bluuebunny/crossref_metadata_2025 huggingface dataset:
From Ethno-Science to Science, or 'What the Indigenous Knowledge Debate Tells Us about How Scientists Define Their Project'
Authors: Ellen Roy
Published: November 2004

This paper begins by examining the response of the organised scientific community to the claims of the indigenous knowledge lobby, and with some observations on the dichotomy between science and traditional technical knowledge. It reiterates the view that the potency of the distinction arises from a fusion of the general human cognitive impulse to simplify the processes by which we understand the world, reinforced by the socially-driven need of science to maintain an effective boundary around the practices which scientists engage in. The paper goes on to argue that the existence of these two epistemological metacategories obscures the presence of different ways of securing predictive knowledge of the material world, each of which is characterised by a distinctive configuration of cognitive and technical features, and which in several ways cut across the usual dualism between science and traditional knowledge. The argument is illustrated using examples from the history of biology and the ethnography of ethnobiological knowledge. It engages critically with insights drawn from cognitive psychology, the philosophy and sociology of science, and cognitive anthropology, as well as with scientists' own descriptions of what distinguishes the mental operations in which they engage.
Cognition, Construction and Culture: Visual Theories in the Sciences
Authors: Gooding David
Published: November 2004

This paper presents a study of the generation, manipulation and use of visual representations in different episodes of scientific discovery. The study identifies a common set of transformations of visual representations underlying the distinctive methods and imagery of different scientific fields. The existence of common features behind the diversity of visual representations suggests a common dynamical structure for visual thinking, showing how visual representations facilitate cognitive processes such as pattern-matching and visual inference through the use of tools, technologies and other cultural resources. This dynamical model suggests a way of theorizing the interaction of cognitive, socio-cultural and technological aspects of science without losing sight of the essential contribution each makes to the processes of discovery. Whereas scientific work is often construed epistemically, as having the aim of improving the fit between theories and phenomena or culturally given notions of what counts as reality, this study shows that scientists use transformations to modify visual representations in ways that achieve other kinds of match: between a representation and the cognitive demands of a task (such as pattern matching or mental rotation) or between an emerging representation and the social need to communicate and negotiate new meanings in a context of culturally embedded conventions. By showing how images connect each of the overlapping contexts of scientific work the proposed model negotiates the sometimes contested boundary between cognitive and social aspects of science.
The Unreasonable Richness of Mathematics
Authors: Van Bendegem Jean Paul , Van Kerkhove Bart
Published: November 2004

The paper gives an impression of the multi-dimensionality of mathematics as a human activity. This 'phenomenological' exercise is performed within an analytic framework that is both an expansion and a refinement of the one proposed by Kitcher (1984). Such a particular tool enables one to retain an integrated picture while nevertheless welcoming an ample diversity of perspectives on mathematical practices, that is, from different disciplines, with different scopes, and at different levels. Its functioning is clarified by fitting in illustrations based on actual research.
Replication and the Experimental Ethnography of Science
Authors: Tweney Ryan
Published: November 2004

The present paper attempts to define an experimental ethnography as an approach to the understanding of scientific thinking. Such an ethnography relies upon the replication of contemporary and historical scientific practices as a means of capturing the cultural and cognitive meanings of the practices in question. The approach is contrasted to the typical kind of laboratory experiment in psychology, and it is argued that replications of scientific practices can reveal dimensions of the microstructure of science and of its context that otherwise may remain invisible. An extended example is presented, based upon replications of the experimental procedures used by Michael Faraday (1791-1867) in 1856 during his examination of the optical properties of gold.
SEXUAL UNION AND SEXUAL OFFENCES IN JUBILEES
Authors: Rothstein David
Published: November 2004

In two recent articles A. Shemesh has argued that the Qumran community viewed the act of sexual intercourse alone as affecting the marital bond. The present paper demonstrates that Jubilees, in its reformulation of the biblical narrative, maintains a position very similar, and possibly identical, to that proposed by Shemesh. On this fundamentally ontological view, the physical union itself is determinative in connection with both permitted and proscribed unions, as reflected in several aspects of Jubilees' narrative.
Terrestrial locomotion in the white stork (Ciconia ciconia): spatio-temporal gait characteristics
Authors: van Coppenolle Isabel , Aerts Peter
Published: November 2004

Slender legged stilt birds give the impression of striding more gracefully and more slowly than other bipeds when moving over ground, a behavioural characteristic often thought to be linked to the challenges imposed by walking on tendril stilts. To test the significance of this impression, video sequences (50 Hz) of free ranging storks were digitised and analysed. Spatio-temporal gait characteristics (stride length, step length, stride frequency, duty factor, swing phase duration) were determined and compared with those of other bird species and humans, taking account of speed of locomotion, leg length and body mass. Storks increase their speed mainly by increasing stride frequency, and to a lesser extent by taking longer strides. Step length is nearly independent of speed. As a result, the duty factor decreases when walking faster, becoming somewhat smaller than 0.5 m only at higher speeds. At speeds below 1.3 m/s swing phase duration decreases with increased walking velocity; at higher speeds swing phase duration remains nearly constant. In general, spatio-temporal gait characteristics do not differ in their dimensionless form from those of other bipeds. However, storks definitely walk much slower than would be expected from their size (leg length and mass). This suggests that these slender legged stilt birds, although walking dynamically similarly to other bipeds, do limit their walking speed, probably to avoid excessive musculo-skeletal stresses.
The Many Faces of Span of Control
Authors: Theobald Nick A. , Nicholson-Crotty Sean
Published: November 2004

