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The goals of today's school athletic programs are vastly different from the original intentions of the administrators who established the first interscholastic athletic teams. For athletics to be anything more than a drain on school and taxpayer resources, these programs must undergo serious changes.

In this paper, we examine the role of the Inter-American Court of Human Rights in its efforts to impose accountability for human rights violations in Latin America. We suggest that, because domestic enforcement mechanisms are irreconcilably deficient in this task, accountability must emanate from beyond the state. We test this contention by examining one of the most challenging nations in the region—Guatemala.

Periostin is predominantly expressed in collagen-rich fibrous connective tissues that are subjected to constant mechanical stresses including: heart valves, tendons, perichondrium, cornea, and the periodontal ligament (PDL). Based on these data we hypothesize that periostin can regulate collagen I fibrillogenesis and thereby affect the biomechanical properties of connective tissues. Immunoprecipitation and immunogold transmission electron microscopy experiments demonstrate that periostin is capable of directly interacting with collagen I. To analyze the potential role of periostin in collagen I fibrillogenesis, gene targeted mice were generated. Transmission electron microscopy and morphometric analyses demonstrated reduced collagen fibril diameters in skin dermis of periostin knockout mice, an indication of aberrant collagen I fibrillogenesis. In addition, differential scanning calorimetry (DSC) demonstrated a lower collagen denaturing temperature in periostin knockout mice, reflecting a reduced level of collagen cross-linking. Functional biomechanical properties of periostin null skin specimens and atrioventricular (AV) valve explant experiments provided direct evidence of the role that periostin plays in regulating the viscoelastic properties of connective tissues. Collectively, these data demonstrate for the first time that periostin can regulate collagen I fibrillogenesis and thereby serves as an important mediator of the biomechanical properties of fibrous connective tissues.

This is a case of a 23-year-old African American male with a history of paranoid schizophrenia that developed neutropenia on a clozapine-topiramate therapy. Clozapine had well addressed the patient’s psychotic symptoms, while topiramate was used as a weight-lowering agent. The patient had fairly stable leukocyte counts for eight months on clozapine 300 mg and topiramate 100 mg daily. Doubling the dosage of topiramate led to severe neutropenia after two months. Reviewing the patient’s laboratory reports showed a gradual decline of neutrophils occurring at a lower dosage, followed by a rapid decline after an increased dosage. In this case, we report that not only did topiramate act as the neutropenic agent, but also it might have done so in a dose-dependent manner.

Myricitrin, a flavonol rhamnoside of myricetin extracted from the Chinese bayberry (Myrica rubra Siebold) plant, has been used in Japan since 1992 as a flavour modifier in snack foods, dairy products, and beverages. It is affirmed as generally recognised as safe (GRAS) by the US Flavour and Extract Manufacturer Association (FEMA) and is considered safe by the Joint FAO/WHO Expert Committee on Food Additives (JECFA) at current estimated dietary exposures. In anticipation of expanded marketing, 97% pure myricitrin was fed to male and female Sprague-Dawley rats at dietary concentrations of 0.5%, 1.5% and 5.0% in a 90-day toxicity study. There was increased food consumption and decreased body weight gain in males exposed to 5% myricitrin. Blood values were within laboratory reference ranges except for mean increases in basophils in low- and high-dose males and serum phosphorus in high-dose males. In the absence of abnormal clinical or histopathological changes, these changes are not considered adverse. Based on the 90-day rat toxicity study, the no observed adverse effect level (NOAEL) is 2926 mg kg(-1) day(-1) in males and 3197 mg kg(-1) day(-1) in females. Gavage administration of myricitrin resulted in blood levels of myricitrin within 1 h after single oral doses of 250, 500 or 1000 mg kg(-1) body weight, indicating direct absorption of the glycosylated form of this flavonoid. Blood levels of myricetin, a metabolite of myricitrin, were not present in rats dosed orally with 1.6 mg kg(-1) myricetin, but were present only at 12 or 24 h in one of five, in three of five, and in four of five rats dosed with 250, 500 and 1000 mg myricitrin kg(-1) body weight, respectively, possibly a result of hepatic conversion of myricitrin to myricetin and enterohepatic recirculation of the resulting myricetin. The current studies further support prior safety assessments of myricitrin as a food flavouring.

