°C, were shifted to 36°C to complete S-phase, origin firing was delayed relative to wild-type cells, but replication fork progression was unaffected. However, when pre-RCs were formed at 36°C, the replication forks formed in S-phase were extremely unstable. In the presence of CPT induced Top1-DNA adducts, such adverse effects on fork stability would increase the potential for fork collapse and the formation of lethal DNA lesions. To further investigate Cdc45 function, a gene dosage screen isolated suppressors of cdc45-10 sensitivity to Top1 poisons. Increased gene dosage of the SUMO E3 ligase, Siz1, partially restored the CPT resistance of cdc45-10 cells; however, it did not restore the viability of a double cdc45-10 , dpb11-10 mutant. These findings led us to ask if mutating the unique SUMO consensus Cdc45SUMO affected its role in DNA replication. Although cell sensitivity to CPT was unaffected, Cdc45SUMO failed to complement the synthetic lethal phenotype of the cdc45-10, dpb11-10 mutant. These data suggest that SUMO modification of Cdc45 is important for the common essential function with Dpb11. Indeed, SUMO-induced alterations in Cdc45 association with the replication machinery are being investigated in ChIPs. Together, our findings indicate the SUMO-dependent functional interactions of Cdc45 with Dpb11 are distinct from Cdc45’s function in maintaining replication fork stability in the presence of CPT.
An unusual presentation of catastrophic failure of hip arthroplasty with a thigh mass

In the advent of increasing demand for total hip arthroplasty, surveillance of these patients is imperative to identify potential complications requiring revision surgery. This is especially important in the young population, as revision is usually necessary during their lifetime. We present a case of a young female patient with a history of total hip arthroplasty 17 years prior, who presented with left hip pain and anterior thigh mass. The prosthetic hip had progressed to catastrophic failure with the cobalt-chrome femoral head having eroded through the polyethylene and acetabular socket. This was associated with significant metal debris and large fluid collection in the thigh. The patient required complex revision surgery but could have had a much lesser procedure with earlier intervention.
Genetic mapping of a major locus controlling pyrethroid resistance in Tribolium castaneum (Coleoptera : Tenebrionidae)

Tribolium castaneum (Herbst) strain QTC279 is highly resistant to deltamethrin and other synthetic pyrethroids. This strain was shown to carry at least 1 resistance gene, PyR-1, on linkage group 9, approximately 20 map units from the visible mutant marker, pearl. Three-point mapping involving pearl and another visible mutant marker, cola, indicated a gene order of pearl-cola-PyR-1. Evidence of a 2nd LG9-linked resistance factor (R) mapping in the gene order R-p-co was also observed. Other resistance factors were clearly present in QTC279, but were not genetically mapped. Piperonyl butoxide, an inhibitor of cytochrome P450-mediated oxidative metabolism, significantly increased the toxicity of deltamethrin to a strain derived from QTC279 that carries PyR-1, strain pR. Compared to susceptible beetles, QTC279 and pR had elevated and comparable levels of cytochrome P450 protein. The significance of pyrethroid resistance in T. castaneum is discussed.
Bounds for eigenvalues of matrix polynomials with applications to scalar polynomials

Abstract We first generalize to complex matrix polynomials an improvement of an upper bound by Cauchy on the zeros of complex scalar polynomials. The bound requires the unique positive root of a real scalar polynomial of the same degree as the given complex scalar or matrix polynomial. We then create a recursive procedure to represent a matrix polynomial by another matrix polynomial of larger size, but of lower degree. We apply this procedure to scalar polynomials, and then apply the generalized improved Cauchy bound to their matrix polynomial representation, often obtaining a better bound by solving a real scalar polynomial equation of significantly reduced degree.
REE Geochemical Characters of the Guocheng Gold Deposit,Eastern Shandong Province and Its Significance to Mineralizations