As an extension of the existing literature on span-of-control relationships, we propose that public bureaucracies are typically faced with multiple goals creating potential conflicts due to structural choices. In other words, optimal span of control for one goal may not be optimal for another. Findings from an analysis of nearly 600 public bureaucracies provide some evidence that structural changes designed to improve performance on one goal may hinder performance on others. The results from our analysis also demonstrate a functional form for the span-of-control relationship that is very different from the one suggested by recent theoretical work.
Dynamic Master Mind
Authors: Saldaña David
Published: November 2004

Master Mind is a commercial game, popular in the 1970s, that has been extensively used in psychological and educational research. Here, a dynamic assessment format is developed in order to test metacognitive skills in individuals with mental retardation. The main objective is to obtain valid scores that adequately reflect individual differences among low-functioning individuals. Sixteen persons with mental retardation and 13 of average intelligence were compared on static and dynamic Master Mind scores. Scores for subjects of the mental retardation sample were also obtained on the ICAP adaptive functioning score (Bruininks et al., 1986), and on a metacognitive functioning scale, the Cognitively Enriched Behaviour Matrix(Mora and Mora-Merchán, 1995). The latter was administered while participating in a thinking skills programme, Comprehending and Transforming (Mora, 1997) following assessment with Master Mind. Differences between persons with average intelligence and mental retardation were statistically significant on all processes and both on dynamic and static scores. More importantly, dynamic scores on Master Mind were related to adaptive behaviour ( d= 0.482, p< 0.001), and predicted metacognitive functioning in the learning environment of the thinking skills programme ( d= 0.727, p< 0.001). Neither IQ nor static scores related significantly to these criteria.
Family physicians' perspectives on practice guidelines related to cancer control
Authors: Zitzelsberger Louise , Grunfeld Eva , Graham Ian D
Published: November 2004

Background

Family physicians (FPs) play an important role in cancer control. While FPs' attitudes towards, and use of guidelines in general have been explored, no study has looked at the needs of FPs with respect to guidelines for the continuum of cancer control. The objective of this study was to understand which guideline topics FPs consider important.

Methods

Five group interviews were conducted by telephone with FPs from across Ontario, Canada. Transcripts were analyzed inductively. Content analysis identified emergent themes. Themes are illustrated by representative quotes taken from the transcripts.

Results

The main areas where FPs felt guidelines were needed most included screening – a traditional area of responsibility for FPs – and treatment and follow-up – areas where they felt they lacked the knowledge to best support patients. Confusion over best practice when faced with conflicting guidelines varied according to disease site. FPs defined good guideline formats; the most often cited forms of presentation were tear-off sheets to use interactively with patients, or a binder. Computer-based dissemination was acknowledged as the best way of widely distributing material that needs frequent updates. However, until computer use is a common aspect of practice, mail was considered the most viable method of dissemination. Guidelines designed for use by patients were supported by FPs.

Conclusions

Preferred guideline topics, format, dissemination methods and role of patient guidelines identified by FPs in this study reflect the nature of their practice situations. Guideline developers and those supporting use of evidence-based guidelines (e.g., Canadian Strategy for Cancer Control) have a responsibility to ensure that FPs are provided with the resources they identify as important, and to provide them in a format that will best support their use.
G-protein inwardly rectifying potassium channel 1 (GIRK 1) gene expression correlates with tumor progression in non-small cell lung cancer
Authors: Takanami Iwao , Inoue Yoshimasa , Gika Masatoshi
Published: November 2004

Background

G-protein inwardly rectifying potassium channel 1 (GIRK1) is thought to play a role in cell proliferation in cancer, and GIRK1 gene expression level may define a more aggressive phenotype. We detected GIRK1 expression in tissue specimens from patients with non-small cell lung cancers (NSCLCs) and assessed their clinical characteristics.

Methods

Using reverse transcription-polymerase chain reaction (RT-PCR) analyses, we quantified the expression of GIRK1 in 72 patients with NSCLCs to investigate the relationship between GIRK1 expression and clinicopathologic factors and prognosis.

Results

In 72 NSCLC patients, 50 (69%) samples were evaluated as having high GIRK1 gene expression, and 22 (31%) were evaluated as having low GIRK1 gene expression. GIRK1 gene expression was significantly associated with lymph node metastasis, stage (p = 0.0194 for lymph node metastasis; p = 0.0207 for stage). The overall and stage I survival rates for patients with high GIRK1 gene expressed tumors was significantly worse than for those individuals whose tumors had low GIRK1 expression (p = 0.0004 for the overall group; p = 0.0376 for stage I).