Compound dichroic polarizers using liquid crystal polymers and dichroic dyes have been studied for their variation of polarization with wavelength. Compound dichroic polarizers are composed of multilayer polarizers, where each layer has a different orientation and absorption spectrum. Several wavelength-dependent transmission axes configurations are proposed and investigated. Polarization properties, such as linear and circular diattenuation of the compound dichroic polarizers, for different wavelengths are measured and compared with simulation. Depending on the configuration, the compound dichroic polarizers can convert polarization signatures into color coding in unique ways.

We consider a generalization of Eulerian numbers which count the number of placements of $cn$ "rooks" on an $n\times n$ board where there are exactly $c$ rooks in each row and each column, and exactly $k$ rooks below the main diagonal. The standard Eulerian numbers correspond to the case $c=1$. We show that for any $c$ the resulting numbers are symmetric and give generating functions of these numbers for small values of $k$., 15 pages

We apply matrix theory over F 2 to understand the nature of so-called “successful pressing sequences” of black-and-white vertex-colored graphs. These sequences arise in computational phylogenetics, where, by a celebrated result of Hannenhalli and Pevzner, the space of sortings-by-reversal of a signed permutation can be described by pressing sequences. In particular, we offer several alternative linear-algebraic and graph-theoretic characterizations of successful pressing sequences, describe the relation between such sequences, and provide bounds on the number of them. We also offer several open problems that arose as a result of the present work.

Research in liquid crystal polymer retarder and polarizer has enabled the development of a new class of full Stokes division-of-focal-plane imaging polarimeter. The construction, calibration and performance of several polarimeters will be presented.

Through the lens of Guatemala’s Jorge Carpio Nicolle case I analyze the mechanisms that preserve impunity in Latin American nations struggling to emerge from violent conflict and embrace, the rule of law. I reveal how the infective influence of parallel powers, the ineffectiveness of the judicial process, and obstructive legal doctrine destroy domestic efforts to prosecute those responsible for human rights violations. The Carpio case exposes the role of international courts in providing justice when domestic courts fail to do so, and it demonstrates the importance of human rights groups in pursuing this justice.

Development of the epicardium is critical to proper heart formation. It provides all of the precursor cells that form the coronary system and supplies signals that stimulate cardiac myocyte proliferation. The epicardium forms from mesothelial cells associated with the septum transversum and is referred to as the proepicardium (PE). Two different methods by which these PE cells colonize the developing heart have been described. In avians, PE cells form a bridge to the heart over which PE cells migrate onto the heart. In fish and mammals, PE cells form vesicles of cells that detach from the mesothelium, float through the pericardial cavity, and attach to the heart. A previous study of rat PE development investigated this process at the histological level. Protein markers have been developed since this study. Thus, we investigated this important developmental process coupled with these new markers using other visualization techniques such as scanning electron microscopy (SEM) and confocal microscopy. Finally, a novel, three-dimensional (3-D) culture system was used to confirm the identity of the PE cells. In this study, we found convincing evidence that the rat PE cells directly attach to the heart in a manner similar to that observed in avians.

In a pilot developmental neurotoxicity study, a protocol was designed to utilize three-dimensional magnetic resonance (MR) images for linear and volumetric measurements of the developing rat brain. MR imaging, because of its non-destructive nature, provides a complement to traditional optical microscopy. Sprague–Dawley dams received 0, 1.25, 4.0 or 7.5 mg/kg methylazoxymethanol acetate (MAM) by intraperitoneal injection during gestation days 13–15. At postnatal days (PND) 23 and 60, brains from representative male and female rats from two dams in each dose group were fixed with 10% neutral buffered formalin by transcardial perfusion for in situ MR imaging. A 7 T small animal magnet system was used to obtain isotropic images at 100 μm resolution for PND 23 and 150 μm resolution for PND 60. Data from a rapid screening method based on midpoint MR slices of whole brain, cerebrum, cerebellum, and hippocampus showed a dose-related decreased volume of whole brain, cerebrum, and hippocampus in treated rats. Subsequent volumetric estimates using the Cavalieri method confirmed these findings. The brains were subsequently removed and processed for conventional histologic examination of hematoxylin and eosin-stained sections. It is concluded that MR imaging in rat developmental neurotoxicity studies offers the advantages of in situ volumetric measurements of brain structures while preserving the samples for conventional optical microscopy.

