bluuebunny/crossref_metadata_2025 huggingface dataset:
The permeability of SPION over an artificial three-layer membrane is enhanced by external magnetic field
Authors: Mondalek Fadee G , Zhang Yuan Yuan , Kropp Bradley , Kopke Richard D , Ge Xianxi , Jackson Ronald L , Dormer Kenneth J
Published: April 2006

Background

Sensorineural hearing loss, a subset of all clinical hearing loss, may be correctable through the use of gene therapy. We are testing a delivery system of therapeutics through a 3 cell-layer round window membrane model (RWM model) that may provide an entry of drugs or genes to the inner ear. We designed an in vitro RWM model similar to the RWM (will be referred to throughout the paper as RWM model) to determine the feasibility of using superparamagnetic iron oxide (Fe3O4) nanoparticles (SPION) for targeted delivery of therapeutics to the inner ear.

The RWM model is a 3 cell-layer model with epithelial cells cultured on both sides of a small intestinal submucosal (SIS) matrix and fibroblasts seeded in between. Dextran encapsulated nanoparticle clusters 130 nm in diameter were pulled through the RWM model using permanent magnets with flux density 0.410 Tesla at the pole face. The SIS membranes were harvested at day 7 and then fixed in 4% paraformaldehyde. Transmission electron microscopy and fluorescence spectrophotometry were used to verify transepithelial transport of the SPION across the cell-culture model. Histological sections were examined for evidence of SPION toxicity, as well to generate a timeline of the position of the SPION at different times. SPION also were added to cells in culture to assess in vitro toxicity.

Results

Transepithelial electrical resistance measurements confirmed epithelial confluence, as SPION crossed a membrane consisting of three co-cultured layers of cells, under the influence of a magnetic field. Micrographs showed SPION distributed throughout the membrane model, in between cell layers, and sometimes on the surface of cells. TEM verified that the SPION were pulled through the membrane into the culture well below. Fluorescence spectrophotometry quantified the number of SPION that went through the SIS membrane. SPION showed no toxicity to cells in culture.

Conclusion

A three-cell layer model of the human round window membrane has been constructed. SPION have been magnetically transported through this model, allowing quantitative evaluation of prospective targeted drug or gene delivery through the RWM. Putative in vivo carrier superparamagnetic nanoparticles may be evaluated using this model.
Oocyte-granulosa cell interactions during mouse follicular development: regulation of kit ligand expression and its role in oocyte growth
Authors: Thomas Fiona H , Vanderhyden Barbara C
Published: April 2006

Ovarian folliculogenesis is regulated by both endocrine and intraovarian mechanisms that coordinate the processes of oocyte growth and somatic cell proliferation and differentiation. Within the follicle, paracrine interactions between the oocyte and surrounding granulosa cells are critical for normal cell development and function. This review focuses on the role of paracrine interactions during early oocyte and follicular development that ensure proper coordination of oocyte and somatic cell function. Particular emphasis is given to granulosa cell-derived Kit Ligand (KitL), whose functional importance for oocyte growth has been demonstrated by a wide range of in vivo and in vitro studies. Reported interactions between KitL and oocyte-derived growth differentiation factor-9 (GDF9) and bone morphogenetic protein-15 (BMP15) suggest the molecular basis of oocyte-granulosa cell interactions, but also hint at the complexity of these communications. These paracrine interactions and the structure of the oocyte-granulosa cell interface are follicle stage-specific and regulated by FSH. Elucidation of the molecular mechanisms that promote the development of healthy oocytes with good developmental competence has potential applications for improving fertility and for in vitro growth systems for oocytes from domestic animals and humans.
Economic evaluations of non-communicable disease interventions in developing countries: a critical review of the evidence base
Authors: Mulligan Jo-Ann , Walker Damian , Fox-Rushby Julia
Published: April 2006

Background

Demographic projections suggest a major increase in non-communicable disease (NCD) mortality over the next two decades in developing countries. In a climate of scarce resources, policy-makers need to know which interventions represent value for money. The prohibitive cost of performing multiple economic evaluations has generated interest in transferring the results of studies from one setting to another. This paper aims to bridge the gap in the current literature by critically evaluating the available published data on economic evaluations of NCD interventions in developing countries.

Methods

We identified and reviewed the methodological quality of 32 economic evaluations of NCD interventions in developing countries. Developing countries were defined according to the World Bank classification for low- and lower middle-income countries. We defined NCDs as the 12 categories listed in the 1993 World Bank report Investing in Health. English language literature was searched for the period January 1984 and January 2003 inclusive in Medline, Science Citation Index, HealthStar, NHS Economic Evaluation Database and Embase using medical subheading terms and free text searches. We then assessed the quality of studies according to a set of pre-defined technical criteria.

Results

We found that the quality of studies was poor and resource allocation decisions made by local and global policy-makers on the basis of this evidence could be misleading. Furthermore we have identified some clear gaps in the literature, particularly around injuries and strategies for tackling the consequences of the emerging tobacco epidemic.