Conclusions

These data indicate that GIRK1 may contribute to tumor progression and GIRK1 gene expression can serve as a useful prognostic marker in the overall and stage I NSCLCs.
Factors involved in nurses' responses to burnout: a grounded theory study
Authors: Rafii Forough , Oskouie Fatemeh , Nikravesh Mansoure
Published: November 2004

Background

Intense and long-standing problems in burn centers in Tehran have led nurses to burnout. This phenomenon has provoked serious responses and has put the nurses, patients and the organization under pressure. The challenge for managers and nurse executives is to understand the factors which would reduce or increase the nurses' responses to burnout and develop delivery systems that promote positive adaptation and facilitate quality care. This study, as a part of more extensive research, aims to explore and describe the nurses' perceptions of the factors affecting their responses to burnout.

Methods

Grounded theory was used as the method. Thirty- eight participants were recruited. Data were generated by unstructured interviews and 21 sessions of participant observations. Constant comparison was used for data analysis.

Results

Nurses' and patients' personal characteristics and social support influenced nurses' responses to burnout. Personal characteristics of the nurses and patients, especially when interacting, had a more powerful effect. They altered emotional, attitudinal, behavioral and organizational responses to burnout and determined the kind of caring behavior. Social support had a palliative effect and altered emotional responses and some aspects of attitudinal responses.

Conclusions

The powerful effect of positive personal characteristics and its sensitivity to long standing and intense organizational pressures suggests approaches to executing stress reduction programs and refreshing the nurses' morale by giving more importance to ethical aspects of caring. Moreover, regarding palliative effect of social support and its importance for the nurses' wellbeing, nurse executives are responsible for promoting a work environment that supports nurses and motivates them.
Antigenized antibodies expressing Vβ8.2 TCR peptides immunize against rat experimental allergic encephalomyelitis
Authors: Musselli Cristina , Daverio-Zanetti Svetlana , Zanetti Maurizio
Published: November 2004

Background

Immunity against the T cell receptor (TCR) is considered to play a central role in the regulation of experimental allergic encephalomyelitis (EAE), a model system of autoimmune disease characterized by a restricted usage of TCR genes. Methods of specific vaccination against the TCR of pathogenetic T cells have included attenuated T cells and synthetic peptides from the sequence of the TCR. These approaches have led to the concept that anti-idiotypic immunity against antigenic sites of the TCR, which are a key regulatory element in this disease.

Methods

The present study in the Lewis rat used a conventional idiotypic immunization based on antigenized antibodies expressing selected peptide sequences of the Vβ8.2 TCR (93ASSDSSNTE101 and 39DMGHGLRLIHYSYDVNSTEKG59).

Results

The study demonstrates that vaccination with antigenized antibodies markedly attenuates, and in some instances, prevents clinical EAE induced with the encephalitogenic peptide 68GSLPQKSQRSQDENPVVHF88 in complete Freunds' adjuvant (CFA). Antigenized antibodies induced an anti-idiotypic response against the Vβ8.2 TCR, which was detected by ELISA and flowcytometry. No evidence was obtained of a T cell response against the corresponding Vβ8.2 TCR peptides.

Conclusions

The results indicate that antigenized antibodies expressing conformationally-constrained TCR peptides are a simple means to induce humoral anti-idiotypic immunity against the TCR and to vaccinate against EAE. The study also suggests the possibility to target idiotypic determinants of TCR borne on pathogenetic T cells to vaccinate against disease.
Soil loss due to crop harvesting: significance and determining factors
Authors: Ruysschaert G. , Poesen J. , Verstraeten G. , Govers G.
Published: November 2004

Water, wind and tillage erosion are well-studied soil erosion processes. However, there is another process of soil erosion that is rarely considered in the field of earth sciences but one that should not be neglected when calculating soil denudation rates and sediment budgets, i.e., soil loss due to crop harvesting (SLCH). Loose soil and soil adhering to the crop and rock fragments are harvested and exported from the field along with crops such as sugar beet (Beta vulgaris L.), potato (Solanum tuberosum L.) and chicory (Cichorium intybus L.). In this paper several assessments of SLCH found in the literature are listed, revealing that soil loss due to crop harvesting may range from a few Mg up to a few tens of Mg per hectare per harvest. As most literature discussing this soil loss does not originate from the field of earth sciences, and terms used to describe this phenomenon are not standardized, a terminology is proposed to describe soil losses due to crop harvesting compatible with terms used in the field of soil erosion. Furthermore, the parameters determining SLCH are reviewed based on a detailed literature study that focuses mainly on sugar beet. These parameters may be grouped into four factors, i.e. soil, crop, agronomic practices and harvest technique. Variations in soil moisture and soil texture cause the largest variations in SLCH, although other factors, such as harvest technique, also play an important role. Given the importance of SLCH in terms of on-site and off-site effects, more research is needed to quantify SLCH under different environmental conditions.
Targeting β-cell cyclic 3′5′adenosine monophosphate for the development of novel drugs for treating type 2 diabetes mellitus. A review
Authors: Furman Brian , Pyne Nigel , Flatt Peter , O'Harte Finbarr
Published: November 2004