In 1980 the Second Circuit Court of Appeals broke with years of legal tradition and ruled that human rights victims could sue their oppressors in federal court—even if the alleged violations occurred outside the country. This court based the extension of its authority on a provision of the 1789 Judiciary Act now referred to as the Alien Tort Claims Act (ATCA). ATCA cases present a unique opportunity to study judicial behavior in the face of separation of powers interests, traditions of judicial restraint, sovereign immunity defenses, and an active internationalist movement to extend human rights guarantees worldwide. Combining legal analysis with quantitative methodology, I find that U.S. federal courts are slowly accepting an internationalist approach to human rights, and that interest groups are largely driving this transformation. Sovereignty concerns and judicial ideology are not conditioning case outcomes, but party resources and separation of powers issues are.

This study examined physical violence portrayed in a sample of televised professional wrestling. Trained research assistants coded the frequency of violent interactions, perpetrator characteristics, and contextual features (extent of violence, use of weapons, consequence of violence, reasons for violence, and reward for violence). Wrestling was compared with a sample of prime-time television from the National Television Violence Study (Smith, Nathanson, & Wilson, 2002). Findings show that the extent of violence in wrestling is significantly greater than other prime-time genres and that wrestling more often portrays violence as justified, likely to go unpunished, and unlikely to produce extreme harm. Overall, wrestling presented violence in amounts and contexts linked with increased risk of harm to viewers. Professional wrestling has smashed its way into American popular culture. Surveys show the magnitude of its appeal as ratings and revenues have risen to unexpected heights. World Wrestling Entertainment’s (WWE) Monday Night Raw program soared in popularity during the late 1990s, reaching as many as 8 million cable viewers a week by 1999 (“Raw Ratings History,” 2003). Although the appeal of professional

Because of environmental concerns, terminals are increasingly looking to reduce their truck turn time. Terminals are also looking to reduce truck turn time so that they can lower the inland transportation cost of shipping a container. For terminals that stack their containers, the solution may seem obvious: add more yard cranes. However, the high cost of those cranes often prohibits terminals from freely buying more. Another reason terminals are reluctant to add more yard cranes is that there is no clear understanding of how yard cranes affect truck turn time. A study introduces a simulation model for the analysis of truck turn time with respect to crane availability and deployment. This effort is accomplished by modeling the precise movements of trucks and yard cranes. The developed model uses the Barbours Cut Container Terminal of the Port of Houston Authority as a test bed to demonstrate how it can be applied to find the number of yard cranes needed to achieve a desired truck turn time. Other uses of the model include testing the crane deployment methodology, examining the effect of crane failure, and analyzing the impact of an appointment system.

Interpolation of contaminant data can present a significant challenge due to sample clustering and sharp gradients in concentration. The research presented in this paper represents a study of commonly used interpolation schemes applied to three-dimensional plume characterization. Kriging, natural neighbor, and inverse distance weighted interpolation were tested on four actual data sets. The accuracy of each scheme was gauged using the cross-validation approach. Each scheme was compared to the other schemes and the effect of various interpolation parameters was studied. The kriging approach resulted in the lowest error at three of the four sites. The simpler and quicker inverse distance weighted approach resulted in a lower interpolation error on the other site and performed well overall. The natural neighbor method had the highest average error at all four sites in spite of the fact that it has been shown to perform well with clustered data. Another unexpected result was that the computationally expensive high order nodal functions resulted in reduced accuracy for the inverse distance weighted and natural neighbor approaches.

This paper examines the rise in Supreme Court dissent and concurrence rates, testing whether modern legal education contributes to the abandonment of the consensual norm. Scholars have pointed out that changing external conditions, changing enforcement mechanisms, and changing values may alter the conceptualization of a norm. Modern legal education trains lawyers to apply case law to conflicting arguments creatively in pursuit of desired outcomes. This paper tests the hypothesis that modern legal education has indoctrinated judges to freely pursue adversarial positions, supported by differing interpretations of precedent. This behavior would manifest itself in greater rates of dissents and special concurrences. Statistical tests examining Supreme Court decisions from 1801 through 1991 strongly support the hypothesis.

