cssi/SciSciGPT-SciSciNet huggingface dataset:
Long-term treatment with temozolomide in malignant glioma.

Six months of maintenance temozolomide (TMZ) following concurrent TMZ chemotherapy and radiation therapy has become the standard of care in the treatment of glioblastoma. In addition, TMZ has also been used to treat other forms of glioma although less evidence of efficacy exists. TMZ administration longer than 6 months is common in clinical practice, but it is unusual for the drug to be administered longer than 1 to 2 years. We report five patients who received long-term treatment with TMZ chemotherapy at normal dosing levels. One of these patients was diagnosed with glioblastoma, two with anaplastic astrocytoma, one with gliosarcoma, and one with oligo-astrocytoma. The length of treatment in our group of patients ranged from 45 to 85 cycles of TMZ. Common Terminology Criteria for Adverse Events (CTCAE) developed by The National Cancer Institute was used to classify toxicity. Two patients experienced no toxicity per CTCAE guidelines. One patient experienced grade I thrombocytopenia, one developed grade I leukopenia, and one experienced both grade I thrombocytopenia and grade I nausea, all which resolved with either withholding TMZ for 1 month or supportive treatment. Our report provides evidence that long-term TMZ chemotherapy is a therapeutic option when appropriately monitored.
From Polarisation to Integration in Vietnam

Every nation, no matter how well governed and fortunate, suffers a certain degree of political and social division. In a country at war, however, polarisation tends to increase as the war goes on b...
Biological extracorporeal liver assist devices: A minireview

During the past decade, whole organ transplantation has become the primary method of treating fulminant hepatic failure and chronic liver failure due to specific genetic, hepatocellular, and anatomic defects of liver function. However, wider application of liver transplantation is restricted by shortage of organ donors, high cost, relatively high morbidity, and need for lifelong immunosuppression. As a result, investigators have attempted to develop alternative methods to treat liver insufficiency. These ranged from use of plasma exchange to utilization of detoxification columns and extracorporeal devices loaded with various liver tissue preparations. Recent advances in hepatocyte isolation and culture techniques, improved understanding of hepatocyte-matrix interactions, availability of new biomaterials, improved hollow-fiber technology, and better understanding of flow and mass transport across semipermeable membranes have resulted in the development of a new generation of liver assist devices. Some of these devices, including the one we developed, are currently being tested in the clinical setting. In this article, past experience with biological liver-assist devices is reviewed, the field's present status is examined, and our own experience with a hepatocyte-based bioartificial liver is summarized. Areas in which further research efforts are particularly needed are briefly characterized.
The Performance of Third Grade Learning Disabled Boys on Tasks at Different Levels of Language A Model-Based Exploration

Twelve learning disabled third graders, 15 normally achieving third graders and 11 normally achieving first graders were given a number of different language tasks to measure language performance at the syntactic, semantic, orthographic, and discourse levels. Results indicate significant overall differences between the learning disabled children and their normally achieving peers, but differences between the learning disabled children and the reading level matched first graders were not significant. The data also were submitted to a set of model based regressions, testing several models used to discuss the language differences of learning disabled children (Rule Abstraction, Language in General, Speed of Processing). Implications for both classroom practice and further research in this area are discussed.
Plastic intensity factors for cracked plates

Abstract An elastic-plastic analysis is performed for two problems relevant to fracture mechanics: a semiinfinite body with an edge crack in a far out-of-plane shearing field and an infinite plate under plane stress conditions containing a finite line crack in a remote tensile field. Amplitudes of the dominant singularity in the plastic region at the crack tip, the plastic stress and strain intensity factors, are calculated for applied stress levels approaching the yield stress. A technique is developed for using the dominant singular solution in conjunction with the finite element method to make accurate calculations for the near-tip fields. Additionally, a comparative study of deformation theory with flow theory is performed for cracks in an anti-plane shear field. Elastic fracture mechanics is extended to high levels of applied stress for which the plastic zone is no longer small compared to the crack length by relating the critical stress for fracture initiation to the plastic intensity factors.
Cross-hybridization modeling on Affymetrix exon arrays

Motivation: Microarray designs have become increasingly probe-rich, enabling targeting of specific features, such as individual exons or single nucleotide polymorphisms. These arrays have the potential to achieve quantitative high-throughput estimates of transcript abundances, but currently these estimates are affected by biases due to cross-hybridization, in which probes hybridize to off-target transcripts. Results: To study cross-hybridization, we map Affymetrix exon array probes to a set of annotated mRNA transcripts, allowing a small number of mismatches or insertion/deletions between the two sequences. Based on a systematic study of the degree to which probes with a given match type to a transcript are affected by cross-hybridization, we developed a strategy to correct for cross-hybridization biases of gene-level expression estimates. Comparison with Solexa ultra high-throughput sequencing data demonstrates that correction for cross-hybridization leads to a significant improve-ment of gene expression estimates. Availability: We provide mappings between human and mouse exon array probes and off-target transcripts and provide software extending the GeneBASE program for generating gene-level expression estimates including the cross-hybridization correction http://biogibbs.stanford.edu/~kkapur/GeneBase/. Contact: whwong@stanford.edu Supplementary information:Supplementary data are available at Bioinformatics online.
Characterization and nanostructured enhancement of boiling incipience in capillary-fed, ultra-thin sintered powder wicks

