bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessing the bioequivalence of analogues of endogenous substances (‘endogenous drugs’): considerations to optimize study design
Authors: Dissanayake Sanjeeva
Published: November 2009

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• The complexities of assessing the bioequivalence of endogenous drugs are recognised.

• The FDA have published guidelines regarding the evaluation of levothyroxine and potassium chloride bioequivalence, whilst other authors have documented specific strategies to counter biases inherent in biostudies of endogenous drugs.

• A consolidated consideration of valid methods to optimise the design of such studies is however lacking.

WHAT THIS STUDY ADDS

• This paper is to the author's knowledge the first summarising various key approaches used to assess the bioequivalence of endogenous drugs, and to propose a series of recommendations for studies in this field.

BACKGROUND Assessment of the bioequivalence of generic versions of certain reference drugs is complicated by the presence of endogenous levels of said compounds which cannot be distinguished from externally derived compound levels following drug administration. If unaccounted for, the presence of endogenous compound biases towards equivalence in bioequivalence studies of these drugs. Bioequivalence assessments may be complicated further as disposition of the exogenous analogue can be subject to various endogenous processes resulting in nonlinear pharmacokinetics. To overcome these inherent biases a number of different strategies have been employed.

AIMS To critically review methods used to overcome confounding biases in bioequivalence studies of ‘endogenous’ drugs.

METHODS A literature search of the EMBASE and PubMed databases was performed.

RESULTS The following strategies were identified: ablation/modulation of baseline endogenous substance levels; recruitment of ‘substance‐deficient’ populations; restriction of dietary intake of the relevant substance; standardization of conditions with the potential to affect relevant homeostatic mechanisms; correction for baseline substance levels; and administration of supra‐therapeutic drug doses.

CONCLUSIONS On the basis of this review key study design concepts, intended to optimize the design of future bioequivalence studies of these so‐called ‘endogenous drugs’, are described. The dual stable isotope method, which could be used in a specific context, is also discussed.
TdT interacting factor 1 enhances TdT ubiquitylation through recruitment of BPOZ‐2 into nucleus from cytoplasm
Authors: Hayano Takahide , Koiwai Kotaro , Ishii Hisataka , Maezawa So , Kouda Kousuke , Motoyama Takuro , Kubota Takashi , Koiwai Osamu
Published: November 2009

We isolated human cDNA clone encoding Bood POZ containing gene type 2 (BPOZ‐2) as a gene with a product that binds to TdT interacting factor 1 (TdIF1) using a yeast two‐hybrid system. BPOZ‐2 is an adaptor for E3 ligase CUL3 and participates in developmental processes. The binding between BPOZ‐2 and TdIF1 was confirmed by GST pull‐down and immunoprecipitation assays using specific antibodies against BPOZ‐2 and TdIF1 in vitro and in vivo. Although when BPOZ‐2 solely was expressed in COS7 cells, BPOZ‐2 was observed mainly within the cytoplasm, co‐transfection of pEGFP‐BPOZ‐2 and pDsRed‐TdIF1 into COS7 cells resulted in co‐localization of EGFP‐BPOZ‐2 and DsRed‐TdIF1 within the nucleus. TdIF1 may recruit BPOZ‐2 into the nucleus from the cytoplasm by directly binding to BPOZ‐2. BPOZ‐2 enhanced TdT ubiquitylation when TdIF1 was expressed together with BPOZ‐2 in 293T cells, strongly suggesting that the recruitment of BPOZ‐2 into the nucleus from the cytoplasm is significant for the TdT ubiquitylation within the nucleus.
Transcriptional regulation of human G2A in monocytes/ macrophages: involvement of c/EBPs, Runx and Pu.1
Authors: Murakami Naoka , Hashidate Tomomi , Harayama Takeshi , Yokomizo Takehiko , Shimizu Takao , Nakamura Motonao
Published: November 2009

G2 accumulation (G2A) is a G‐protein coupled receptor, activated by several ligands and stimuli, such as lysophosphatidylcholine (LPC), extracellular low pH and oxidized phospholipids including 9‐ and 13‐hydroxyoctadecadienoic acid, and has been implicated in mediating inflammatory process under oxidative conditions. Recently, it was demonstrated that G2A in monocytes/macrophages plays critical roles in atherosclerosis deterioration, and therefore its transcriptional regulation in monocytes/macrophages is of great interest. Here, we first confirmed the expression of human G2A (hG2A) in lymph nodes, spleen and peripheral blood leukocytes, including monocytes. Thereafter, transcription start site (TSS) of hG2A was determined by 5′‐rapid amplification of cDNA ends analysis. In the course of the analysis, we found that two transcriptional variants, hG2A‐a and ‐b, are produced by alternative splicing, resulting in the production of N‐terminal different hG2A proteins with similar sensitivity to low pH and LPC. Using a monocytic cell line THP‐1 as a model, transcription of hG2A was precisely examined, and we demonstrated that it is dependent both on the chromatin structure around TSS, and on the binding of the transcription factors (c/EBPα and β, Runx1 and Pu.1) to their cis‐elements, located at the core promoter just upstream of TSS.
Insertion and management of percutaneous veno‐venous bypass cannula for liver transplantation: a reference for transplant anesthesiologists
Authors: Sakai Tetsuro , Gligor Silviu , Diulus John , McAffee Richard , Wallis Marsh J. , Planinsic Raymond M.
Published: November 2009

Sakai T, Gligor S, Diulus J, McAffee R, Marsh JW, Planinsic RM. Insertion and management of percutaneous veno‐venous bypass cannula for liver transplantation: a reference for transplant anesthesiologists. Clin Transplant 2009 DOI: 10.1111/j.1399‐0012.2009.01145.x © 2009 John Wiley & Sons A/S.

