bluuebunny/crossref_metadata_2025 huggingface dataset:
Vitamin D and Chronic Pain in Immigrant and Ethnic Minority Patients—Investigation of the Relationship and Comparison with Native Western Populations
Authors: Straube Sebastian , Moore R. Andrew , Derry Sheena , Hallier Ernst , McQuay Henry J.
Published: October 2009

Vitamin D deficiency has been implicated in chronic pain. Immigrant and ethnic minority populations have been shown to have lower vitamin D levels than native Western populations and often to be vitamin D deficient. This systematic review investigates the relationship between vitamin D and chronic pain in immigrant and ethnic minority populations. Included were studies reporting on 25-OH vitamin D levels in immigrant/ethnic minority populations affected by chronic pain, and/or reporting on the treatment of chronic pain with vitamin D preparations in such populations. We found that 25-OH vitamin D levels were low and often deficient in immigrant/ethnic minority populations. Vitamin D levels depended on the latitude of the study location and hence sunlight exposure. There was insufficient evidence to reach a verdict on the value of treating chronic pain in immigrant/ethnic minority patients with vitamin D preparations because the studies were few, small, and of low quality.
Binding Sites for ETS Family of Transcription Factors Dominate the Promoter Regions of Differentially Expressed Genes in Abdominal Aortic Aneurysms
Authors: Nischan Jennifer , Gatalica Zoran , Curtis Mindee , Lenk Guy M. , Tromp Gerard , Kuivaniemi Helena
Published: October 2009

Background—

Previously, we identified 3274 distinct differentially expressed genes in abdominal aortic aneurysm (AAA) tissue compared with nonaneurysmal controls. As transcriptional control is responsible for these expression changes, we sought to find common transcriptional elements in the promoter regions of the differentially expressed genes.

Methods and Results—

We analyzed the up- and downregulated gene sets with Whole Genome rVISTA to determine the transcription factor (TF) binding sites overrepresented in the 5-kb promoter regions of the 3274 genes. The downregulated gene set yielded 144 TF binding sites that were overrepresented in the subset when compared with the entire genome. In contrast, the upregulated gene set yielded only 13 distinct overrepresented TF binding sites. Interestingly, as classified by TRANSFAC, 8 of the 13 TFs binding to these regions belong to the ETS family. Additionally, nuclear factor kB and its subunits p50 and p65 showed enrichment. Immunohistochemical analyses of 10 TFs from the upregulated set showed 9 to be present in AAA tissue. Based on gene ontology analysis of biological process categories of the upregulated target genes of enriched TFs, 10 TFs had enrichment in immune system process among their target genes.

Conclusions—

Our genome-wide analysis provides further evidence of ETS and nuclear factor kB involvement in AAA. Additionally, our results provide novel insight for future studies aiming to dissect the pathogenesis of AAA and have uncovered potential therapeutic targets for AAA prevention.
Tobacco Smoke Exposure in Either the Donor or Recipient Before Transplantation Accelerates Cardiac Allograft Rejection, Vascular Inflammation, and Graft Loss
Authors: Khanna Ashwani K. , Xu Jianping , Uber Patricia A. , Burke Allen P. , Baquet Claudia , Mehra Mandeep R.
Published: October 2009

Background—

Tobacco exposure in cardiac transplant recipients, before and after transplantation, may increase the risk of cardiac allograft vasculopathy and allograft loss, but no direct evidence for this phenomenon is forthcoming. In this experimental study, we investigated early consequences of tobacco smoke exposure in cardiac transplant donors and recipients with an emphasis on alloinflammatory mediators of graft outcome.

Methods and Results—

Using heterotopic rat cardiac transplantation, we tested the effects of donor or recipient tobacco smoke exposure in 6 groups of animals (rat heterotopic cardiac transplantation) as follows: tobacco-naïve allogeneic rejecting controls (n=6), tobacco-naïve nonrejecting controls (n=3; killed on day 5 to simulate survival times of tobacco-treated animals), isografts (n=3), both donor and recipient rats exposed to tobacco smoke (n=4), only donor rats exposed to tobacco smoke (n=7), and only recipient rats exposed to tobacco smoke (n=6). Polymerase chain reaction studies of tissue and peripheral (systemic) protein expression were performed to evaluate inflammatory (tumor necrosis factor-α, interferon-γ, interleukin-6) and alloimmune (interleukin-1 receptor 2, programmed cell death-1, and stromal cell-derived factor-1) pathways, as was histological analysis of the cardiac allografts. Our experiments reveal that pretransplantation tobacco exposure in donors and/or recipients results in heightened systemic inflammation and increased oxidative stress, reduces posttransplantation cardiac allograft survival by 33% to 57%, and increases intragraft inflammation (tumor necrosis factor-α, interferon-γ, interleukin-6) and alloimmune activation (CD3, interleukin-1 receptor 2, programmed cell death-1, and stromal cell-derived factor-1) with consequent myocardial and vascular destruction.

Conclusions—

These sentinel findings confirm that tobacco smoke exposure in either donors or recipients leads to accelerated allograft rejection, vascular inflammation, and graft loss. Molecular pathways that intersect as arbiters in this phenomenon include instigation of alloimmune activation associated with tobacco smoke–induced inflammation.
Peripheral Vascular Adaptation and Orthostatic Tolerance in Fontan Physiology
Authors: Krishnan Usha S. , Taneja Indu , Gewitz Michael , Young Richard , Stewart Julian
Published: October 2009

Background—

The Fontan circulation is critically dependent on elevated venous pressures to sustain effective venous return. We hypothesized that chronically increased systemic venous pressures lead to adaptive changes in regional and peripheral vessels to maintain cardiac output, especially when patients are upright.