Next-generation thermal management applications will require passive heat spreading at a lower thermal resistance, higher dryout tolerance, and with thinner profile devices than current vapor chambers. Such performance improvements may be achieved by augmenting evaporation and boiling heat transfer via patterning the internal wick or nanostructuring the wick surface in the region of heat input. Test samples composed of 200 µm thick sintered copper powder layers are investigated because they can be integrated into vapor chambers with an overall thickness of 1 mm. Carbon nanotubes (CNTs) are grown onto patterned and monolithic samples by a microwave plasma chemical vapor deposition synthesis technique, and are functionalized to ensure high wettability with the test fluid, water. Performance of the test samples is evaluated in an experimental facility which replicates the heat input and capillary fluid-feeding mechanisms at the evaporator section of a vapor chamber. High-speed visualizations are performed to identify the vapor formation regimes. Monolithic samples are shown to dissipate heat fluxes greater than 400 W/cm2 over 0.25 cm2 prior to dryout. A noteworthy heat transfer enhancement mechanism observed is reduction of the required superheat for boiling incipience by addition of a CNT coating. Predictable transition from the evaporation to boiling regimes at a lowered superheat is critical due to the lower thermal resistance associated with boiling. Multiple repeated tests on identically prepared samples reveal that the CNT coating reduces the average incipience substrate superheat by 5.6 °C compared to uncoated samples.
Material Removal Mechanisms of Oxide and Nitride CMP with Ceria and Silica-Based Slurries - Analysis of Slurry Particles Pre- and Post-Dielectric CMP

The effect of CMP process parameters (pressure and pad hardness) on the ceria and silica abrasive particle-size distribution (PSD), morphology, and surface composition when polishing oxide and nitride surfaces was investigated in detail. The PSD was observed to shift post-CMP, with ceria and silica exhibiting a decrease and increase, respectively, in the number of particles towards the tail end of the distribution. The shift in ceria PSD was observed to increase as pad hardness increased. An increase in polish pressure and work surface hardness resulted in an equivalent shift in the PSD when polished on a soft pad. The inclusion of an additive reduced the oxide removal rate, and the abrasive particles exhibited the presence of a thin organic coating on the surface. The difference in material removal mechanisms and selectivity when polishing oxide and nitride with ceria and silica-based slurries was also investigated in detail.
SEU-aware resource binding for modular redundancy based designs on FPGAs

Although Triple Modular Redundancy (TMR) has been widely used to mitigate single event upsets (SEUs) in SRAM-based FPGAs, SEU-caused bridging faults between the TMR modules do not guarantee correctness of TMR design under SEU. In this paper, we present a novel approximation algorithm for resource binding on scheduled datapaths at the presence of TMR, which aims at containment of each SEU within a single replica of tripled operations. The key challenges are to avoid resource sharing between modular redundant operations and also to reduce the possibility of TMR masking breaches in resource allocation. We introduce the notion of vulnerability gap during resource sharing to potentially reduce the effort for white space allocation at the physical design stage in order to avoid bridging faults between TMR resources. The experimental results show that our proposed resource binding algorithm, followed by floorplanner, reduces the potential of TMR breaches by 20%, on average.
The Arabidopsis Chloroplast Stromal N-Terminome: Complexities of Amino-Terminal Protein Maturation and Stability

Protein amino (N) termini are prone to modifications and are major determinants of protein stability in bacteria, eukaryotes, and perhaps also in chloroplasts. Most chloroplast proteins undergo N-terminal maturation, but this is poorly understood due to insufficient experimental information. Consequently, N termini of mature chloroplast proteins cannot be accurately predicted. This motivated an extensive characterization of chloroplast protein N termini in Arabidopsis (Arabidopsis thaliana) using terminal amine isotopic labeling of substrates and mass spectrometry, generating nearly 14,000 tandem mass spectrometry spectra matching to protein N termini. Many nucleus-encoded plastid proteins accumulated with two or three different N termini; we evaluated the significance of these different proteoforms. Alanine, valine, threonine (often in N-α-acetylated form), and serine were by far the most observed N-terminal residues, even after normalization for their frequency in the plastid proteome, while other residues were absent or highly underrepresented. Plastid-encoded proteins showed a comparable distribution of N-terminal residues, but with a higher frequency of methionine. Infrequent residues (e.g. isoleucine, arginine, cysteine, proline, aspartate, and glutamate) were observed for several abundant proteins (e.g. heat shock proteins 70 and 90, Rubisco large subunit, and ferredoxin-glutamate synthase), likely reflecting functional regulation through their N termini. In contrast, the thylakoid lumenal proteome showed a wide diversity of N-terminal residues, including those typically associated with instability (aspartate, glutamate, leucine, and phenylalanine). We propose that, after cleavage of the chloroplast transit peptide by stromal processing peptidase, additional processing by unidentified peptidases occurs to avoid unstable or otherwise unfavorable N-terminal residues. The possibility of a chloroplast N-end rule is discussed.
Effect of Environmental Conditions and Toxic Compounds on the Locomotor Activity of Pediculus humanus capitis (Phthiraptera: Pediculidae)