Abstract:  Surgical advances using the retrohepatic caval preservation technique in liver transplantation (LT) has significantly decreased the need for veno‐venous bypass (VVB). However, VVB still remains a viable adjunct of LT. The venous return cannula has traditionally been inserted using a cut‐down technique via the axillary vein, but this technique carries significant risks for lymphorrhea, infection, or nerve damage. Since 2001, our institution has routinely used VVB in adult LT surgery. Percutaneous insertion of an internal jugular venous return cannula is performed by the attending anesthesiologist. The aim of this report is to describe the method of insertion and management of a percutaneous veno‐venous return cannula in the internal jugular vein during LT. In‐depth detail as well as video clips will provide a reference for LT centers wishing to apply this method in their practice.
Filamentous fungi found on foundress queens of leaf‐cutting ants (Hymenoptera: Formicidae)
Authors: Rodrigues A. , Silva A. , Bacci Jr M. , Forti L. C. , Pagnocca F. C.
Published: November 2009

Queens of the leaf‐cutting ant species Atta laevigata and Atta capiguara were collected soon after their mating flight and maintained in the laboratory until death. Ant corpses showing signs of contamination by insect pathogenic fungi were selected for fungal identification. Filamentous fungi such as Beauveria bassiana and Paecilomyces lilacinus actively sporulated in the ant’s corpses. This is the first report of the latter fungus on reproductives of leaf‐cutting ants. The fact that queens may acquire filamentous fungi including saprophytic and potential insect pathogens after their mating event is especially interesting regarding the impacts of such microbes on the establishment of a new nest.
Emergency department performance at a small rural hospital: An independent in‐depth review
Authors: Tescher Paul , Chen Tony Mengxi
Published: November 2009

Objectives:  This study aims to provide a retrospective review of the recent performance of the emergency department of Cobram District Hospital, a small rural hospital located on the border of Victoria and New South Wales.

Design:  Retrospective review.

Setting:  Small rural accident and emergency department.

Intervention:  All available data collected from the emergency department from the previous three financial years (July 2005 to June 2008) were compiled onto a computerised spreadsheet and analysed by two independent investigators.

Main outcome measures:  Key performance indicators, including time for patient to be seen by a doctor and frequency of patient presentations to the emergency department.

Results:  Cobram District Hospital has fewer than 5000 patients presenting to the emergency department each year. 12 p.m. to 12 a.m. accounts for 69% of all presentations, with three notable time periods that experience most presentations. Life‐threatening emergencies represented <3% of all presentations to the emergency department. Patients in triage categories 1–3 did not met Australasian triage scale (ATS)‐suggested time for maximum waiting timing, while categories 4 and 5 well exceeded ATS standards.

Conclusion:  The small size and lack of dedicated emergency department staff place restrictions on the ability of an unfunded rural hospital to match the performance of major metropolitan emergency departments. ATS guidelines should be revised to improve clarity and reflect the different performance capabilities between metropolitan and rural centres.
Mapping oncology services in regional and rural Australia
Authors: Underhill Craig , Bartel Rebecca , Goldstein David , Snodgrass Helen , Begbie Stephen , Yates Patsy , White Kate , Jong Kathy , Grogan Paul
Published: November 2009

Objective:  To map clinical oncology services in regional and rural Australia.

Design and setting:  A self‐administered survey was sent to 161 regional hospitals administering chemotherapy (RHAC) in Australia. RHAC were categorised by state, Hospital Peer Group and the Australian Standard Geographical Classification (ASGC) Remoteness Areas classification.

Main outcome measure(s):  Survey data provided percentage and aggregate figures about availability of medical, radiation and surgical oncologists, chemotherapy nurses, breast cancer nurses, palliative care physicians and allied health professionals according to remoteness and state. Chemotherapy prescribing practices, adherence to occupational health and safety guidelines and availability of multidisciplinary clinics were also explored.

Results:  A 98% survey completion rate was achieved. Significant deficiencies in service provision were identified in RHAC. Only 21% of RHAC reported a resident medical oncology service, 7% had a radiation oncology unit, and 6% had a resident surgical oncologist. Only 24% of RHAC reported a dedicated palliative care specialist and 39% identified a dedicated oncology counselling service. Other issues included administration of chemotherapy by nurses outside a recognised facility or by nurses without recognised oncology training, limited availability of funded breast care nurses and lack of multidisciplinary clinics.