Cyclic 3′5′AMP is an important physiological amplifier of glucose-induced insulin secretion by the pancreatic islet β-cell, where it is formed by the activity of adenylyl cyclase, especially in response to the incretin hormones GLP-1 (glucagon-like peptide-1) and GIP (glucose-dependent insulinotropic peptide). These hormones are secreted from the small intestine during and following a meal, and are important in producing a full insulin secretory response to nutrient stimuli. Cyclic AMP influences many steps involved in glucose-induced insulin secretion and may be important in regulating pancreatic islet β-cell differentiation, growth and survival. Cyclic AMP (cAMP) itself is rapidly degraded in the pancreatic islet β-cell by cyclic nucleotide phosphodiesterase (PDE) enzymes. This review discusses the possibility of targeting cAMP mechanisms in the treatment of type 2 diabetes mellitus, in which insulin release in response to glucose is impaired. This could be achieved by the use of GLP-1 or GIP to elevate cAMP in the pancreatic islet β-cell. However, these peptides are normally rapidly degraded by dipeptidyl peptidase IV (DPP IV). Thus longer-acting analogues of GLP-1 and GIP, resistant to enzymic degradation, and orally active inhibitors of DPP IV have also been developed, and these agents were found to improve metabolic control in experimentally diabetic animals and in patients with type 2 diabetes. The use of selective inhibitors of type 3 phosphodiesterase (PDE3B), which is probably the important pancreatic islet β-cell PDE isoform, would require their targeting to the islet β-cell, because inhibition of PDE3B in adipocytes and hepatocytes would induce insulin resistance.
Emblica officinalis reverses thioacetamide-induced oxidative stress and early promotional events of primary hepatocarcinogenesis
Authors: Sultana Sarwat , Ahmed Salahuddin , Sharma Sonia , Jahangir Tamanna
Published: November 2004

Emblica officinalis is widely used in Indian medicine for the treatment of various diseases. In the present study, it was found that fruits of E. officinalis inhibit thioacetamide-induced oxidative stress and hyper-proliferation in rat liver. The administration of a single necrotic dose of thioacetamide (6.6 mM kg−1) resulted in a significant (P< 0.001) increase in serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT) and γ-glutamyl transpeptidase (GGT) levels compared with saline-treated control values. Thioacetamide caused hepatic glutathione (GSH) depletion and a concomitant increase in malanodialdehyde (MDA) content. It also resulted in an increase (P< 0.001) in the activity of glutathione-S-transferase (GST), glutathione reductase (GR), glucose 6-phosphate dehydrogenase (G6PD) and a decrease in glutathione peroxidase (GPx) activity (P< 0.001). Hepatic ornithine decarboxylase activity and thymidine incorporation in DNA were increased by thioacetamide administration. Prophylactic treatment with E. officinalis for 7 consecutive days before thioacetamide administration inhibited SGOT, SGPT and GGT release in serum compared with treated control values. It also modulated the hepatic GSH content and MDA formation. The plant extract caused a marked reduction in levels of GSH content and simultaneous inhibition of MDA formation. E. officinalis also caused a reduction in the activity of GST, GR and G6PD. GPx activity was increased after treatment with the plant extract at doses of 100 mg kg−1 and 200 mg kg−1. Prophylactic treatment with the plant caused a significant down-regulation of ornithine decarboxylase activity (P< 0.001) and profound inhibition in the rate of DNA synthesis (P< 0.001). In conclusion, the acute effects of thioacetamide in rat liver can be prevented by pre-treatment with E. officinalis extract.
Carbonyl reduction of naltrexone and dolasetron by oxidoreductases isolated from human liver cytosol
Authors: Breyer-Pfaff U , Nill K
Published: November 2004

The opioid receptor antagonist naltrexone and the antiemetic 5-HT3 receptor antagonist dolasetron are ketonic drugs that are efficiently reduced to their corresponding alcohols in-vivo. These experiments aimed at characterizing the role in these reactions of individual oxidoreductases present in human liver cytosol. Aldo-keto reductases (AKRs) and carbonyl reductase (CR, EC 1.1.1.184) purified from human liver cytosol were incubated with varying substrate concentrations and 6β-naltrexol or reduced dolasetron were analysed by HPLC. AKR1C1, AKR1C2, and AKR1C4 were able to reduce both substrates. On the basis of kcat/Km values, AKR1C4 was nearly 1000-fold more efficient in reducing naltrexone than was AKR1C1, while AKR1C2 was of intermediate efficiency. Substrate inhibition was observed on incubating AKR1C2 or AKR1C4 with naltrexone. In contrast, dolasetron was also a substrate of CR. AKR1C1 and AKR1C4 were the most efficient enzymes in producing reduced dolasetron. We concluded that the efficient reduction of naltrexone by AKR1C4 probably causes the high 6β-naltrexol/naltrexone ratio in man. The rapid disappearance from human plasma of dolasetron given intravenously and its virtual absence after oral dosage are explained by its liability to reduction by several enzymes, including CR which shows widespread expression in human tissues.
Effects of oral administration of extracts of Hypericum perforatum (St John's wort) on brain serotonin transporter, serotonin uptake and behaviour in mice
Authors: Hirano Kazufumi , Kato Yasuhiro , Uchida Shinya , Sugimoto Yumi , Yamada Jun , Umegaki Keizo , Yamada Shizuo
Published: November 2004

