bluuebunny/crossref_metadata_2025 huggingface dataset:
Reconstructing Allyn A. Young's Theory of Increasing Returns
Authors: Colacchio Giorgio
Published: September 2005

In this essay we are going to closely analyze the importance of Allyn A. Young's theory of increasing returns. In truth, we could also discuss his position on economies of scale, in that the analytical definitions suggested by the theory, as we shall shortly see, are not that helpful in understanding exactly what this writer meant by (the principle of) increasing returns: in fact, the latter are always linked to the more general, all-pervasive concept of economic progress, as is evident from the title of his most famous work. Young's contribution to the debate (one only has to think of the cost controversy of the 1920s) over returns and economies (and diseconomies) of scale, was in truth somewhat marginal. His only work that dealt with these questions, besides his 1928 celebrated paper (Young 1928), dates back to 1913, when in an important critical note (Young 1913), which we shall briefly analyze in section 2, he criticized a number of economic policy rules deriving from Arthur C. Pigou's (1912) famous work. To put it more precisely, Young did not have any substantial role to play in the construction and perfection of the neoclassical theoretical paradigm; in fact, as we argue in section 3, there is significant evidence to suggest that he was probably moving increasingly further away from such a position. The essence of Young's work, summarized in the article written in 1928, would seem to consist in the request for a theoretical redirection, in the analysis of the dynamics of capitalist economies, along the lines of some of the classical economists, thus carrying the various suggestions on this matter already present in Alfred Marshall's theoretical contribution to extremes. In sections 4 and 5, dedicated to the discussion of this article and of its appendix respectively, we maintain that the logic of Young's analysis is based on a multi-sectoral model subject to qualitative and quantitative transformations, i.e., to structural change. Such a view enables us to understand: (1) the author's emphasis on the proportionality among different productive branches needed in order to ensure balanced economic expansion; (2) the attempt (made by the author in the appendix to his 1928 article) to explain the dynamics of the economic system in the presence of different intersectoral growth rates. In the concluding section we maintain that it is the alternative nature of his position compared with the “standard theory”—the reference here is particularly to Pigou's transcription of Marshall's economics—that represents the main feature of Young's work.
Pupil commentary on assessment for learning
Authors: Cowie Bronwen
Published: September 2005

This article draws on data generated through interviews with Years 7 to 10 pupils in New Zealand to propose that pupils experience assessment for learning as embedded in, and accomplished through, interactions with peers and teachers. Pupil commentary indicated they perceived assessment for learning as having cognitive, social relationship and affective purposes and consequences. Pupils used a range of criteria to assess their learning. Pupils with learning goals viewed assessment for learning as a joint teacher–pupil responsibility. They expressed a preference for teacher feedback in the form of suggestions because these maintained an active role for them in making sense of ideas. Pupils with performance goals intimated they viewed assessment as a teacher's sole responsibility. They preferred feedback on how to complete tasks. A lack of mutual trust and respect was said to lead pupils to limit the disclosure of their ideas. Overall, pupils intimated that they experience assessment for learning as a complex activity in which they are active and intentional participants.
Two teachers making assessment for learning their own
Authors: Sato Mistilina , Coffey Janet , Moorthy Savitha
Published: September 2005

The Classroom Assessment Project to Improve Teaching and Learning (CAPITAL) set out to understand how teachers attempt to modify their classroom practices as they grapple with new ideas about using assessment in their own classrooms to improve learning. CAPITAL documented the classroom activities and discussions among groups of middle school science teachers over four years. Through the stories of two of the teachers in the project, this article describes some of the variations in how the teachers in the project integrated, adapted and incorporated assessment for learning into their everyday teaching practice. We see Louise draw upon her background as a scientist to use student work as data that drive her teaching decisions, and we see Anthony approach his assessment work within a curricular framework with the ultimate goal of influencing his colleagues in the school district. The variations between the two teachers are significant, emphasizing the highly contextualized and personal nature of change for teachers.
The importance of pedagogical content knowledge in assessment for learning practices: a case‐study of a whole‐school approach
Authors: Jones Alister , Moreland Judy
Published: September 2005

Eastern Heights Primary School's involvement with research on assessment for learning began in 1998 with a focus on technology education as a new learning area. The initial research outcomes highlighted the impact that teachers' pedagogical content knowledge has on classroom and school practices in assessment for learning. In the subsequent years, enhancing teachers' planning, teaching and assessment knowledge and practices were key foci, as were developing teachers' understandings of subject ideas and how these might be translated to best fit their students. Teachers' formative interactions and summative assessment practices became focused on encouraging and supporting student engagement with key subject ideas in order to move student learning forward. For effective learning to occur, it was crucial for teachers to have conversations with students around these ideas. The impact of the intervention programme on teachers' assessment for learning practices and student learning was so significant that changes were made to classroom practices at the wider school level in technology, and were also incorporated effectively into science programmes and other curriculum areas. This article describes why the research and intervention programmes undertaken with a few teachers impacted positively on a school‐wide basis. The school culture, the positive research outcomes and the nature of the research process contributed to school‐wide changes in assessment for learning practices. This long‐term research programme provides insights into how enhanced assessment for learning practices at the individual teacher level might expand to a school‐wide level.
Is Perioperative Hypothermia a Risk Factor for Post‐CesareanInfection?
Authors: Edwards Rodney K. , Madani Kaivou , Duff Patrick
Published: September 2005

Objective: To determine whether hypothermia during Cesarean delivery is a risk factor for postoperative
infection.