In this work, we evaluated the effect of environmental variables such as temperature, humidity, and light on the locomotor activity of Pediculus humanus capitis. In addition, we used selected conditions of temperature, humidity, and light to study the effects of cypermethrin and N,N-diethyl-3-methylbenzamide (DEET) on the locomotor activity of head lice. Head lice increased their locomotor activity in an arena at 30°C compared with activity at 20°C. When we tested the influence of the humidity level, the locomotor activity of head lice showed no significant differences related to humidity level, both at 30°C and 20°C. Concerning light influence, we observed that the higher the intensity of light, the slower the movement of head lice. We also demonstrated that sublethal doses of toxics may alter locomotor activity in adults of head lice. Sublethal doses of cypermethrin induced hyperactivated responses in adult head lice. Sublethal doses of DEET evocated hypoactivated responses in head lice. The observation of stereotyped behavior in head lice elicited by toxic compounds proved that measuring locomotor activity in an experimental set-up where environmental conditions are controlled would be appropriate to evaluate compounds of biological importance, such as molecules involved in the host-parasite interaction and intraspecific relationships.
Complications and Outcomes of Brown Recluse Spider Bites in Children

Brown recluse spider bites may cause severe local and systemic morbidity, but data regarding morbidity in children are limited. This study reviewed inpatient medical records (n = 26; 10 years) with a discharge diagnosis of "spider bite" from a tertiary pediatric hospital. The majority (85%) of children had an inflammatory response accompanying necrosis, usually with signs of secondary cellulitis (77%). Hemolytic anemia (50%), rhabdomyolysis (27%), and acute renal failure (12%) were the most prevalent systemic effects. Hemolytic anemia was bimodal in distribution relative to the time-of-onset of the bite (early, 2.2 ± 0.4; late, 6.9 ± 1.5 days postbite, respectively; P = .004). Although no fatalities occurred in the population, 65% of children had major morbidity, including wound complications requiring surgical care and acute orbital compartment syndrome. The findings emphasize the importance of anticipatory patient/family education for outpatients and careful monitoring for systemic morbidity in inpatients. Timely and appropriate supportive care should yield favorable outcomes in most cases.
Cellular responses to bacterial lipopolysaccharide: T cells recognize LPS determinants.

An in vitro proliferative system was used to assess the capacity of lipopolysaccharide (LPS) to induce a specific T-cell response in mice. Sensitized T cells were generated in vivo by subcutaneous inoculation with LPS. These T cells, which were purified on nylon wool columns, were stimulated to proliferate in vitro by LPS. Results of several lines of experimentation confirmed that the responding cells were T cells. Additional experiments indicated that sensitized T cells could distinguish between LPS and ovalbumin. Finally, it was found that genetic responsiveness to the biological effects of lipid A was required for full clicitation of LPS-induced T-cell proliferation. The data were interpreted to indicate that LPS interacted with, and stimulated, antigen-specific murine T cells.
Distributed filtering using set models

A distributed filtering algorithm using set models with confidence values is derived. No noise distribution statistics are needed. The only information required is the confidence values from which the modeling and measurement errors and the initial values are obtained. Therefore, the algorithm has great potential for real-world applications. >
Analyzing Effects of Intra-Uterine Cocaine Exposure on Adolescent Brain Structure with Symmetric Diffeomorphisms

Cocaine exposure (CE) nzug conzpronzise the developing brain through disruption of neural ontogeny in dopaminergic systems, erects seconda? to fetal hypoxenzia, and, perhaps, via altered cei-ebro\iascular I-eactivity. Although studies in adult cocaine addicts show decreases in gi-ay nzattel; white inattel; and fiinctional connectivity there are few investigations to date regarding intra-uterine cocaine exposure (IUCE) in young subjects. The existing literature suggests that long term CE coitsequeitces irt adolescents nzap be subtle 01- nzasked by other variables. Tlzei-efore, sensitive nzethods of analysis are needed. Here, we describe our most recent methods for deriving an optiinal pediatric atlas froin the 49 subject IUCE population invoh>edi n this study. Our nzetlzod, synznzetric nornzalization (SyN), is entirely syimnetric, in that both the pair wise registmtion and gi-oup wise I-egistmtion methods do not depend on the ordering of the input data. The method eliminates atlas selection by deriving an optiinal shape and intensity atlas fioin the data. PreliininaFy results using SyN indicate signijcant size dvfei- ewes in caudate rtuclei arid the spleniunz of the c o p i s callosunz, suggesting CE-i-elated detrinzent to the dopanzinergic and visiial systems. Fiirthernzore, we have found that, in conzparison, statistical parametric mapping (SPM) does not pi-oduce sigrti$cartt I-esults.
Feasibility experiments for the development of a midbrain auditory prosthesis