Conclusion

In the face of poor evidence the role of so-called generalised cost-effectiveness analyses has an important role to play in aiding public health decision-making at the global level. Further research is needed to investigates the causes of variation among cost, effects and cost-effectiveness data within and between settings. Such analyses still need to take a broad view, present data in a transparent manner and take account of local constraints.
Accuracy and completeness of mortality data in the Department of Veterans Affairs
Authors: Sohn Min-Woong , Arnold Noreen , Maynard Charles , Hynes Denise M
Published: April 2006

Background

One of the national mortality databases in the U.S. is the Beneficiary Identification and Record Locator Subsystem (BIRLS) Death File that contains death dates of those who have received any benefits from the Department of Veterans Affairs (VA). The completeness of this database was shown to vary widely from cohort to cohort in previous studies. Three other sources of death dates are available in the VA that can complement the BIRLS Death File. The objective of this study is to evaluate the completeness and accuracy of death dates in the four sources available in the VA and to examine whether these four sources can be combined into a database with improved completeness and accuracy.

Methods

A random sample of 3,000 was drawn from 8.3 million veterans who received benefits from the VA between 1997 and 1999 and were alive on January 1, 1999 according to at least one source. Death dates found in BIRLS Death File, Medical SAS Inpatient Datasets, Medicare Vital Status, and Social Security Administration (SSA) Death Master File were compared with dates obtained from the National Death Index. A combined dataset from these sources was also compared with National Death Index dates.

Results

Compared with the National Death Index, sensitivity (or the percentage of death dates correctly recorded in a source) was 77.4% for BIRLS Death File, 12.0% for Medical SAS Inpatient Datasets, 83.2% for Medicare Vital Status, and 92.1% for SSA Death Master File. Over 95% of death dates in these sources agreed exactly with dates from the National Death Index. Death dates in the combined dataset demonstrated 98.3% sensitivity and 97.6% exact agreement with dates from the National Death Index.

Conclusion

The BIRLS Death File is not an adequate source of mortality data for the VA population due to incompleteness. When the four sources of mortality data are carefully combined, the resulting dataset can provide more timely data for death ascertainment than the National Death Index and has comparable accuracy and completeness.
Evolution of the uniquely adaptable lentiviral envelope in a natural reservoir host
Authors: Demma LJ , Vanderford TH , Logsdon JM , Feinberg MB , Staprans SI
Published: April 2006

Background

The ability of emerging pathogens to infect new species is likely related to the diversity of pathogen variants present in existing reservoirs and their degree of genomic plasticity, which determines their ability to adapt to new environments. Certain simian immunodeficiency viruses (SIVcpz, SIVsm) have demonstrated tremendous success in infecting new species, including humans, resulting in the HIV-1 and HIV-2 epidemics. Although SIV diversification has been studied on a population level, the essential substrates for cross-species transmission, namely SIV sequence diversity and the types and extent of viral diversification present in individual reservoir animals have not been elucidated. To characterize this intra-host SIV diversity, we performed sequence analyses of clonal viral envelope (env) V1V2 and gag p27 variants present in individual SIVsm-infected sooty mangabeys over time.

Results

SIVsm demonstrated extensive intra-animal V1V2 length variation and amino acid diversity (le38%), and continual variation in V1V2 N-linked glycosylation consensus sequence frequency and location. Positive selection was the predominant evolutionary force. Temporal sequence shifts suggested continual selection, likely due to evolving antibody responses. In contrast, gag p27 was predominantly under purifying selection. SIVsm V1V2 sequence diversification is at least as great as that in HIV-1 infected humans, indicating that extensive viral diversification in and of itself does not inevitably lead to AIDS.

Conclusion

Positive diversifying selection in this natural reservoir host is the engine that has driven the evolution of the uniquely adaptable SIV/HIV envelope protein. These studies emphasize the importance of retroviral diversification within individual host reservoir animals as a critical substrate in facilitating cross-species transmission.
Inhibition of constitutively active Jak-Stat pathway suppresses cell growth of human T-cell leukemia virus type 1-infected T-cell lines and primary adult T-cell leukemia cells
Authors: Tomita Mariko , Kawakami Hirochika , Uchihara Jun-nosuke , Okudaira Taeko , Masuda Masato , Matsuda Takehiro , Tanaka Yuetsu , Ohshiro Kazuiku , Mori Naoki
Published: April 2006

Background

Human T-cell leukemia virus type 1 (HTLV-1), the etiologic agent for adult T-cell leukemia (ATL), induces cytokine-independent proliferation of T-cells, associated with the acquisition of constitutive activation of Janus kinases (Jak) and signal transducers and activators of transcription (Stat) proteins. Our purposes in this study were to determine whether activation of Jak-Stat pathway is responsible for the proliferation and survival of ATL cells, and to explore mechanisms by which inhibition of Jak-Stat pathway kills ATL cells.

Results

Constitutive activation of Stat3 and Stat5 was observed in HTLV-1-infected T-cell lines and primary ATL cells, but not in HTLV-1-negative T-cell lines. Using AG490, a Jak-specific inhibitor, we demonstrated that the activation of Stat3 and Stat5 was mediated by the constitutive phosphorylation of Jak proteins. AG490 inhibited the growth of HTLV-1-infected T-cell lines and primary ATL cells by inducing G1cell-cycle arrest mediated by altering the expression of cyclin D2, Cdk4, p53, p21, Pim-1 and c-Myc, and by apoptosis mediated by the reduced expression of c-IAP2, XIAP, survivin and Bcl-2. Importantly, AG490 did not inhibit the growth of normal peripheral blood mononuclear cells.