Methods: An historical cohort investigation was conducted on all women delivered by Cesarean at our center
during 2001. Initial recovery‐room temperature, taken via the oral or axillary route, was used as a surrogate
for intraoperative temperature. Adding 0.5 °Cto axillary temperatures generated oral temperature equivalents.
Women with chorioamnionitis were excluded, as were those with an initial recovery‐room temperature that
exceeded 37.9 °C or was recorded more than 20 minutes after the end of surgery. Prophylactic antibiotics
(cefazolin, 1 g) were given during Cesarean delivery.

Results: A total of 42 women (7.6%) were diagnosed with postoperative infections. Infections included
endometritis (n= 25), wound abscess (n = 7), wound cellulitis (n = 7) and urinary tract infection (UTI) (n = 4).
No cases of septic pelvic thrombophlebitis or pelvic abscess occurred. One woman had both endometritis and a
UTI. Mean temperatures were higher, rather than lower, for women who subsequently had postoperative
infections compared with those who did not (36.4 ± 0.8 °Cvs. 35.9 ± 0.7 °C; p < 0.001). Mean temperatures
for the various postoperative infections were as follows: endometritis, 36.5 ± 0.8 °C (p < 0.001 vs. uninfected
group); wound abscess 36.0 ± 0.8 °C (p = 0.63); wound cellulitis, 36.3 ± 0.6 °C (p = 0.14); UTI, 36.7 ± 0.9 °C
(p = 0.04).

Conclusions: Women who develop post‐Cesarean infections have higher initial recovery‐room temperatures
than those who do not develop such infections. This suggests the presence of subclinical infection at the time
of Cesarean. Evaluating whether intraoperative warming has any role during Cesarean delivery requires a
randomized clinical trial.
Inhibition of Vaginal Lactobacilli by a Bacteriocin‐Like InhibitorProduced by Enterococcus faecium 62‐6: Potential Significancefor Bacterial Vaginosis
Authors: Kelly Maureen C. , Mequio Michael J. , Pybus Vivien
Published: September 2005

Objective: Bacterial vaginosis (BV) is characterized by a shift in vaginal tract ecology, which includes a decrease
in the concentration and/or prevalence of facultative lactobacilli. Currently, mechanisms which could account
for the disappearance of lactobacilli are not well understood. The objective of this study was to determine whether
vaginal streptococci/enterococci can produce bacteriocin‐like inhibitors antagonistic to vaginal lactobacilli.

Methods: Seventy strains of vaginal streptococci or enterococci were tested for antagonistic activities against
vaginal lactobacilli using the deferred antagonism technique.

Results: One strain, Enterococcus faecium 62‐6, which strongly inhibited growth of lactobacilli was selected for
further characterization. The spectrum of inhibitory activity of strain 62‐6 included Gram‐positive organisms
from the vaginal environment, although native lactobacilli from the same host were resistant to inhibitor action.
Following growth inMRSbroth the strain 62‐6 inhibitor was shown to be heat‐ (100℃, 30 minutes), cold‐ (4℃, less
than 114 days) and pH‐ (4–7) stable. The sensitivity of inhibitor‐containing supernatants to pepsin and
α‐chymotrypsin suggested an essential proteinaceous component. The inhibitor was sensitive to lipase but resistant
to lysozyme. Dialysis of inhibitor‐containing culture supernatants suggested a molecular mass greater than
12 000 Da. All physicochemical properties were consistent with its classification as a bacteriocin‐like inhibitor.
Kinetic assays demonstrated a sharp onset of inhibitor production coinciding with a concentration of 62‐6 of
107 cfu/ml, suggesting that production may be regulated by quorum sensing.

Conclusions: These results may have clinical significance as a novel mechanism to account for the decline of vaginal
Lactobacillus populations and contribute to both the establishment and recurrence of BV.
Detection of Candida Species in Vaginal Samples in a Clinical Laboratory Setting
Authors: Trama Jason P. , Adelson Martin E. , Raphaelli Israel , Stemmer Shlomo M. , Mordechai Eli
Published: September 2005

Objective. To present the detection rates of Candida species in vaginal samples from patients visiting physicians.

Methods. The presence of C. albicans, C. glabrata, C. parapsilosis and C. tropicalis in 3978 vaginal swabs from patients in six US states was detected by PCR amplification.

Results. Candida DNA was detected in 33.1% of the population studied. Of the 1316 positive samples, 80.2% contained C. albicans, 14.3% contained C. glabrata, 5.9% contained C. parapsilosis and 8.0% contained C. tropicalis. Comparing samples by patients′ state of residence revealed an association with the detection of C. glabrata (p =0.029). Comparing samples by
patients′ age revealed a decrease in the overall detection of Candida (p < 0.001) and C. albicans (p < 0.001), concomitant with an increase in the detection of C. glabrata (p < 0.001) and C. parapsilosis (p = 0.025).