This paper presents a new approach for hearing restoration in patients suffering from sensorineural hearing loss. We focus on the development of a midbrain auditory prosthesis, implanted into the central nucleus of the inferior colliculus (ICC). We performed experiments in a guinea pig model to initially explore the tonotopic map that exists between ICC and the primary auditory cortex (A1), the initial center for auditory perception. Using multichannel electrodes, we were able to stimulate along 16 different ICC sites and simultaneously record from 16 different Al sites. Both electrodes were placed along similar tonotopic gradients. ICC stimulation in low frequency regions induced activity in low frequency regions of A1, and similar trends were seen for higher frequencies. ICC stimulation appears to be very specific, causing minimal spreading of activity across A1 sites, and stimulation threshold levels were significantly lower than that currently obtained using cochlear prostheses. These results indicate that an ICC-based auditory implant may provide a more focused means of stimulation at lower threshold levels for hearing restoration compared to current cochlear prostheses. The tonotopic map between ICC and A1 suggests that a frequency place code may be utilized in a midbrain auditory prosthesis.
Coarray synthesis with circular and elliptical boundary arrays

An elliptical boundary aperture is a collection of points lying on an ellipse from which energy is transmitted and/or received. An important special case is the circular boundary aperture. When these apertures are used with beamforming to produce a narrowband image of a far-field source, the corresponding point spread function (PSF) is characterized by high sidelobes. The concept of the coarray of an imaging system is used here to develop techniques which synthesize the effect of a more desirable PSF with an elliptical boundary aperture. Techniques are given for use in active imaging of spatially coherent sources, as well as passive imaging of spatially incoherent sources. Discrete arrays and continuous apertures are considered separately. The approach shows that the PSF synthesis problem can be solved in many more ways than previously recognized, and this fact is exploited to develop procedures which have a least-squares optimality property. >
HST/WFPC2 imaging of the dwarf satellites And XI and And XIII: horizontal branch morphology and RR Lyraes★

We present a study of the stellar populations in two faint M31 dwarf satellites, Andromeda XI and Andromeda XIII. Using archival images from the Wide Field Planetary Camera 2 onboard theHubble Space Telescope, we characterize the horizontal branch (HB) morphologies and the RR Lyrae (RRL) populations of these two faint dwarf satellites. Our new template light-curve fitting routine (Robust RR Lyrae light curve FITing (RRFIT)) has been used to detect and characterize RRL populations in both galaxies. The mean periods of RRab (RR0) stars in And XI and And XIII arePab �= 0.621 ± 0.026 (error1) ± 0.022 (error2) and 0.648 ± 0.026 (error1) ± 0.022 (error2), respectively, where 'error1' represents the standard error of the mean, while 'error2' is based on our synthetic light-curve simulations. The RRL populations in these galaxies show a lack of RRab stars with high amplitudes (Amp(V ) > 1.0 mag) and relatively short periods (Pab ∼ 0.5 d), yet their period-V-band amplitude (P -Amp(V )) relations track the relation defined by the M31 field halo RRL populations at ∼11 kpc from the centre of M31. The metallicities of the RRab stars are calculated via a relationship between (Fe/H), logPab and Amp(V). The resultant abundances ((Fe/H)And XI =− 1.75; (Fe/H)And XIII =− 1.74) are consistent with the values calculated from the red giant branch slope, indicating that our measurements are not significantly affected by RRL evolutionary away from the zero-age HB. The distance to each galaxy, based on the absolute V magnitudes of the RRab stars, is (m − M)0,V = 24.33 ± 0.05 for And XI and (m −M)0,V = 24.62 ± 0.05 for And XIII. We discuss the origins of And XI and And XIII based on a comparative analysis of the luminosity-metallicity relation of Local Group dwarf galaxies.
Antihormones and Their Use in Studies of Reproduction

The biological consequences of immunological inhibition of gonadotropin activity by use of antihormones is discussed by a review of recent research. Investigation in the human male has centered on the effect of follicle-stimulating hormone (FSH) on spermatogenesis and the role of interstitial cell-stimulating hormone (ICSH) on male gonad tissue metabolism. Some research has indicated that ICSH has a dramatic inhibitory effect on sexual drive. Recent research indicates that FSH may not play as an important role in spermatogenesis as luteinizing hormone (LH). The relationship of the gonadotropins to female reproductive activity remains in need of abundant study. LH and FSH have been found to be responsible for follicular development ovulation and corpus luteum formation. LH and FSH immunization has resulted in a loss of libido and a reduced ability to reproduce in some test animals. The separate effects of these 2 hormones and the precise site of their activity remain to be elucidated. Studies with anti-H serum seem to indicate that the functional luteal tissue of pregnancy is regulated by a placental hormone. Again further research is necessary. Though these investigations into hormonal immunization are still preliminary and in need of clarification there appear to be ample grounds for the development of an effective immunological approach to birth control.
Pattern of Multiple Drug Abuse Among Adolescents