In vitro studies have demonstrated that the aqueous solubility of the tyrosine kinase inhibitor ponatinib decreases as pH increases. The primary aim of this study was to assess the effects of the gastric proton pump inhibitor lansoprazole on the pharmacokinetics of ponatinib. The single-dose safety profile of ponatinib with and without coadministration of lansoprazole was also characterized. This was a phase I, open-label, non-randomized, two-period crossover study in 20 healthy subjects aged 18–55 years. Subjects received a single oral dose of ponatinib 45 mg alone on day 1, an oral dose of lansoprazole 60 mg on day 14, and ponatinib 45 mg plus lansoprazole 60 mg on day 15. Lansoprazole coadministration resulted in a 1-h increase in the time to maximum plasma concentration (t max) of ponatinib (6 vs. 5 h post-dose; P

Ponatinib, an oral tyrosine kinase inhibitor with significant activity in heavily pretreated patients with chronic myeloid leukemia, is a CYP3A4 substrate. This open-label, nonrandomized, fixed-order crossover study evaluated the effect of multiple oral doses of rifampin, a strong CYP3A4 inducer, on the pharmacokinetics of ponatinib (45 mg, single dose). Twenty healthy adults received ponatinib on day 1, rifampin 600 mg alone on days 8-13, 15, and 16, and rifampin 600 mg with ponatinib on day 14. Rifampin decreased maximum plasma concentration (Cmax ) and area under the plasma concentration-time curve (AUC) from time zero to time of last measurable concentration (AUC0-t ) and from time zero to infinity (AUC0-∞ ) of ponatinib by 42%, 59%, and 63%, respectively, with no effect on time to Cmax . The limits of the 90% confidence intervals of the estimated geometric mean ratios of ponatinib Cmax , AUC0-t , and AUC0-∞ did not fall within the 80-125% margins for equivalence, suggesting a statistically significant interaction. Coadministration of ponatinib with strong CYP3A4 inducers should be avoided unless the benefit outweighs the possible risk of ponatinib underexposure, because the safety of ponatinib dose increases has not been studied in this context.

This study evaluated the effects of chronic hepatic impairment on the single-dose pharmacokinetics (PK) of the tyrosine kinase inhibitor ponatinib.Subjects (n = 16) had Child-Pugh class A (mild, n = 6), B (moderate, n = 6), or C (severe, n = 4) hepatic impairment and were matched with healthy controls (n = 8). Each subject received a single oral dose of ponatinib 30 mg under fasting conditions, and PK parameters were assessed in blood samples collected through 96 h post-dose.Ponatinib maximum plasma concentrations (C max) were observed after 5-6 h in Child-Pugh A, Child-Pugh B, and healthy subjects, and after ~3 h in Child-Pugh C subjects. The estimated % geometric mean ratios for C max, area under the plasma concentration-time curves from time zero to last observation (AUC0-t ) and to infinity (AUC0-∞) suggested a slightly lower exposure in Child-Pugh B (61.4, 89.1, and 90.6%, respectively) and Child-Pugh C subjects (62.8, 77.1, and 79.4%) versus healthy subjects. Child-Pugh A subjects had similar estimated % geometric mean ratio for C max (106.7%), and slightly greater estimated % geometric mean ratios for AUC0-t (133.0%) and AUC0-∞ (122.8%), versus healthy subjects. Mean elimination half-life was extended in subjects with hepatic impairment (43-47 vs 36 h). Ponatinib was generally well tolerated. A single serious AE (pancreatitis) in the Child-Pugh C group resolved with treatment.As no major differences in ponatinib single-dose PK were observed in patients with hepatic impairment versus healthy subjects, a reduction of ponatinib starting dose in these patients is not necessary, but caution is recommended when administering ponatinib to these patients.

Uropathogenic E. coli (UPEC) strains are described as extraintestinal pathogenic E. coli with preference for the urinary tract. Bottone et al2 recently described the first documentation of a hypermucoviscous phenotype of a UPEC strain that displays a "stringing" phenomenon analogous to those produced by Klebsiella pneumonia strains known to invade the liver. The occurrence of this hypermucoviscous phenotype of UPEC strains causing urinary tract infection has not been well established. Following, we present a case report of two separate renal isolates from a patient with recurrent renal abscesses yielding the aforementioned hypermucoviscous phenotype of UPEC strains.