Conclusion:  Survey data highlight marked cancer service deficiencies in rural and regional Australia. It is not unreasonable to conclude that these deficiencies might contribute to poorer outcomes for cancer patients living in these areas. The results suggest the need for short‐ and long‐term measures to improve access to best‐practice cancer services for patients living in regional, rural and remote areas of Australia.
Clinical manifestations and survival of patients with hepatocellular carcinoma and cardiac metastasis
Authors: Liu Yu‐Chun , Ho Yi‐Lwun , Huang Guan‐Tarn , Chen Ding‐Shinn , Sheu Jin‐Chuan , Chen Chien‐Hung
Published: November 2009

Background and Aim:  Antemortem diagnosis of hepatocellular carcinoma (HCC) with cardiac metastasis is uncommon. To clarify the clinical manifestation and survival of HCC patients with cardiac metastases, we initiated the present study.

Methods:  We retrospectively analyzed 48 HCC patients with metastases into cardiac cavity diagnosed antemortem. The baseline clinical characteristics, echocardiogram, treatment modality and the outcome data were collected.

Results:  The most common symptoms of cardiac metastasis included asymptomatic in 19 cases (39.5%), bilateral lower leg edema in 18 cases (37.5%) and exertional dyspnea in 15 cases (31.3%). The median and mean survival times from the time of diagnosis of cardiac metastasis were 102 days and 161 days, respectively. Compared with another cohort of 48 patients with age‐, gender‐, and stage‐matched HCC patients without cardiac metastasis, the median survival in the cardiac metastasis group was similar to the control group (68 days) (P = 0.67). The cause of death was HCC in 29, hepatic failure in seven, multiple organ failure in four, gastrointestinal bleeding in three, sepsis in two, pulmonary embolism in one, respiratory failure in one, and acute myocardial infarction in one.

Conclusions:  Hepatocellular carcinoma patients with cardiac metastases were in the advanced stages. These patients had limited survival from the diagnosis of cardiac metastases. The most common cause of death was related to HCC per se or the underlying liver disease. Only a few patients expired because of cardiac metastases.
Do we need an ‘in‐house’ neutralization assay for confirmation of hepatitis B surface antigen? Answers from a tertiary care hospital in India
Authors: Fletcher Gnanadurai J , Gnanamony Manu , David Joel , Ismail Ashrafali M , Subramani Thenmozhi , Abraham Priya
Published: November 2009

Background and Aims:  Hepatitis B surface antigen (HBsAg) is an important serological marker for diagnosis of hepatitis B virus (HBV) infection. Commercial kits for detection of HBsAg emphasize confirmation by neutralization assays. In this study, we have standardized an ‘in‐house’ neutralization test for HBsAg confirmation.

Methods:  Among 6684 HBsAg‐positive samples, 615 were subjected to an ‘in‐house’ HBsAg neutralization test (NT). Of these, 91 (100%) high‐reactive samples (optical density [OD] 1.000–3.000) and 286 (93%) of 289 low‐reactive samples (OD < 1.000) were neutralized, and 235 (100%) grey‐zone reactive samples were ‘in‐house’ NT negative. Eighty‐four samples of varying reactivities that were tested by the ‘in‐house’ NT were compared with a commercial NT (AxSYM, Abbott).

Results:  The ‘in‐house’ NT showed an excellent agreement (κ = 0.83, P < 0.001) with the commercial confirmatory assay. The sensitivity, specificity, positive and negative predictive values were 90%, 94%, 96% and 87%, respectively.

Conclusion:  The enzyme immunoassay‐based ‘in‐house’ HBsAg neutralization assay is a feasible alternative to the commercial HBsAg confirmatory assay. This technique is easily adaptable, cost‐effective and reliable for the confirmation of HBsAg in a low resource setting, enhancing the overall quality of HBsAg screening.
The Prostate Cancer gene 3 assay: indications for use in clinical practice
Authors: Schilling David , De Reijke Theo , Tombal Bertrand , De La Taille Alexandre , Hennenlotter Jörg , Stenzl Arnulf
Published: November 2009

The Prostate CAncer gene 3 (PCA3) assay is a novel tool that might aid in the diagnosis of prostate cancer and that might indicate the significance of the disease. In this review we discuss five clinical cases in which the PCA3 assay can be considered, based on scientific evidence and key patient cases from real‐life clinical practice. The PCA3 assay might be used to guide biopsy decisions in: (i) Men with an elevated serum total prostate specific antigen (tPSA) level and one or more previous negative biopsies; (ii) men with a normal tPSA level and a family history of prostate cancer; (iii) men with an elevated tPSA level (2.5–10 ng/mL) and no previous biopsy; (iv) men with an elevated tPSA level and a concomitant urinary condition. In addition, in men diagnosed with prostate cancer, the PCA3 assay could aid in the decision of whether active therapy is needed or active surveillance is appropriate.
Other biomarkers for detecting prostate cancer
Authors: Nogueira Lucas , Corradi Renato , Eastham James A.
Published: November 2009

Prostate‐specific antigen (PSA) has been used for detecting prostate cancer since 1994. Although it is the best cancer biomarker available, PSA is not perfect. It lacks both the sensitivity and specificity to accurately detect the presence of prostate cancer. None of the PSA thresholds currently in use consistently identify patients with prostate cancer and exclude patients without cancer. Novel approaches to improve our ability to detect prostate cancer and predict the course of the disease are needed. Additional methods for detecting prostate cancer have been evaluated. Despite the discovery of many new biomarkers, only a few have shown some clinical value. These markers include human kallikrein 2, urokinase‐type plasminogen activator receptor, prostate‐specific membrane antigen, early prostate cancer antigen, PCA3, α‐methylacyl‐CoA racemase and glutathione S‐transferase π hypermethylation. We review the reports on biomarkers for prostate cancer detection, and their possible role in the clinical practice.
High‐grade prostate cancer and finasteride
Authors: Lebdai Souhil , Bigot Pierre , Azzouzi Abdel‐Rahmène
Published: November 2009