Statistics regarding drug abuse among adolescents seem few and far between, and of questionable accuracy when available. This is easy to understand. In the present adolescent setting, those who have abused drugs may deny it to avoid being "busted," and those who have not used drugs may claim that they have in order to appear to "groove." Articles such as that by Dodson and colleagues are to be encouraged. Hopefully, treatment centers and consultation agencies involved with the problem of teenage drug abuse will continue to try to support their impressions, which may lag behind changes in drug abuse patterns, by keeping similar statistics.
Control of apoptosis by using small molecule regulators of Bcl-2 family proteins

The potent biological activity of CPM-1285 suggests that it may represent a promising lead for the development of new anticancer agents. The cell permeable Bcl-2 inhibitor can also be used as a chemical probe to study the in vivo mechanism and signaling pathway of the Bcl-2 family. Unlike other peptides that are active only in vitro or in the cell-free system, the cell-permeable peptide approach described here provides a new tool to analyze the function of the Bcl-2 family in living cells and animals.
Accountability Standards for Nonprofit Organizations: Do Organizations Benefit from Certification Programs?

ABSTRACTStakeholders are demanding nonprofit organizations (NPOs) continually improve and work effectively in an ever-changing environment. While there are many ways to approach this operational challenge, this paper examines the impact of acquiring an accountability certification, specifically the Standards for Excellence® Certification. Using a sample of 102 NPOs that have received the Standards for Excellence certification, we find that the certification is associated with increases in public support relative to a control group that did not receive the certification. These results suggest that some stakeholders favorably respond to the certification process, and NPOs can realize tangible benefits from becoming certified.
The Employment of Exotic Entomophagous Insects in Pest Control

In order for an exotic entomophagous insect to establish itself when colonized in a new country, it must frequent the habitat of the host species at a time when the susceptible stages of the host are present. Establishment has maximum insurance when the colonizations are numerically adequate and are placed in contact with susceptible host populations which are not regressing. Effective entomophagous insects are usually derived from the native habitat of the host, provided that the host in that habitat exists at low population densities. The dominant entomophagous species obtained under such conditions is likely to be the most effective, particularly if it is host specific. Importations should be made from representative types of host environments, since no one species of entomophagous insect is likely to be effective throughout the range of its host. After establishment, artificial exposure of host populations provides a means of demonstrating the effectiveness of the entomophagous insect. However, where two or more entomophagous insects are concerned, evaluation may be difficult since the species which are responsible for the reduction of high host densities may not be the species responsible for the maintenance of the host populations at the average level or steady density.
Anomaly induced chiral magnetic current in a Weyl semimetal: Chiral electronics

Electric circuits involving Weyl semimetals possess unusual properties induced by the quantum anomaly. The chiral magnetic current in a Weyl semimetal subjected to magnetic field modifies the behavior of such circuits in a drastic way. We consider two explicit examples: (i) a circuit involving the ``chiral battery'' and (ii) a circuit that can be used as a ``quantum amplifier'' of magnetic field. The unique properties of these circuits stem from the chiral anomaly and may be utilized for creating ``chiral electronic'' devices.
Gambles of gastroenterology.

Background Diagnostic and therapeutic procedures of gastroenterology can frequently tax a patient's health. In addition to the risk of side-effects such procedures may also reduce the patient's well-being. The probability of achieving cure depends on the interplay between the patient's initial health status and the expected efficacy of the gastroenterological interventions. Methods The mathematical concept of the 'gambler's ruin' from probability theory is used to model the interplay among the various factors affecting clinical outcome. Results The model illustrates in a quantitative manner how the physician's ultimate success in achieving cure depends on a given patient's initial health status, and the characteristics of the interventional procedures used. The analysis also illustrates that in some dire clinical situations, risking the patient's life in one single and bold step can yield a better overall outcome than trying to advance the patient's health by multiple small and cautious steps. Conclusion Using the gambler's ruin as a model for medical risk taking could contribute to medical teaching and promote the understanding of the some general principles that shape many clinical decisions in gastroenterology.
One-stage Transanal Rectosigmoidectomy for Hirschsprung Disease in Children:a Preliminary Outcome of 23 Cases

【Objective】To investigate the indications and the effect of one-stage rectosigmoidectomy for Hirschsprung disease(HD) in children.【Methods】The clinical data of 23 children with Hirschsprung disease undergoing the operation were analyzed retrospectively.【Results】All the cases were cured and there was no mortality.Of these patients,fecal soiling was observed in one case in the early stage after the operation and diffiicult fecal discharge in another case.【Conclusion】One-stage transanal rectosigmoidectomy is one of the excellent operations in the treatment of Hirschsprung disease in children.It is worthy to popularize.
On Parallelizing Streaming Algorithms.