Methods and Results—

Nine post–Fontan procedure patients (aged 13 to 24 years) and 6 age- and sex-matched controls were compared with techniques to measure circulatory responses (peripheral and compartmental blood flow, venous capacity, and microvascular filtration). Parameters studied included strain-gauge plethysmography measures of peripheral circulatory function, regional blood volume distribution by impedance plethysmography, and head-up tilt testing. Important differences between Fontan patients and controls were seen in several vascular compartments: (1) Calf capacitance was lower (median, 3.5 versus 5.5 mL/100 mL tissue;
P
=0.005), and resting venous pressure was higher (13.0 versus 10.5 mm Hg;
P
=0.004); (2) higher leg arterial resistance was observed (32.1 versus 22.2;
P
=0.03); (3) microvascular filtration pressures and threshold for edema were elevated; and (4) with head-up tilt testing, splanchnic flow was not reduced in Fontan patients versus controls (fractional change, +4% versus −32%;
P
=0.004), and splanchnic arterial resistance did not increase as expected (fractional change, +8% versus +79%;
P
=0.003).

Conclusions—

Reduced venous compliance and increased filtration thresholds may act as adaptive mechanisms in maintaining venous return in Fontan circulation. Well-compensated Fontan subjects demonstrate superior orthostatic tolerance resulting from decreased compartmental fluid shifts in response to head-up tilt and higher vascular resistance. This results from increased venous stiffness and decreased splanchnic capacitance and may also be an adaptive mechanism to maintain venous return in these patients while standing.
Genetic Testing for Long-QT Syndrome
Authors: Kapa Suraj , Tester David J. , Salisbury Benjamin A. , Harris-Kerr Carole , Pungliya Manish S. , Alders Marielle , Wilde Arthur A.M. , Ackerman Michael J.
Published: October 2009

Background—

Genetic testing for long-QT syndrome (LQTS) has diagnostic, prognostic, and therapeutic implications. Hundreds of causative mutations in 12 known LQTS-susceptibility genes have been identified. Genetic testing that includes the 3 most commonly mutated genes is available clinically. Distinguishing pathogenic mutations from innocuous rare variants is critical to the interpretation of test results. We sought to quantify the value of mutation type and gene/protein region in determining the probability of pathogenicity for mutations.

Methods and Results—

Type, frequency, and location of mutations across
KCNQ1
(LQT1),
KCNH2
(LQT2), and
SCN5A
(LQT3) were compared between 388 unrelated “definite” (clinical diagnostic score ≥4 and/or QTc ≥480 ms) cases of LQTS and >1300 healthy controls for each gene. From these data, estimated predictive values (percent of mutations found in definite cases that would cause LQTS) were determined according to mutation type and location. Mutations were 10 times more common in cases than controls (0.58 per case versus 0.06 per control). Missense mutations were the most common, accounting for 78%, 67%, and 89% of mutations in
KCNQ1
,
KCNH2
, and
SCN5A
in cases and >95% in controls. Nonmissense mutations have an estimated predictive value >99% regardless of location. In contrast, location appears to be critical for characterizing missense mutations. Relative frequency of missense mutations between cases and controls ranged from ≈1:1 in the SCN5A interdomain linker to infinity in the pore, transmembrane, and linker in KCNH2. These correspond to estimated predictive values ranging from 0% in the interdomain linker of SCN5A to 100% in the transmembrane/linker/pore regions of KCNH2. The estimated predictive value is also high in the linker, pore, transmembrane, and C terminus of KCNQ1 and the transmembrane/linker of SCN5A.

Conclusions—

Distinguishing pathogenic mutations from rare variants is of critical importance in the interpretation of genetic testing in LQTS. Mutation type, mutation location, and ethnic-specific background rates are critical factors in predicting the pathogenicity of novel mutations. Novel mutations in low-estimated predictive value regions such as the interdomain linker of
SCN5A
should be viewed as variants of uncertain significance and prompt further investigation to clarify the likelihood of disease causation. However, mutations in regions such as the transmembrane, linker, and pore of
KCNQ1
and
KCNH2
may be defined confidently as high-probability LQTS-causing mutations. These findings will have implications for other genetic disorders involving mutational analysis.
Dietary-Induced Obesity Hastens the Progression From Concentric Cardiac Hypertrophy to Pump Dysfunction in Spontaneously Hypertensive Rats
Authors: Majane Olebogeng H.I. , Vengethasamy Leanda , du Toit Eugene F. , Makaula Siyanda , Woodiwiss Angela J. , Norton Gavin R.
Published: October 2009