The Guocheng gold deposit,which is located in the northeastern margin of the Jiaolai Basin,with orebodies occurring in the Jingshan Group and ores predominately pyritized and pyrrhotitized,formed under more special geological conditions compared with other gold deposits in Jiaodong Peninsula. The REE analyses for Guocheng gold ore,Muniu mountains rock and mafic dikes were carried out using the method of ICP-MS and the source of ore-forming material and ore-forming fluid was discussed in this paper. The results show that REE Partition curves have two types,including rightist and flat type. The flat-type partition curve of ore is similar,in strong correlation,to that of granite,while the rightist-type partition curve of ore is analogous,in good correlation,to that of dikes. The late carbonated ore has high rare earth content. And there is an obvious negative Eu anomaly in ores except dikes. It indicates that the ore-forming materials are derived from Muniu mountains rock and deep crust,while the ore-forming fluid is derived from deep magma evolution. The formation of the orebody involves multi-stages.
The abuse of volatile substances.

Common practices involving the inhalation of volatile substances are reviewed in this article. The clinical syndromes and toxicities resulting from use of these agents are presented. The agents reviewed are toluene, gasoline, halogenated hydrocarbons, nitrous oxide, and the alkyl nitrites.
Abstract 4977: Immunogenic chemotherapy synergize PD-1 blockade by enhancing dendritic cells infiltration in triple-negative breast cancer (TNBC)

Targeting immune checkpoints such as programmed cell death protein 1 (PD1), programmed cell death 1 ligand 1 (PDL1) has achieved noteworthy benefit in multiple cancers. However, their efficacy remains unsatisfactory in triple-negative breast cancer (TNBC). Breast cancer is not highly mutagenic and immune checkpoints blockade therapies for TNBC is not as effective as for melanoma or lung cancer with high mutation rates. Combination of different modalities offers an opportunity to enhance their effect. We studied the synergistic effect of cancer chemotherapy and immunotherapy in TNBC mouse model. Here we report that the combination of Doxisome (liposomal encapsulated formulation of Doxorubicin) and anti-PD-1 antibody suppresses tumor growth, reduces lung metastasis and improves survival of mice bearing 4T1-triple negative breast cancer. Moreover, the combination of Doxisome and anti-PD-1 was able to overcome low dose Doxisome resistance in mouse models of TNBC. The success of anticancer chemotherapy is linked to a durable immune response of targeting tumor. We present evidence that the synergistic therapeutic activity of Doxisome with anti-PD1 blockade results in enhanced T cell anti-tumor immune responses. Moreover, the synergetic effect is due to increased dendritic cells (DCs) infiltration in tumor microenvironment, which internalize tumor antigens and subsequently activate tumor-reactive T cells. In TNBC mouse model, by combining anti-PD1 checkpoint blockade while shifting the immune response towards CD4+ Th1 with Doxisome, immune tolerance to TNBC tumor can be overcome. Enhancing antigen presenting cells (APCs, e.g. DCs) infiltration by immunogenic chemotherapy and T cell activation by anti-PD1 blockade increase therapy response in TNBC. These results provide rationale for several newly planned clinical trials combining immunogenic chemotherapy with PD-1 or PD-L1 blockade in breast cancer and exploration of such a combination in others solid tumors. Citation Format: Xiangliang Yuan, Yi Xiao, Wenling Kuo, Dihua Yu. Immunogenic chemotherapy synergize PD-1 blockade by enhancing dendritic cells infiltration in triple-negative breast cancer (TNBC). [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4977.
Negative Radiation Resists

In Chapter 4, we discussed negative photoresist compositions and polymeric factors which affect resolution; in Chapter 3, we considered exposure tools and radiation chemistry principles; and in Chapter 10, we discuss the swelling of negative resists in a developer. These chapters form the principal backgrounds for the processing aspects of negative radiation resists.
Neuromuscular responses differ between slip-induced falls and recoveries in older adults.