The pharmacological effects of extracts of Hypericum perforatum (St John's wort) were characterized in-vitro and ex-vivo, in relation to its behavioural effects. In in-vitro experiments, St John's wort inhibited brain synaptosomal [3H]serotonin uptake in mice with little effect on specific [3H]paroxetine binding. For selective serotonin-reuptake inhibitors (SSRIs), the IC50 value for [3H]serotonin uptake (molar concentration of unlabelled drug necessary to displace 50% of specific uptake) correlated well with the inhibition constant Ki value for [3H]paroxetine binding in mouse brain. Oral administration of St John's wort (900 mg kg−1), paroxetine (1 mg kg−1) and sertraline (10 mg kg−1) brought about significant increases in the Km value for [3H]serotonin uptake into brain synaptosomes 4 h later, and only SSRIs suppressed specific [3H]paroxetine binding in mouse brain. St John's wort and SSRIs significantly inhibited marble-burying behaviour in mice and the time-course of attenuation of this behaviour by St John's wort was similar to that of [3H]serotonin uptake inhibition. In the forced swimming test, St John's wort, but not SSRIs, suppressed the immobility time of mice after oral administration. These results provide the first in-vivo evidence to suggest that the mode of antidepressant action of St John's wort differs from that of SSRIs. Thus, this study may have a significant impact on phytotherapy with St John's wort.
GDF11 modulates NGN3+ islet progenitor cell number and promotes β-cell differentiation in pancreas development
Authors: Harmon Erin B. , Apelqvist Åsa A. , Smart Nora G. , Gu Xueying , Osborne Douglas H. , Kim Seung K.
Published: November 2004

Identification of endogenous signals that regulate expansion and maturation of organ-specific progenitor cells is a major goal in studies of organ development. Here we provide evidence that growth differentiation factor 11(GDF11), a member of the TGF-β ligand family, governs the number and maturation of islet progenitor cells in mouse pancreas development. Gdf11 is expressed in embryonic pancreatic epithelium during formation of islet progenitor cells that express neurogenin 3. Mice deficient for Gdf11 harbor increased numbers of NGN3+ cells,revealing that GDF11 negatively regulates production of islet progenitor cells. Despite a marked expansion of these NGN3+ islet progenitors, mice lacking Gdf11 have reduced β-cell numbers and evidence of arrested β-cell development, indicating that GDF11 is also required for β-cell maturation. Similar precursor and islet cell phenotypes are observed in mice deficient for SMAD2, an intracellular signaling factor activated by TGF-β signals. Our data suggest that Gdf11 and Smad2 regulate islet cell differentiation in parallel to the Notch pathway, which previously has been shown to control development of NGN3+ cells. Thus, our studies reveal mechanisms by which GDF11 regulates the production and maturation of islet progenitor cells in pancreas development.
Regional requirements for Dishevelled signaling duringXenopusgastrulation: separable effects on blastopore closure, mesendoderm internalization and archenteron formation
Authors: Ewald Andrew J. , Peyrot Sara M. , Tyszka J. Michael , Fraser Scott E. , Wallingford John B.
Published: November 2004

During amphibian gastrulation, the embryo is transformed by the combined actions of several different tissues. Paradoxically, many of these morphogenetic processes can occur autonomously in tissue explants, yet the tissues in intact embryos must interact and be coordinated with one another in order to accomplish the major goals of gastrulation: closure of the blastopore to bring the endoderm and mesoderm fully inside the ectoderm, and generation of the archenteron. Here, we present high-resolution 3D digital datasets of frog gastrulae, and morphometrics that allow simultaneous assessment of the progress of convergent extension, blastopore closure and archenteron formation in a single embryo. To examine how the diverse morphogenetic engines work together to accomplish gastrulation, we combined these tools with time-lapse analysis of gastrulation, and examined both wild-type embryos and embryos in which gastrulation was disrupted by the manipulation of Dishevelled (Xdsh)signaling. Remarkably, although inhibition of Xdsh signaling disrupted both convergent extension and blastopore closure, mesendoderm internalization proceeded very effectively in these embryos. In addition, much of archenteron elongation was found to be independent of Xdsh signaling, especially during the second half of gastrulation. Finally, even in normal embryos, we found a surprising degree of dissociability between the various morphogenetic processes that occur during gastrulation. Together, these data highlight the central role of PCP signaling in governing distinct events of Xenopusgastrulation, and suggest that the loose relationship between morphogenetic processes may have facilitated the evolution of the wide variety of gastrulation mechanisms seen in different amphibian species.
ENU induced mutations causing congenital cardiovascular anomalies
Authors: Yu Qing , Shen Yuan , Chatterjee Bishwanath , Siegfried Brett H. , Leatherbury Linda , Rosenthal Julie , Lucas John F. , Wessels Andy , Spurney Chris F. , Wu Ying-Jie , Kirby Margaret L. , Svenson Karen , Lo Cecilia W.
Published: November 2004