Prostate cancer is the most common neoplasm in men. Encouraging results are emerging in prostate cancer risk reduction with 5α‐reductase (5AR) inhibitors. The Prostate Cancer Prevention Trial (PCPT) showed that prostate cancer risk is reduced by finasteride. However, there was an increase in the incidence of high‐grade prostate cancer with finasteride treatment vs placebo. The number of cases should have increased during the study in the finasteride group with the length of exposure to the drug. But, in fact the ratio between the two groups was lower during the fourth year. This therefore favours the hypothesis of a bias in the results. There are many hypotheses to explain the increase in the prevalence of high‐grade tumours with finasteride therapy. The effects of finasteride on prostate volume rather than on the tumour’s morphology and a selective inhibition of low‐grade cancers may have contributed to the increase the number of high‐grade cancers with finasteride in the PCPT. Despite the current trend to explain the increase of high‐grade tumours with finasteride therapy by a detection bias, other studies underline the potential role of low levels of dihydrotestosterone in the genesis of high‐grade tumours. In May 2008, a re‐analysis of the PCPT results showed a significant decrease of 30% in the overall risk of prostate cancer in the finasteride group vs the placebo group, but it also found a statistically non‐significant and less important increase of the prevalence of high‐grade cancers in the finasteride group. However, the 5AR isoenzyme type 1 is present at higher rates than type 2 in high‐grade cancers. Thus, finasteride is probably not the ideal drug to prevent high‐grade cancers.
Understanding of Logical Necessity: Developmental Antecedents and Cognitive Consequences
Authors: Morris Anne K. , Sloutsky Vladimir M.
Published: November 2009

Does abstract reasoning develop naturally, and does instruction contribute to its development? In an attempt to answer these questions, this article specifically focuses on effects of prolonged instruction on the development of abstract deductive reasoning and, more specifically, on the development of understanding of logical necessity. It was hypothesized that instructional emphasis on the metalevel of deduction within a knowledge domain can amplify the development of deductive reasoning both within and across this domain. The article presents 2 studies that examine the development of understanding of logical necessity in algebraic and verbal deductive reasoning. In the first study, algebraic and verbal reasoning tasks were administered to 450 younger and older adolescents selected across different instructional settings in England and in Russia. In the second study, algebraic and verbal reasoning tasks were administered to 287 Russian younger and older adolescents selected across different instructional settings. The results support the hypothesis, indicating that prolonged instruction with an emphasis on the metalevel of algebraic deduction contributes to the development of understanding of logical necessity in both algebraic and verbal deductive reasoning. Findings also suggest that many adolescents do not develop an understanding of logical necessity naturally.
TRANS‐WORLD: DEBATING THE PLACE AND BORDERS OF PLACES IN THE AGE OF TRANSNATIONALISM
Authors: ERNSTE HUIB , VAN HOUTUM HENK , ZOOMERS ANNELIES
Published: November 2009

In this introductory contribution to this special issue of TESG, we want to question the usual way of conceptualising places and borders in the debate about transnationalism. We argue, that in studies of transnationalism, on the one hand the idea of nation‐states as spatial containers is overcome, but on the other hand also reproduces the same spatial containers. Instead we suggest the use of the term ‘trans‐world’ to avoid any connotation suggesting spatial containers. In this framework, places and borders are instead seen as multi‐dimensional and dynamic concepts which can be applied to almost any kind of relationships transgressing and reconfiguring borders and places at all scales. The papers which follow this introduction show how in particular situations and contexts, these transgressing and reconfiguring activities can be conceptualised in very different ways.
POWER OF BORDERS AND SPATIALITY OF TRANSNATIONALISM: A STUDY OF CHINESE‐OPERATED TOURISM BUSINESSES IN EUROPE
Authors: LEUNG MAGGI W.H.
Published: November 2009

This paper examines the spatiality of transnationalism and meanings of borders as displayed in the tourism business sector operated by Chinese migrants in Europe. Drawing upon empirical research conducted from 1999 to 2002 and from 2006 to 2007, it will illustrate how Chinese migrants practise transnationalism and transculturality in their entrepreneurial activities. Instead of serving simply as a bridge between their two home economies, migrants engaged in the tourism sector are active and innovative agents in crossing and redrawing the borders of different geo‐cultural spheres they are embedded in, producing modified tourism landscapes that suit the desire of their compatriot travellers. An examination of the spatiality of their business networks also suggests that transnationalism and diaspora studies should go beyond focusing only on ties between the sending and receiving societies. Furthermore, an analysis of the interactions among members of this business community from different places will exemplify the power of borders in the Chinese diaspora.
THEOLOGY, EVOLUTION, AND THE HUMAN MIND: HOW MUCH CAN BIOLOGY EXPLAIN?
Authors: Haught John F.
Published: November 2009

Evolutionary biology contributes much to our present understanding of life, and it promises also to deepen our understanding of human intelligence, ethics, and even religion. For some scientific thinkers, however, Darwin's science seems so impressive that it now supplants theology altogether by providing the ultimate explanation of all manifestations of life, not only biologically but also metaphysically. By focusing on human intelligence as an emergent aspect of nature this essay examines the question of whether theology can still have an explanatory role to play alongside biology in attempts to understand mind.
Prognostic factors for cure following treatment of onychomycosis
Authors: Sigurgeirsson B
Published: November 2009

Objective  To examine if host baseline factors and week 24 mycology results are associated with mycological and clinical cure in patients with onychomycosis treated with oral terbinafine.