Conclusions. These results provide geographic‐ and age‐specific data on four Candida species associated with vaginitis.
Epidemiological Study in Okinawa, Japan, of Human Papillomavirus Infection of the Uterine Cervix
Authors: Maehama Toshiyuki
Published: September 2005

Objective. To investigate the prevalence and type distribution of human papillomavirus (HPV) in women with normal cervical cytology and with cervical intraepithelial neoplasia I to III(CIN) or carcinoma of the cervix in Okinawa, Japan.

Methods. We investigated HPV DNA in 4,078 subjects with cytologically normal cervices, 279 subjects with CIN, and 383 subjects with cervical cancer in Okinawa Prefecture in Japan. The presence of HPV DNA was also compared among
generations. HPV DNA was both detected and typed using polymerase chain reaction (PCR).

Results. The HPV positivity rate was 10.6% in the subjects who were normal on cervical cytodiagnosis. In each generation, the positivity rate was 20.4% in women aged 20–29 years and approximately 10% in the groups aged 30–89 years, with significant differences among generations. The HPV positivity rates in CIN and cervical cancer groups were 76.0% and 86.2%, respectively, with no significant difference between the groups. The positivity rate of HPV 16 decreased with age in both CIN and cervical cancer groups.

Conclusion. Among non‐cancer subjects, HPV infection rates were almost 20% in women aged 20–29 years and 10% in women aged 30–89 years. HPV16‐positive CIN or carcinoma were more prevalent in the younger women, suggesting that HPV16‐infected epithelial cells rapidly progress to cervical cancer.
Seroprevalence of Bordetella pertussis Antibodies in Mothers and their Newborn Infants
Authors: Gonik Bernard , Puder Karoline S. , Gonik Nathan , Kruger Michael
Published: September 2005

Background. Pertussis is a highly communicable, vaccine‐preventable respiratory disease. Although the largest number of reported cases is among young infants, the most rapidly increasing incidence in the USA is in adolescents and young adults. Importantly, adult family members are the likely major reservoir, infecting susceptible infants before completion of childhood vaccination. We studied maternal‐neonatal paired blood samples for the presence of pertussis‐related antibodies
to assess level of immunity and passive transplacental antibody passage.

Methods. Unselected maternal‐neonatal cord blood samples were collected from 101 term deliveries in a single urban uninsured/underinsured hospital setting. Sera were analyzed for anti‐pertussis toxin (PT), filamentous hemagglutinin (FHA)
and pertactin (PRN) IgG antibodies by enzyme‐linked immunosorbent assay (ELISA). Antibody titers were calculated using reference line methodology. Antibody values were log‐transformed to establish geometric mean titers (GMT) for analysis. Student′s t‐test, Mann–Whitney, Pearson correlation and chi square were used for statistical comparisons as appropriate.

Results. Mean (SD) maternal age, gestational age and birth weight were 26.8 (6.8) years, 38.9 (1.4) weeks and 3239 (501) g, respectively. Detectable maternal levels of anti‐PT, FHA and PRN were found in 34.7%, 95.0% and 80.2%, respectively. Maternal GMT (SD) for PT, FHA and PRN were 4.4 (2.6), 26.6 (3.1) and 12.3 (2.9), respectively. There was no significant relationship between PT, FHA or PRN detection or antibody GMT and maternal age. Maternal anti‐PT, FHA and PRN
were highly correlated with neonatal cord blood values.

Conclusion. Despite previous childhood immunization, a large number of parous women have low or undetectable pertussis‐related antibody levels, suggesting susceptibility to infection. Even with efficient transplacental passage of these
antibodies, neonates similarly have limited measurable protection as detected by cord blood sampling. These data support the need for adolescent or adult vaccination against Bordetella pertussis. Healthcare providers and their clients should be aware
of the risk for infant infection via family member transmission.
Effects of ETA Receptor Antagonism on Proinflammatory Gene Expression and Microcirculation Following Hepatic Ischemia/Reperfusion
Authors: UHLMANN DIRK , GÄBEL GABOR , LUDWIG STEFAN , ARMANN BARBARA , HESS JOCHEN , PIETSCH UTA‐CAROLIN , TANNAPFEL ANDREA , FIEDLER MARTIN , KRATZSCH JUERGEN , HASS JOHANN , WITZIGMANN HELMUT
Published: September 2005

Background: The objective of this study was to investigate the effect of a specific endothelinA receptor antagonist (ETA‐RA) on mRNA expression of genes encoding vasoactive mediators and proinflammatory cytokines and on the microhemodynamics (assessed by measurement of laser Doppler flow and tissue blood gases) following complete vascular exclusion of the porcine liver.

Study design: Sixteen adult German landrace pigs were subjected to 120 min of warm hepatic ischemia by total vascular exclusion. To avoid portal congestion, a passive porto‐femoro/jugular bypass was implanted. The animals were divided into 2 groups: the control group received saline solution and the therapy group was given the selective ETA‐RA BSF 208075. Hepatic microcirculation was evaluated by pO2 and pCO2 measurement with the Paratrend sensor and by laser Doppler flow measurement. Liver tissue samples were collected 1 h after reperfusion and quantitative mRNA expression for prepro‐ET‐1, pro‐IL‐1β, pro‐IL‐6, pro‐TNF‐α, eNOS was analyzed using the TaqMan system. Additionally, immunohistochemical analysis using a semiquantitative score for ET‐1 was performed. Postischemic liver damage was monitored by measurement of liver enzymes and assessed by histological analysis using a semiquantitative scoring classification.