We used non-invasive high frequency ultrasound to screen N-ethyl-N-nitrosourea mutagenized mouse fetuses for congenital cardiovascular anomalies. We ultrasound scanned 7546 mouse fetuses from 262 mutagenized families, and identified 124 families with cardiovascular defects. Represented were most of the major congenital cardiovascular anomalies seen clinically. The ENU-induced mutations in several families were mapped using polymorphic microsatellite DNA markers. One family with forelimb anomalies and ventricular septal defects, phenotypes similar to Holt-Oram syndrome, and one family with transposition of the great arteries and heart situs anomalies were mapped to different regions of mouse chromosome 4. A third mutation causing persistent truncus arteriosus and craniofacial defects, phenotypes reminiscent of DiGeorge syndrome, was mapped to mouse chromosome 2. We note that mouse chromosomes 4 and 2 do not contain Tbx5 or Tbx1, genes previously linked to Holt-Oram and DiGeorge syndromes, respectively. In two other families, the ENU-induced mutation was identified – Sema3CL605P was associated with persistent truncus arteriosus with interrupted aortic arch, and the Gja1W45Xconnexin43 mutation caused conotruncal malformation and coronary aneurysms. Although our screen was designed as a recessive screen, a number of the mutations showed cardiovascular phenotypes in both heterozygote and homozygote animals. These studies show the efficacy of ENU mutagenesis and high-throughput ultrasound phenotyping in recovering mutations causing a wide spectrum of congenital heart defects. These ENU-induced mutations hold promise in yielding new insights into the genetic basis for human congenital heart disease.
Plasma concentrations of tumour dimeric pyruvate kinase are increased in patients with chronic cardiac failure
Authors: McDowell G , Gupta S , Dellerba M , Coppinger T , Levy RD , Keevil BG
Published: November 2004

Background: The aim of the study was to assess the effect of chronic cardiac failure (CCF) on circulating plasma concentrations of tumour metabolic marker dimeric pyruvate kinase type M2 (M2-PK).

Methods: Fifty patients with clinically stable CCF were studied. Patients with a history of past or ongoing malignancy were excluded. Dimeric M2-PK was measured by enzyme-linked immunosorbent assay in EDTA plasma.

Results: Dimeric M2-PK concentration increased significantly ( P = 0.005) with increasing clinical severity of CCF as assessed by the New York Heart Association classification grade.

Conclusions: Chronic cardiac failure results in an increased circulating plasma concentration of M2-PK, probably related to increased glycolytic flux. The physiological significance of the results is at present unclear but may relate to maintaining a balance between energy production and the supply of glycolytic intermediates to maintain synthetic processes. The results of this investigation will also have significance in the clinical interpretation of M2-PK concentrations.
Haptoglobin phenotype as a predictive factor of mortality in diabetic haemodialysis patients
Authors: Burbea Zvi , Nakhoul Farid , Zoabi Roaa , Hochberg Irit , Levy Nina S , Benchetrit Sidney , Weissgarten Joshua , Tovbin David , Knecht Aaron , Iaina Adrian , Herman Michal , Kristal Batya , Levy Andrew P
Published: November 2004

Introduction: The mortality rate in diabetic dialysis patients (DDPs) is over 15% per year, with the cause of death most often attributed to cardiovascular disease (CVD) or bacterial infection (sepsis). Identification of genetic markers predictive of early mortality would be useful in the evaluation of therapies for the reduction of mortality rate in this population. Haptoglobin (Hp) is a polymorphic protein which appears to confer differential susceptibility to bacterial infection and CVD. We therefore proposed that Hp phenotype can predict mortality in DDPs.

Methods: We tested this hypothesis prospectively in a longitudinal study of 392 dialysis patients from eight medical centres in Israel. Hp was determined by polyacrylamide gel electrophoresis. Patients were followed for all-cause mortality over a 3-year period.

Results: We found that Hp phenotype was a significant predictor of mortality in DDPs stratified by age. In diabetic individuals over 60 years of age there was a decrease in mortality associated with the Hp 1-1 phenotype ( P = 0.03). However, in younger DDPs the Hp 2-2 phenotype was associated with a decreased mortality rate ( P = 0.003).

Conclusion: Hp phenotype may be useful in the risk stratification algorithm and management of DDPs.
Wegener’s granulomatosis and subglottic stenosis: management of the airway
Authors: Alaani A. , Hogg R.P. , Drake Lee A.B.
Published: November 2004

Wegener’s granulomatosis is a multisystemic disease characterized by foci of necrotizing vasculitis and granuloma formation. Subglottic stenosis may occur either asa presenting feature or a late-stage manifestation of the disease, but will occur in approximately 10–20 per cent of cases.

