bluuebunny/crossref_metadata_2025 huggingface dataset:
p53 Improves Aerobic Exercise Capacity and Augments Skeletal Muscle Mitochondrial DNA Content
Authors: Park Joon-Young , Wang Ping-yuan , Matsumoto Takumi , Sung Ho Joong , Ma Wenzhe , Choi Jeong W. , Anderson Stasia A. , Leary Scot C. , Balaban Robert S. , Kang Ju-Gyeong , Hwang Paul M.
Published: August 2009

Rationale:

Exercise capacity is a physiological characteristic associated with protection from both cardiovascular and all-cause mortality.
p53
regulates mitochondrial function and its deletion markedly diminishes exercise capacity, but the underlying genetic mechanism orchestrating this is unclear. Understanding the biology of how p53 improves exercise capacity may provide useful insights for improving both cardiovascular as well as general health.

Objective:

The purpose of this study was to understand the genetic mechanism by which p53 regulates aerobic exercise capacity.

Methods and Results:

Using a variety of physiological, metabolic, and molecular techniques, we further characterized maximum exercise capacity and the effects of training, measured various nonmitochondrial and mitochondrial determinants of exercise capacity, and examined putative regulators of mitochondrial biogenesis. As p53 did not affect baseline cardiac function or inotropic reserve, we focused on the involvement of skeletal muscle and now report a wider role for p53 in modulating skeletal muscle mitochondrial function. p53 interacts with
Mitochondrial Transcription Factor A
(
TFAM
), a nuclear-encoded gene important for mitochondrial DNA (mtDNA) transcription and maintenance, and regulates mtDNA content. The increased mtDNA in
p53
+/+
compared to
p53
−/−
mice was more marked in aerobic versus glycolytic skeletal muscle groups with no significant changes in cardiac tissue. These in vivo observations were further supported by in vitro studies showing overexpression of p53 in mouse myoblasts increases both TFAM and mtDNA levels whereas depletion of TFAM by shRNA decreases mtDNA content.

Conclusions:

Our current findings indicate that p53 promotes aerobic metabolism and exercise capacity by using different mitochondrial genes and mechanisms in a tissue-specific manner.
Neurological Outcomes in Patients With Ischemic Stroke Receiving Enoxaparin or Heparin for Venous Thromboembolism Prophylaxis
Authors: Kase Carlos S. , Albers Gregory W. , Bladin Christopher , Fieschi Cesare , Gabbai Alberto A. , O'Riordan William , Pineo Graham F.
Published: August 2009

Background and Purpose—

The Prevention of VTE after Acute Ischemic Stroke with LMWH (PREVAIL) study demonstrated that enoxaparin was superior to unfractionated heparin (UFH) in preventing venous thromboembolism in patients with ischemic stroke and was associated with a small but statistically significant increase in extracranial hemorrhage rates. In this PREVAIL subanalysis, we evaluate the long-term neurological outcomes associated with the use of enoxaparin compared with UFH. We also determine predictors of stroke progression.

Methods—

Acute ischemic stroke patients aged ≥18 years, who could not walk unassisted, were randomized to receive enoxaparin (40 mg once daily) or UFH (5000 U every 12 hours) for 10 days. Patients were stratified according to baseline stroke severity using the National Institutes of Health Stroke Scale score. End points for this analysis included stroke progression (≥4-point increase in National Institutes of Health Stroke Scale score), neurological outcomes up to 3 months postrandomization (assessed using National Institutes of Health Stroke Scale score and modified Rankin Scale score), and incidence of intracranial hemorrhage.

Results—

Stroke progression occurred in 45 of 877 (5.1%) patients in the enoxaparin group and 42 of 872 (4.8%) of those receiving UFH. Similar improvements in National Institutes of Health Stroke Scale and modified Rankin Scale scores were observed in both groups over the 90-day follow-up period. Incidence of intracranial hemorrhage was comparable between groups (20 of 877 [2.3%] and 22 of 872 [2.5%] in enoxaparin and UFH groups, respectively). Baseline National Institutes of Health Stroke Scale score, hyperlipidemia, and Hispanic ethnicity were independent predictors of stroke progression.

Conclusions—

The clinical benefits associated with use of enoxaparin for venous thromboembolism prophylaxis in patients with acute ischemic stroke are not associated with poorer long-term neurological outcomes or increased rates of symptomatic intracranial hemorrhage compared with UFH.
Medical (Nonsurgical) Intervention Alone Is Now Best for Prevention of Stroke Associated With Asymptomatic Severe Carotid Stenosis
Authors: Abbott Anne L.
Published: August 2009

Significant advances in vascular disease medical intervention since large randomized trials for asymptomatic severe carotid stenosis were conducted (1983–2003) have prompted doubt over current expectations of a surgical benefit. In this systematic review and analysis of published data it was found that rates of ipsilateral and any-territory stroke (+/−TIA), with medical intervention alone, have fallen significantly since the mid-1980s, with recent estimates overlapping those of operated patients in randomized trials. However, current medical intervention alone was estimated at least 3 to 8 times more cost-effective. In conclusion, current vascular disease medical intervention alone is now best for stroke prevention associated with asymptomatic severe carotid stenosis given this new evidence, other cardiovascular benefits, and because high-risk patients who benefit from additional carotid surgery or angioplasty/stenting cannot be identified.
Inflammatory Biomarkers of Vascular Risk as Correlates of Leukoariosis
Authors: Wright Clinton B. , Moon Yeseon , Paik Myunghee C. , Brown Truman R. , Rabbani LeRoy , Yoshita Mitsuhiro , DeCarli Charles , Sacco Ralph , Elkind Mitchell S.V.
Published: August 2009

Background and Purpose—

Inflammatory biomarkers, including lipoprotein-associated phospholipase A2 (Lp-PLA2), myeloperoxidase (MPO), and high-sensitivity C-reactive protein (hsCRP) are associated with ischemic stroke risk. White matter hyperintensities (WMH) seen on brain MRI scans are associated with vascular risk factors and an increased risk of incident stroke, but their relation to inflammatory biomarkers is unclear.