We study the complexity of parallelizing streaming algorithms (or equivalently, branching programs). If M(f) denotes the minimum average memory required to compute a function f(x1, x2, . . . , xn) how much memory is required to compute f on k independent streams that arrive in parallel? We show that when the inputs (updates) are sampled independently from some domain X and M(f) = Ω(n), then computing the value of f on k streams requires average memory at least Ω ( k · M(f) n ) . Our results are obtained by defining new ways to measure the information complexity of streaming algorithms. We define two such measures: the transitional and cumulative information content. We prove that any streaming algorithm with transitional information content I can be simulated using average memory O(n(I+ 1)). On the other hand, if every algorithm with cumulative information content I can be simulated with average memory O(I + 1), then computing f on k streams requires average memory at least Ω(k · (M(f)− 1)).
Changes in growth hormone and luteinizing hormone following acute or chronic administration of an opioid agonist, FK33-824, in wethers.

Two experiments were conducted to determine the effect of acute or chronic administration of an opioid agonist, (D-Ala2,MePhe4,Met(O)5-ol)-enkephalin (FK33-824), on concentrations of growth hormone (GH) and LH in castrate sheep (wethers). In Exp. 1, we evaluated the effect of acute administration (two injections or infusion for 2 h) of FK33-824 on GH and LH. Wethers (31 +/- 1 kg; n = 12) received FK33-824 or saline via one of the three following routes of deliver: 1) i.v. (8 micrograms/kg) at 0 and 60 min (i.v., n = 4), 2) s.c. (16 micrograms/kg) at 0 and 60 min (s.c., n = 4), or 3) i.v. infusion (8 micrograms.kg-1.h-1) for 120 min (inf., n = 4) preceded by a single injection (8 micrograms/kg). Wethers received FK33-824 and saline on d 1 and 2 or d 2 and 1, respectively. Concentrations of GH were consistently elevated (P less than .05) by FK33-824 regardless of route of delivery. Infusion of FK33-824 for 120 min maintained GH concentrations greater (P less than .05) than pretreatment or those during infusion of saline. Average LH was decreased consistently by FK33-824, independent of its route of administration; episodic release of LH was suppressed. In Exp. 2, crossbred wethers (36 +/- 2 kg; n = 12) were used to determine the effect of chronic administration (s.c.) of FK33-824 on the concentrations of GH and LH and retention of N and energy.(ABSTRACT TRUNCATED AT 250 WORDS)
MO-DE-207B-03: Improved Cancer Classification Using Patient-Specific Biological Pathway Information Via Gene Expression Data

Purpose: To develop an efficient, pathway-based classification system using network biology statistics to assist in patient-specific response predictions to radiation and drug therapies across multiple cancer types. Methods: We developed PICS (Pathway Informed Classification System), a novel two-step cancer classification algorithm. In PICS, a matrix m of mRNA expression values for a patient cohort is collapsed into a matrix p of biological pathways. The entries of p, which we term pathway scores, are obtained from either principal component analysis (PCA), normal tissue centroid (NTC), or gene expression deviation (GED). The pathway score matrix is clustered using both k-means and hierarchical clustering, and a clustering is judged by how well it groups patients into distinct survival classes. The most effective pathway scoring/clustering combination, per clustering p-value, thus generates various ‘signatures’ for conventional and functional cancer classification. Results: PICS successfully regularized large dimension gene data, separated normal and cancerous tissues, and clustered a large patient cohort spanning six cancer types. Furthermore, PICS clustered patient cohorts into distinct, statistically-significant survival groups. For a suboptimally-debulked ovarian cancer set, the pathway-classified Kaplan-Meier survival curve (p = .00127) showed significant improvement over that of a prior gene expression-classified study (p = .0179). For a pancreatic cancer set, the pathway-classified Kaplan-Meier survival curve (p = .00141) showed significant improvement over that of a prior gene expression-classified study (p = .04). Pathway-based classification confirmed biomarkers for the pyrimidine, WNT-signaling, glycerophosphoglycerol, beta-alanine, and panthothenic acid pathways for ovarian cancer. Despite its robust nature, PICS requires significantly less run time than current pathway scoring methods. Conclusion: This work validates the PICS method to improve cancer classification using biological pathways. Patients are classified with greater specificity and physiological relevance as compared to current gene-specific approaches. Focus now moves to utilizing PICS for pan-cancer patient-specific treatment response prediction.
Adaptation of Postural Stability following Stroke

Activities of daily living require both anticipatory and reactive postural adjustments. The influence of stroke on anticipatory and reactive balance behaviors is addressed in this article. Two primary deficits appear to underlie postural instability following stroke. The first deficit type is characterized by a loss of postural muscle recruitment in both lower extremities (not hyperactive stretch reflexes). The second deficit type is related specifically to the lack of limb stabilization on the paretic side of the body. These two categories of deficit might result from the disruption of geocentric and egocentric references for postural stability with cerebrovascular disease. Context-dependent postural responses are either relearned or retained following stroke, but deficits in the sequencing and timing of stabilizing neuromuscular responses appear to be resistant to adaptation. Prior knowledge of an impending balance disturbance improves the initiation of reactive postural adjustments in subjects with stroke but has no effect on the initiation of stabilizing responses associated with voluntary motion. The results suggest that reactive and anticipatory postural adjustments are controlled by different neural mechanisms and may require separate attention in a rehabilitation program.
High-Risk of Adverse Pathologic Features in Patients With Clinical T1 High-Grade Bladder Cancer Undergoing Radical Cystectomy.