Design  Open pilot study to determine prognostic factors in the treatment of onychomycosis.

Setting  Outpatient dermatology clinic.

Patients  A total of 199 patients from the Icelandic arm of a trial comparing continuous terbinafine with intermittent terbinafine in onychomycosis were recruited for additional observation.

Main outcome measures  Mycological, clinical and complete cure of the target toenail 72 weeks after treatment was initiated.

Results  Patients with matrix involvement or slow nail growth were less likely to reach mycological, clinical and complete cure. Lateral involvement affected complete and mycological cure rates negatively. Patients with a dermatophytoma were less likely to reach mycological cure. Patients with a history of prior infection, men and older patients were less likely to reach clinical cure. Positive culture at 24 weeks affected mycological and clinical cure at 72 weeks negatively.

Limitations  Only patients treated with terbinafine were considered.

Conclusions  Several host‐related factors at baseline and positive culture at 24 weeks had negative effects on cure of onychomycosis 72 weeks after treatment was initiated. This finding merits a large study on prognostic outcome factors in onychomycosis.
No association between nickel allergy and reporting cosmetic dermatitis from mascara or eye shadow: a cross‐sectional general population study
Authors: Thyssen JP , Linneberg A , Menné T , Nielsen NH , Johansen JD
Published: November 2009

Background  In theory, all pigmented make‐up products may contain metal allergens including nickel. Eyelid dermatitis has previously been observed among nickel allergic dermatitis patients following exposure to nickel containing mascara and eye shadow. However, an association between nickel eyelid dermatitis and nickel in make‐up products remains controversial.

Objective  This cross‐sectional patch test study investigated whether the frequency of self‐reported cosmetic dermatitis from mascara or eye shadow use was higher among nickel allergic Danish women than women without nickel allergy.

Methods  In 2006, a total of 1843 18–69 year old women completed a postal questionnaire including questions on cosmetic dermatitis and were patch tested with nickel sulphate. Data were analysed by logistic regression analyses and associations were expressed as odds ratios (ORs) with 95% confidence intervals (CIs).

Results  The prevalence of nickel allergy was similar among women who reported cosmetic dermatitis from eye shadow or mascara and among women who did not report such symptoms. Cosmetic dermatitis was positively associated with self‐reported atopic dermatitis and age.

Conclusion  Overall, no association between having nickel allergy and reporting cosmetic dermatitis from mascara or eye shadow use was found in the general population. This does not exclude a causal relationship in selected cases.
ORIGINAL ARTICLE: Teaching methods and curriculum models used in Finland in the education of students diagnosed with having severe/profound intellectual disabilities
Authors: Kontu Elina K. , Pirttimaa Raija A.
Published: November 2009

Accessible summary

To find out what models for educational planning and which methods are currently in use with severely intellectually disabled students in Finland.

Teaching praxis is based on small child’s normal psychological development and behavioral analytic tradition.

Ten years ago children diagnosed as having severe/profound intellectual disabilities were allowed to attend and study in Finnish comprehensive schools. The nationwide intensive developmental work for creating a curriculum for this group of students began earlier, in the 1980s.The aim of this study was to discover what types of models of curriculums and which teaching methods are currently in use. The reason for this was the lack of recent research in this area, and the current strong emphasis on developing quality education for this group which continues to be focused away from segregated systems. The findings of this survey indicated that the most widely used principle for planning teaching directed at this group of students is based on normal psychological development of a young child. Of all teaching methods used the most popular ones were categorized as sensory and environmental enrichment and stimulation. Another large group of teaching methods was discovered to be based on behavior analysis.
Fitness Among Individuals with Early Childhood Deafness: Studies in Alumni Families from Gallaudet University
Authors: Blanton Susan H. , Nance Walter E. , Norris Virginia W. , Welch Katherine O. , Burt Amber , Pandya Arti , Arnos Kathleen S.
Published: November 2009

The genetic fitness of an individual is influenced by their phenotype, genotype and family and social structure of the population in which they live. It is likely that the fitness of deaf individuals was quite low in the Western European population during the Middle Ages. The establishment of residential schools for deaf individuals nearly 400 years ago resulted in relaxed genetic selection against deaf individuals which contributed to the improved fitness of deaf individuals in recent times. As part of a study of deaf probands from Gallaudet University, we collected pedigree data, including the mating type and the number and hearing status of the children of 686 deaf adults and 602 of their hearing siblings. Most of these individuals had an onset of severe to profound hearing loss by early childhood. Marital rates of deaf adults were similar to their hearing siblings (0.83 vs. 0.85). Among married individuals, the fertility of deaf individuals is lower than their hearing siblings (2.06 vs. 2.26, p = 0.005). The fitness of deaf individuals was reduced (p = 0.002). Analysis of fertility rates after stratification by mating type reveals that matings between two deaf individuals produced more children (2.11) than matings of a deaf and hearing individual (1.85), suggesting that fertility among deaf individuals is influenced by multiple factors.
Art and the theatre of mind and body: how contemporary arts practice is re‐framing the anatomo‐clinical theatre
Authors: Ingham Karen
Published: November 2009