Results: Partial oxygen pressure in the hepatic tissue and laser Doppler flow were significantly improved in the therapy group. One hour after reperfusion, quantitative RT‐PCR revealed significantly lower expression of prepro‐ET‐1, eNOS, pro‐TNF‐α, and pro‐IL‐6 in the therapy group compared to controls. Immunohistochemical analysis demonstrated significantly reduced ET‐1 immunostaining after therapy. Furthermore, blockade of ETA receptors prevents tissue damage.

Conclusions: Treatment with the selective ETA‐RA BSF 208075 has protective effects on microcirculation after 120 min liver ischemia and reperfusion. The authors were able to show that ETA‐RA not only affects the expression of vasoactive genes, but also decreases gene expression of proinflammatory cytokines such as TNF‐α and IL‐6.
Lipopolysaccharide: A p38 MAPK‐Dependent Disrupter of Neutrophil Chemotaxis
Authors: KHAN ADIL I. , HEIT BRYAN , ANDONEGUI GRACIELA , COLARUSSO PINA , KUBES PAUL
Published: September 2005

In sepsis, and in models of sepsis including endotoxemia, impaired neutrophil recruitment and chemotaxis have been reported. The inability of the endotoxemic neutrophil to chemotax could be attributed to the fact that intracellular signaling via LPS overrides signals from endogenous chemokines or, alternatively, that sequestration of neutrophils into lungs prevents access to peripheral tissues. Using both in vitro and in vivo chemotaxis assays the authors established that neutrophils from healthy mice chemotaxed in vivo toward MIP‐2, whereas endotoxemic neutrophils did not. Since LPS activates leukocytes via the p38 MAPK pathway, SKF86002, a p38 MAPK inhibitor, was given to endotoxemic animals. SKF86002 significantly reversed the LPS‐induced impairment in emigration of endotoxic neutrophils in response to MIP‐2. Neutrophil chemotaxis in vitro was also impaired by LPS, via a p38 MAPK‐dependent pathway, and this impairment could be reversed via p38 MAPK inhibition. Although neutrophil numbers dropped in the circulation and trapped in lungs during endotoxemia, SKF86002 did not reverse these parameters, demonstrating that p38 MAPK inhibition did not release trapped neutrophils from the lungs. In conclusion, the data suggest that the impaired emigration and chemotaxis of neutrophils at peripheral sites during endotoxemia may be partially due to a p38 MAPK‐mediated inhibition of neutrophil responses to endogenous chemokines.
LPS Inhibits Endothelin‐1‐Mediated eNOS Translocation to the Cell Membrane in Sinusoidal Endothelial Cells
Authors: MERKEL SANDRA M. , KAMOUN WALID , KARAA AMEL , KORNESZCZUK KATARZYNA , SCHRUM LAURA W. , CLEMENS MARK G.
Published: September 2005

Objective: The objectives of this study were to develop a model for studying endothelin‐1‐mediated eNOS regulation in cultured sinusoidal endothelial cells and determine the effect of endothelin‐1 and endotoxin (LPS) on eNOS localization.

Methods: Changes in caveolin‐1, calmodulin, and eNOS expression were determined by western blot and densitometric analysis. Endothelin receptor expression and localization and the intracellular localization of eNOS and caveolin‐1 were assessed by confocal microscopy.

Results: Sinusoidal endothelial cells expressed caveolin‐1 and calmodulin, and expression was altered in cultured and passaged cells. eNOS expression decreased significantly in 24‐h cultured cells, with expression dropping below the level of detection in passaged cells. Both endothelin A and endothelin B receptors were expressed on the cell surface after 24 h in culture. In 24‐h cultured cells, caveolin‐1 was localized in the perinuclear region and cell membrane, while eNOS was predominantly localized in the perinuclear region, where it co‐localized with caveolin‐1. Endothelin‐1 stimulated eNOS translocation to the cell membrane. Pretreatment with LPS markedly inhibited the endothelin‐1‐mediated eNOS translocation.

Conclusions: These studies demonstrate an LPS‐mediated uncoupling of endothelin receptor activation and eNOS translocation. This functional uncoupling may, in part, account for the hyperconstrictive effects of endothelin‐1 during inflammatory conditions.
Applications of Emerging Technologies in Toxicology and Safety Assessment
Authors: Reynolds Vincent L.
Published: September 2005