Background Radical cystectomy (RC) is used to treat select patients with T1 high-grade (T1HG) bladder cancer. However, population-level utilization trends and outcomes for these patients are not well-known. We sought to evaluate treatment patterns and clinicopathologic outcomes of RC for T1HG bladder cancer. Patients and methods Using the National Cancer Data Base (NCDB) for 1998-2012, we conducted a retrospective cohort study of patients with clinical T1HG bladder cancer. The prevalence of RC used to treat T1HG bladder cancer from 1998-2012 was determined. For years 2010-2012, demographic and cancer-related factors were described and regression analysis was used to examine associations with RC. Oncologic outcomes of RC were described and related to mortality using Cox proportional hazards regression. Results Treatment of T1HG bladder cancer with RC nearly doubled, from 5.5% during 1998-2000 to 9.9%, during 2010-2012. For 2010-2012, 18,277 patients with T1HG bladder cancer were analyzed. Patients who underwent RC were younger, had fewer comorbidities, and were more often treated at an academic center than those who did not undergo RC. At the time of RC, 41% of patients with T1HG bladder cancer were upstaged (pT2 or greater) and 12.7% had lymph node metastases. The 1- and 3-year survival rates were 0.89 and 0.68, respectively. Extravesical (T3+) disease at RC had the strongest independent hazard (hazard ratio [HR], 2.32; 95% CI, 1.72-3.11) of death other than age of 82 years or older (HR, 3.40; 95% CI, 2.28-5.07). Conclusions The use of RC for T1HG bladder cancer has increased in prevalence in recent years but is still not widely used. There are concerning pathologic outcomes in patients with clinical T1HG bladder cancer treated with RC, including high rates of pathologic upstaging and nodal metastases. Future studies are necessary to better risk-stratify patients with T1HG bladder cancer to best select those who will benefit from aggressive therapy with RC.
Delayed Platelet Recovery After Allogeneic Peripheral Blood, Marrow and Umbilical Cord Stem Cell Transplantation: Risk Factors and Clinical Outcomes.

Abstract 867 Introduction: Several reports have shown that despite prompt neutrophil engraftment after allogeneic stem cell transplantation, there can be delayed platelet recovery, especially in umbilical cord blood (UCB) stem cell transplant recipients. This dichotomy in platelets and neutrophils engraftment is poorly explained. In addition, the risk factors and complications associated with delayed platelet recovery are not clearly identified. Methods: We conducted a retrospective analysis to characterize the frequency of delayed platelet recovery and its associated risk factors and related complications. All allografts at the University of Minnesota between 2000 and 2005 were included. Results: 875 patients with hematologic malignancies or benign disorders were included. Myeloablative conditioning was used in 576 (66%) patients and non-myeloablative conditioning in 299 (34%) patients. 343 (39%) patients received related donor and 532 (61%) unrelated grafts. The source of the graft was bone marrow in 226 (26%) patients, peripheral blood in 255 (29%) patients and UCB in 394 (45%) patients. 150 (17%) patients were excluded due to early death (n=87, 10%), graft failure (n=62, 7%) and second transplant without engraftment (n=1). The 60 day cumulative incidence of platelet recovery by donor type was UCB single cord 39% (n=180, CI 31-47%), UCB double cord 40% (n=206, CI 32-48%), URD mismatched 57% (n=28, CI 39-75%), URD matched 56% (n=117, 48-64%) and sibling 74% (n=319, 65-85%). Overall, 232 (32%) had delayed platelet recovery (platelets 50K by day 60). Cox regression analysis showed that variables significantly associated with delayed platelet recovery were donor type (UCB RR 0.3 [CI 0.2-0.35], p 35 (RR 1.6 [CI 1.0-2.5], p=0.03 vs age Conclusions: These results suggest that delayed platelet recovery and poor graft function are common complications of allogeneic stem cell transplantation, especially after UCB grafts. Further study is needed to determine if modification of these associated risk factors will reduce the risks of severe complications and improve survival. Disclosures: No relevant conflicts of interest to declare.
Scavenger receptor B1 (SR-B1) profoundly excludes high density lipoprotein (HDL) apolipoprotein AII as it nibbles HDL-cholesteryl ester