Conclusion

Our results indicate that activation of Jak-Stat pathway is responsible for the proliferation and survival of ATL cells. Inhibition of this pathway may provide a new approach for the treatment of ATL.
Variation at APOE and STH loci and Alzheimer's disease
Authors: Zuo Lingjun , van Dyck Christopher H , Luo Xingguang , Kranzler Henry R , Yang Bao-zhu , Gelernter Joel
Published: April 2006

Background

The apolipoprotein E (APOE) and tau proteins play important roles in the pathological development of Alzheimer's disease (AD). Many studies have shown an association between the APOE gene and AD. Association between AD and the newly discovered saitohin (STH) gene, nested within the intron of the tau gene, has been reported. The present study aimed to elucidate the association between APOE and AD, and between STH and AD in our sample.

Methods

The functional polymorphisms, rs429358 and rs7412, in the APOE gene (which together define the ε 2, ε 3, and ε 4 alleles), and the Q7R SNP in the STH gene, were genotyped in 369 patients with AD and 289 healthy European-Americans. The associations between these two genes and AD were analyzed in a case-control design.

Results

Consistent with previously reported results, the frequencies of the APOE ε 4 allele, ε 4/ε 4 genotype and ε 3/ε 4 genotype were significantly higher in AD cases than controls; the ε 4/ε 4 genotype frequency was significantly higher in early-onset AD (EOAD) than late-onset AD (LOAD); the frequencies of the ε 2 allele, ε 3 allele, ε 3/ε 3 genotype and ε 2/ε 3 genotype were significantly lower in AD cases than controls. Positive likelihood ratios (LRs+) of APOE alleles and genotypes increased in a linear trend with the number of ε 4 alleles and decreased in a linear trend with the number of ε 2 or ε 3 alleles. There was no significant difference in the STH allele and genotype frequency distributions between AD cases and controls.

Conclusion

This study confirmed that the ε 4 allele is a dose-response risk factor for AD and the ε 4/ε 4 genotype was associated with a significantly earlier age of onset. Moreover, we found that the ε 2 allele was a dose-response protective factor for AD and the ε 3 allele exerted a weaker dose-response protective effect for risk of AD compared with ε 2. In a clinical setting, APOE genotyping could offer additional biological evidence of whether a subject may develop AD, but it is not robust enough to serve as an independent screening or predictive test in the diagnosis of AD. STH variation was not significantly associated with AD in our sample.
Initial breastfeeding attitudes and practices of women born in Turkey, Vietnam and Australia after giving birth in Australia
Authors: McLachlan Helen L , Forster Della A
Published: April 2006

Background

Cultural variations exist in the proportion of women who breastfeed. For some cultural groups, migration to a new country is associated with a reduction in the initiation and duration of breastfeeding. This paper describes the initial breastfeeding attitudes and practices of women born in Vietnam, Turkey and Australia who gave birth in Australia.

Methods

The study included 300 women: 100 hundred Turkish-born, 100 Vietnamese-born and 100 Australian-born women who had given birth in a large public, tertiary referral maternity hospital between January 1998 and May 1999 in Melbourne, Australia. Women were interviewed in hospital, between 24 hours after the birth and discharge from hospital. Data were collected using a structured questionnaire with some open-ended questions. Only women who had a normal vaginal birth and who gave birth to a healthy baby were included in the study.

Results

Almost all Turkish women initiated breastfeeding (98%) compared with 84% of Australian women. Vietnamese women had the lowest rate of breastfeeding initiation (75%), perceived their partners to be more negative about breastfeeding and did not value the health benefits of colostrum to the same extent as the other two groups. Forty percent of Vietnamese women gave their baby formula in hospital. The results of this study add to the previously reported finding that immigrant Vietnamese women have low breastfeeding rates compared with other groups.

Conclusion

Despite the Baby Friendly status of the hospital where the study was conducted, major differences were found in breastfeeding initiation. Future research should develop and test interventions aimed at increasing breastfeeding initiation in Vietnamese women where initiation is low.
Tumor-specific expression of αvβ3 integrin promotes spontaneous metastasis of breast cancer to bone
Authors: Sloan Erica K , Pouliot Normand , Stanley Kym L , Chia Jenny , Moseley Jane M , Hards Daphne K , Anderson Robin L
Published: April 2006

Introduction

Studies in xenograft models and experimental models of metastasis have implicated several β3 integrin-expressing cell populations, including endothelium, platelets and osteoclasts, in breast tumor progression. Since orthotopic human xenograft models of breast cancer are poorly metastatic to bone and experimental models bypass the formation of a primary tumor, however, the precise contribution of tumor-specific αvβ3 to the spontaneous metastasis of breast tumors from the mammary gland to bone remains unclear.

Methods

We used a syngeneic orthotopic model of spontaneous breast cancer metastasis to test whether exogenous expression of αvβ3 in a mammary carcinoma line (66cl4) that metastasizes to the lung, but not to bone, was sufficient to promote its spontaneous metastasis to bone from the mammary gland. The tumor burden in the spine and the lung following inoculation of αvβ3-expressing 66cl4 (66cl4beta3) tumor cells or control 66cl4pBabe into the mammary gland was analyzed by real-time quantitative PCR. The ability of these cells to grow and form osteolytic lesions in bone was determined by histology and tartrate-resistant acid phosphatase staining of bone sections following intratibial injection of tumor cells. The adhesive, migratory and invasive properties of 66cl4pBabe and 66cl4beta3 cells were evaluated in standard in vitro assays.