Using a standardized schedule of questions, this study examined (a) the prevalence of self-report of violent thoughts by patients hospitalized for mental disorders compared with nonpatients, (b) the persistence of violent thoughts after discharge, and (c) the relation between patients' violent thoughts while hospitalized and violent acts within 20 weeks after hospital discharge. About 1/3 of the patients reported thoughts of violence while hospitalized, more than twice the proportion found among nonpatients. Reporting violent thoughts in hospital was significantly related to engaging in violent acts within 20 weeks after discharge for non-White patients, patients without major mental disorder but with substance abuse diagnoses, patients with high symptom severity, and patients whose reports of violent thoughts persisted after discharge. Reporting violent thoughts was significantly related to measures of psychopathy, anger, and impulsiveness.

Background: Gray, 1982 proposed that the septo-hippocampal system, which plays an important role in learning and memory, may partially mediate anxiety. Thus, patients with anxiety disorders may manifest neurocognitive performance deficits. We hypothesized that patients with panic disorder would demonstrate learning and memory deficits relative to normal comparison subjects. Method: Comprehensive neuropsychological batteries were administered to 69 panic disorder subjects and 19 normal volunteers. Results: There were no significant group differences in any neuropsychological performance domain including learning, memory, attention, visuospatial functioning, and psychomotor speed. Multiple regression conducted to evaluate the contribution of clinical symptoms to neuropsychological impairment within the panic disorder sample revealed that anxiety severity did not affect neuropsychological test performance. Limitations: Most patients had mild or moderate, rather than severe, panic disorder. Conclusion: Neuropsychological dysfunction was not associated with panic disorder.

Detailed methods are provided for the preparation and confocal imaging of cardiac myocyte development and differentiation. Examples include protocols for the analysis of cultured myocytes as well as vibratome sections of hearts from embryonic and adult tissue. Techniques include routine labeling of F-actin with phalloidin as well as multiple labeling protocols for colocalization studies and cell volume analysis.

Detailed methods are provided for the preparation and confocal imaging of cardiac myocyte development and differentiation. Examples include protocols for the analysis of cultured myocytes as well as vibratome sections of hearts from embryonic and adult tissue. Techniques include routine labeling of F-actin with phalloidin as well as multiple labeling protocols for colocalization studies and cell volume analysis.

Before remediation of a site with contaminated soil or groundwater, the contaminant plume must first be characterized. This involves sampling the contaminant concentration at a set of locations in and around the contaminated area. To present the measured concentrations in a meaningful form, the concentrations are typically interpolated to the nodes of a three-dimensional grid, and the plume is visualized by constructing iso-surfaces from the gridded data. The critical step in this process is the interpolation stage. Improper application of an interpolation scheme can result in grossly misleading three-dimensional plume maps. There are a number of problems that often occur when interpolating contaminant plume data, including generation of negative concentrations, oscillation of interpolated values, improper estimation of maximum concentrations, and skewing of the results due to data clustering. These and other difficulties associated with plume characterization are discussed, along with a simple set of guidelines for detecting and overcoming these problems.

50-year-old man presented to the Emergency Departent with 3 days of dysphagia and odynophagia. He also eported 1 day of subjective dyspnea when supine. Imunizations were up to date, he had not traveled reently, and he had no sick contacts. Past medical history, ocial history, and family history, as well as review of ymptoms were unremarkable. Vital signs were within normal limits with the excepion of a temperature of 38.9°C (102.1°F). The patient as speaking in full sentences, in no respiratory distress nd without stridor. He was sitting upright on a gurney, ccasionally spitting up red-tinged sputum. The head xamination was significant for facial asymmetry; the ight submandibular area was markedly edematous and ender with a non-fluctuant mass approximately 3 cm in ize (Figure 1). The oropharynx was significant for ildly erythematous mucosa. The posterior pharynx was ifficult to view, however, flexible indirect laryngoscopy evealed a narrowed trachea. Laboratory results were significant for WBC of 7,000, with 76% segmented neutrophils and 11% bands. lectrolytes and liver function tests were within normal imits. Imaging consisted of computed tomography (CT) can that revealed an inflammatory mass measuring 4 cm n the area of the right submandibular gland (Figure 2). n the center of the mass, there was a 1.4 1.7 cm stone. he mass extended into the lateral oropharynx and hy