A central question relevant to the prevention of falls is: How does the robust control of walking and balance break down during a fall? Previous work has focused on muscle coordination during succe...
Comparison of Yttrium-90 therapy for unresectable liver metastasis: glass versus biocompatible resin microspheres

Yttrium-90 radioembolization is a hepatic intra-arterial-based therapy using glass- or resin-based microspheres as carriers to deliver high-dose radiation to tumors to maximize dose while minimizing collateral damage. This study aimed to compare the safety and efficacy of glass (TheraSphere) versus resin (Selective Internal Radiation Spheres, SIR-Spheres) Y-90 in the treatment of intrahepatic metastatic disease. A review of a prospectively collected, institutional review board-approved database was conducted to identify patients who underwent Y-90 therapy, excluding those with hepatocellular carcinoma (HCC). Of 119 patients, 79 received SIR-Spheres and 40 received TheraSphere therapy. For intrahepatic cholangiocarcinoma, mean survival was 10.6 months in the SIR-Spheres group compared to 29.2 months in the TheraSphere group (log-rank 0.05). In colorectal cancer (CRC), mean survival was 16.3 months for SIR-Spheres therapy and 26.8 for TheraSphere therapy (log-rank 0.097). There were no documented severe (grade 3) side effects in the TheraSphere group compared to 14 % of patients who experienced side effects in the SIR-Spheres group. TheraSphere microsphere appears superior to SIR-Spheres in treating non-HCC intrahepatic malignancy. However, patient selection and better multi-disciplinary care may play a role in these differences. Continued studies in combination therapies for all hepatic malignancies is critical to the long-term success and sustainability of Y-90 therapy.
Soil microbial communities buffer physiological responses to drought stress in three hardwood species.

Trees possess myriad adaptations for coping with drought stress, but the extent to which their drought responses are influenced by interactions with soil microbes is poorly understood. To explore the role of microbes in mediating tree responses to drought stress, we exposed saplings of three species (Acer saccharum, Liriodendron tulipifera, and Quercus alba) to a four week experimental drought in mesocosms. Half of the pots were inoculated with a live soil slurry (i.e., a microbial inoculum derived from soils beneath the canopies of mature A. saccharum, L. tulipifera or Q. alba stands), while the other half of the pots received a sterile soil slurry. Soil microbes ameliorated drought stress in L. tulipifera by minimizing reductions in leaf water potential and by reducing photosynthetic declines. In A. saccharum, soil microbes reduced drought stress by lessening declines in leaf water potential, though these changes did not buffer the trees from declining photosynthetic rates. In Q. alba, soil microbes had no effects on leaf physiological parameters during drought stress. In all species, microbes had no significant effects on dynamic C allocation during drought stress, suggesting that microbial effects on plant physiology were unrelated to source–sink dynamics. Collectively, our results suggest that soil microbes have the potential to alter key parameters that are used to diagnose drought sensitivity (i.e., isohydry or anisohydry). To the extent that our results reflect dynamics occurring in forests, a revised perspective on plant hydraulic strategies that considers root-microbe interactions may lead to improved predictions of forest vulnerability to drought.
Equilibria of online scheduling algorithms

We describe a model for competitive online scheduling algorithms. Two servers, each with a single observable queue, compete for customers. Upon arrival, each customer strategically chooses the queue with minimal expected wait time. Each scheduler wishes to maximize its number of customers, and can strategically select which scheduling algorithm, such as First-Come-First-Served (FCFS), to use for its queue. This induces a game played by the servers and the customers. We consider a non-Bayesian setting, where servers and customers play to maximize worst-case payoffs. We show that there is a unique subgame perfect safety-level equilibrium and we describe the associated scheduling algorithm (which is not FCFS). The uniqueness result holds for both randomized and deterministic algorithms, with a different equilibrium algorithm in each case. When the goal of the servers is to minimize competitive ratio, we prove that it is an equilibrium for each server to apply FCFS: each server obtains the optimal competitive ratio of 2.
TP53 Mutation Is Rare In Primary Myelofibrosis