Methods—

The Northern Manhattan Study includes a stroke-free community-based sample of Hispanic, black, and white participants with quantitative measurement of WMH volume (WMHV) and inflammatory biomarkers. We measured the association between Lp-PLA2, MPO, and hsCRP levels, and log-transformed WMHV after adjusting for sociodemographic and vascular risk factors.

Results—

The hsCRP (median, 2.42 mg/L; IQR, 1.04, 5.19), Lp-PLA2 (median, 220.97 ng/mL; IQR, 185.77, 268.05), and MPO (median, 15.14 ng/mL; IQR, 12.32, 19.69) levels were available in 527 The Northern Manhattan Study participants with WMHV data but no subclinical infarcts. Those with hsCRP in the upper quartile (Q4 >4.92 mg/L or >3 mg/L), Lp-PLA2 in Q4 (≥264.9 ng/mL), or MPO levels in Q3 (15.04–19.39 ng/mL) or Q4 (>19.39 ng/mL) each had greater WMHV, adjusting for sociodemographic and vascular risk factors. Adjusting for all biomarkers simultaneously, WMHV was 1.3-fold greater for Lp-PLA2 levels in Q4 compared to Q1 (β=0.28;
P
=0.008) and 1.25-fold greater for MPO levels above the median compared to below (β=0.22;
P
=0.02), but hsCRP was not associated with WMHV.

Conclusions—

Relative elevations of the inflammatory markers Lp-PLA2 and MPO were associated with a greater burden of WMH independent of hsCRP.
Plasma β-Amyloid 1-40 Is Associated With the Diffuse Small Vessel Disease Subtype
Authors: Gomis Meritxell , Sobrino Tomás , Ois Angel , Millán Mònica , Rodríguez-Campello Ana , de la Ossa Natalia Pérez , Rodríguez-González Raquel , Jiménez-Conde Jordi , Cuadrado-Godia Elisa , Roquer Jaume , Dávalos Antoni
Published: August 2009

Background and Purpose—

The underlying mechanisms of small vessel disease (SVD) subtypes are diffuse arteriopathy (diffuse-SVD) or microatheroma (focal-SVD). Endothelial dysfunction by β-amyloid peptide (Aβ) deposition has been associated with lacunar infarcts and leukoaraiosis, but its specific relationship with SVD subtypes is unknown. We hypothesized that plasma Aβ levels can play a different role in SVD subtypes in patients with acute lacunar stroke.

Methods—

We studied 149 patients with acute ischemic stroke of SVD etiology according to Trial Of Org 10172 In Acute Stroke Treatment criteria and 25 age-matched control subjects. Patients were classified into focal-SVD: 39 patients with isolated lacunar infarct without leukoaraiosis and diffuse-SVD: 110 patients with an isolated lacunar infarct with leukoaraiosis or with multiple lacunar infarcts with or without leukoaraiosis. Baseline data included vascular risk factors and extensive laboratory tests, including plasma Aβ levels.

Results—

Median [quartiles] Aβ
1-40
levels (40.4 [35.1, 50.5] versus 55.1 [42.3, 69.6] pg/mL), but not Aβ
1-42
levels, were significantly higher in the diffuse-SVD group than in focal-SVD group (
P
<0.001) and control subjects (
P
<0.001). No differences in Aβ
1-40
levels were found between focal-SVD and control subjects. Logistic regression analysis showed that age (OR, 1.06; 95% CI, 1.01 to 1.12), history of hypertension (OR, 3.5; 95% CI, 1.3 to 9.2), and plasma β-amyloid
1-40
levels over the median value (OR, 17.3; 95% CI, 3.0 to 99 for the third quartile and OR, 6.0; 95% CI, 1.6 to 23 for the fourth quartile) were independently associated with the diffuse-SVD subtype.

Conclusions—

Plasma β-amyloid
1-40
levels are independently associated with the diffuse-SVD subtype. These results are consistent with the pathophysiological role of fraction Aβ
1-40
in disrupting endothelial vascular function.
Total Mismatch
Authors: Cho Tae-Hee , Hermier Marc , Alawneh Josef A. , Ritzenthaler Thomas , Desestret Virginie , Østergaard Leif , Derex Laurent , Baron Jean-Claude , Nighoghossian Norbert
Published: August 2009

Background and Purpose—

The perfusion-weighted imaging (PWI)/diffusion-weighted imaging (DWI) mismatch may identify patients who benefit from thrombolysis. However, some patients exhibit a “total mismatch,” ie, negative DWI but extensive PWI defect. We aimed to assess clinical and MRI data of these patients.

Methods—

From June 2007 to December 2008, patients with anterior circulation ischemic stroke were evaluated for a “total mismatch” profile. MRI was performed at admission and at day 1. The score was assessed at baseline and the modified Rankin scale score was assessed at day 30.