Standardized protocols for repeat-dose toxicity studies have many advantages, including experimental redundancy (i.e., the use of more than a single experimental approach in the assessment of a given organ or tissue) and evaluation of numerous tissues to ensure detection of adverse effects, as well as the ability to develop robust historical control databases. However, traditional toxicology study designs may not adequately address questions of a mechanistic nature that might provide insights on whether particular toxicology findings in animals are relevant to humans. Such questions may be more readily answered using mechanism-based technologies such as toxicogenomics, proteomics, or metabonomics. Such newer approaches may permit, for example, the detailed assessment of the transcriptional profile differences that distinguish a normal healthy tissue from a diseased or damaged tissue. The resultant information can be used to elucidate the mechanism and accompanying biomarkers for toxicity, as well as to identify potential molecular targets for therapeutic intervention by drugs. Despite their conceptual appeal, the use of emerging technologies in toxicology is accompanied by significant challenges. For example, toxicogenomic assessments entail the generation of large amounts of bioinformatic data that must be interpretable for their full value to be realized. Also, none of these newer approaches have established uniformly acceptable quality standards (e.g., such as may be defined in inter-laboratory validation studies) or a track record of achievement in guiding regulatory decisions. As a result, newer techniques, at least for the present, are more likely to be focused on mechanistic questions with compounds of known toxicity (either positive indicator compounds or “failed” pharmaceutical candidates). If the use of a nascent or emerging technology is contemplated for mechanistic studies of pharmaceutical compounds later in preregistration development, it will be crucial for toxicologists to engage their regulatory colleagues in discussions at an early stage to ensure closer alignment in thought. The successful use of emerging technologies to address toxicology issues will require a close partnership between industry and regulatory agencies.
Understanding Biology Through Bioinformatics
Authors: Rajpal Deepak K.
Published: September 2005

During the journey from the discovery of DNA to be the source of genetic information and elucidation of double-helical nature of DNA molecule to the assembly of human genome sequence and there after, bioinformatics has become an integral part of modern biology. Bioinformatics relies substantially on significant contributions made by scientists in various fields, including but not limited to, linguistics, biology, mathematics, computer science, and statistics. There is an ever increasing amount of data to elucidate toxic mechanisms and/or adverse effects of xenobiotics in the field of toxicogenomics. Annotation in combination with various bioinformatics analytical tools can play a crucial role in the understanding of genes and proteins, and can potentially help draw meaningful conclusions from various data sources. This article attempts to present a simple overview of bioinformatics, and an effort is made to discuss annotation.
An In Vivo Bioassay for Detecting Antiandrogens Using Humanized Transgenic Mice Coexpressing the Tetracycline-Controlled Transactivator and Human CYP1B1 Gene
Authors: Hwang Dae Y. , Cho Jung S. , Oh Jae H. , Shim Sun B. , Jee Seung W. , Lee Su H. , Seo Su J. , Kang Hyun G. , Sheen Yhun Y. , Lee Seok H. , Kim Yong K.
Published: September 2005

The typical strategy used in analysis of antiandrogens involves the morphological changes of a marker in castrated rats Hershberger assay for the prostate, seminal vesicle, levator ani plus bulbocavernosus muscles (LABC), Cowper’s gland, and glans penis. However, there are disadvantages to this approach, such as the time required, and the results may not correspond to those in actual human exposure. To evaluate its ability for detecting antiandrogens, in vivo the dose effect of di-(2-ethylhexyl) phthalate (DEHP) and time effect of five antiandrogens, DEHP, di-n-butyl phthalate (DBP), diethyl phthalate (DEP), linuron (3-(4-dichlorophenyl)-methoxy-1-methylurea), and 2,4′-DDE (1,1-dichloro-2-( p-chlorophenyl)-2-( o-chlorophenyl)ethylene), were investigated using humanized transgenic mice coexpressing tetracycline-controlled transactivator (tTA) and the human cytochrome P450 (CYP) enzyme CYP1B1 (hCYP1B1). Adult transgenic males were treated with each of the five antiandrogens, and their tTA-driven hCYP1B1 expressions analyzed by real-time polymerase chain reaction (PCR) and/or Western blot and for O-debenzylation activity. Herein, the treatments of adult males with the five antiandrogens were shown to affect the increased levels of tTA-driven hCYP1B1 expression in both dose-dependent and repeated experiments. Thus, this novel in vivo bioassay, using humanized transgenic mice, is useful for measuring antiandrogens, and is a means to a more relevant bioas-say relating to actual human exposure.
Use of Genotoxicity Data to Support Clinical Trials or Positive Genetox Findings on a Candidate Pharmaceutical or Impurity …. Now What?
Authors: Jacobson-Kram David , Jacobs Abigail
Published: September 2005

Results from carcinogenicity studies are generally not available for drugs until the time of approval. Many people, including healthy volunteers are often exposed to pharmacologically active doses of the drug before carcinogenicity results are available. The Food and Drug Administration (FDA) Center for Drug Evaluation and Research uses results of genetic toxicology studies as a surrogate for carcinogenicity during the drug development phase (clinical trials). A number of issues are considered in deciding whether drugs that give positive results in genetic toxicology studies can be given to subjects in clinical trials. These relate to the drug indication, the target population, duration of treatment, and importance of the drug. In general, single-dose clinical studies are permitted regardless of the genetox results. In situations where a genetic toxicology assay showed a positive result, some review divisions have asked sponsors to perform a Syrian hamster embryo (SHE) cell transformation assay or a p53 carcinogenicity study prior to allowing repeat-dose clinical trials to proceed. This paper discusses alternatives to SHE cell and p53 assays when faced with a positive result in a genetic toxicology assay. In addition, this paper discusses factors to consider when setting limits for genotoxic impurities in drug substances and products.
Differential Effects of Mixtures of Cholesterol Oxidation Products on Bovine Aortic Endothelial Cells and Human Monocytic U937 Cells
Authors: O’Sullivan Aaron J. , O’Callaghan Yvonne C. , O’Brien Nora M.
Published: September 2005