We explored whether dietary-induced obesity hastens the transition from concentric left ventricular (LV) hypertrophy to pump dysfunction in spontaneously hypertensive rats (SHRs) and the mechanisms thereof. After feeding rats a diet for 4 to 5 months, obesity was induced in SHRs and Wistar-Kyoto (WKY) control rats. Obesity was not associated with abnormal blood glucose control (glycosylated hemoglobin) or with increases in systolic blood pressure. However, in SHRs, but not in WKY rats, obesity was associated with a reduced LV chamber systolic function, as determined by echocardiography, and in isolated perfused heart studies. A marked increase in LV end diastolic diameter and a right shift in the LV diastolic pressure-volume relation were noted in obese SHRs but not in obese WKY rats. Moreover, LV intrinsic myocardial systolic function, as determined from the slope of the linearized LV systolic stress-strain relationship (LV myocardial end systolic elastance), was markedly reduced in obese as compared with lean SHRs, whereas LV myocardial end systolic elastance was maintained in obese WKY rats. Obesity increased LV weight, cardiomyocyte width, cardiomyocyte apoptosis (TUNEL), the activity of myocardial matrix metalloproteinases (zymography), and serum leptin concentrations in SHRs but not in WKY rats. In conclusion, SHRs are susceptible to the adverse effects of dietary-induced obesity on the heart, an effect that hastens the progression from concentric LV hypertrophy to pump dysfunction independent of blood pressure changes or alterations in glycosylated hemoglobin. This effect may be mediated through a proclivity of SHRs to developing both obesity-induced effects on cardiomyocyte apoptosis and activation of myocardial collagenases through leptin resistance and obesity-induced hypertrophy.
Role of Proinflammatory Cytokines and Redox Homeostasis in Exercise-Induced Delayed Progression of Hypertension in Spontaneously Hypertensive Rats
Authors: Agarwal Deepmala , Haque Masudul , Sriramula Srinivas , Mariappan Nithya , Pariaut Romain , Francis Joseph
Published: October 2009

Hypertension is a well-known risk factor for various cardiovascular diseases. Recently, exercise has been recommended as a part of lifestyle modification for all hypertensive patients. However, the precise mechanisms of exercise training (ExT)–induced effects on the development of hypertension are poorly understood. Therefore, we hypothesized that chronic ExT would delay the progression of hypertension in young spontaneously hypertensive rats (SHRs). In addition, we explored whether the beneficial effects of chronic ExT were mediated by reduced proinflammatory cytokines and improved redox status. We also investigated the involvement of nuclear factor-κB in exercise-induced effects. To test our hypotheses, young normotensive (Wistar-Kyoto) and SHRs were given moderate-intensity ExT for 16 weeks. Blood pressure was determined by the tail-cuff method, and cardiac function was assessed by echocardiography. Myocardial total reactive oxygen species and superoxide production were measured by electron paramagnetic resonance spectroscopy; tumor necrosis factor-α, interleukin-1β, gp91phox, and inducible NO synthase by real-time PCR; and nuclear factor κB activity by electrophoretic mobility shift assay. Chronic ExT in hypertensive rats resulted in significantly reduced blood pressure, reduced concentric hypertrophy, and improved diastolic function. ExT significantly reduced proinflammatory cytokines and inducible NO synthase, attenuated total reactive oxygen species and superoxide production, and increased antioxidants in SHRs. ExT also resulted in increased NO production and decreased nuclear factor κB activity in SHRs. In summary, chronic ExT delays the progression of hypertension and improves cardiac function in young SHRs; these ExT-induced beneficial effects are mediated by reduced proinflammatory cytokines and improved redox homeostasis via downregulation of nuclear factor-κB.
Accelarated Skeletal Maturation in Children With Primary Hypertension
Authors: Pludowski Pawel , Litwin Mieczyslaw , Niemirska Anna , Jaworski Maciej , Sladowska Joanna , Kryskiewicz Edyta , Karczmarewicz Elzbieta , Neuhoff-Murawska Joanna , Wierzbicka Aldona , Lorenc Roman S.
Published: October 2009

It is hypothesized that primary hypertension (PH) is a disorder with origins in childhood linked to, at least in part, aberrations of growth and maturation processes. To evaluate the possible relation between the rate of biological maturity and development of PH, bone age (BA) assessments on the basis of dual x-ray absorptiometry–derived hand scans were performed in 54 newly diagnosed children and adolescents with PH and 54 healthy controls matched for body mass index (BMI), age and sex. Chronological age (CA), body height (in centimeters), body weight (in kilograms), BMI (in kilograms per meter squared), and blood pressure were assessed. Healthy controls had a mean BA of 14.7±2.3 years that was not significantly different from their mean CA of 14.2±2.1 years. In the PH group, the BA of 16.0±2.0 years was higher by 1.9±0.9 years compared with their CA of 14.1±2.0 years (
P
<0.0001). The magnitude of acceleration of skeletal maturation (BA-CA) and its prevalence (88.9%) were significantly higher in PH compared with BMI-matched controls (37.0%; χ
2
=31.4;
P
<0.0001). BA-CA values of PH patients were higher by 1.24 years in normal weight (
P
<0.0001), 1.80 years in overweight (
P
<0.01), and 1.40 years in obese (
P
<0.0001) subgroups of BMI
z
score–matched controls. Stepwise regression revealed that predictors of blood pressure status from normotension through prehypertension stages 1 and 2 of hypertension were BA-CA (β=0.530;
P
<0.0.001), height (β=−0.379;
P
<0.01), and CA (β=0.298;
P
<0.05;
R
2
=0.43). In conclusion, irrespective of BMI, advanced biological maturation should be considered as an independent marker for the development of hypertension.
Precise Capacity Analysis in Binary Networks with Multiple Coding Level Inputs
Authors: Amit Yali , Huang Yibi
Published: October 2009