Results—

Among 52 patients, 3 showed a total mismatch with arterial occlusion confirmed on magnetic resonance angiography. All had fluctuating symptoms (National Institutes of Health Stroke Scale scores, 0 to 10) and received intravenous tissue plasminogen activator. Day 1 DWI disclosed minimal changes in all patients. Outcome was favorable in all patients (day 30 modified Rankin scale, 0–1).

Conclusion—

PWI may be helpful for treatment decisions in patients without DWI damage and fluctuating clinical course.
The Sacred Aryan Forest in the Avestan and Pahlavi Texts
Authors: Hambartsumian Arthur
Published: August 2009

This article is dedicated to the interpretation of the Avestan razura- "forest, grove", its Middle Persian derivation razūr, and the related place-name, the so called "White Forest" (Avestan Spaēitita razura-, and Middle Persian Arus-razūr and Spēd-razūr). The author investigates all passages in the Avestan and Middle Iranian texts, where the lexeme is found. The Avestan razura- is attested predominantly in the Young Avestan texts (Aban Yasht, Den Yasht, Zamyad Yasht) and in Videvdat, while as a component of the place-name it may be found in Ram Yasht. In most cases, it is mentioned in connection with war campaigns and important battles of the ancient Iranians with their enemies. More detailed accounts on "White Forest" have been preserved in the Middle Persian sources, such as Ayādgār ī Zarērān (the Pahlavi text of Parthian origin), Bundahishn, and in the apocalyptic writing Zand ī Vohuman Yasn. The battle of king Vishtasp with the Khyons is held near this "White Forest", Arusrazūr, which is also mentioned in Zand ī Vohuman Yasn as Spēd-razūr. Evidently, this place had a great importance for the ancient Iranians; Ilya Gershevitch called it, following Ram Yasht, "the Pan-Iranian forest"; for Mary Boyce it was "the forest of All-Aryans".
Mul "Wine" in Classical Persian Poetry
Authors: Sadeqi-Zadeh Mahmud
Published: August 2009

The paper examines the historical and literary characteristics of mul "wine" in Persian poetry. Unlike may, which is a wide-spread term denoting "wine" in New Persian, mul is never employed in the writings of many outstanding representatives of Persian poetry—from the early period until Rūdakī and Daqīqī. The first occurrences of this lexeme are attested in the Shahnameh by Firdousū.
Notes on the Secret Language of House-builders in Ābāde
Authors: Sadeqpur Abdolrasul
Published: August 2009

The paper introduces some materials from a professional argot, now spoken by a few members of the traditional house-builder's guild in Ābāde township near Shiraz, in Iran. The vocabulary of this language consists mostly of words with unknown origin, while the morphology and syntax are based on the local Persian dialect.
Iranian Kurds in an Age of Globalisation
Authors: Gresh Geoffrey
Published: August 2009

Since 2003 and the establishment of Iraq's Kurdish Regional Government, Iran has witnessed a rise in ethnonationalist activity among its Kurdish population. Much of the motivation for this activity stems from the political success of the Kurds in Iraq. The spread of Iranian Kurdish nationalism has also been influenced by globalisation forces, such as global communications technologies, transnational networks, and increased mobility across borders. In this age of globalisation, the Iranian government's ability to rule over the Kurds will continue to erode, unless it caters toward Kurdish demands of minority rights.
A Multivariate Analysis of the Sociodemographic Predictors of Methamphetamine Production and Use
Authors: Armstrong Todd A. , Armstrong Gaylene S.
Published: August 2009

To date, research testing the community characteristics associated with methamphetamine production and use has found that the community-level sociodemographic predictors of methamphetamine production and use vary from those of drug use in general. In this study, the authors furthered the research in this area using data from all 102 counties in Illinois. These data included measures of sociodemographic characteristics taken from the U.S. census, measures of methamphetamine production and use, and a measure of arrests for controlled-substance violations. Negative binomial regression models showed that poverty and the racial and ethnic compositions of communities were the strongest and most consistent predictors of the authors’ methamphetamine measures. The results also showed that the sociodemographic characteristics associated with methamphetamine measures were different in important ways from those associated with arrests for controlled-substance violations.
Casino Décor Effects on Gambling Emotions and Intentions
Authors: Finlay Karen , Marmurek Harvey H. C. , Kanetkar Vinay , Londerville Jane
Published: August 2009

A sample of 484 gamblers (241 males) viewed simulations of casino settings varying in their macro design ( playground vs. gaming) and their micro décor elements (lighting, human crowding, color, machine clustering, and layout symmetry). The décor element levels were manipulated to reflect information load (e.g., flashing lights afford more information than do static lights). The participants provided three measures for each simulation: at-risk gambling intention, pleasure, and restoration. Overall, the playground design and females yielded higher scores on each measure than did the gaming design and males. Also, the relationship between pleasure and at-risk gambling intention was fully mediated by restoration. The effects of information load on the three dependent measures were complex as they depended on the macro design and the gender of the participant. These results are discussed within a framework where affect and cognition mediate atmospheric effects on gambling.
Perception of Robot Passability With Direct Line of Sight and Teleoperation
Authors: Moore Kristin S. , Gomer Joshua A. , Pagano Christopher C. , Moore D. DeWayne
Published: August 2009