Cholesterol oxidation products or oxysterols are of interest due to their hypothesized role in the development of atherosclerosis. The objective of the present study was to assess the cytotoxic effects of mixtures of oxysterols: 25-hydroxycholesterol (25-OHC), 7 β-hydroxycholesterol (7 β-OHC), and cholesterol-5 β,6 β-epoxide ( β-epox) on two cell types associated with the atherosclerotic process, bovine aortic endothelial (BAE) cells and human monocytic U937 cells. Cells were exposed to 25-OHC, 7 β-OHC, or β-epox, or equimolar mixtures (30 μM) of 25-OHC and 7 β-OHC, 25-OHC and β-epox, or 7 β-OHC and β-epox for 48 h. Cell viability was assessed using the fluorescein diacetate/ethidium bromide (FDA/ EtBr) assay and nuclear morphology following staining with Hoechst 33342. 25-OHC was the least toxic of the oxysterols and did not induce apoptosis in either cell line. Both 7 β-OHC and β-epox treatments were cytotoxic and induced apoptosis in the cells. Cotreatment with 25-OHC did not alter the toxicity of 7 β-OHC and β-epox in U937 cells but did decrease the percentage apoptotic cell death. In contrast, in the BAE cells cotreatment with 25-OHC had a slight protective effect on 7 β-OHC and β-epox–induced toxicities and a marked decrease in apoptotic cell death. The 7 β-OHC and β-epox mixture induced a significant increase in apoptotic cell death in U937 cells but decreased this mode of cell death in the BAE cells. The effects of oxysterols on glutathione levels also differed between the cells with changes noted in U937 and not in BAE cells. Results demonstrate interactive effects when oxysterols are studied as mixtures rather than single compounds in vitro.
Cutaneous Angiosarcoma of the Scalp: A Case Report of Sustained Complete Response Following Liposomal Doxorubicin and Radiation Therapy
Authors: Holloway Caroline L. , Turner A. Robert , Dundas George S.
Published: September 2005

Cutaneous angiosarcomas of the head and neck are aggressive cancers with a mean overall survival of 30 months. We add to the literature a case report of a 65‐year‐old man with a large, >10 cm, unresectable, angiosarcoma of the scalp who was treated with two cycles of liposomal doxorubicin (Caelyx ®) followed by electron beam radiation therapy (30 Gy in 10 fractions over 2 weeks) who has sustained a complete response with a 4‐year follow‐up. The dose and fractionation of
the radiation therapy in this case was palliative and was not expected to give lasting local control of this lesion. It is therefore possible that either the genetic profile of the tumour conferred radiosensitivity or that the radiation therapy induced a recall phenomenon of the liposomal doxorubicin.
Clear Cell Chondrosarcoma in Association With Niemann‐Pick Disease
Authors: Srikanth K. N. , Kulkarni A. , Davies A. M. , Sumathi V. P. , Grimer R. J.
Published: September 2005

Purpose: The purpose of this case report is to bring to light this unusual combination of two rare diseases, namely
Neimann‐Pick disease Type B and clear cell chondrosarcoma occurring in the same patient. This has not previously been
reported in the world literature.

Subject: Niemann‐Pick disease (NPD) is a rare autosomal recessive inborn error of metabolism. Type B NPD is even rarer.
It is a lysosomal storage disorder affecting children and adolescents often causing death in early childhood, although in
milder form patients may survive up to adulthood, like our patient. Clear cell chondrosarcoma is a very rare type of
chondrosarcoma affecting the epiphyseo‐metaphyseal region of long bones. We present a patient suffering from a milder
form of Neimann Pick disease who developed a clear cell chondrosarcoma. We investigated to find if there was likely to be
any relationship between these two events.

Results: NPD type B is caused by a three‐base deletion in chromosome 11. Chondrosarcoma and multiple exostoses occur
due to loss of tumour suppressor gene EXT 2 from centromeric region on chromosome 11, though it is difficult to establish
the link between the two, as the two together have not yet been reported in the literature. NPD may present diagnostic
difficulties when it occurs with chondrosarcoma.

Discussion: We conclude that the two diseases have not been reported together in the world literature and there is some
evidence to show that chromosome 11 is central to both diseases. More research is needed to see if one leads to the other.
Dermatofibrosarcoma Protuberans Arising in a Decorative Tattoo
Authors: Baker Paul A. , O′Dowd Geraldine J. , Khan Irfan U.
Published: September 2005

Dermatofibrosarcoma protuberans (DFSP) is an uncommon, locally aggressive cutaneous tumour of intermediate grade
malignancy. A number of reports have linked local trauma of varying aetiology with the later development of DFSP.
In addition, a variety of skin disorders and, in rare cases, cutaneous tumours, have been described in association with
decorative tattoos. This is often associated with delayed diagnosis. We report the first case of DFSP arising in a tattoo and
discuss the available evidence for a causative link between DFSP and local trauma of this nature.
Operation Notes Illustrated With Digital Images
Authors: Haywood R. M. , Heaton M. , McCulloch T. A. , Sokal M. , Perks A. G. B.
Published: September 2005