We compute retrieval probabilities as a function of pattern age for networks with binary neurons and synapses updated with the simple Hebbian learning model studied in Amit and Fusi ( 1994 ). The analysis depends on choosing a neural threshold that enables patterns to stabilize in the neural dynamics. In contrast to most earlier work, where selective neurons for each pattern are drawn independently with fixed probability f, here we analyze the situation where f is drawn from some distribution on a range of coding levels. In order to set a workable threshold in this setting, it is necessary to introduce a simple inhibition in the neural dynamics whose magnitude depends on the total activity of the network. Proper choice of the threshold depends on the value of the covariances between the synapses for which we provide an explicit formula. Retrieval probabilities depend on the distribution of the fields induced by a learned pattern. We show that the field induced by the first learned pattern evolves as a Markov chain during subsequent learning epochs, leading to a recursive formula for the distribution. Alternatively, the distribution can be computed using a normal approximation, which involves the value of the synaptic covariances. Capacity is computed as the sum of the retrival probabilities over all ages. We show through simulation that the chosen threshold enables retrieval with asynchronous dynamics even in the presence of significant noise in the initial state of the pattern. The computed probabilities with both methods are shown to be very close to probabilities estimated from simulation. The analysis is extended to randomly connected networks.
Growing Self-Organizing Surface Map: Learning a Surface Topology from a Point Cloud
Authors: Mole Vilson Luiz Dalle , Araújo Aluizio Fausto Ribeiro
Published: October 2009

The growing self-organizing surface map (GSOSM) is a novel map model that learns a folded surface immersed in a 3D space. Starting from a dense point cloud, the surface is reconstructed through an incremental mesh composed of approximately equilateral triangles. Unlike other models such as neural meshes (NM), the GSOSM builds a surface topology while accepting any sequence of sample presentation. The GSOSM model introduces a novel connection learning rule called competitive connection Hebbian learning (CCHL), which produces a complete triangulation. GSOSM reconstructions are accurate and often free of false or overlapping faces. This letter presents and discusses the GSOSM model. It also presents and analyzes a set of results and compares GSOSM with some other models.
Dynamics and Robustness of Familiarity Memory
Authors: Cortes J. M. , Greve A. , Barrett A. B. , van Rossum M. C. W.
Published: October 2009

When presented with an item or a face, one might have a sense of recognition without the ability to recall when or where the stimulus has been encountered before. This sense of recognition is called familiarity memory. Following previous computational studies of familiarity memory, we investigate the dynamical properties of familiarity discrimination and contrast two different familiarity discriminators: one based on the energy of the neural network and the other based on the time derivative of the energy. We show how the familiarity signal decays rapidly after stimulus presentation. For both discriminators, we calculate the capacity using mean field analysis. Compared to recall capacity (the classical associative memory in Hopfield nets), both the energy and the slope discriminators have bigger capacity, yet the energy-based discriminator has a higher capacity than one based on its time derivative. Finally, both discriminators are found to have a different noise dependence.
Prisoners of War: A Comparative Study of the Principles of International Humanitarian Law and the Islamic Law of War
Authors: El Zeidy Mohamed , Murphy Ray
Published: October 2009

The treatment of prisoners of war (POWs) has been an issue of concern to all those engaged in armed conflict for centuries. The problem of how to deal with POWs is not a new one and their treatment is a question with which the laws of war have been particularly concerned. Not all persons captured in the course of armed conflict are entitled to POW status. Generally, only persons recognized as "combatants" in accordance with international humanitarian law are entitled to POW status upon capture by an adverse party in armed conflict. Under the Third Geneva Convention of 1949, POWs are the responsibility of the capturing power from the moment of capture, and not of the individual or military units, which actually capture them. POWs must at all times be humanely treated and the Third Convention provides clear rules in relation to their camps, quarters, food and clothing. The principles embodied in the Islamic Law of War also provide a comprehensive framework for the protection of POWs. Nevertheless, there are some important differences between Islamic Law of War and the principles contained in the Geneva Conventions and Hague Regulations, especially in relation to triggering the application of the laws of war and the concept of armed conflict. What is most striking is the similarity in the protection provided by both legal frameworks. However, the single biggest challenge to both regimes remains the implementation of the relevant principles.
The Concept of Crime in the Afghan Criminal Justice System: The Paradox between Secular, Tradition and Islamic Law: A Viewpoint of an International Practitioner
Authors: Tawfik Ahmed Hamdy
Published: October 2009

In modern Afghanistan, one major problem with which legal scholars struggle is identification of the concept of crime. While crime is identified and defined in the Afghani Secular Penal Code of 1976, as well in Islamic Law (Shari'ah), jurisprudence of the courts and traditions take precedence in the everyday lives of Afghanis. Court's jurisprudence and the traditional dispute-resolution system are deemed to be a product of Islamic jurisprudence, notwithstanding that, in some cases, they represent an erroneous interpretation and application of Shari'ah as this article will examine. This article focuses on the concept of crime in Islamic law and analyses the court's jurisprudence and traditional system, which are widely applied throughout different parts of Afghanistan, and seeks to identify their relationship between Islamic and secular laws and whether they are consistent with Islamic Shari'ah.
The Disunity of Islamic Criminal Law and the Modern Role of Ijtihād
Authors: Bantekas Ilias
Published: October 2009