The correspondences and disparities between how artists and anatomists view the body have historically been a source of creative collaboration, but how is this imaginative interdisciplinarity sustained and expressed in a contemporary context? In this review I suggest that contemporary artists engaging with the body, and the corresponding biomedical and architectural spaces where the body is investigated, are engendering innovative and challenging artworks that stimulate new relationships between art and anatomy. Citing a number of examples from key artists and referencing some of my own practice‐based research, I posit that creative cross‐fertilization provokes a discourse between mediated public perceptions of disease, death and the disposal of morbid remains, and the contemporary reality of biomedical practice. This is a dialogue that is complex, rich and diverse, and ultimately rewarding for both art and anatomy.
ON THE WHITE AND COLOURED MARBLES OF THE ROMAN TOWN OF CUICUL (DJEMILA, ALGERIA)
Authors: ANTONELLI F. , LAZZARINI L. , CANCELLIERE S. , DESSANDIER D.
Published: November 2009

This paper reports the results of an archaeometric study of the local and imported marbles found in the Roman town of Cuicul (now Djemila, Algeria), a research project funded by the Sixth Framework Programme of the European Union. Of the few imported coloured lithotypes that have been found, four are of Greek origin and one was imported from Asia Minor. In addition, two other classical Roman coloured stones found on the site are probably of local North African origin (most likely one from Numidia and one from Algeria). With regard to the grey and white marbles employed in the statuary and architecture, petrographic study in thin section and the δ13C and δ18O isotopic data emphasize the frequent use of the local fine‐grained lithotype from Filfila (Skikda) together with imported Greek lithotypes (i.e., Pentelic marble, the dolomitic variety of Thasian marble, and Parian marble from Lakkoi) as well as different varieties of the so‐called ‘greco scritto’, whose provenance in some cases still remains uncertain. In fact, the petrographic and geochemical features of the marbles do not always match those known for the classical ‘greco scritto’ from the quarry of Cap de Garde, near Annaba (Algeria).
Brief Motivational Interviewing for DWI Recidivists Who Abuse Alcohol and Are Not Participating in DWI Intervention: A Randomized Controlled Trial
Authors: Brown Thomas G. , Dongier Maurice , Ouimet Marie Claude , Tremblay Jacques , Chanut Florence , Legault Lucie , Ng Ying Kin Ng Mien Kwong
Published: November 2009

Background:  Driving while impaired (DWI) recidivists with unresolved alcohol use problems pose an ongoing risk for traffic safety. Following conviction, many do not participate in mandated alcohol evaluation and intervention programs, or continue to drink problematically after being relicensed. This study investigated if, in DWI recidivists with alcohol problems and not currently involved in DWI intervention, Brief Motivational Interviewing (BMI) produced greater reductions in risky drinking at 6‐ and 12‐month follow‐up compared to an information‐advice control condition. Additional analyses explored whether BMI was associated with greater readiness to change, subsequent substance abuse treatment service utilization, and satisfaction compared to the control condition.

Methods:  Male and female recidivists with drinking problems and not currently engaged in DWI intervention were recruited, evaluated, and then randomly assigned to receive 1 of 2 manualized interventions: 30‐minute BMI session or information‐advice. Participants, interviewers, researchers, and statisticians were blind to assignment. Outcomes were changed in: percent of risky drinking days (i.e., ≥3 standard drinks/d for males; ≥2 for females) in the previous 6 months derived from the Timeline Followback, biomarkers of alcohol abuse (GGT, AST, ALT, MCV) by blood assay, and alcohol abuse‐related behaviors using the MMPI‐Mac scale. Data from the Readiness to Change Questionnaire, a substance abuse service utilization questionnaire, and the Client Satisfaction Scale were also collected.

Results:  Analyses revealed significant declines in risky drinking with both interventions. BMI (n = 92) resulted in a 25% reduction in risky drinking days at 12‐month follow‐up, which compared to the control intervention (n = 92) represented a significant decline from 6‐month levels. Exposure to BMI also produced significantly greater improvement at 6‐month follow‐up in a biomarker of alcohol abuse and a behavioral measure related to recidivism risk. Exploration of readiness to change, substance abuse service utilization, and satisfaction with intervention indicated a perception of BMI being more useful in coping with problems.

Conclusions:  Brief MI approaches warrant further implementation and effectiveness research as an opportunistic DWI intervention strategy to reduce risks associated with alcohol use outside of clinical and DWI relicensing settings.
Brain Microstructure Is Related to Math Ability in Children With Fetal Alcohol Spectrum Disorder
Authors: Lebel Catherine , Rasmussen Carmen , Wyper Katy , Andrew Gail , Beaulieu Christian
Published: November 2009

Background:  Children with fetal alcohol spectrum disorder (FASD) often demonstrate a variety of cognitive deficits, but mathematical ability seems to be particularly affected by prenatal alcohol exposure. Parietal brain regions have been implicated in both functional and structural studies of mathematical ability in healthy individuals, but little is known about the brain structure underlying mathematical deficits in children with FASD. The goal of this study was to use diffusion tensor imaging (DTI) to investigate the relationship between mathematical skill and brain white matter structure in children with FASD.