Objective: To examine participants’ abilities to judge the passability of robots through apertures in direct-line-of-sight (DLS) and teleoperation (TO) conditions, two experiments were conducted. Background: Past work has demonstrated that operators find it difficult to perceive aspects of remote environments during TO. For example, urban search-and-rescue operators have experienced difficulty judging whether a robot could pass through openings or over obstacles. Although previous research has discussed perceptual difficulties in TO, the differences between DLS and TO have not been quantified. Method: In the first experiment, participants judged the smallest passable aperture widths for three robot sizes for both DLS and TO conditions. In the second experiment, aperture widths were judged for three camera heights and two robot distances during TO. Results: In the DLS condition, participants produced similar judgments for the three robot sizes using dimensionless measurements. In the TO condition, participants’ judgments were more variable and they judged smaller apertures as passable. Conclusion: Overall, participants judged apertures that were too small for the robot to pass as passable. This tendency was more pronounced in four instances: as robot size increased, during TO, when the camera was at its lowest height, and as distance between the robot and the aperture increased. Application: Judgments of passability help to quantify differences in perception between DLS and TO. These results will be useful in the design of training regimes for TO tasks. Increasing operator understanding of performance differences under varying conditions will lead them to be more accurate when making critical decisions in remote environments.
Understanding and Addressing Psychological and Social Problems: the Mediating Psychological Processes Model
Authors: Kinderman Peter
Published: August 2009

Background: Psychological and social problems such as mental disorder, unemployment, substance misuse and crime are personally distressing and absorb huge proportions of Government effort. Addressing these is a multi-agency, multidisciplinary exercise, but there is evidence of a marked policy shift toward the provision of psychological therapies and interventions.

Aim: To offer a distinctively psychological perspective on these key social and mental health problems.

Method: Scholarly review of the relevant literature.

Results: This article presents a coherent model — the mediating psychological processes model — addressing the complex, interconnected, nature of these problems. The mediating psychological processes model suggests that disruption or dysfunction in psychological processes is a final common pathway in the development of mental disorder and social problems. The model proposes that biological, social and circumstantial factors lead to mental disorder, crime and other social problems through their conjoint effects in influencing or disrupting relevant psychological processes.

Conclusions: The implications for policy, and implementation of policy, are discussed.
Examining Student Perspectives On Suicidal Behaviour and Its Prevention in Sri Lanka
Authors: Ratnayake Ruwan , Links Paul
Published: August 2009

Background: Suicidal behaviour, primarily through self-poisoning, is a major public health problem among youth in Sri Lanka.

Methods: This article describes a qualitative study of student perspectives on suicidal behaviour and its prevention. Focus groups were held with students 17—20 years of age. A discussion of the perceived causes of suicidal behaviour provided the context for discussing prevention efforts.

Conclusion: Participants identified pathways to suicidal behaviour and emphasized experiential aspects and the variability of fatal intent. Suggestions for prevention tended to emphasize the strengthening of community-oriented actions in order to better realize lethal means restrictions.
The Cattle Motif in Sol T. Plaatje’s Publications in English
Authors: Haire Karen , Matjila D.S.
Published: August 2009

Afrocentricity is the paradigm that underpins this study, which adapts the analytical construct “motif” from Welsh-Asante’s Nzrui aesthetic model. “Motif” highlights “cattle,” an image drawn from Batswana culture. Traditionally, the life of the Batswana is centered on cattle. Right up to the present, cattle feed the creative imagination in proverbs. This study traces the cattle motif in Sol. T. Plaatje’s three most important publications in English: The Mafikeng Diary, Native Life in South Africa, and Mhudi. Cattle raids in The Mafikeng Diary of Sol T. Plaatje dignify Batswana heroism during the siege of Mafikeng. Tenacious shepherding during shellfire reveals the calm composure that rendered Africans skillful in covert operations. Dying cattle in Native Life in South Africa signify the economic ruin of the Batswana. Dispossessed of the right to rent grazing land, the Batswana risked extinction of social and spiritual identities, because cattle were the symbolic means of negotiation relationships among the living and with the ancestors.
Physico-chemical and Dyeing Properties of Raw Wool Extracted By Pressurized CO2/Modifiers
Authors: Domínguez Carmen , Erra Pilar , Bayona Josep Maria
Published: August 2009

Raw wool fibers were extracted with CO2 with different organic modifiers (acetone, ethanol and methanol) at constant pressure and temperature. The influence of experimental extraction conditions on the properties of extracted wools was studied to determine the suitability of the fibers for textile applications. Suitable wool wax removal from raw wool fibers was qualitatively evaluated by optical microscopy and scanning electron microscopy observation as well as by whiteness, yellowness and brightness measurements. Moreover, the possible bulk fiber modification as a consequence of internal wool lipid extraction belonging to the cell membrane complex was assessed by determining the bursting resistance and dyeing behavior. The results suggest that both CO2/ethanol and CO2/methanol extraction methods provide well-scoured wool fibers with an acceptable dyeing behavior, the bulk modification being negligible.
Infallibilism and Human Kinds
Authors: Guala Francesco
Published: August 2009

Infallibilism and apriorism are still influential in the philosophy of social science. Infallibilists about human kinds claim that there are features of institutional entities about which we cannot possibly be wrong. But infallibilism is not implied by the theory of collective intentionality that supposedly grounds it. Moreover, it fails to account for the mode of existence of important institutional kinds, including the paradigmatic example of money.
Knowledge About Type 2 Diabetes Risk and Prevention of African-American and Hispanic Adults and Adolescents With Family History of Type 2 Diabetes
Authors: Weber Cullen Karen , Buzek Bonnie B.
Published: August 2009

Purpose

The purpose of this study was to assess type 2 diabetes knowledge, perceptions, risk factor awareness, and prevention practices among African American and Hispanic families with a history of diabetes.