Islamic law, and criminal law in particular, have been closed since its heyday of legal scholarship to external influences and new theoretical arguments and constructs. This, it is argued, is due to the lack of enlightened and revered scholarship that will enhance Islamic law and which is currently unavailable. This situation is unlike early and classical Islam where legal argumentation flourished and Islamic scholarship was generally open to external currents and philosophical ideas. Despite these limitations Islamic criminal law has not coalesced to shield itself from foreign elements, but instead lacks a single voice not only in practice but also in its theoretical bases among Muslim nations. We cannot therefore speak of 'an' Islamic criminal law nor can Muslims continue to ignore the beneficial role of ijtihād that should be utilised at least as a forum for discussion about bridging classic Islamic criminal law with contemporary Muslim needs. Many contemporary issues in Islamic criminal law are evidently based on prejudice, culture and less on a coherent understanding of Islamic theology itself. Islam possesses a plethora of outstanding legal scholars that should be allowed to contribute to an ijtihādī scholarly 'revolution'.
Overview of Islamic Law
Authors: Alarefi Abdullah Saad
Published: October 2009

Islamic law is known as the Shari'ah, which means the path to follow God's law. The Shari'ah controls, rules and regulates all public and private behaviour. Shari'ah law does not exclude any knowledge from other sources and is viewed by the Muslim world as a vehicle to solve all problems – civil, criminal and international. The article offers a brief insight into Islamic law and provides a full understanding of the nature of Islamic law and its jurisprudential and legal concepts.
African States and Participation in Deep Seabed Mining: Problems and Prospects
Authors: Egede Edwin
Published: October 2009

The Law of the Sea Convention requires that effective participation of developing States Parties in activities in the deep seabed beyond national jurisdiction (the Area) should be promoted having due regard to their special interests and needs (especially those of landlocked and geographically disadvantaged states). This article examines the difficulties in actual, direct and effective participation by African states in deep seabed mining and possible co-operative endeavours that African states may embark upon to overcome some of these constraints in order to advance the prospects of their actual, direct and effective participation in deep seabed mining.
Architects as Nowcasters of Housing Construction
Authors: Holmes Mark J. , Mitchell James , Silverstone Brian
Published: October 2009

For more than four decades, the New Zealand Institute of Economic Research (NZIER) has conducted a two-question, quarterly survey of architect forecasts of public and private sector construction expenditure. This qualitative survey is published one week after the end of each quarter and nine weeks ahead of the official quantitative data thereby giving architect opinion nowcasting status. This paper covers selected aspects of this unexplored series with particular reference to residential housing construction and the value-added information from architects as nowcasters. Specifically, we consider several qualitative-to-quantitative conversion methods, in-sample and out-of-sample performance, cyclical features and respondent dynamics. Although our work relates to architects — a sub-sector of the service industry — our results have a wider application to business survey questions using ordered qualitative responses.
Projecting Felony Intakes to the Justice System
Authors: Martinez Pablo E.
Published: October 2009

Prison populations in this country continue to increase even during a period of decline in the crime rate. There is a need for a model that simulates how offenders are admitted, how they move in and out of the system, and how capable it is of answering “what if ” type of questions. For example, what impact would it have on the prison system population if there was a policy that would result in an increase in the parole revocation rate for administrative violations? This article presents a methodology to forecast correctional admissions. Projected admissions are derived by separately projecting felony probation placements, direct court prison commitments, and felony probation and parole revocation to prison.
A Comparative Study of Some Comfort-related Properties of Socks of Different Fiber Types
Authors: Cimilli S. , Nergis B.U. , Candan C. , Özdemir M.
Published: October 2009

Socks need to perform better in comfort properties than other garments, as less air circulation occurs in socks in shoes than in garments on other parts of the body. In this paper, we studied the comfort properties of socks made from new fibers, such as modal, micro modal, bamboo, soybean, and chitosan. In order to compare their properties with conventional fibers such as cotton and viscose, these fibers were also included in the study. Water vapor transfer, air permeability, wicking, wetting and heat transfer — properties which are related to comfort — were evaluated. In order to conduct thermal conductivity measurements, a special experimental setup was designed according to the hot plate method (ISO 8302). The results suggested that the fiber type, together with regain and fabric properties such as thickness, appears to affect some comfort-related properties of the fabrics. It is suggested that for certain end uses, various combinations of fiber blends can be used.
Systemic Bioavailability of Topical Diclofenac Sodium Gel 1% Versus Oral Diclofenac Sodium in Healthy Volunteers
Authors: Kienzler Jean‐Luc , Gold Morris , Nollevaux Fabrice
Published: October 2009

Systemic bioavailability and pharmacodynamics of topical diclofenac sodium gel 1% were compared with those of oral diclofenac sodium 50‐mg tablets. In a randomized, 3‐way crossover study, healthy volunteers (n = 40) received three 7‐day diclofenac regimens: (A) 16 g gel applied as 4 g to 1 knee 4 times daily (4 g on surface area 400 cm2), (B) 48 g gel applied as 4 g per knee 4 times daily to 2 knees plus 2 g gel per hand applied 4 times daily to 2 hands (12 g on 1200 cm2), and (C) 150 mg oral diclofenac applied as 50‐mg tablets 3 times daily. Thirty‐nine participants completed all 3 regimens. Systemic exposure was greater with oral diclofenac (AUC0–24, 3890 ± 1710 ng·h/mL) than with topical treatments A (AUC0–24, 233 ± 128 ng·h/mL) and B (AUC0–24, 807 ± 478 ng·h/mL). Oral diclofenac inhibited platelet aggregation, cyclooxygenase‐1 (COX‐1), and COX‐2. Topical diclofenac did not inhibit platelet aggregation and inhibited COX‐1 and COX‐2 less than oral diclofenac. Treatment‐related adverse events were mild and limited to application site reactions with diclofenac sodium gel 1% (n = 4) and gastrointestinal reactions with oral diclofenac (n = 3). Systemic exposure with diclofenac sodium gel 1% was 5‐ to 17‐fold lower than with oral diclofenac. Systemic effects with topical diclofenac were less pronounced.
Quantitative Analysis of T‐wave Morphology Increases Confidence in Drug‐Induced Cardiac Repolarization Abnormalities: Evidence From the Investigational IKr Inhibitor Lu 35–138
Authors: Graff Claus , Matz Jørgen , Christensen Ellen B. , Andersen Mads P. , Kanters Jørgen K. , Toft Egon , Pehrson Steen , Hardahl Thomas B. , Nielsen Jimmi , Struijk Johannes J.
Published: October 2009