We would like to report on our experience of illustrating our operation notes with pre‐, per‐ and post‐operative digital
images.
How effective is therapy for childhood stuttering? Dissecting and reinterpreting the evidence in light of spontaneous recovery rates
Authors: Saltuklaroglu Tim , Kalinowski Joseph
Published: September 2005

Background: Similar positive results (e.g. immediate decreases in stuttering frequency and a 60–80% recovery rate from stuttering) have been reported for numerous therapeutic protocols for treating childhood stuttering, many of which have been diametrically opposite in their orientations and implementations. For example, Johnson advocated indirect treatments that simply advocated refraining from drawing any negative attention to childhood disfluencies as persistent and chronic stuttering was thought to progress via negative parental reactions to normal disfluencies. In contrast, direct interventionists sought immediately to eliminate stuttered speech patterns by training ‘corrected’ speech models that usually involved some form of prolonged speech. However, reports from speech and language therapists around North Carolina, USA, suggest much lower recovery rates in the children they treat (i.e. 13.9% over a median therapeutic period of 3 years, which to the present authors is an indicator of therapeutic inefficiency and ineffectiveness).

Aims: The discrepancy between these recovery rates calls for a re‐examination of the efficacy of stuttering therapy for children, especially in light of recent statements from some therapies suggesting that therapy might be curative in nature.

Main contribution: Spontaneous and complete recovery (removing all overt and covert markers of the pathology) occurs in 60–80% of all children who display incipient stuttering behaviours. As such, it appears that many claims of therapeutic success in children who stutter are confounded by the possibility of spontaneous recovery during the testing and intervention period. Simply put, it is impossible to discriminate between recovery that would occur naturally over time, and what may have been simply accelerated via therapy. Based on stable prevalence rates and the data in the present paper, it is suggested that therapy does little to boost recovery rates from incipient stuttering. Therapy can provide ‘inhibitory’ symptomatic relief with varying degrees of success with respect to decreasing stuttering severity and the need for continued therapy. However, it must be made clear that curing stuttering is not a likely outcome of therapy, although successful management can decrease the severity of the problem. It is argued that all forms of stuttering inhibition, including those at work during spontaneous recovery, are all mediated by the degree of mirror neuron engagement in the brain.

Conclusions: It is proposed that in children who stutter, the best source of relief from stuttering is in the effective and efficient engagement of mirror neurons via methods that best replicate choral speech. In order to induce natural sounding, fluent speech, it is suggested that one uses primarily derivations of choral speech such as altered auditory feedback. Motoric techniques might also be used synergistically to provide supplementary sources of mirror neuron engagement.
WELFARE STATE POLICIES AND THE DEVELOPMENT OF CARE ARRANGEMENTS
Authors: Pfau-Effinger Birgit
Published: September 2005

In many European welfare states in the last decades, the state provision of social care services has increased, in part even in spite of retrenchment policies in other areas of state welfare policies. Informal childcare has, however, survived everywhere in Europe, until today a substantial proportion of care is provided informally in the family. The degree to which informal care has been formalised, and the social rights and state provision in relation to formal and informal care, differ substantially in comparison of European societies. In comparative social policy analyses, the explanatory framework is often based on a kind of evolutionary approach. According to this argument, the degree of formalisation of informal care is determined by the degree to which welfare states support gender equality and the labour market integration of women. It is argued here that such explanatory framework is not sufficient. It is not taken into consideration that informal care has itself been modernised: and that the promotion of informal family care does not necessarily contradict ideas about gender equality. Within Western Europe, with respect to the role of informal care, at least two different development paths can be distinguished. Differences with respect to the underlying family values contribute considerably to the explanation of such differences. The quality of social rights in relation to informal care, on the other hand, varies according to the welfare regime and the underlying welfare values.
‘The threat of the Other’: Using mixed quantitative and qualitative methods to elucidate racial and cultural dynamics in the counselling process
Authors: Tuckwell Gill
Published: September 2005

This paper examines the use of mixed quantitative and qualitative methods in the study of racial and cultural dynamics in the counselling process. The approach is illustrated by the author's own research which combined quantitative survey instruments with a blend of qualitative methods. Emphasis is given to complex racial and cultural phenomena arising from the qualitative methods of data collection and data analysis, particularly the pervasive experience of ‘threat of the Other’. These phenomena were seen to permeate the counselling interactions both explicitly and implicitly. The emerging racial dynamics are discussed with reference to theoretical concepts which stress the interrelationship between intrapsychic development and sociopolitical issues. The effectiveness of employing pluralistic methods in this field of enquiry is also evaluated.
It takes two to tango: Research and practice as an amazing dance
Authors: Martin Peter
Published: September 2005