Abstract Abstract 5241 Introduction TP53 is the most frequently mutated tumor suppressor gene in human cancers and is usually associated with an aggressive disease course. TP53 mutation has been described in a variety of hematopoietic neoplasms, and has been suggested to play a role in leukemic transformation of myeloproliferative neoplasms (MPN). However, the incidence as well as the clinical and pathogenetic implications of TP53 mutation in each sub-category of MPN, including primary myelofibrosis, have not been described. In this study, we investigated the presence and potential clinical significance of TP53 mutations in a large series of primary myelofibrosis cases. Patients and Methods We retrieved archival bone marrow DNA from 51 consecutive patients diagnosed with primary myelofibrosis at The University of Texas MD Anderson Cancer Center between the years 2005 and 2007. Diagnosis was based on morphologic, immunophenotypic, cytogenetic and molecular evaluation of bone marrow in conjunction with clinical data. Only 2 patients had blast counts >10% (11 and 14%). Twenty nine of 50 (58%) patients showed JAK2 p.V617F mutation and all patients were negative for BCR-ABL1 translocation on routine clinical testing. DNA samples were assessed for sequence variation in exons 4 through 9 of TP53 by both high resolution melting curve (HRM) analysis using LightCycler® 480 System (Roche, Indiana IN) and bidirectional Sanger sequencing using 3730XL DNA Analyzer (Life technologies, Carlsbad CA). Results The mean overall survival was 5.7 years. Five patients developed acute leukemia, all of whom died of disease. By Sanger sequencing, only one (1.9%) case showed an amino acid-altering mutation in TP53: c.707A>G (TAC to TGC) in codon 236 (p.Y236C) of exon 7. In addition, 8 cases showed silent mutations/single nucleotide polymorphisms of unknown significance - c.36G>A (CCG to CCA) in exon 4 (n=3) and c.213A>G (CGA to CGG) in exon 6 (n=6). The p.R72P polymorphism in exon 4 which has been described in other hematopoietic neoplasms was present in 1 patient. All cases with a mutant sequence by Sanger sequencing also showed a variant melting curve pattern by HRM analysis. The patient with TP53 mutation died 2 years after presentation from progressive myelofibrosis without developing acute leukemia. Conclusion TP53 mutation is very rare in primary myelofibrosis. Disclosures: No relevant conflicts of interest to declare.
Splenectomy Does Not Improve Long-Term Outcome After Stroke

Background and Purpose— Immune responses to brain antigens after stroke contribute to poor outcome. We hypothesized that splenectomy would lessen the development of such responses and improve outcome. Methods— Male Lewis rats (275–350 g) underwent 2-hour middle cerebral artery occlusion immediately after splenectomy or sham splenectomy. Animals were survived to 4 weeks (672 hrs), and immune responses to myelin basic protein determined at euthanasia. Infarct volume was determined in a subset of animals euthanized at 72 hours. Behavioral outcomes were assessed to 672 hours. Results— Splenectomy was associated with worse neurological scores early after stroke, but infarct size at 72 hours was similar in both groups. Behavioral outcomes and immune responses to myelin basic protein were also similar among splenectomized and sham-operated animals 672 hours after middle cerebral artery occlusion. Conclusions— Splenectomy did not alter the immune responses to brain antigens or improve outcome after stroke. Differences between this study and other studies of splenectomy and stroke are examined.
Student self-assessment of strengths and needed improvements during a family medicine clerkship