Results

The 66cl4beta3 tumors showed a 20-fold increase in metastatic burden in the spine compared with 66cl4pBabe. A similar trend in lung metastasis was observed. αvβ3 did not increase the proliferation of 66cl4 cells in vitro or in the mammary gland in vivo. Similarly, αvβ3 is not required for the proliferation of 66cl4 cells in bone as both 66cl4pBabe and 66cl4beta3 proliferated to the same extent when injected directly into the tibia. 66cl4beta3 tumor growth in the tibia, however, increased osteoclast recruitment and bone resorption compared with 66cl4 tumors. Moreover, αvβ3 increased 66cl4 tumor cell adhesion and αvβ3-dependent haptotactic migration towards bone matrix proteins, as well as their chemotactic response to bone-derived soluble factors in vitro.

Conclusion

These results demonstrate for the first time that tumor-specific αvβ3 contributes to spontaneous metastasis of breast tumors to bone and suggest a critical role for this receptor in mediating chemotactic and haptotactic migration towards bone factors.
The impact of an hematocrit of 20% during normothermic cardiopulmonary bypass for elective low risk coronary artery bypass graft surgery on oxygen delivery and clinical outcome – a randomized controlled study [ISRCTN35655335]
Authors: von Heymann Christian , Sander Michael , Foer Achim , Heinemann Anja , Spiess Bruce , Braun Jan , Krämer Michael , Grosse Joachim , Dohmen Pascal , Dushe Simon , Halle Jürgen , Konertz Wolfgang F , Wernecke Klaus-Dieter , Spies Claudia
Published: April 2006

Introduction

Cardiopulmonary bypass (CPB) induces hemodilutional anemia, which frequently requires the transfusion of blood products. The objective of this study was to evaluate oxygen delivery and consumption and clinical outcome in low risk patients who were allocated to an hematocrit (Hct) of 20% versus 25% during normothermic CPB for elective coronary artery bypass graft (CABG) surgery.

Methods

This study was a prospective, randomized and controlled trial. Patients were subjected to normothermic CPB (35 to 36°C) and were observed until discharge from the intensive care unit (ICU). Outcome measures were calculated whole body oxygen delivery, oxygen consumption and clinical outcome. A nonparametric multivariate analysis of variance for repeated measurements and small sample sizes was performed.

Results

In a total of 54 patients (25% Hct, n = 28; 20% Hct, n = 26), calculated oxygen delivery (p = 0.11), oxygen consumption (p = 0.06) and blood lactate (p = 0.60) were not significantly different between groups. Clinical outcomes were not different between groups.

Conclusion

These data indicate that an Hct of 20% during normothermic CPB maintained calculated whole body oxygen delivery above a critical level after elective CABG surgery in low risk patients. The question of whether a transfusion trigger in excess of 20% Hct during normothermic CPB is still supported requires a larger prospective and randomized trial.
A3 adenosine receptors and mitogen-activated protein kinases in lung injury following in vivo reperfusion
Authors: Matot Idit , Weiniger Carolyn F , Zeira Evelyne , Galun Eithan , Joshi Bhalchandra V , Jacobson Kenneth A
Published: April 2006

Introduction

Although activation of A3adenosine receptors attenuates reperfusion lung injury and associated apoptosis, the signaling pathway that mediates this protection remains unclear. Adenosine agonists activate mitogen-activated protein kinases, and these kinases have been implicated in ischemia/reperfusion injury; the purpose of this study was therefore to determine whether A3adenosine receptor stimulation with reperfusion modulates expression of the different mitogen-activated protein kinases. In addition, we compared the effect of the A3adenosine agonist IB-MECA with the newly synthesized, highly selective A3adenosine receptor agonist MRS3558 on injury in reperfused lung.

Method

Studies were performed in anin vivospontaneously breathing cat model, in which the left lower lobe of the lung was isolated and subjected to 2 hours of ischemia and 3 hours of reperfusion. The selective A3adenosine receptor agonists IB-MECA (0.05 mg/kg, 0.1 mg/kg, or 0.3 mg/kg) and MRS3558 (0.05 mg/kg or 0.1 mg/kg) were administered before reperfusion.

Results

Both A3adenosine receptor agonists administered before reperfusion markedly (P< 0.01) attenuated indices of injury and apoptosis, including the percentage of injured alveoli, wet/dry weight ratio, myeloperoxidase activity, TUNEL (in situTdT-mediated dUTP nick end labeling)-positive cells, and caspase 3 activity and expression. The more pronounced effects at low doses were observed with MRS3558. Increases in phosphorylated c-Jun amino-terminal protein kinase (JNK), p38, and extracellular signal-regulated kinase (ERK)1/2 levels were observed by the end of reperfusion compared with controls. Pretreatment with the A3agonists upregulated phosphorylated ERK1/2 levels but did not modify phosphorylated JNK and p38 levels.