Methods:  Twenty‐one children aged 5 to 13 years diagnosed with FASD underwent DTI on a 1.5‐T MRI scanner and cognitive assessments including the Woodcock‐Johnson Quantitative Concepts test. Voxel‐based analysis was conducted by normalizing subject images to a template and correlating fractional anisotropy (FA) values across the brain white matter with age‐standardized math scores.

Results:  Voxel‐based analysis revealed 4 clusters with significant correlations between FA and math scores: 2 positively‐correlated clusters in the left parietal region, 1 positively‐correlated cluster in the left cerebellum, and 1 negatively‐correlated cluster in the bilateral brainstem. Diffusion tractography identified the specific white matter tracts passing through these clusters, namely the left superior longitudinal fasciculus, left corticospinal tract and body of the corpus callosum, middle cerebellar peduncle, and bilateral projection fibers including the anterior and posterior limbs of the internal capsule.

Conclusions:  These results identify 4 key regions related to mathematical ability and provide a link between brain microstructure and cognitive skills in children with FASD. Given previous findings in typically developing children and those with other abnormal conditions, our results highlight the consistent importance of the left parietal area for mathematical tasks across various populations, and also demonstrate other regions that may be specific to mathematical processing in children with FASD.
IMMUNOHEMATOLOGY: Generation of histo‐blood group B transferase by replacing the N‐acetyl‐d‐galactosamine recognition domain of human A transferase with the galactose‐recognition domain of evolutionarily related murine α1,3‐galactosyltransferase
Authors: Yamamoto Fumiichiro , Yamamoto Miyako , Blancher Antoine
Published: November 2009

BACKGROUND: The α1,3‐galactosyl epitope (α1‐3Gal epitope), a major xenotransplant antigen, is synthesized by α1,3‐galactosyltransferase (α1‐3Gal transferase), which is evolutionarily related to the histo‐blood group A/B transferases.

STUDY DESIGN AND METHODS: We constructed structural chimeras between the human type A and murine α1‐3Gal transferases and examined their activity and specificity.

RESULTS: In many instances, a total loss of transferase activity was observed. Certain areas could be exchanged, with a potential diminishing of activity. With a few constructs, changes in acceptor substrate specificity were suspected. Unexpectedly, a functional conversion from A to B transferase activity was observed after replacing the short sequence of human A transferase with the corresponding sequence from murine α1‐3Gal transferase.

CONCLUSION: Because these two paralogous enzymes differ in 16 positions of the 38 amino acid residues in the replaced region, our finding may suggest that despite separate evolution and diversified acceptors, these glycosyltransferases still share the three‐dimensional domain structure that is responsible for their sugar specificity, arguing against the functional requirement of a strong purifying selection playing a role in the evolution of the ABO family of genes.
Paired crossover study of two plateletpheresis systems concerning platelet product quality and donor comfort
Authors: Flesch Brigitte K. , Adamzik Ilse , Steppat Dagmar , Miller Joanna , Carstensen Liane , Schapke Martin , Davey Jason
Published: November 2009

BACKGROUND: Two plateletpheresis cell separator systems were compared in a paired crossover study with respect to the product quality, the number of platelet (PLT) units per donation, and the donor comfort.

STUDY DESIGN AND METHODS: Forty‐four female and 47 male donors were distributed to three body weight groups. Double PLT units with 6 × 1011 PLTs were collected from three Fenwal Amicus Crescendo (AC) and three CaridianBCT Trima Accel (TA) machines. Each donor made one donation on each randomly assigned system and answered a questionnaire on the subjective donor comfort. The answers were scored from 5 (best) to 1 (worst).

RESULTS: Based on 182 donations, with 91 donations on AC and TA separators each, 179 runs resulted in double PLT units and three (2×AC, 1×TA) in single units. The white blood cell counts were below 1 × 106 in all but eight therapeutic units (8×TA; mean, 1.98 × 106). The mean PLT yield (AC 6.00 × 1011, TA 5.98 × 1011), the collection rate, and the PLT extraction coefficient did not significantly differ between the two devices. Differences of the donor comfort over all groups were only observed for the loudness of the instrument (4.63 AC vs. 4.24 TA, p < 0.001) and the subjective impression of the run time (4.24 AC vs. 4.48 TA, p < 0.05). Male donors greater than 88 kg preferred the TA instruments concerning the impact of the needle, run time, overall experience (p < 0.01 each), and willingness to donate on the same instrument again (p < 0.05).

