bluuebunny/crossref_metadata_2025 huggingface dataset:
Alanine Metabolism in Isolated Human Kidney Tubules
Authors: Fouque Denis , Dugelay Sylvie , Martin Guy , Combet Jacqueline , Baverel Gabriel
Published: August 2004

To gain insight into the fate of alanine nitrogen and carbon taken up by the human kidney under certain conditions, isolated human kidney cortex tubules were incubated in Krebs‐Henseleit medium with l‐alanine as substrate. The tubules metabolized alanine at high rates and in a dose‐dependent manner. Most of the alanine nitrogen removed was recovered as ammonia and to a lesser extent as glutamate. Glucose, lactate and glutamate were also found to be significant products of alanine carbon metabolism. A simple mathematical model allowing one to calculate flux of alanine carbon through the various metabolic steps involved is proposed and applied to data obtained in experiments in which 5 mM [U‐14C]‐, [1‐14C]‐, [2‐14C]‐ and [3‐14C]alanine were used as substrates in parallel. About 40% of the alanine carbon removed was recovered as CO2 and oxidation of C1 of alanine accounted for most of the CO2 released from alanine. Calculations reveal that the ATP produced exceeded 3.2‐fold the ATP consumed in relation to alanine metabolism. It is concluded that, in human kidney, alanine may serve as an energy supplier and as a precursor of glucose and ammonia.
Dissociation of C‐fos Induction and Mitogen‐Activated‐Protein Kinase Activation from the Hepatocyte‐Growth‐Factor‐Induced Motility Response in Human Gastric Carcinoma Cells
Authors: Nagamine Kentaro , Shibamoto Sayumi , Takeuchi Kenji , Miyazawa Keiji , Kitamura Naomi , Chatani Yuji , Kohno Michiaki , Ito Fumiaki
Published: August 2004

The function of hepatocyte growth factor/scatter factor (HGF/SF) is to increase proliferation as well as to stimulate motility and disperse cell colonies of epithelial cells. In this study, we examined the motogenic and mitogenic responses of two human gastric carcinoma cell types, MKN7 and MKN74. Cell motility of both cell lines was markedly stimulated by HGF/SF. In contrast, HGF/SF stimulated cell growth of MKN74 cells, but did not stimulate growth of MKN7 cells. To address the cause of the difference in response of these cells, which may reflect some differences in signaling pathways downstream from the HGF/SF receptor, c‐Met, we investigated the induction of the proto‐oncogene c‐fos. The level of c‐fos mRNA increased and reached a maximum approximately 40 min after HGF/SF stimulation in MKN74 cells, and thereafter its level rapidly decreased. In contrast, the level of c‐fos expression was very low irrespective of the stimulation in MKN7 cells. c‐fos protein was transiently induced only in MKN74 cells 1 h after treatment with HGF/SF, and its levels subsequently decreased. We subsequently examined the activation of mitogen‐activated‐protein kinase, which is a major mediator in the signaling pathway leading to the stimulation of c‐fos transcription, after HGF/SF treatment in both cell lines. Mitogen‐activated‐protein kinase was markedly activated by this treatment in MKN74 cells, but was only slightly activated in MKN7 cells. These results suggest that although mitogen‐activated‐protein kinase activation and c‐fos induction play an essential role in the signaling pathway leading to cell growth, they are not required for the motility response induced by HGF/SF.
Comparative Study of the Sugar Chains of Alkaline Phosphatases Purified from Rat Liver and Rat AH–130 Hepatoma Cells
Authors: Endo Tamao , Fujiwara Toshiyuki , Ikehara Yukio , Kobata Akira
Published: August 2004

The N‐linked sugar chains of alkaline phosphatases, purified from rat AH‐130 hepatoma and from normal rat liver, were released quantitatively as oligosaccharides by hydrazinolysis and were labeled by reduction with NaB3H4. A comparative study of their structures revealed that the following structural differences are induced by hepatocyte carcinogenesis: complex–type tetraantennary sugar chains and hybrid–type sugar chains appear; outer‐chain moieties of the sugar chains of the hepatoma enzyme contain exclusively the Gal(β1‐4)GlcNAc groups (type 2 chains) but those of the normal enzyme contain other Gal(β1‐)GlcNAc groups and type 2 chains; and novel fucosylated high‐mannose‐type sugar chains are found in the oligosaccharides of the hepatoma enzyme.
The Caudal ‐Type Homeobox Protein Cdx‐2 Binds to the Colon Promoter of the Carbonic Anhydrase 1 Gene
Authors: Drummond Felicity , Sowden Jane , Morrison Katie , Edwards Yvonne H.
Published: August 2004