Conclusion

The protective effects of A3adenosine receptor activation are mediated in part through upregulation of phosphorylated ERK. Also, MRS3558 was found to be more potent than IB-MECA in attenuating reperfusion lung injury. The results suggest not only that enhancement of the ERK pathway may shift the balance between cell death and survival toward cell survival, but also that A3agonists have potential as an effective therapy for ischemia/reperfusion-induced lung injury.
Intensive care acquired infection is an independent risk factor for hospital mortality: a prospective cohort study
Authors: Ylipalosaari Pekka , Ala-Kokko Tero I , Laurila Jouko , Ohtonen Pasi , Syrjälä Hannu
Published: April 2006

Introduction

The aim of this study was to elucidate the impact of intensive care unit (ICU)-acquired infection on hospital mortality.

Methods

Patients with a longer than 48 hour stay in a mixed 10 bed ICU in a tertiary-level teaching hospital were prospectively enrolled between May 2002 and June 2003. Risk factors for hospital mortality were analyzed with a logistic regression model.

Results

Of 335 patients, 80 developed ICU-acquired infection. Among the patients with ICU-acquired infections, hospital mortality was always higher, regardless of whether or not the patients had had infection on admission (infection on admission group (IAG), 35.6% versus 17%, p = 0.008; and no-IAG, 25.7% versus 6.1%, p = 0.023). In IAG (n = 251), hospital stay was also longer in the presence of ICU-acquired infection (median 31 versus 16 days, p < 0.001), whereas in no-IAG (n = 84), hospital stay was almost identical with and without the presence of ICU-acquired infection (18 versus 17 days). In univariate analysis, the significant risk factors for hospital mortality were: Acute Physiology and Chronic Health Evaluation (APACHE) II score >20, sequential organ failure assessment (SOFA) score >8, ICU-acquired infection, age ≥ 65, community-acquired pneumonia, malignancy or immunosuppressive medication, and ICU length of stay >5 days. In multivariate logistic regression analysis, ICU-acquired infection remained an independent risk factor for hospital mortality after adjustment for APACHE II score and age (odds ratio (OR) 4.0 (95% confidence interval (CI): 2.0–7.9)) and SOFA score and age (OR 2.7 (95% CI: 2.9–7.6)).

Conclusion

ICU-acquired infection was an independent risk factor for hospital mortality even after adjustment for the APACHE II or SOFA scores and age.
Differential responsiveness to IFN-α and IFN-β of human mature DC through modulation of IFNAR expression
Authors: Severa Martina , Remoli Maria Elena , Giacomini Elena , Ragimbeau Josiane , Lande Roberto , Uzé Gilles , Pellegrini Sandra , Coccia Eliana M
Published: April 2006

In human monocyte-derived dendritic cells (DC), infection with Mycobacterium tuberculosis and viruses or stimulation with Toll-like receptor type 3 and 4 agonists causes the release of type I interferon (IFN). Here, we describe that the IFN-β released upon stimulation with lipopolysaccharide (LPS) or polyinosinic:polycytidylic acid (poly I:C) is responsible for a rapid and sustained signal transducer and activator of transcription 1 and 2 activation and expression of IFN-stimulated genes, such as the transcription factor IFN regulatory factor 7 and the chemokine CXC chemokine ligand 10. The autocrine production of IFN-β from LPS and poly I:C-matured DC (mDC) induced a temporary saturation of the response to type I IFN and a marked decline in the level of the two IFN receptor (IFNAR) subunits. It is interesting that we found that upon clearing of the released cytokines, LPS-stimulated DC reacquired full responsiveness to IFN-β but only partial responsiveness to IFN-α, and their maturation process was unaffected. Monitoring of surface and total levels of the receptor subunits showed that maximal expression of IFNAR2 resumed within 24 h of clearing, and IFNAR1 expression remained low. Thus, mDC can modulate their sensitivity to two IFN subtypes through a differential regulation of the IFNAR subunits.
Justice in the Pursuit of Truth: A Moral Defence of the Similar Facts Rule
Authors: Ho H. L.
Published: April 2006

The law of evidence serves an important function in ensuring the legitimacy of trial deliberation. One way of discharging this function is through ‘regulation’, effected in the form of rules forbidding reliance on particular lines of evidential reasoning. An example of such a rule is that on similar facts. The rationale for regulation will be explored by engaging in two kinds of analysis. Traditionally, an ‘external’ approach is taken. There are, so it is hoped to show, deficiencies in this approach. A different method of analysis, one conducted from an ‘internal’ perspective, will be proposed to meet these deficiencies. In many cases, values other than truth have to be pursued, not simply as subsidiary considerations, but as values which are integral to the nature and purpose of fact-finding. A party has not merely a right that the substantive law be correctly applied to objectively true findings of fact, and a right to procedure that is rationally structured to determine the truth; he has, more broadly, a right to a just verdict, where justice must be understood to incorporate an ethical evaluation of the process (of evidential reasoning) which led to the outcome (in the form of conclusions of fact). Truth and justice, so it will be argued, are not opposing considerations; rather, principles of one kind reinforce demands of the other. This article seeks to instantiate these general themes in a discussion of the similar facts rule.
Sustainable Development in Scotland Post Devolution
Authors: Ross Andrea
Published: April 2006