Methods

Ninth and tenth grade Houston area students who had a parent who spoke English or Spanish and had a family history of type 2 diabetes were recruited. Student interviews took place during lunch. Parents were interviewed via telephone. Open-ended questions in the interview guide assessed knowledge of diabetes and risk factors, diabetes prevention practices, and perceived risk. Students reported dietary behaviors. Responses were recorded.

Results

Interviews were conducted with 39 parents (95% female, 49% African-American, 51% Hispanic) and 21 ninth and tenth grade adolescents (71% female, 43% African-American, 57% Hispanic). The majority were overweight. Approximately one-half of both groups reported some knowledge of diabetes. The majority (74%) of parents correctly identified family history as a risk factor, but few adolescents responded correctly. Being overweight was identified as a risk factor by 26% of the parents and 10% of the adolescents. Losing weight was not acknowledged as a way to reduce diabetes risk. Sweetened beverage consumption consisted of 2 cans/day and 43% reported to have skipped breakfast.

Conclusions

Overall, there was a lack of knowledge about risk and prevention of type 2 diabetes among African American and Hispanic families at risk. From a public health perspective, there is a critical need for innovative prevention programs targeting families at risk for diabetes.
A Review of Software for Sample Size Determination
Authors: Dattalo Patrick
Published: August 2009

The size of a sample is an important element in determining the statistical precision with which population values can be estimated. This article identifies and describes free and commercial programs for sample size determination. Programs are categorized as follows: (a) multiple procedure for sample size determination; (b) single procedure for sample size determination; and (c) Web-based. Programs are described in terms of (a) cost; (b) ease of use, including interface, operating system and hardware requirements, and availability of documentation and technical support; (c) file management, including input and output formats; and (d) analytical and graphical capabilities.
Neoplastic and Non-neoplastic Changes in F-344 Rats Treated with Naveglitazar, a γ-Dominant PPAR α/γ Agonist
Authors: Long Gerald G. , Reynolds Vincent L. , Dochterman L. Wayne , Ryan Thomas E.
Published: August 2009

The carcinogenic potential of naveglitazar, a γ-dominant peroxisome proliferator-activated receptor (PPAR) α/γ dual agonist, was evaluated in a two-year study in F344 rats (0, 0.3, 1.0, or 3.0 mg/kg, males; 0, 0.1, 0.3, or 1.0 mg/kg, females). Increased mortality in male rats of the high-dose group was related to cardiac-associated lesions, neoplasms, and undetermined causes. Degeneration and hypertrophy of the myocardium occurred with dose-responsive increased incidence and severity. Neoplasms with increased incidence included sarcomas in male rats and urinary bladder neoplasms in female rats. Most sarcomas in male rats occurred in the adipose tissue of the subcutis and were diagnosed as fibrosarcomas, with fewer liposarcomas and other histologic types. Non-neoplastic changes in adipose tissue included expansion of adipose tissue in multiple sites, alterations in cytoplasmic vesicular pattern in brown and white fat, increases in stroma and mesenchymal cells, and fibrosis. The severity of chronic progressive nephropathy was decreased in a dose-responsive manner in males, and hyperplasia and neoplasia of the mammary gland were decreased in incidence in females. The adverse effects of cardiotoxicity and increased incidence of neoplasms occurred with dose-responsive incidence and/or severity, and a no-effect level for these effects was not achieved in this study.
Longitudinal Studies of Cardiac Troponin-I Concentrations in Serum from Male Sprague Dawley Rats: Baseline Reference Ranges and Effects of Handling and Placebo Dosing on Biological Variability
Authors: Schultze A. Eric , Carpenter Kent H. , Wians Frank H. , Agee Sara J. , Minyard Jennifer , Lu Quynh Anh , Todd John , Konrad Robert J.
Published: August 2009

Serum cardiac troponin-I has been validated as a biomarker for cardiotoxicity in numerous animal models; however, baseline reference ranges for cTnI concentration in a healthy population of laboratory rats, as well as an investigation of biological cTnI variability in rats with respect to time, handling, and placebo dosing methods, have not been reported. In this study, we used an ultrasensitive cTnI immunoassay to quantify hourly concentrations of cTnI in live rats handled under standard laboratory conditions using 15 μL of serum per determination. The baseline reference range (mean 4.94 pg/mL, range 1–15 pg/mL, 99% confidence interval [CI]) of cTnI concentration in rats was consistent with previously reported reference ranges for cTnI in humans (1–12 pg/mL) and with preliminary studies in dogs (1–4 pg/mL) and monkeys (4–5 pg/mL) using the same cTnI assay method. In addition, cTnI concentrations in individual rat serum samples show minimal biological variability over a twenty-four-hour interval when compared to a meaningful reference change value of 193% to 206%. Furthermore, measurements of cTnI concentration were consistent within the reference limits in individual rats over long periods and under three different standard laboratory handling conditions. Thus, using this new method, rats can be followed longitudinally at hourly intervals, and a doubling of cTnI concentration would be significant above biological variability. This is a new paradigm for preclinical testing, which allows transient changes in cTnI concentration to be accurately quantified. This understanding of baseline and biological variability in rats will be fundamental for designing and analyzing future studies that assess potential cardiotoxicity in drug development.
A Data-Based Assessment of Alternative Strategies for Identification of Potential Human Cancer Hazards
Authors: Boobis Alan R. , Cohen Samuel M. , Doerrer Nancy G. , Galloway Sheila M. , Haley Patrick J. , Hard Gordon C. , Hess Frederick G. , Macdonald James S. , Thibault Stéphane , Wolf Douglas C. , Wright Jayne
Published: August 2009