Carbonic anhydrase 1 (CA1) is an abundant enzyme in colon epithelia. In the gastrointestinal tract, carbonic anhydrase is vital for NaCl resorption, alkalinization of gut contents, and absorption of short‐chain fatty acids. The CA1 gene has two promoters, one of which is specifically active in colon epithelia and the other in erythroid cells. We are investigating the factors that regulate CA1 expression from the colon‐specific promoter. Colon‐specific deoxyribonuclease I hypersensitive sites (DHS) have been mapped close to the colon transcription initiation site (DHS6c) and in the upstream intron (DHS5c). Using electrophoretic mobility‐shift assays to search the 650‐bp region which contains DHS6c, we have identified sequences that bind a colon‐specific factor (COF1) and by deletion analysis we have narrowed down the COF1‐binding motif to a 17‐bp sequence. A comparison of this motif with a protein‐binding motif in the sucrase‐isomaltase gene promoter, competition assays, and antibody studies indicate that COF1 is identical to the homeodomain protein Cdx‐2. We propose that Cdx‐2 plays an important role in the intestine‐specific expression of CA1.
The Importance of Conserved Residues in Human Liver UDPglucose Pyrophosphorylase
Authors: Chang Hwan‐You , Peng Hwei‐Ling , Chao Yu Chyi , Duggleby Ronald G.
Published: August 2004

Comparison of the amino acid sequences of five eukaryotic UDPglucose pyrophosphorylases has identified a number of conserved residues that may be important for substrate binding or catalysis. Using the cloned cDNA for the human liver enzyme, we have investigated the role of several of these residues by site‐directed mutagenesis. Changing the single conserved cysteine (residue 123) to serine resulted in an active enzyme, as did mutating the single conserved histidine (residue 266) to arginine. The two conserved tryptophans were each altered to serine; W218S is active while W333S is not. In the latter case, the enzyme does not appear to fold correctly, and a similar result was obtained by mutation to lysine at one (residue 391) of the four conserved arginines. The other three arginines are not essential, as judged by the observation that R389H, R422Q and R445H are all active. The kinetic properties of each active mutant were investigated and in most cases were found to be similar to those of wild‐type. The most dramatic change is a sevenfold increase in the Km for magnesium pyrophosphate with C123S. Overall, none of these conserved residues appears to be essential for activity, although such a role cannot be ruled out for W333 and R391 where mutation resulted in defective folding.
Direct Activating Effects of Dexamethasone on Glycogen Metabolizing Enzymes in Primary Cultured Rat Hepatocytes
Authors: Baqué Susanna , Roca Àngela , Guinovart Joan J. , Gómez‐foix Anna M.
Published: August 2004

The direct effects of dexamethasone on glycogen synthase and phosphorylase and glycogen content have been investigated in primary cultured rat hepatocytes. Dexamethasone induced the transient translocation of glycogen synthase from the soluble to the 10000 ×g pelletable fraction and the activation of this enzyme, although more significant, longer‐standing activation was achieved in the pelletable fraction. Neither total glycogen synthase content nor glycogen synthase mRNA levels were modified. Dexamethasone also caused the sustained activation (up to 6 h) of glycogen phosphorylase, which was not accompanied by an increase in its mRNA level. Glycogen cell content and the incorporation of [14C] glucose into glycogen decreased after dexamethasone treatment. The data show that dexamethasone, unlike other glycogenolytic hormones, at concentrations of 10 nM or higher, stimulate hepatocyte glycogenolysis without inducing the inverse coupling of synthase and phosphorylase. The co‐existence of active forms of both glycogen synthase and phosphorylase promoted by dexamethasone leads to a situation that is analogous to that of the fasted liver.
A Regulatory Domain within the Virus‐Response Element of the Interferon α1 Gene Acts as a Transcriptional Repressor Sequence and Determinant of Cell‐Specific Gene Expression
Authors: Dent Carolyn L. , Gewert Dirk R.
Published: August 2004