CONCLUSIONS: Only minor differences were observed despite the fact that the AC separators are run with two needles and the TA with one needle.
Experimental investigation on the local scour characteristics around groynes using a hydraulic model
Authors: Kang Joongu , Yeo Hongkoo , Kim Sungjung , Ji Un
Published: November 2009

Scour holes resulting from the installation of a groyne are considered to perform the environmental function of providing a habitat and a haven for various aquatic organisms during floods, hence, the need for studies on the scour area and its volume near a groyne beyond the scope of past discussions on their stability. In this study, hydraulic experiments were conducted in fixed and movable beds to examine the flow pattern, bed change and scour depth and hole around a groyne. The results of the fixed‐bed experiment indicated an effect on the flow change in the main channels and recirculation zones following the installation of a groyne. Changes in tip velocity and flow angle as the scour factors around a groyne were quantitatively compared as well. Through the movable‐bed experiment, the scour‐hole shape, scour area, scour depth and volume of bed change were examined and compared.
Intestinal Dipeptidases: Dipeptidase Activity in the Mucosa of the Gastrointestinal Tract of the Adult Human
Authors: Lindberg Tor
Published: November 2009

Five dipeptidase activities in the mucosa of the gastrointestinal tract from 25 patients between 22 and 80 years of age were determined. The influence of pH and bivalent metal ions on the various activities was studied. Equally low activities were found in the stomach and the large intestine. In the small intestine, low activities were found in the mucosa of the proximal duodenum, whereas that of the jejunum and ileum contained high activities. The results have been discussed in relation to our previous informa‐ tion about the intestinal dipeptidases.
Effect of Respiratory Acidosis on Vasoconstrictor Effects of Directly and Indirectly Acting Sympathomimetic Amines in Cats
Authors: Bygdeman S.
Published: November 2009

The peripheral vasoconstrictor effects of bilateral carotid occlusion were compared with those of the directacting sympathomimetic drugs noradrenaline and dopamine and of the indirectly acting drugs tyramine and phenylethylamine on the perfused hindleg of cats during normal ventilation and respiratory acidosis. It was observed that while ventilation with 15 % C02 decreased the vasoconstrictor response to injected noradrenaline and dopamine by 60 per cent effects of tyramine, phenylethylamine and carotid occlusion remained unchanged. The results suggest that hypercarbia does not interfere with the action of the endogenously liberated transmitter in the synaptic region but blocks the effect of injected noradrenaline and dopamine on receptors situated outside this region.
Excitatory Synapses on Hippocampal Apical Dendrites Activated by Entorhinal Stimulation
Authors: Andersen P. , Holmqvist B. , Voorhoeve P. E.
Published: November 2009

In rabbits anesthetized with urethane‐chloralose, the responses produced in the field CA1 by stimulation of the entorhinal area were studied with intracellular and extracellular recording. The most important pathway involved was found to be the three‐synaptic path: Entorhinal area — dentate granule cells— CA3 pyramids— CA1 pyramids. This conclusion is based upon the following experimental data: The main CA1 activity occurred later than expected for a monosynaptic path, it was always secondary to dentate granule cell discharges, it disappeared after a section severing the Schaffer collaterals at the CA2/CA1 border, it showed longer latency the longer the recording electrode was placed from the fimbria. The final link in this three‐synaptic pathway is the Schaffer collaterals. Their synapses produce a large negative field potential at the level of the profuse branching of the apical dendrites. The negativity is most likely due to the inward current flowing across the activated excitatory synapses. Extracellular recording of the population spike, produced by the Schaffer collateral synaptic activity, showed the spike to be initiated in that part of the dendritic membrane which borders the territory of the Schaffer synapses. The spike was conducted towards the soma with a speed of about 0.4 m/sec. Intracellular recording from cat CA1 pyramids gave as a rule no sign of soma epolarization in spite of the appearance of synaptically initiated action potentials. The results indicate that synapses located to the dendrites can initiate a local spike that may be conducted towards the soma with a low conduction velocity, and probably, with a low safety factor.
The Effect of Vagal Stimulation on the Bronchial Tree in the Cat
Authors: Schwieler GÖSTA H.
Published: November 2009

A method is described whereby bronchial diameter changes can be recorded in artificially ventilated lungs. It is shown that the bronchi dilate during positive inflation. When the peripheral ends of the cut vagal nerves are stimulated in the cervical region, this dilatation decreases and the bronchi become stiff. It is concluded that this is an effect of bronchial smooth muscle contraction.

The results are confirmed in spontaneously ventilating animals by bronchography and measurements of dynamic compliance.
Selective and frequency dependent predation of aquatic mosquito predator Diplonychus indicus Venkatesan & Rao (Hemiptera: Belostomatidae) on immature stages of three mosquito species
Authors: SIVAGNANAME Narayanasamy
Published: November 2009

Frequency dependent mosquito larval size (II and IV instars) and species selection by the water bug Diplonychus indicus against three mosquito species Culex quinquefasciatus, Aedes aegypti and Anopheles stephensi was studied in the laboratory. The different frequencies used for each species selection were 20:30:50, 30:50:20, 50:20:30, 25:35:40, 35:40:25 and 40:25:35 of fourth instars of the respective three prey species. All nymphal water bugs (I–V instars) selected IV instar mosquito larvae and the mean proportion of late (larger) larvae eaten by the predator instars was significantly higher than the mean proportion of early (smaller) larvae eaten (F= 2.28; P < 0.001). In all six ratios used to determine the frequency dependent mosquito species selection, all the stages of the water bug selected Ae. aegypti over the other two species (F= 452.43; P < 0.001). The mean number of mosquito larvae eaten increased as its density increased based on various ratios of larvae offered. The study indicated that the predatory efficiency of D. indicus was high when Ae. aegypti was offered as prey, suggesting the utility of this mosquito predator in the control of dengue vectors.