Objective There are few reports on how students self-assess their performance on a family medicine clerkship. We studied what students perceived as their strengths and areas of needed improvement at the mid-point in our family medicine clerkship. Methods We introduced a form for family medicine clerkship students to self-assess their strengths and areas of needed improvements using the clerkship objectives as a standard. We calculated the frequency in which each clerkship objective was reported as a strength or an area of needed improvement. For students’ open-ended comments, two reviewers independently organized students’ comments into themes, then negotiated any initial differences into a set of themes that incorporated both the reviewers’ findings. We performed χ2 tests to determine any significant differences in the frequency of responses between male and female students. Results During the study period (July 2012 to June 2014), 372 students submitted completed self-assessment forms. The most frequently reported strengths were professional objectives (48.9%) and interpersonal communication objectives (43.0%) The most frequently reported areas of needed improvement were the ability to explain key characteristics of commonly used medications (29.3%) and the ability to develop a management plan (28.5%). There were no significant differences in the frequency of responses between male and female students. Conclusion We now have a better understanding of students’ perceived strengths and areas of needed improvement in our family medicine clerkship. We have shared this information with our community faculty preceptors so that they will be better prepared to work with our students. Family medicine clerkship preceptors at other institutions may also find these results useful.
Abstract 139: Comparison of Access to Care and Quality of Care in Veterans versus Non-veterans With Cardiovascular Disease

Background: Improved access to care and quality of care can mitigate population level risk of heart disease and improve health outcomes. We sought to compare access to care in veterans versus non-veterans with cardiovascular disease (CVD) in the U.S. Methods: The 2013 Centers for Disease Control’s Behavioral Risk Factor Surveillance Survey was utilized to identify a cohort of 57,171 adults with CVD. Presence of CVD was noted with a single affirmative response to the following questions: “Has a health care professional ever told you that you had any of the following:” (1) a heart attack or myocardial infarction, (2) angina or coronary heart disease, (3) a stroke? Demographic data, clinical history and medication use were recorded in these patients. Access to care variables included report of financial barriers to medical care and/or prescription drug costs and report of delay in receiving medical care. Quality of care variables included annual blood cholesterol check, blood sugar testing, flu shot administration, antihypertensive use, and aspirin use. Results: Among 57,171 adults with CVD studied, 13,205 (23.1%) were veterans while 43,966 (76.9%) were non-veterans. Veterans with CVD tended to be older (p Conclusion: Veterans with CVD receive improved access to care and quality of care compared to their non-veteran counterparts.
Distributed Intrinsic Functional Connectivity Patterns Predict Diagnostic Status in Large Autism Cohort

Diagnosis of autism spectrum disorder (ASD) currently relies on behavioral observations because brain markers are unknown. Machine learning approaches can identify patterns in imaging data that predict diagnostic status, but most studies using functional connectivity MRI (fcMRI) data achieved only modest accuracies of 60-80%. We used conditional random forest (CRF), an ensemble learning technique protected against bias from feature correlation (which exists in fcMRI matrices). We selected 252 low-motion resting-state functional MRI scans from the Autism Brain Imaging Data Exchange, including 126 typically developing (TD) and 126 ASD participants, matched for age, nonverbal IQ, and head motion. A matrix of functional connectivities between 220 functionally defined regions of interest was used for diagnostic classification. In several runs, we achieved accuracies of 92-99% for classifiers with >300 features (most informative connections). Features, including pericentral somatosensory and motor regions, were disproportionately informative. Findings differed partially from a previous study in the same sample that used feature selection with random forest (which is biased by feature correlations). External validation in a smaller in-house data set, however, achieved only 67-71% accuracy. The large number of features in optimal models can be attributed to etiological heterogeneity under the clinical ASD umbrella. Lower accuracy in external validation is expected due to differences in unknown composition of ASD variants across samples. High accuracy in the main data set is unlikely due to noise overfitting, but rather indicates optimized characterization of a given cohort.
Using Linguistics to Mine Unstructured Data from FASB Exposure Drafts

ABSTRACT Accounting standard setting is a high-stakes, political, and market process influenced by constituents through a public commenting mechanism. Comment letters are widely studied by research...
The International Legal Environment for Serious Political Reporting has Fundamentally Changed: Understanding the Revolutionary New Era of English Defamation Law