We present a series of seven cases of Wegener’s granulomatosis with subglottic stenosis and discuss our management of this condition. Where there is active disease, tracheostomy is the first-line surgical treatment of respiratory obstruction, as an adjunct to full medical therapy.More aggressive or elaborate surgical treatments should be reserved for non-active cases in which patients have not required medical treatment for one year.
Nd: YAG laser treatment for adult hypopharyngeal haemangioma
Authors: Katori Hideaki , Tsukuda Mamoru
Published: November 2004

Adult hypopharyngeal haemangioma is an uncommon neoplasm. We present three cases of adult hypopharyngeal haemangioma which were successfully treated with a neodymium: yttrium–aluminium–garnet (Nd: YAG) laser in our hospital between 2000 and 2003. The patients in this series experienced no untoward events from the use of the laser. Excessive bleeding and airway problems were not encountered. Postoperative pain was minimal. Excellent long-term function and a full resolution of symptoms can be obtained using Nd: YAG laser. The laser provides a bloodless field and complete healing of the hypopharynx, without stenosis or scar formation.
Preoperative evaluation of bone destruction using three-dimensional computed tomography in cholesteatoma
Authors: Jang Chul Ho , Wang Pa-Chun
Published: November 2004

This study investigated the usefulness of three-dimensional computed tomography (3DCT) in the evaluation of bony defects caused by cholesteatoma. Fifteen patients with chronic otitis media with cholesteatoma who showed bony destruction or suspicious destruction in two-dimensional CT were examined using 3DCT. The CT data were transferred to a workstation witha real-time image processor. We used three-dimensional reconstruction software enabling image processing. In all patients, 3DCT clearly delineated the destruction of bony structures by cholesteatoma. The 3DCT-generated images provided spatial relationships, which were not easily appreciated on two-dimensional CT. Intraoperative bony destruction findings correlated with 3DCT findings. From these results, 3DCT could be useful to evaluate the invasiveness of cholesteatoma to the cranial base. It could also be helpful in planning reconstruction during surgery.
Pancuronium Bromide (Pavulon) Isolation and Identification in Aged Autopsy Tissues and Fluids
Authors: Andresen BD , Alcaraz A , Grant PM
Published: November 2004

The isolation and detection of pancuronium bromide was developed for aged autopsy samples to identify and confirm this compound in questioned tissue samples. A novel protocol was optimized for the isolation of the target drug in highly decomposed tissues. Solid-phase extraction (SPE) cartridges containing styrene-divinylbenzene were investigated. This polymer retained quaternary drugs and facilitated sequential elution upon washing with commonly available solvents. The semi-purified SPE samples were prescreened by pyrolysis GC-MS. A candidate specimen was then confirmed by microbore high-performance liquid chromatography/electrospray-ionization/mass spectrometry (µHPLC-ESI-MS/MS) with a triple-quadrupole mass spectrometer. The developed procedures provided a qualitative or semiquantitative (at best) basis for the investigation of difficult cases involving overdoses of polar drugs.
The Application of Pancuronium Bromide (Pavulon) Forensic Analyses to Tissue Samples from an “Angel of Death” Investigtion
Authors: Andresen BD , Alcaraz AM , Grant PM
Published: November 2004

The case report of a serial killer who worked at several hospitals as a respiratory therapist is presented. The suspect was initially labeled a benevolent Angel of Death who ended the suffering of elderly patients through mercy killing. However, his subsequently declared motive for homicide was very different from other similar cases in medical settings. The application of new analysis techniques for the detection of pancuronium bromide in a series of aged exhumation tissues gave positive results and led to the resultant conviction of the therapist.
Three-dimensional Cranio-Facial Reconstruction in Forensic Identification: Latest Progress and New Tendencies in the 21st Century
Authors: De Greef S , Willems G
Published: November 2004

Three-dimensional (3D) cranio-facial reconstruction can be useful in the identification of an unknown body. The progress in computer science and the improvement of medical imaging technologies during recent years had significant repercussions on this domain. New facial soft tissue depth data for children and adults have been obtained using ultrasound, CT-scans and radiographies. New guidelines for facial feature properties such as nose projection, eye protrusion or mouth width, have been suggested, but also older theories and "rules of thumbs" have been critically evaluated based on digital technology. New fast, flexible and objective 3D reconstruction computer programs are in full development. The research on craniofacial reconstruction since the beginning of the 21st century is presented, highlighting computer-aided 3D facial reconstruction. Employing the newer technologies and permanently evaluating and (re)questioning the obtained results will hopefully lead to more accurate reconstructions.
Determination of Elemental Sulfur in Explosives and Explosive Residues by Gas Chromatography-Mass Spectrometry
Authors: Bradley KS
Published: November 2004

A new method for the positive identification of elemental sulfur in explosives and explosive residues is developed. Following a carbon disulfide wash of explosives or explosive residues, a sample of the extracted material is injected onto a gas chromatography (GC) column, then analyzed via mass-selective (MS) detection. A positive identification of elemental sulfur is based on both retention time and fragmentation pattern. The GC-MS method is demonstrated to be useful in detecting and positively identifying elemental sulfur from both burned and unburned explosive mixtures. With a detection limit of 2.5 ng (2.5 × 10-9 grams) of elemental sulfur on the column, it is shown to be 400 times more sensitive than the presumptive chemical color test that is currently the method employed for detection of small amounts of sulfur.
The Detection and Enhancement of Latent Fingermarks Using Infrared Chemical Imaging
Authors: Tahtouh M , Kalman JR , Roux C , Lennard C , Reedy BJ
Published: November 2004