Following the publication of a critical report by the WWF in October 2001, the Scottish Executive promised ‘a Scotland that delivers sustainable development; that puts environmental concerns at the heart of public policy and secures environmental justice for all of Scotland's communities’. This paper examines the Scottish Executive's recent approach to sustainable development, and in particular, the processes and mechanisms used by the Scottish Executive with the aim of delivering sustainable development. It then uses this detailed analysis to test the theory that devolution is itself a policy for sustainable development. The paper concludes that generally, the Scottish Executive has made great strides in its commitment to sustainable development since the publication of the WWF report in 2001 and in many instances the devolution arrangements in Scotland have acted as a catalyst to the sustainable development agenda. However, the failure to produce a strategy severely limits the potential of other measures to deliver and implement sustainable development in an effective fashion. Without a strategy and action plan the danger is that these other measures can be piecemeal, inconsistent and counterproductive.
Classroom Cops, What Do the Students Think? A Case Study of Student Perceptions of School Police and Security Officers Conducted in an Hispanic Community
Authors: Brown Ben , Benedict Wm. Reed
Published: April 2006

Although the number of police officers serving in schools has escalated in recent years, few studies of student perceptions of school police have been conducted. This study presents an analysis of data on student perceptions of school police officers and school security officers which were obtained from surveys administered to a sample of predominantly Hispanic students who reside in a predominantly Hispanic community. Descriptive analyses of the data show that the majority of students view the officers favourably, but comparisons of the present findings with previously published research on adult perceptions of the police indicate that the percentage of students who view the officers favourably is lower than the percentage of adults who view the police favourably. Regression analyses of the data indicate that gender has a varying impact on different measures of attitudes toward the officers, that year in school has no impact on perceptions of the officers and that personal knowledge of crime and delinquency in the schools has a negative impact on perceptions of the officers. The regression analyses also suggest that race/ethnicity has no impact on student perceptions of the officers; a finding which is consistent with prior research on perceptions of the police conducted in areas with sizeable racial/ethnic minority populations.
Recruiting: A Comparative Study of the Recruiting Practices of State Police Agencies
Authors: Whetstone Thomas S. , Reed John C. , Turner Phillip C.
Published: April 2006

This study focused on recruiting practices in state police organisations. A survey was mailed to the 49 state police agencies and state highway patrols in the United States. Numerous advertising and recruiting methods were employed by the responding departments. Traditional advertising methods were seen by respondents as relatively ineffectual and aggressive face-to-face recruiting efforts at job fairs and community gatherings were deemed more effective. The use of internet websites also showed promise for increasing the number of viable candidates.
Two-Stage Designs in Case–Control Association Analysis
Authors: Zuo Yijun , Zou Guohua , Zhao Hongyu
Published: April 2006

DNA pooling is a cost-effective approach for collecting information on marker allele frequency in genetic studies. It is often suggested as a screening tool to identify a subset of candidate markers from a very large number of markers to be followed up by more accurate and informative individual genotyping. In this article, we investigate several statistical properties and design issues related to this two-stage design, including the selection of the candidate markers for second-stage analysis, statistical power of this design, and the probability that truly disease-associated markers are ranked among the top after second-stage analysis. We have derived analytical results on the proportion of markers to be selected for second-stage analysis. For example, to detect disease-associated markers with an allele frequency difference of 0.05 between the cases and controls through an initial sample of 1000 cases and 1000 controls, our results suggest that when the measurement errors are small (0.005), ∼3% of the markers should be selected. For the statistical power to identify disease-associated markers, we find that the measurement errors associated with DNA pooling have little effect on its power. This is in contrast to the one-stage pooling scheme where measurement errors may have large effect on statistical power. As for the probability that the disease-associated markers are ranked among the top in the second stage, we show that there is a high probability that at least one disease-associated marker is ranked among the top when the allele frequency differences between the cases and controls are not <0.05 for reasonably large sample sizes, even though the errors associated with DNA pooling in the first stage are not small. Therefore, the two-stage design with DNA pooling as a screening tool offers an efficient strategy in genomewide association studies, even when the measurement errors associated with DNA pooling are nonnegligible. For any disease model, we find that all the statistical results essentially depend on the population allele frequency and the allele frequency differences between the cases and controls at the disease-associated markers. The general conclusions hold whether the second stage uses an entirely independent sample or includes both the samples used in the first stage and an independent set of samples.
On Locating Multiple Interacting Quantitative Trait Loci in Intercross Designs
Authors: Baierl Andreas , Bogdan Małgorzata , Frommlet Florian , Futschik Andreas
Published: April 2006

A modified version (mBIC) of the Bayesian Information Criterion (BIC) has been previously proposed for backcross designs to locate multiple interacting quantitative trait loci. In this article, we extend the method to intercross designs. We also propose two modifications of the mBIC. First we investigate a two-stage procedure in the spirit of empirical Bayes methods involving an adaptive (i.e., data-based) choice of the penalty. The purpose of the second modification is to increase the power of detecting epistasis effects at loci where main effects have already been detected. We investigate the proposed methods by computer simulations under a wide range of realistic genetic models, with nonequidistant marker spacings and missing data. In the case of large intermarker distances we use imputations according to Haley and Knott regression to reduce the distance between searched positions to not more than 10 cM. Haley and Knott regression is also used to handle missing data. The simulation study as well as real data analyses demonstrates good properties of the proposed method of QTL detection.
The Hitchhiking Effect of an Autosomal Meiotic Drive Gene
Authors: Chevin Luis-Miguel , Hospital Frédéric
Published: April 2006