On October 11, 2006, Britain's highest court, the House of Lords, issued a blockbuster ruling that completely changed the landscape of libel law and press freedoms in the United Kingdom. The Times of London described the case, Jameel v. Wall Street Journal, as, "a judgment that lawyers predict will usher in a new era of journalism." Given England's reputation as an attractive jurisdiction for defamation plaintiffs and a frequent destination for "libel tourism," this case is likely to alter the environment for serious political journalism throughout Europe and North America. This article carefully describes the case, including its key holdings and the important changes that it makes to traditional British libel law. It then goes on to analyze the doctrine of qualified privilege that emerges from the decision and to compare it to the constitutional protections from defamation liability that have been developed in the United States beginning with the U.S. Supreme Court case of New York Times v. Sullivan in 1964. The critical role that the fourth estate rationale plays in both approaches is discussed. Important differences in both the doctrinal definition of protected speech and the mechanism of protection employed in England and the United States are recognized and evaluated. Fundamental trade-offs inherent in the crafting of special protection from defamation liability for highly-valued speech are identified and applied to the approaches adopted in the United States and in Jameel. Finally, the article offers some suggestions on the likely future development of the qualified privilege doctrine in Great Britain.
Trophic cascades at multiple spatial scales shape recovery of young aspen in Yellowstone

Abstract Throughout much of the 20th century, the heights of young quaking aspen (Populus tremuloides) in Yellowstone National Park’s northern ungulate winter range were suppressed due to intensive herbivory by Rocky Mountain elk (Cervus elaphus). However, following the 1995–96 reintroduction of gray wolves (Canis lupus), completing the park’s large predator guild, young aspen in various portions of the northern range began to increase in height. From 1999 to 2015, a 17-yr period of declining elk densities in the northern range, browsing rates declined and young aspen heights increased once elk densities dropped below ∼4 elk/km2. The inverse relationship between browsing rate and young aspen height, a relationship linking elk and plants, was consistent with a re-established trophic cascade. Within the Glen Creek study area (8.3 km2), decreased browsing and increased heights of young aspen were associated, at least in part, with two hypothesized small-scale predation risk factors (i.e., escape impediment, view impediment). However, the young aspen height increases did not occur in the Mammoth study area (6.0 km2) and heights there remained short. With high levels of human activity at the Mammoth townsite, wolf activity near the townsite remained low, an example of “human shielding,” thereby allowing elk browsing to continue the suppression of young aspen. Overall, results indicated that Yellowstone’s contemporary large predator guild, by altering elk behavior and density at several spatial scales, has not only contributed to a relatively widespread pattern of increased young aspen heights across much of the park’s northern range, but also greater spatial variation in those heights.
Immunocytologic Characteristics of Mononuclear Cell Populations Found in Nonseptic Olecranon Bursitis

OBJECTIVE: To determine the immunocytologic characteristics of the various subsets of nonseptic olecranon bursal fluid mononuclear cells. METHODS: Twenty consecutive patients with culture negative olecranon bursitis had immunocytochemical and flow cytometric analysis performed using a panel of monoclonal antibodies to determine lymphocyte and monocyte/macrophage population subtypes and proportions. RESULTS: In traumatic bursitis (n = 9), the mean (+/- SD) white blood cell (WBC) count/mm3 was 1,368 +/- 1,559; WBC mononuclear differential count was 29.5 +/- 19% lymphocytes and 55 +/- 26% monocyte/macrophages. In idiopathic bursitis (n = 11), the mean WBC/mm3 was 376 +/- 515; WBC mononuclear differential count was 28.5 +/- 16% lymphocytes and 52 +/- 27% monocytes/macrophages. Flow cytometry revealed 88% CD2+ T lymphocytes in the lymphocyte population, 3% B lymphocytes and CD4/CD8 T cell mean ratio of 2.5 +/- 1.5 for traumatic bursitis and 88% CD2+ T lymphocytes, 4% B lymphocytes and CD4/Cd8 ratio of 1.4 +/- 0.6 for idiopathic bursitis (p < 0.05, t test). Both groups contained increased proportions of lymphocyte subtypes expressing activation markers: CD25+, CD26+ and HLA DR+ compared to normal peripheral blood. In traumatic bursitis, the mean percent of CD14+ cells (monocyte/macrophages) was 62 +/- 24; in idiopathic bursitis, the mean percent was 51 +/- 28. The vast majority expressed high levels of HLA-DR indicating activation. CONCLUSION: We observed a preponderance of activated T cell subpopulations and monocyte/macrophages suggesting an immunologic role for these cell populations in the development and perpetuation of nonseptic bursitis.
Heat transfer simulation of solid state fermentation in a packed-bed bioreactor