The two-year cancer bioassay in rodents remains the primary testing strategy for in-life screening of compounds that might pose a potential cancer hazard. Yet experimental evidence shows that cancer is often secondary to a biological precursor effect, the mode of action is sometimes not relevant to humans, and key events leading to cancer in rodents from nongenotoxic agents usually occur well before tumorigenesis and at the same or lower doses than those producing tumors. The International Life Sciences Institute (ILSI) Health and Environmental Sciences Institute (HESI) hypothesized that the signals of importance for human cancer hazard identification can be detected in shorter-term studies. Using the National Toxicology Program (NTP) database, a retrospective analysis was conducted on sixteen chemicals with liver, lung, or kidney tumors in two-year rodent cancer bioassays, and for which short-term data were also available. For nongenotoxic compounds, results showed that cellular changes indicative of a tumorigenic endpoint can be identified for many, but not all, of the chemicals producing tumors in two-year studies after thirteen weeks utilizing conventional endpoints. Additional endpoints are needed to identify some signals not detected with routine evaluation. This effort defined critical questions that should be explored to improve the predictivity of human carcinogenic risk.
Kainic Acid-induced F-344 Rat model of Mesial Temporal Lobe Epilepsy: Gene Expression and Canonical Pathways
Authors: Sharma Alok K. , Searfoss George H. , Reams Rachel Y. , Jordan William H. , Snyder Paul W. , Chiang Alan Y. , Jolly Robert A. , Ryan Timothy P.
Published: August 2009

Mesial temporal lobe epilepsy (MTLE) is a severe neurological condition of unknown pathogenesis for which several animal models have been developed. To obtain a better understanding of the underlying molecular mechanisms and identify potential biomarkers of lesion progression, we used a rat kainic acid (KA) treatment model of MTLE coupled with global gene expression analysis to examine temporal (four hours, days 3, 14, or 28) gene regulation relative to hippocampal histopathological changes. The authors recommend reviewing the companion histopathology paper ( Sharma et al. 2008 ) to get a better understanding of the work presented here. Analysis of filtered gene expression data using Ingenuity Pathways Analysis (Ingenuity Systems, http://www.ingenuity.com ) revealed that a number of genes pertaining to neuronal plasticity (RhoA, Rac1, Cdc42, BDNF, and Trk), neurodegeneration (Caspase3, Calpain 1, Bax, a Cytochrome c, and Smac/Diablo), and inflammation/immune-response pathways (TNF-α, CCL2, Cox2) were modulated in a temporal fashion after KA treatment. Expression changes for selected genes known to have a role in neuronal plasticity were subsequently validated by quantitative polymerase chain reaction (qPCR). Notably, canonical pathway analysis revealed that a number of genes within the axon guidance signaling canonical pathway were up-regulated from Days 3 to 28, which correlated with aberrant mossy fiber (MF) sprouting observed histologically beginning at Day 6. Importantly, analysis of the gene expression data also identified potential biomarkers for monitoring neurodegeneration (Cox2) and neuronal/synaptic plasticity (Kalrn).
Effects of the Antifungal Agent Itraconazole on Proliferative Changes of the Forestomach Mucosa in Alloxan-induced Diabetic Rats
Authors: Sano Tomoya , Ozaki Kiyokazu , Kodama Yasushi , Matsuura Tetsuro , Narama Isao
Published: August 2009

Alloxan-induced diabetic rats frequently exhibit proliferative lesions of squamous hyperplasia accompanied by chronic inflammation and Candida albicans infection in the forestomach, and some lesions progress to squamous cell carcinoma (SCC). Candida infection causes not only hyperplastic changes with inflammation but might also lead to SCC in human oral mucosa. Thus, the present study was conducted to examine the effects of the antifungal agent itraconazole (ITCZ) on proliferative and inflammatory changes of the forestomach in alloxan-induced diabetic WBN/Kob rats. Diabetes was induced by alloxan at fifteen weeks of age. Rats were allocated to three groups at forty-five weeks of age and were given ITCZ by gavage 0 (vehicle control), 5, and 10 mg/kg/day for four weeks, and they were sacrificed at the sixty-fifth week of age. Mucosal hyperplastic changes were consistently accompanied by inflammation and Candida infections in the 0 mg/kg group. These lesions were reduced by ITCZ (0 mg/kg; 100%, 5 mg/kg; 53.5%, 10 mg/kg; 61.5%). Squamous cell carcinoma was detected in three rats from the 0 mg/kg, but only one rat from the 10 mg/kg dose groups in this study. Itraconazole reduced the degree of mucosal hyperplasia, inflammatory changes, and Candida infection. Therefore, C. albicans infection was an important factor in pathogenesis of mucosal proliferation and inflammation.
Activation of Calcitonin Gene-Related Peptide Receptor during Ozone Inhalation Contributes to Airway Epithelial Injury and Repair
Authors: Oslund Karen L. , Hyde Dallas M. , Putney Leialoha F. , Alfaro Mario F. , Walby William F. , Tyler Nancy K. , Schelegle Edward S.
Published: August 2009