Transmission-ratio distortion is a departure from a 1:1 segregation of alleles in the gametes of a heterozygous individual. The so-called driving allele is strongly selected regardless of its effect on the fitness of the carrying individual. It may then have an important impact on neutral polymorphism due to the genetic hitchhiking effect. We study this hitchhiking effect in the case of true meiotic drive in autosomes and show that it is more dependent on the recombination rate than in the classical case of a gene positively selected at the organism level.
Inbreeding by Environmental Interactions Affect Gene Expression inDrosophila melanogaster
Authors: Kristensen Torsten Nygaard , Sørensen Peter , Pedersen Kamilla Sofie , Kruhøffer Mogens , Loeschcke Volker
Published: April 2006

Genomewide gene expression patterns were investigated in inbred and noninbred Drosophila melanogaster lines under benign and stressful (high temperature) environmental conditions in a highly replicated experiment using Affymetrix gene chips. We found that both heat-shock protein and metabolism genes are strongly affected by temperature stress and that genes involved in metabolism are differentially expressed in inbred compared with noninbred lines, and that this effect is accentuated after heat stress exposure. Furthermore we show that inbreeding and temperature stress cause increased between-line variance in gene expression patterns. We conclude that inbreeding and environmental stress both independently and synergistically affect gene expression patterns. Interactions between inbreeding and the environment are often observed at the phenotypic level and our results reveal some of the genes that are involved at the individual gene level. Our observation of several metabolism genes being differentially expressed in inbred lines and more so after exposure to temperature stress, together with lower fitness in the investigated inbred lines, supports the hypothesis that superiority of heterozygous individuals partly derives from increased metabolic efficiency.
Partitioning of the Maize Epigenome by the Number of Methyl Groups on Histone H3 Lysines 9 and 27
Authors: Shi Jinghua , Dawe R Kelly
Published: April 2006

We report a detailed analysis of maize chromosome structure with respect to seven histone H3 methylation states (dimethylation at lysine 4 and mono-, di-, and trimethylation at lysines 9 and 27). Three-dimensional light microscopy and the fine cytological resolution of maize pachytene chromosomes made it possible to compare the distribution of individual histone methylation events to each other and to DNA staining intensity. Major conclusions are that (1) H3K27me2 marks classical heterochromatin; (2) H3K4me2 is limited to areas between and around H3K27me2-marked chromomeres, clearly demarcating the euchromatic gene space; (3) H3K9me2 is restricted to the euchromatic gene space; (4) H3K27me3 occurs in a few (roughly seven) focused euchromatic domains; (5) centromeres and CENP-C are closely associated with H3K9me2 and H3K9me3; and (6) histone H4K20 di- and trimethylation are nearly or completely absent in maize. Each methylation state identifies different regions of the epigenome. We discuss the evolutionary lability of histone methylation profiles and draw a distinction between H3K9me2-mediated gene silencing and heterochromatin formation.
Probabilistic modelling of saturated/unsaturated hydraulic conductivity for compacted glacial tills
Authors: Watabe Y. , LeBihan J.-P. , Leroueil S.
Published: April 2006

A probabilistic model including some previous probabilistic studies is proposed to evaluate hydraulic conductivity from pore entrance size distribution. The model considers multi-pores in series of paths through capillary networks in the soil fabric. The average number of connected pores is a representative value of the fabric, greater than two but not too large. The hydraulic conductivity of three glacial tills from northern Québec with different grain-size distributions has been examined by horizontal permeability tests in saturated conditions, and suction tests with vertical permeability measurement in unsaturated conditions. The hydraulic conductivity is strongly influenced by compaction conditions corresponding to different microfabrics. The model is applicable not only in saturated conditions but also in unsaturated conditions with different microfabrics.
Total and Labile Soil Organic Matter in Organic and Conventional Farming Systems
Authors: Marriott Emily E. , Wander Michelle M.
Published: April 2006

Even though organic management practices are intended to enhance soil performance by altering the quantity or quality of soil organic matter (SOM), there is no consensus on how to measure or manage SOM status. We investigated the veracity of common perceptions about SOM quantity in organically and conventionally managed soils by evaluating the relative responsiveness to organic management of particulate organic matter (POM) and the Illinois Soil N Test (IL‐N), which has been proposed as a direct measure of labile N. Soil samples were obtained from nine farming systems trials in the USA. Soil organic C (SOC), total N (TN), POM‐C, POM‐N, and IL‐N were compared among manure + legume‐based organic, legume‐based organic, and conventional farming systems. The organic systems had higher SOC and TN concentrations than conventional systems whether or not manure was applied. The POM‐C, POM‐N, and IL‐N concentrations did not differ between manure + legume‐ and legume‐based organic systems. The amount of N recovered in POM and IL‐N was similar. Organic management enriched soil POM‐C and ‐N by 30 to 40% relative to the conventional control and this level of enrichment was two to four times greater than that in any other fraction. The IL‐N fraction was not a good measure of labile N as it was less enriched than POM and included recalcitrant components. This is evidenced by the strong correlation between IL‐N and SOC, TN, climate and textural characteristics. Particulate organic matter provided clearer evidence of SOM and labile N accrual under organic management. Direct links between POM status and soil N supply and physical condition are being pursued to help farmers manage biologically based fertility.
Organic Amendment Based on Fresh and Composted Beet Vinasse
Authors: Tejada M. , Garcia C. , Gonzalez J. L. , Hernandez M. T.
Published: April 2006