This study investigates repolarization changes induced by a new candidate drug to determine whether a composite electrocardiographic (ECG) measure of T‐wave morphology could be used as a reliable marker to support the evidence of abnormal repolarization, which is indicated by QT interval prolongation. Seventy‐nine healthy subjects were included in this parallel study. After a baseline day during which no drug was given, 40 subjects received an IKr‐blocking antipsychotic compound (Lu 35–138) on 7 consecutive days while 39 subjects received placebo. Resting ECGs were recorded and used to determine a combined measure of repolarization morphology (morphology combination score [MCS]), based on asymmetry, flatness, and notching. Replicate measurements were used to determine reliable change and study power for both measures. Lu 35–138 increased the QTc interval with corresponding changes in T‐wave morphology as determined by MCS. For subjects taking Lu 35–138, T‐wave morphology was a more reliable indicator of IKr inhibition than QTcF (χ2 = 20.3, P = .001). At 80% study power for identifying a 5‐millisecond placebo‐adjusted change from baseline for QTcF, the corresponding study power for MCS was 93%. As a covariate to the assessment of QT interval liability, MCS offered important additive information to the effect of Lu 35–138 on cardiac repolarization.
Silymarin Ascending Multiple Oral Dosing Phase I Study in Noncirrhotic Patients With Chronic Hepatitis C
Authors: Hawke Roy L. , Schrieber Sarah J. , Soule Tedi A. , Wen Zhiming , Smith Philip C. , Reddy K. Rajender , Wahed Abdus S. , Belle Steven H. , Afdhal Nezam H. , Navarro Victor J. , Berman Josh , Liu Qi‐Ying , Doo Edward , Fried Michael W. ,   The SyNCH Trial Group
Published: October 2009

Silymarin, derived from the milk thistle plantSilybum marianum, is widely used for self‐treatment of liver diseases, including hepatitis C virus (HCV), and its antiviral activity has been demonstrated in vitro and in HCV patients administered an intravenous formulation of the major silymarin flavonolignans, silybin A and silybin B. The safety and dose‐exposure relationships of higher than customary oral doses of silymarin and its acute effects on serum HCV RNA were evaluated in noncirrhotic HCV patients. Four cohorts of 8 patients with well‐compensated, chronic noncirrhotic HCV who failed interferon‐based therapy were randomized 3:1 to silymarin or placebo. Oral doses of 140, 280, 560, or 700 mg silymarin were administered every 8 hours for 7 days. Steady‐state exposures for silybin A and silybin B increased 11‐fold and 38‐fold, respectively, with a 5‐fold increase in dose, suggesting nonlinear pharmacokinetics. No drug‐related adverse events were reported, and no clinically meaningful reductions from baseline serum transaminases or HCV RNA titer were observed. Oral doses of silymarin up to 2.1 g per day were safe and well tolerated. The nonlinear pharmacokinetics of silybin A and silybin B suggests low bioavailability associated with customary doses of silymarin may be overcome with doses above 700 mg.
Understanding Tokenism: Antecedents and Consequences of a Psychological Climate of Gender Inequity
Authors: King Eden B. , Hebl Michelle R. , George Jennifer M. , Matusik Sharon F.
Published: October 2009

Extending tokenism theory, the authors investigate psychological climate of gender inequity as a way to understand how token women experience their work environments. In the first study, responses from a sample of 155 women across varied occupations confirm the expectation that token women tend to perceive their organizational climates to be inequitable for women. The results of a second survey of 196 female managers suggest that the subjective processes of tokenism give rise to inequitable climate perceptions. Finally, the responses of 312 women in the construction industry indicate that the climate of gender inequity is related to job attitudes and behaviors.
Team Empowerment and the Organizational Context
Authors: Hempel Paul S. , Zhang Zhi-Xue , Han Yulan
Published: October 2009

A great deal is known about how managers influence team empowerment, but very little is known about what organizations do to influence empowerment. Using teams drawn from 94 Chinese high-technology companies, the authors show that organizational decentralization enhances empowerment when decision making is delegated downward even when not directly delegated to teams. Prior research has presented both a positive and negative view of formalization, and this study found that the organizational level to which formalization is applied makes a difference. Formalization of organizational processes enhances team empowerment by reducing uncertainty within the firm, whereas formalization of jobs and roles moderates the effect of decentralization and reduces team empowerment by reducing teams’ flexibility in taking advantage of decentralization. These results show the importance of organization structure as an antecedent of empowerment and highlight the contrasting effects of different types of formalization.
Legitimacy, Visibility, and the Antecedents of Corporate Social Performance: An Investigation of the Instrumental Perspective
Authors: Chiu Shih-Chi , Sharfman Mark
Published: October 2009