Gum ghatti, a polysaccharide of natural origin, is used in foods as a thickening, gelling, emulsifying and stabilizing agent. In a 90-day toxicity study following Organization for Economic Co-operation and Development (OECD) Guideline #408, male and female Sprague–Dawley rats were exposed to 0 (control), 0.5, 1.5 and 5% gum ghatti in AIN-93M basal diet. Expected changes included increased full and empty cecal weights in 5% groups. Incidentally 2/10 females from the 5% gum ghatti group had a single colon ulcer with associated acute inflammation. In a second 90-day study increased cecal weights were present in Sprague–Dawley females exposed to 5% gum ghatti in AIN-93M and NIH-07 basal diets. A single colon ulcer with associated acute inflammation occurred in 1/20 control females given AIN-93M basal diet. The colon ulcers were considered a sporadic change possibly attributable to AIN-93M basal diet. In the second study a few statistically significant alterations in clinical chemistry were considered sporadic and unrelated to treatment. Feed consumption among treated and control groups was similar for each sex. Gum ghatti intake at the 5% dietary level ranged from 3044 to 3825 mg/kg body weight/day. The 5% dietary administration was a NOAEL in both studies. NOAELs for males and females in the first study were 3044 and 3309 mg/kg/day, respectively. NOAELs for females in the second study were 3670 and 3825 mg/kg/day for AIN-93M and NIH-07 diets, respectively.

Gum ghatti is a food additive in some parts of the world, serving as an emulsifier, a stabilizer, and a thickening agent. To evaluate its genotoxic potential, we conducted Good Laboratory Practice compliant in vitro and in vivo studies in accordance with the Organisation for Economic Co-operation and Development (OECD) guidelines. No evidence of toxicity or mutagenicity was detected in a bacterial reverse mutation assay using five tester strains evaluating gum ghatti at up to 6 mg/plate, with or without metabolic activation. Gum ghatti also did not induce chromosome structural damage in a chromosome aberration assay using Chinese hamster ovary cells. To assess the ability to induce DNA damage in rodents, a combined micronucleus/Comet assay was conducted in male B6C3F1 mice. Gum ghatti was administered at 1000, 1500, and 2000 mg/kg/day by gavage once daily for 4 days and samples were collected 4 h after the final dosing. No effect of gum ghatti was measured on micronucleated reticulocyte (MN-RET) frequency in peripheral blood, or DNA damage in blood leukocytes or liver as assessed by the Comet assay. Our results show no evidence of genotoxic potential of gum ghatti administered up to the maximum concentrations recommended by OECD guidelines.

Validation of the 15-day intact adult male rat screening assay (IAMRSA), an endocrine activity screen, was extended beyond the 28 substances evaluated to date. Two independent laboratories evaluated specificity using allyl alcohol (AA), a putative negative control, and DE-71 (technical grade pentabromodiphenyl ether) for comparison with previous pubertal assays that demonstrated thyroid effects. Male rats (15/group) were gavaged daily with AA (0, 10, 30, or 40 mg/kg/day) or DE-71 (0, 3, 30, or 60 mg/kg/day) for 15 days. Body and organ weights and serum hormone concentrations were measured, and a limited histopathological assessment was conducted. AA results were considered negative at doses that did not exceed the maximum tolerated dose (MTD); effects reported were dose-related decreases in weight gain, increased liver weights and, although the pattern varied across studies, alterations in some androgen-sensitive endpoints in the high-dose where the maximum tolerated dose was exceeded. In the DE-71 studies, dose-dependent increases in liver weights (consistent with hepatic enzyme induction), decreases in tri-iodothyronine and thyroxine, concomitant thyroid stimulating hormone increases were observed and one laboratory reported histopathological thyroid changes in mid- and high-dose groups, and the other increased thyroid weights. For DE-71, the IAMRSA was comparable in sensitivity to the pubertal assays. Overall, the specificity and sensitivity of the IAMRSA for deployment in an endocrine screening battery are supported. However, differentiating primary endocrine-mediated effects from secondary effects caused by systemic toxicity will be challenging, emphasizing the need to utilize a battery of assays and a weight of evidence approach when evaluating the potential endocrine activity of chemicals.