The use of a new technique, Fourier transform infrared (FTIR) chemical imaging, has been demonstrated for the enhancement of latent fingermarks on a number of surfaces. Images of untreated fingermarks on glass backgrounds with excellent ridge detail were acquired using infrared chemical imaging. High quality fingermarks on glass backgrounds were also developed using ethyl cyanoacrylate (super glue) fuming and subsequent infrared chemical imaging. This new method allows the collection of images from backgrounds that traditionally pose problems for current fingermark detection methods. The background may, for example, be highly colored, have a complex pattern, or possess other pattern or image characteristics that make it difficult to separate fingermark ridges using traditional optical or luminescent visualization. One background that has proven to be a challenging surface for the development of latent fingermarks is the Australian polymer banknote. To demonstrate the power and applicability of infrared chemical imaging, fingermarks fumed with ethyl cyanoacrylate were successfully imaged from Australian polymer banknotes.
Analysis of Explosive Damage in Metals Using Orientation Imaging Microscopy
Authors: Chumbley LS , Laabs FC
Published: November 2004

The goal of this project was to determine whether quantitative information concerning the size and nature of an explosive blast could be determined using Orientation Imaging Microscopy (OIM) to analyze the texture of blast-affected metal. Selected 1018 steel and 2024 aluminum samples were subjected to various explosive blasts chosen to simulate a wide range of possible pressure waves. The explosives used were PBX 9404, Comp-C4, Gelmax, and Bullseye. The explosive tests were carried out at Sandia National Laboratory, and the OIM analysis was conducted at Ames Laboratory. It was discovered that while suitable patterns could be obtained from the steel samples, the oxide layer present on the surface of the aluminum samples prevented these samples from being studied. The results of the OIM studies on the steel samples indicate that damage can be tracked using OIM imaging and that Comp-C4 seems to produce patterns significantly different than the other explosives.
Review of: Forensic Facial Reconstruction
Authors: Ubelaker DH
Published: November 2004

Facial reconstruction, as defined in this book, refers to the process “whereby the face of an individual is built onto the skull for the purpose of identification.” The volume joins a growing literature on this subject, reflecting advances in artistic techniques and the underlying science, as well as the sustained need to present facial imagery to the public with the goal of obtaining information helful in identification of unknown remains.
Review of: Techniques of Crime Scene Investigation, 7th edition, and Techniques of Crime Scene Investigation Interactive Training CD-ROM
Authors: Bashinski JS , Crim M
Published: November 2004

The seventh edition of Barry Fisher's classic work on crime scene investigation, based on an earlier text by Arne Svensson and Otto Wendel, carries on the tradition of its predecessors. This widely used textbook is designed as a basic reference for students of crime scene investigation, including police investigators, crime scene technicians, and forensic scientists. new with this edition is an companion interactive training CD ROM developed by Jane Homeyer and Sarah Mikolajczyk.
Quantitative structure-activity relationship methods: Perspectives on drug discovery and toxicology
Authors: Perkins Roger , Fang Hong , Tong Weida , Welsh William J.
Published: November 2004

Quantitative structure—activity relationships (QSARs) attempt to correlate chemical structure with activity using statistical approaches. The QSAR models are useful for various purposes including the prediction of activities of untested chemicals. Quantitative structure—activity relationships and other related approaches have attracted broad scientific interest, particularly in the pharmaceutical industry for drug discovery and in toxicology and environmental science for risk assessment. An assortment of new QSAR methods have been developed during the past decade, most of them focused on drug discovery. Besides advancing our fundamental knowledge of QSARs, these scientific efforts have stimulated their application in a wider range of disciplines, such as toxicology, where QSARs have not yet gained full appreciation. In this review, we attempt to summarize the status of QSAR with emphasis on illuminating the utility and limitations of QSAR technology. We will first review two-dimensional (2D) QSAR with a discussion of the availability and appropriate selection of molecular descriptors. We will then proceed to describe three-dimensional (3D) QSAR and key issues associated with this technology, then compare the relative suitability of 2D and 3D QSAR for different applications. Given the recent technological advances in biological research for rapid identification of drug targets, we mention several examples in which QSAR approaches are employed in conjunction with improved knowledge of the structure and function of the target receptor. The review will conclude by discussing statistical validation of QSAR models, a topic that has received sparse attention in recent years despite its critical importance.
Quantitative structure-activity relationships for predicting potential ecological hazard of organic chemicals for use in regulatory risk assessments
Authors: Comber Mike H. I. , Walker John D. , Watts Chris , Hermens Joop
Published: November 2004

The use of quantitative structure-activity relationships (QSARs) for deriving the predicted no-effect concentration of discrete organic chemicals for the purposes of conducting a regulatory risk assessment in Europe and the United States is described. In the United States, under the Toxic Substances Control Act (TSCA), the TSCA Interagency Testing Committee and the U.S. Environmental Protection Agency (U.S. EPA) use SARs to estimate the hazards of existing and new chemicals. Within the Existing Substances Regulation in Europe, QSARs may be used for data evaluation, test strategy indications, and the identification and filling of data gaps. To illustrate where and when QSARs may be useful and when their use is more problematic, an example, methyl tertiary-butyl ether (MTBE), is given and the predicted and experimental data are compared. Improvements needed for new QSARs and tools for developing and using QSARs are discussed.