Using institutional theory as the foundation, this study examines the role of organizational visibility from a variety of sources (i.e., slack visibility, industry visibility, and visibility to multiple stakeholders) in influencing corporate social performance (CSP). The conceptual framework offers important insights regarding the instrumental motives of managers in performing CSP initiatives. Based on a sample of 124 S&P 500 firms, the authors found that it is a firm’s visibility to stakeholders, rather than its economic performance, that has the larger impact on managers’ decisions regarding how much CSP their firms exhibit. The results show that more profitable firms may not be motivated to engage actively in CSP unless they are under greater scrutiny by various firm stakeholders. The authors also found that organizational slack (estimated as cost of capital) is positively associated with a Social CSP dimension but negatively associated with a Strategic CSP dimension. This research contributes to the current CSP literature by demonstrating that motivations in addition to normative or ethical ones may be at play in the decisions firms make regarding their CSP.
Anger in Organizations: Review and Integration
Authors: Gibson Donald E. , Callister Ronda Roberts
Published: October 2009

Organizations are rife with situations likely to cause employee anger, including complex relationships, chronic pressure, high stakes, and factors beyond individual control. The importance of this discrete emotion has led to a range of studies exploring the implications of anger for critical organizational phenomena, including emotion norms, leadership, gender issues, status and power, and cross-cultural differences. Despite the dramatic increase in scholarly attention over the past decade to understanding anger experience and expression in organizations, there exist few current reviews and little integration of this diverse literature. By combining a psychological perspective of anger as an episodic process with an organizational perspective emphasizing contextual effects and norms, this review will summarize current research in this vital area, provide a model for understanding and integrating this work, and propose themes for future research.
Relational Harmony: A New Model of Collectivism and Gender Equality Among Chinese American Couples
Authors: Quek Karen Mui-Teng , Knudson-Martin Carmen , Rue Deborah , Alabiso Claudia
Published: October 2009

Social harmony is a valued relational rule in collectivism. Using data from in-depth interviews with 20 Chinese American couples, the authors study how husbands and wives interpret and negotiate marital harmony within a multicultural context and how gender relates to this process. Although all participants appear to seek harmony, the result indicates two quite different forms. Structural harmony is based on traditional social norms that emphasize obligation to the whole. Relational harmony is “we-centered” and prioritizes the marriage relationship itself. Not all couples fall neatly in either category; couples in transition experience a push-and-pull process between the multiple influences in their lives. These tensions are explored through six dimensions: (a) conflict between relational and structural goals, (b) communal versus dyadic obligation, (c) unclear authority structure, (d) intersection of family and workplace, (e) harmonizing multiple voices, and (f) incorporating personal agency. Implications for research and practice are addressed.
Differential Effects of 17β-Estradiol and of Synthetic Progestins on Aldosterone-Salt–Induced Kidney Disease
Authors: Arias-Loza Paula-Anahi , Muehlfelder Melanie , Elmore Susan A. , Maronpot Robert , Hu Kai , Blode Hartmut , Hegele-Hartung Christa , Fritzemeier Karl Heinrich , Ertl Georg , Pelzer Theo
Published: October 2009

Elevated mineralocorticoid levels and female sex hormones have been shown to confer opposing effects on renal injury, but their combined effects are still unknown.

Objective:

Identify the function of estrogens and of different synthetic progestins on aldosterone salt–mediated renal disease.

Methods:

The role of 17β-estradiol, medroxyprogesterone acetate (MPA), and drospirenone during renal injury was studied in Wistar rats subjected to uni-nephrectomy plus aldosterone salt treatment.

Results:

Aldo-salt treatment of intact, ovariectomized, and estradiol-treated female rats resulted in remnant kidney hypertrophy without structural damage. Co-treatment with MPA, but not with drospirenone, increased kidney hypertrophy, fluid turnover, sodium retention, and potassium excretion. Medroxyprogesterone acetate also caused glomerular, vascular, tubular, and interstitial lesions that were accompanied by increased blood pressure and enhanced NADPH oxidase (p67phox) and sodium channel (α-ENaC) expression. Drospirenone, a progestin with anti-mineralocorticoid function, and spironolactone prevented kidney hypertrophy, hypertension, and sodium retention. Drospirenone and spironolactone also increased renal angiotensin II type 2 receptor expression and relieved aldosterone-induced suppression of serum angiotensin II levels.