Industry byproducts present an alternative to inorganic fertilizer use. Fresh and composted organic wastes (non‐depotassified beet [Beta vulgarisL. subsp.Vulgaris] vinasse [BV]compost, BV, and a cotton gin crushed compost [CGCC], which was also included as structural agent in the first compost) were applied for 4 yr to a Typic Xerofluvent in dryland conditions near Sevilla (Guadalquivir Valley, Andalusia, Spain). The effect on the soil's physical properties, soil microbial biomass, and five soil enzymatic activities (dehydrogenase activity, protease activity, β‐glucosidase activity, arylsulfatase activity, and phosphatase activity) and the yield parameters of wheat (Triticum aestivumcv. Cajeme) were determined. Organic wastes were applied at 5, 7.5, and 10 Mg organic matter ha−1rates, respectively. The application of fresh BV had a detrimental impact on the soil's physical (structural stability, bulk density), chemical (exchangeable sodium percentage), and biological (microbial biomass, soil respiration, and enzymatic activities) properties and the wheat yield parameters, probably because high quantities of monovalent cations, such as Na, and fulvic acids were introduced into the soil by the vinasse, thus destabilizing its structure. However when non‐depotassified BV was co‐composted with a CGCC, the resulting compost had a positive effect on the physical, chemical, and biological properties of the soil. The application of fresh BV resulted in a significant decrease in wheat yield (30% after 4 yr when compared with composted BV.
‘Mon Livre et Moi’: Montaigne's Deepening Evaluation of his own Work
Authors: Winter Ian J.
Published: April 2006

None of the many studies on Montaigne appears to have pursued in a consequential manner the attitudes which the author of the Essais assumes towards his own work in the course of his twentyone years of literary production. For the most part, Montaigne's allusions to his book have been related to the moment when he made them (as facilitated by Pierre Villey's fine work on the chronology of the various chapters), or to whatever major theme the commentator has been developing. The aim of this essay is to assemble in chronological order Montaigne's observations concerning his book in order not only to compare one phase with another, but also to demonstrate the progressive manner in which the book becomes an integral, organic function of the essayist's introspective odyssey.
Some Medieval Elements and Structural Unity in Erasmus' The Praise of Folly
Authors: Miller Clarence H.
Published: April 2006

In the course of editing and annotating Erasmus’ The Praise of Folly for the forthcoming Amsterdam edition of his complete works, I have come to believe that the 461 years since its first publication have produced only two original commentaries on the Moria. In 1515 a fairly thorough commentary, almost as long as the work itself and of a sort usually reserved for ancient works, was published with The Praise ofFolly. Reprinted eleven times during Erasmus’ lifetime, it has retained some currency, though not much, because it was reprinted in the Leyden Opera omnia of 1703-06. Though it goes under the name of Girardus Listrius, we know from one of Erasmus’ letters that he himself wrote part of it—how much we do not know. The second major commentary was that by I. B. Kan, published at The Hague in 1898. In our own century some useful information and suggestions have been provided by Maurice Rat and Hoyt Hudson. The rest, alas, is not silence, but (as Douglas Bush once said about Shakespearean criticism) fearless repetition.
Seventeenth-Century Identifications of Jonson's Sources in the Classics
Authors: Riddell James A.
Published: April 2006

Jonson himself began the practice of identifying passages in his work which were virtually translations from the classics. In the margins of the quarto edition of Sejanus (1605), for instance, there appeared an elaborate apparatus intended to enlighten the reader who might not recognize the way in which Jonson had employed material from Tacitus, Persius, Juvenal, Seneca, et al. Furthermore, Jonson sought to explain his reason for including such apparatus in his ‘Note to to the Readers’ of Sejanus: ‘Least in some nice nostrill, the Quotations might savour affected, I doe let you know, that I abhor nothing more; and have onely done it to shew my integrity in the Story.’ Although his purpose has in large part been ignored, his practice has not. Commentators and annotators since Jonson's time have striven to augment his efforts, whether, like John Upton in 1749, to show that Jonson was merely piecing together those writings he was pleased to call ‘Poems,’ or for reasons more benign.
Boccaccio in the Quattrocento: Manetti's Dialogus in symposio
Authors: Marsh David
Published: April 2006

Acentral issue of Quattrocento cultural history is the reevaluation of Dante, Petrarch, and Boccaccio by Florentine humanists. Yet whereas humanists could finally endorse the accomplishments of Dante and Petrarch, the third of the "three crowns," Boccaccio, seems to have presented a stumbling block to those concerned with affirming the continuity of humanistic studies with Trecento culture. Boccaccio's volgare works suffer from a comparison with Dante's linguistic and poetic achievement, while the Latin compendia of Boccaccio reveal none of the historical erudition of his mentor Petrarch.