The authors investigated the importance of the neuropeptide, calcitonin gene-related peptide (CGRP), in epithelial injury, repair, and neutrophil emigration after ozone exposure. Wistar rats were administered either a CGRP-receptor antagonist (CGRP8–37) or saline and exposed to 8 hours of 1-ppm ozone or filtered air with an 8-hour postexposure period. Immediately after exposure, ethidium homodimer was instilled into lungs as a marker of necrotic airway epithelial cells. After fixation, airway dissected lung lobes were stained for 5′-bromo-2′-deoxyuridine, a marker of epithelial proliferation. Positive epithelial cells were quantified in specific airway generations. Rats treated with CGRP8–37 had significantly reduced epithelial injury in terminal bronchioles and reduced epithelial proliferation in proximal airways and terminal bronchioles. Bronchoalveolar lavage and sections of terminal bronchioles showed no significant difference in the number of neutrophils emigrating into airways in CGRP8–37-treated rats. The airway epithelial cell line, HBE-1, showed no difference in the number of oxidant stress positive cells during exposure to hydrogen peroxide and a range of CGRP8–37 doses, demonstrating no antioxidant effect of CGRP8–37. We conclude that activation of CGRP receptors during ozone inhalation contributes to airway epithelial injury and subsequent epithelial proliferation, a critical component of repair, but does not influence neutrophil emigration into airways.
Body Dissatisfaction and Eating Disturbances in Early Adolescence: A Structural Modeling Investigation Examining Negative Affect and Peer Factors
Authors: Hutchinson Delyse M. , Rapee Ronald M. , Taylor Alan
Published: August 2009

This study tested five proposed models of the relationship of negative affect and peer factors in early adolescent body dissatisfaction, dieting, and bulimic behaviors. A large community sample of girls in early adolescence was assessed via questionnaire ( X age = 12.3 years). Structural equation modeling (SEM) indicated that negative affect mediated the relationship between body dissatisfaction and bulimic behaviors. Body dissatisfaction also contributed independently to the concurrent prediction of bulimic behaviors. The proposed pathways from dieting to negative affect and dieting to bulimic behaviors were not supported. However, perceived peer influence, perceived weight-related teasing, and the self-reported eating behaviors of friendship clique members all contributed significantly to the concurrent prediction of individual eating pathology. These findings highlight the importance of negative affect and both perceived and actual peer attitudes and behaviors in early adolescent eating pathology.
Normative approaches to critical health geography
Authors: Connolly Carmalt Jean , Faubion Todd
Published: August 2009

This article builds on geography’s engagement with ethics by asking what normative geographies focused on human health might look like. We use the ethics of care and human rights law to frame a normative approach to health geography. The article explores the content of these frameworks before grounding them in a particular instance of inequality found in South Africa. Our goal is to demonstrate how care ethics and human rights can powerfully complement one another and inspire a new type of praxis relevant to geographers engaged with ethics and ethical philosophy.
How Personal Is the Political? Democratic Revolution and Fertility Decline
Authors: Bailey Amy Kate
Published: August 2009

Existing theory has identified the capacity of political revolutions to effect change in a variety of social institutions, although relationships between revolution and many institutions remain unexplored. Using historical data from twenty-two European and four diaspora countries, the author examines the temporal relationship between timing of revolution and onset of fertility decline. The author hypothesizes that specific kinds of revolutionary events affect fertility by engendering ideological changes in popular understandings of the individual’s relationship to society and ultimately the legitimacy of couples’ authority over their reproductive capacities. Results demonstrate that popular democratic revolutions—but not institutionalized democratic structures—predict the timing of the onset of fertility decline.
Status Homogamy in the Preindustrial Marriage Market: Partner Selection According to Age, Social Origin, and Place of Birth in Nineteenth-century Rural Sweden
Authors: Dribe Martin , Lundh Christer
Published: August 2009

This article studies partner selection according to three dimensions: social origin, age, and place of birth. The authors use micro-level data from local population registers in five parishes in southern Sweden from 1815 to 1895.The results confirm that all three aspects were important but that socioeconomic status was the most important characteristic,structuring much of the selection process.The importance of social and age homogamy remained stable over the period, while geographic exogamy became more frequent, which could be interpreted in terms of an increasing openness of rural society.The authors also find some indications of exchange of characteristics in the partner selection process.
Eight dimensions for the emotions
Authors: Cochrane Tom
Published: August 2009

The author proposes a dimensional model of our emotion concepts that is intended to be largely independent of one’s theory of emotions and applicable to the different ways in which emotions are measured. He outlines some conditions for selecting the dimensions based on these motivations and general conceptual grounds. Given these conditions he then advances an 8-dimensional model that is shown to effectively differentiate emotion labels both within and across cultures, as well as more obscure expressive language. The 8 dimensions are: (1) attracted—repulsed, (2) powerful—weak, (3) free—constrained, (4) certain—uncertain, (5) generalized—focused, (6) future directed—past directed, (7) enduring—sudden, (8) socially connected—disconnected.
Peut-on traduire une émotion érotique? L’exemple des traductions françaises de l’ode 31 de Sappho
Authors: Bouvier David
Published: August 2009