Conclusion:

The choice of specific synthetic progestins has profound implications on the development of kidney injury and renal gene expression under conditions of elevated aldosterone serum levels and salt intake.
Dietary Fat–Influenced Development of Colon Neoplasia in ApcMin Mice Exposed to Benzo(a)pyrene
Authors: Harris Deacqunita L. , Washington Mary K. , Hood Darryl B. , Roberts L. Jackson , Ramesh Aramandla
Published: October 2009

Colorectal cancer, responsible for 50,000 deaths per year, is a contributing factor for considerable mortalities in the United States. Consumption of well-done red meat and saturated fats rich in polycyclic aromatic hydrocarbons may be one of the causative factors for sporadic colon cancer. The objective of this study was to investigate whether the formation of colon tumors in adult Apc Min mice was influenced by the ingestion of different types of fat containing benzo(a)pyrene [B(a)P], a polycyclic aromatic hydrocarbon compound. Treatment consisted of 50 and 100 μg B(a)P/kg body weight dissolved in peanut or coconut oil (representatives of unsaturated and saturated fats, respectively) administered daily to six-week-old male Apc Min mice via oral gavage for sixty days. At the end of exposure, mice were sacrificed; jejunum and colons were retrieved and preserved in 10% formalin for observation for gross pathological changes. An increased prevalence of adenomas in colons of mice that ingested B(a)P through saturated dietary fat compared to unsaturated fat and controls ( p < .05) was noticed. Interestingly, we also observed adenomas with high-grade dysplasia in the B(a)P + saturated fat group, and these incidences were frequent at the 100 μg/kg B(a)P dose. On the other hand, the B(a)P-alone and unsaturated-fat groups did not show significant differences in the numbers of adenomas and invasive tumors in the both jejunum and the colon. Our studies established that dietary fat, especially saturated fat, potentiates the development of colon tumors caused by B(a)P in the Apc Min mouse.
Global Gene Expression Profiling of Hyperkeratotic Skin Lesions from Inner Mongolians Chronically Exposed to Arsenic
Authors: Bailey Kathryn , Xia Yajuan , Ward William O. , Knapp Geremy , Mo Jinyao , Mumford Judy L. , Owen Russell D. , Thai Sheau-Fung
Published: October 2009

The skin is an organ that is highly sensitive to chronic arsenic (As) exposure. Skin lesions such as hyperkeratoses (HKs) are common early manifestations of arsenicosis in humans. HKs can be precursor lesions of nonmelanoma skin cancers (NMSCs), but the driving forces behind their formation and how they may ultimately progress to NMSCs are unknown. The goal of this study was to examine the global gene expression profiles of As-related HKs in an effort to better understand gene expression changes that are potentially associated with early stages of As carcinogenesis. HK biopsies were removed from individuals living in an arsenicosis-endemic region in Inner Mongolia who had been exposed to high As levels in their drinking water for >20 years. Gene expression profiling was performed on RNA isolated from 7 individuals in this group and from 4 lesion-free skin samples from healthy individuals. Consistent with the pathological characteristics of the HK lesions, major functional categories and known canonical pathways represented by altered transcripts include those involved in development, differentiation, apoptosis, proliferation, and stress response. The results of this study may help define a signature profile of gene expression changes associated with long-term As exposure in the skin.
Development of a Medicaid Behavioral Health Case-Mix Model
Authors: Robst John
Published: October 2009

Many Medicaid programs have either fully or partially carved out mental health services. The evaluation of carve-out plans requires a case-mix model that accounts for differing health status across Medicaid managed care plans. This article develops a diagnosis-based case-mix adjustment system specific to Medicaid behavioral health care. Several different model specifications are compared that use untransformed, square root transformed, and log-transformed expenditures.
A Comparative Analysis of 7.0-Tesla Magnetic Resonance Imaging and Histology Measurements of Knee Articular Cartilage in a Canine Posterolateral Knee Injury Model
Authors: Pepin Scott R. , Griffith Chad J. , Wijdicks Coen A. , Goerke Ute , McNulty Margaret A. , Parker Josh B. , Carlson Cathy S. , Ellermann Jutta , LaPrade Robert F.
Published: October 2009

Background

There has recently been increased interest in the use of 7.0-T magnetic resonance imaging for evaluating articular cartilage degeneration and quantifying the progression of osteoarthritis.

Purpose

The purpose of this study was to evaluate articular cartilage cross-sectional area and maximum thickness in the medial compartment of intact and destabilized canine knees using 7.0-T magnetic resonance images and compare these results with those obtained from the corresponding histologic sections.

Study Design

Controlled laboratory study.

Methods

Five canines had a surgically created unilateral grade III posterolateral knee injury that was followed for 6 months before euthanasia. The opposite, noninjured knee was used as a control. At necropsy, 3-dimensional gradient echo images of the medial tibial plateau of both knees were obtained using a 7.0-T magnetic resonance imaging scanner. Articular cartilage area and maximum thickness in this site were digitally measured on the magnetic resonance images. The proximal tibias were processed for routine histologic analysis with hematoxylin and eosin staining. Articular cartilage area and maximum thickness were measured in histologic sections corresponding to the sites of the magnetic resonance slices.

Results

The magnetic resonance imaging results revealed an increase in articular cartilage area and maximum thickness in surgical knees compared with control knees in all specimens; these changes were significant for both parameters (P <.05 for area; P<.01 for thickness). The average increase in area was 14.8% and the average increase in maximum thickness was 15.1%. The histologic results revealed an average increase in area of 27.4% (P <.05) and an average increase in maximum thickness of 33.0% (P 5 .06). Correlation analysis between the magnetic resonance imaging and histology data revealed that the area values were significantly correlated (P <.01), but the values for thickness obtained from magnetic resonance imaging were not significantly different from the histology sections (P > 1).

Conclusion

These results demonstrate that 7.0-T magnetic resonance imaging provides an alternative method to histology to evaluate early osteoarthritic changes in articular cartilage in a canine model by detecting increases in articular cartilage area.

Clinical Relevance

The noninvasive nature of 7.0-T magnetic resonance imaging will allow for in vivo monitoring of osteoarthritis progression and intervention in animal models and humans for osteoarthritis.