This paper offers an appreciative critique of Kim Etherington's recent book, Narrative Approaches to Working with Adult Male Survivors of Male Child Sexual Abuse. I discuss the issues raised in the book with reference to one of my current clients. Etherington does not produce new substantive theory: the power of this work is in the narrative. Her important contribution lies in the reflexivity with which she encounters her material. The use of critical reflexivity challenges the subject/object dichotomy inherent in much positivistic research, and presents a much‐needed approach to process that is congruent with the lived experience of counselling. I would suggest that research is more likely to succeed in informing practice if the material is open to personal interpretation by the reader/therapist. Further, I would claim that the activity of using research creatively is itself a heuristic process: useful learning is most likely to occur if the dialogic relationship with the client and therapist is mirrored in the relationship between the therapist and the research text.
Is touch a valid therapeutic intervention? Early returns from a qualitative study of therapists' views
Authors: Tune David
Published: September 2005

Findings are reported from six semi‐structured interviews with experienced psychotherapists, focusing on the reasons for using touch and the sort of touch used. They suggest that there is a distinction being made by therapists between ‘social space’ and ‘therapeutic space’, and a different view of touch taken if it is judged by the therapist to be ‘out of the therapeutic environment’. Whether or not touch was initiated by the therapist or the client would also appear to influence its further discussion by the therapist, either in processing it with the client or in supervision. What also emerged from the interviews was the finding that an exploration of touch in supervision was unusual. The implications for practice, supervision and training are discussed as areas for further exploration in the main survey, which will be conducted in the second year of the research.
Inviting passage to new discourse: ‘Alive moments’ and their spiritual significance
Authors: Fuller Margaret , Strong Tom
Published: September 2005

Some social constructionists assert that therapeutic change occurs when clients' meanings for problems and solutions shift from those found in resource‐impoverished discourses to those affording resourceful and preferred possibilities. Referred to as ‘positioning theory’, our research examined this assertion by inviting clients and therapists to speak of a significant, but ambiguous, experience in unfamiliar discourse: spiritual discourse. Clients were asked to review videotapes of their sessions, selecting moments that felt most ‘alive’ to them for discussions with the researcher, including inquiries as to whether ‘alive’ moments held any spiritual significance. The outcomes are portrayed as a ‘poetic collaboration’ between the researcher, clients and therapists — while clients' and therapists' reported experiences for changes in discourse and meaning are highlighted. Implications regarding sensitivities required when co‐constructing meanings for ambiguous but significant experiences in therapy are discussed. Possibilities for more research examining poetic practices and processes in therapy are also considered in terms of positioning theory.
An administratively created reality: Some problems with the use of self‐report questionnaire measures of adjustment in counselling/psychotherapy outcome research
Authors: McLeod John
Published: September 2005

Outcome research in counselling and psychotherapy has come to rely heavily on the use of self‐report questionnaire measures of anxiety, depression and general symptomatology. The validity of these measures in the context of psychotherapy research has, in general, been taken for granted. This paper proposes that, despite the success of self‐report questionnaires in personality research and personnel selection, there are significant problems involved in the use of these methods in research into therapeutic change. Specifically, three areas of difficulty are reviewed. First, questionnaires are completed in a social setting that itself changes as a result of therapy. Second, the experience of psychotherapy changes the way that clients make sense of questionnaire items (the ‘response shift’ phenomenon). Third, the conceptualisation of the person implicit in questionnaire design is not compatible with the conceptualisation of persons espoused by most contemporary therapeutic approaches. It is argued that the continuing popularity of self‐report questionnaires can be understood in terms of Kurt Danziger's model of the social construction of psychological knowledge.
The client as a self‐aware agent in counselling and psychotherapy
Authors: Rennie David L.
Published: September 2005

Clients' recollections of their experiences of counselling and psychotherapy were stimulated using the technique of Interpersonal Process Recall. Their reports were analysed in terms of the grounded theory method of qualitative research. The analysis resulted in the interpretation that the core category of their experience is clients' reflexivity, or self‐awareness and agency flowing from it and returning to it. The focus of this paper is directed at the client's reflexivity in response to the counsellor's operations. Its organizing theme is that how clients respond to counsellors' operations depends on what clients desire and what they feel they can say safely. Particular desires arise from an over‐arching desire either to enter into or avoid inner experience. Moreover, the relation with self is influenced by the relationship with the therapist. This complexity makes it difficult to predict responses to non‐directive and directive counsellor performances alike. Vignettes selected from the participants' reports illustrate the theme. Implications for the practice of counselling and psychotherapy are discussed.
The significance of psycho‐peristalsis and tears within the therapeutic relationship
Authors: Sussman Susan
Published: September 2005

This paper represents a heuristic study of the significance of involuntary, intuitive gut responses (psycho‐peristalsis) and tears within the therapeutic relationship. Autobiographical material and qualitative data were gathered from case‐notes and semi‐structured interviews with four client/co‐participants. Data on occurrences of psycho‐peristalsis and tears were collected from 92 clients seen within a six‐year period. Eleven elements of a ‘general constitutional structure of experience’ were identified. A central finding of the study concerns the gut's apparent ability to ‘pick up’, at an unconscious level, significant material that might otherwise have been overlooked. The research suggests some possible clues to the process of unconscious communication and healing, and adds an interesting psychological dimension to recent findings in the fields of neuroscience and cell biology which amount to the discovery of a ‘second brain’ in the walls of the small intestine. These phenomena are examined in the light of theoretical debates in counselling and psychotherapy.