Une étude des nombreuses traductions françaises de l’ode 31 de Sappho permet de mettre en question certains postulats sur l’universalité de la perception des émotions. L’importance des variations subies, en traduction, par le texte de départ invite à s’interroger sur les facteurs qui peuvent influencer les modes et les tendances de la sensibilité occidentale. Evocation poétique d’une émotion amoureuse, l’ode 31 confond deux ordres d’émotivité, poétique et érotique. Exprimant l’amour, la jalousie ou la crainte, masculins ou féminins, affectant l’âme ou le corps, les symptômes décrits par l’ode 31 évoluent d’une traduction à l’autre et renvoient effectivement à des tendances propres à chaque époque. Une explication plus profonde de ces variations est alors la mémoire dont se chargent mots et métaphores au cours de leurs emplois. Sappho qui emprunte à la poésie homérique des métaphores qui exprimaient la peur guerrière joue sur un registre que les traducteurs ne peuvent retrouver: leurs vocabulaires et leurs métaphores étant chargés d’une autre mémoire.
Territorial Dimensions of Enduring Internal Rivalries
Authors: Fuhrmann Matthew , Tir Jaroslav
Published: August 2009

This paper explores the territorial dimensions of enduring internal rivalries (EIRs), which are defined as protracted domestic violent conflicts between governments and insurgent groups. It argues that the nature of domestic-level territorial conflicts, such as tactical advantages facing the rebels, allow the fighting to continue.Three specific hypotheses flow from this argument including that territorial disputes are likely to evolve into EIRs and that territorial EIRs are more likely to recur and produce shorter peace spells than other types of domestic conflict.We test these hypotheses by conducting statistical analyses of 220 internal armed conflicts and find robust and substantively strong empirical support.This article suggests that territorial issues should be studied from an enduring, protracted standpoint for their effect on domestic conflict to be fully appreciated. It also offers new insights into how territory matters and suggests that territorial issues are not simply reducible to the concerns of ethnicity and identity in explaining protracted civil wars, as much of the conventional wisdom suggests.
Settling Civil Wars
Authors: Hartzell Caroline A.
Published: August 2009

Two different positions regarding the impact the fate of factions has on the duration of the peace appear in theories of civil war termination. One holds that the peace will be long-lived when the organizational structures of all but one of the factions that compete in a war are destroyed or dismantled at the conflict’s end.The other position maintains that the peace can best be preserved when rival groups agree to share state power at the war’s end. I examine the evidence for these competing arguments, drawing on a new dataset on the fate of factions that participated in civil wars between 1945 and 1999.The results of this analysis indicate that although destroying opposing groups’ organizations has little effect on the duration of the peace, an agreement among rivals to share power can help to prolong the peace.
The Duration of Civil War Peace Agreements*
Authors: Derouen Karl , Lea Jenna , Wallensteen Peter
Published: August 2009

The focus of this article is civil war peace agreement duration from 1989 to 2005. Recent work by Hartzell and Hoddie (2003, 2007) has argued that power-sharing provisions have a cumulative impact. In other words, the more power-sharing provisions there are built into an agreement, the greater the prospects for peace. Our basic theoretical premise is that power-sharing provisions that are costlier to government and more difficult to implement will decrease the life span of the peace agreement because of government motivations to renegotiate and rebel incentive to strike preemptively before the government does or out of frustration because of delays in implementing costly provisions. In other words, governments will abandon the agreement because it concedes too much or rebels will abandon the agreement because of delays in implementation and/or to move preemptively. We look at three forms of power-sharing provisions: military (integration of rebels into army), territorial (autonomy), and political (shared government). Civil war peace agreements can expire after being replaced by a new agreement or if at least one party abandons the agreement. Hazard models are specified controlling for democracy score at time of signing, intensity of war, GDP per capita, and type of agreement.The results indicate that the less costly concessions by government of military integration and autonomy increase the duration of peace agreements, while political power-sharing provisions have a negative though insignificant impact on duration.
Selected To Go Where Murderers Lurk?
Authors: Melander Erik
Published: August 2009

This study examines the preventive effect of peacekeeping on mass killings of civilians in intrastate conflicts. Peacekeepers may be sent to the most difficult conflicts. Control variables might capture the difficultness, for example, measures of the intensity of fighting.This is insufficient if there are factors that are difficult to pinpoint and measure that affect both the likelihood that peacekeepers are sent in and the risk of mass killings. Such unmeasured explanatory factors may bias our results.This paper applies a statistical technique, seemingly unrelated probit, that corrects for this problem and reveals a previously undetectable benign effect of peace keeping.
Giving Up Something Good for Something Better
Authors: Dollahite David C. , Layton Emily , Bahr Howard M. , Walker Anthony B. , Thatcher Jennifer Y.
Published: August 2009

The concept of sacrifice was formerly a key variable in theorizing about religion and society. Secularization theory and conceptual models equating sacrifice with cost have reduced its usage and apparent relevance, although it continues to be of interest in anthropology and religious studies. Research on sacrifice has been neglected in the social sciences, especially in studies of religiosity and families. Seventy-seven religious adolescents in 55 religious Jewish, Christian, Muslim, and Mormon families in New England and northern California were interviewed about whether they felt they had been asked to make sacrifices for their faith as they were growing up. This article discusses how contemporary religious youth view the sacrifices they make for religious reasons. Adolescents reported sacrifices in five domains: societal expectations, popular culture, comforts and pleasures, time and activities, and peer relations. Youth gave the following reasons for being willing to make sacrifices: connecting to a higher meaning or purpose, connecting to God, connecting to the faith tradition or community, fulfilling expectations, feeling affective benefits, and avoiding problems.