Reverse cholesterol transport (transfer of macrophage-cholesterol in the subendothelial space of the arterial wall to the liver) is terminated by selective high density lipoprotein (HDL)-cholesteryl ester (CE) uptake, mediated by scavenger receptor class B, type 1 (SR-B1). We tested the validity of two models for this process: "gobbling," i.e. one-step transfer of all HDL-CE to the cell and "nibbling," multiple successive cycles of SR-B1-HDL association during which a few CEs transfer to the cell. Concurrently, we compared cellular uptake of apoAI with that of apoAII, which is more lipophilic than apoAI, using HDL-[3H]CE labeled with [125I]apoAI or [125I]apoAII. The studies were conducted in CHO-K1 and CHO-ldlA7 cells (LDLR-/-) with (CHO-SR-B1) and without SR-B1 overexpression and in human Huh7 hepatocytes. Relative to CE, both apoAI and apoAII were excluded from uptake by all cells. However, apoAII was more highly excluded from uptake (2-4×) than apoAI. To distinguish gobbling versus nibbling mechanisms, media from incubations of HDL with CHO-SR-B1 cells were analyzed by non-denaturing PAGE, size-exclusion chromatography, and the distribution of apoAI, apoAII, cholesterol, and phospholipid among HDL species as a function of incubation time. HDL size gradually decreased, i.e. nibbling, with the concurrent release of lipid-free apoAI; apoAII was retained in an HDL remnant. Our data support an SR-B1 nibbling mechanism that is similar to that of streptococcal serum opacity factor, which also selectively removes CE and releases apoAI, leaving an apoAII-rich remnant.
Parent disclosure of complementary health approaches used for children with autism spectrum disorder: Barriers and facilitators.

Abstract Background and objectives Complementary health approaches (CHA) are widely used among children with autism spectrum disorder (ASD). As part of shared treatment decision-making, healthcare providers are encouraged to discuss CHA with parents of children with ASD. Yet prior research suggests that parents often do not disclose CHA used for children, and their reasons for nondisclosure are poorly understood. We, therefore, aimed to identify barriers and facilitators to parent disclosure of CHA used for children with ASD. Design and setting In-depth interviews were conducted with 31 parents who reported that they were currently using CHA for their child’s ASD in Denver, Colorado or Portland, Oregon. Results We used content analysis to identify six main themes indicating that the following factors play a role in disclosure: parents’ drive to optimize their child’s health, parent self-efficacy discussing CHA with healthcare providers, parent beliefs about the effectiveness of CHA, parent-provider relationship quality, provider attitudes and knowledge regarding CHA and ASD, and visit characteristics. Conclusions Study findings suggest that family and health system factors, together, influence parent disclosure of CHA used for children with ASD. Multifaceted intervention concurrently targeting the CHA-related knowledge, beliefs, and self-efficacy of parents whose children have been recently diagnosed with ASD, in addition to the CHA-related attitudes and knowledge of their healthcare providers may promote disclosure and shared treatment decision-making about the use of CHA.
Applying the Seattle Heart Failure Model in the Office Setting in the Era of Electronic Medical Records.

BACKGROUND Prediction models such as the Seattle Heart Failure Model (SHFM) can help guide management of heart failure (HF) patients, but the SHFM has not been validated in the office environment. This retrospective cohort study assessed the predictive performance of the SHFM among patients with new or pre-existing HF in the context of an office visit.Methods and Results:SHFM elements were ascertained through electronic medical records at an office visit. The primary outcome was all-cause mortality. A "warranty period" for the baseline SHFM risk estimate was sought by examining predictive performance over time through a series of landmark analyses. Discrimination and calibration were estimated according to the proposed warranty period. Low- and high-risk thresholds were proposed based on the distribution of SHFM estimates. Among 26,851 HF patients, 14,380 (54%) died over a mean 4.7-year follow-up period. The SHFM lost predictive performance over time, with C=0.69 and C<0.65 within 3 and beyond 12 months from baseline respectively. The diminishing predictive value was attributed to modifiable SHFM elements. Discrimination (C=0.66) and calibration for 12-month mortality were acceptable. A low-risk threshold of ∼5% mortality risk within 12 months reflects the 10% of HF patients in the office setting with the lowest risk. CONCLUSIONS The SHFM has utility in the office environment.
Effect of the Opioid Crisis on the Donor Pool for Kidney Transplantation: An Analysis of National Kidney Deceased Donor Trends from 2010-2016.

Background The opioid crisis has led to a dramatic increase in the number of drug overdose deaths in the United States. Little is known about the effect of the opioid crisis on the kidney transplant donor pool, particularly on hepatitis C virus (HCV)-infected donors. Methods This is a retrospective analysis of the data from the Organ Procurement and Transplantation Network from 2010 to 2016. We determined the changes in characteristics of kidney transplant donors and evaluated which changes may be directly related to the opioid crisis. Results Between 2010 and 2016, we found a 26% increase in overall donors, including a 277% increase in the number of donors who died from drug overdose. Nineteen percent of donors who died of drug overdose had HCV infection. Donors who die from drug overdose and donors with HCV infection are younger, less likely to have diabetes or hypertension, and have favorable kidney donor profile index scores compared to average donors. Despite these favorable characteristics, HCV-infected donors appear to be notably underutilized, with substantially lower kidneys per donor being transplanted compared to HCV uninfected donors. Conclusion The opioid crisis in the United States has substantially altered the kidney donor pool. Strategies to increase utilization of all potentially viable kidneys for transplant are needed, particularly in this era of new, highly effective, direct-acting antiviral therapy for HCV infection.