A dynamic two-dimensional mathematical model was developed to simulate the heat transfer in solid state fermentation of rice bran inoculated with Aspergillus niger. Two bioreactors of 47 mm diameter and 300 mm height were used. Forced aeration conditions were simulated and saturated air with 60 ml/g h flow at 30°C and a bed porosity equal to 0.3 were determined as being the optimum operating conditions for the used packed-bed bioreactor. © Rapid Science Ltd. 1998
Editorial Commentary: Reducing the Tibial Tuberosity-Trochlear Groove Distance in Patella Stabilization Procedure. Too Much of a (Good) Thing?

Abstract A recent study suggests that aggressive correction of the tibial tuberosity-trochlear groove (TT-TG) distance by tibial tubercle osteotomy and medialization during patellar stabilization surgery can result in diminished outcomes. The mechanism may be overmedialization resulting in excessive medial patellofemoral and tibial-femoral pressure. Measurement of TT-TG may be inaccurate, and medialization of the tibial tubercle may not be required in cases of lateral patellar instability with TT-TG >20 mm (which is a current algorithm). My indication for tibial tubercle osteotomy, generally anteromedialization, is lateral patellofemoral chondrosis, and my goal is to create an intraoperative tubercle-sulcus angle of 0, which can be readily visualized with the knee at 90°. This is true regardless of the preoperative TT-TG measurement, and this intraoperative measurement mitigates against an excessive tubercle-sulcus angle of 0, which can be readily visualized with the knee at 90° and is true regardless of the preoperative TT-TG medialization.
Perceptions of Campus Climate at the Intersections of Disability and LGBTQIA+ Identities

Though research on the higher education experiences of college students with disabilities and lesbian, gay, bisexual, transgender, and queer (LGBTQ) college students has increased in recent years, scholars have rarely addressed intersections of these two identities. Miller and Dika highlight the experiences of 13 LGBTQ students with disabilities at a predominantly white research university in the Southern United States, supplemented by analysis of SERU survey data at the same institution from LGBTQ students with disabilities. The authors include a brief demographic portrait of the undergraduate student participants and the ways in which they describe their multiple, intersecting identities. Presenting results from the study, Miller and Dika address students’ perceptions of the campus climate as well as their recommendations for improving the climate and for others on campus seeking to become allies.
Finite-Time Cooperative Engagement

A smooth finite-time distributed control architecture is introduced and analyzed for the cooperative engagement problem. Using a time transformation method as well as Lyapunov stability theory, it is shown that the proposed architecture guarantees finite-time cooperative engagement in that the difference between the positions of each agent and a time-varying target, where this difference represents a dynamic equilibrium point, vanishes in a-priori given, user-defined finite time. In addition, this finite-time convergence is achieved without dependence on the initial conditions of agents and in the presence of unknown but bounded velocity of the target. Specifically, we first time transformed the proposed smooth finite-time distributed control architecture into an infinite-time (that is, stretched) interval. This time transformation method is then allowed to utilize tools from standard Lyapunov stability theory in which we analyze convergence properties of this architecture and boundedness of local control signals of each agent in this infinite-time interval. While this note focuses on a particular problem in the context of multiagent systems, the proposed time transformation method and the analysis procedure can be used for many other problems, where a-priori given, user-defined finite-time convergence is necessary with smooth control laws.
The feasibility and acceptability of assessing inhibitory control and working memory among adolescents via an ecological momentary assessment approach.

Early adolescence is a critical period for the development of executive function (EF). EF deficits are associated with increased engagement in multiple health risk behaviors and may be influenced b...