Type‐I interferons are encoded by a multigene family, the major members of which are at least 13 IFN A subtypes and a single IFN B gene. IFNs A and B are induced in response to similar stimuli, such as virus infection and double‐stranded RNA, but in different cell types: the induction of IFN A is almost exclusively restricted to cells of lymphoid origin, while IFN B has been found to be induced in a variety of cell types including fibroblasts. The virus‐responsive enhancer element in the promoter region of IFN A family members is largely responsible for the differential expression of individual subtypes in responsive cells. In this paper we describe experiments which address the issue of the differential expression of IFN A and IFN B in different cell types. We show that IFN‐β is induced in a variety of cells of different origin, while not all of these are able to secrete IFN‐α. By transfection of reporter gene constructs comprising the virus‐responsive enhancer from the IFN A1 and IFN B genes, we show that this differential response is mediated at the level of transcription via these control elements. More detailed analysis of the function of these regions identifies specific sequences within the IFN A1 virus response element that has an inhibitory effect on expression in cells that are normally inducible, and is also implicated in the overall suppression of IFN A induction in non‐inducible cells.
A social stakeholder model
Authors: Verdeyen Vanessa , Put Johan , van Buggenhout Bea
Published: August 2004

Corporate governance is a concept that attracted the attention of jurists and economists in the US in the 1970s and 1980s. The concept then became widespread on the European continent in the 1990s. More recently, corporate governance elements have turned up in other fields as well. When applied to social institutions, this model is referred to as ‘social governance’. The (corporate) governance concept can be valuable in the social area. The debate on corporate governance is much more fundamental than the debate on the relationship between shareholders and management or between minority and majority shareholders. The essence of corporate governance can be found in the pursuit of a situation of ‘checks and balances’, which gives the stakeholders the possibility to complement and control each other. This article analyses the different stakeholders in the social area, their legitimisation as stakeholders and the practicability of a social stakeholder model.
Graduating from the child welfare system: a comparison of the UK and Australian leaving care debates
Authors: Mendes Philip , Moslehuddin Badal
Published: August 2004

Historically, insufficient resources and assistance have been provided to young people leaving state care. Care leavers have been found to experience significant health, social and educational deficits including homelessness, disproportionate involvement in juvenile crime and prostitution, poor social supports and early parenthood. This paper compares the UK and Australian debates around improving outcomes for care leavers. Whilst there are some minor differences in the respective legislative frameworks and responses, the similarities are far greater. Both countries have failed to provide the range of in‐care, transitional and post‐care supports and services required to ensure improved outcomes for care leavers.
GRID COMPUTING FOR THE ANALYSIS OF REGULATORY ELEMENTS IN CO-REGULATED SETS OF GENES
Authors: GEIJER JOHAN , LENHARD BORIS , MERINO-MARTINEZ ROXANA , NORSTEDT GUNNAR , FLORES-MORALES AMILCAR
Published: August 2004

We describe an initial implementation of a platform for the analysis of gene promoter architecture for sets of genes from human and other higher organisms, using NorduGrid as the Grid Virtual Organization. The procedure leading from a set of co-regulated genes to a set of inferred common regulatory elements involves a number of computationally intensive, but well scalable steps. We show it is feasible to implement a high performance genomic regulatory sequence analysis pipeline on the Grid with minimal modification to the existing computational biology software components. We applied a job binning step to dramatically reduce the overhead for submitting a set of many small jobs to the Grid. Even with simple jobs and a relatively small size of the Grid, we observed up to 25-fold performance improvement over a comparable or more powerful single or dual-CPU platform. Our implementation of biological sequence alignment and transcription factor binding site algorithms on the Grid proves that even simple applications can take advantage of computational resources that adopted this computational paradigm.
THE POTENTIAL OF GRID COMPUTING IN THREE-DIMENSIONAL ELECTRON MICROSCOPY
Authors: Bilbao-Castro J. R. , Marabini R. , Carazo J. M. , Garcia I. , Fernandez J. J.
Published: August 2004

This article describes a potential application of grid computing in structural biology. Three-dimensional electron microscopy allows the investigation of biological structures over a wide range of sizes, from cells to single macromolecules. Knowledge of the structure is critical to understanding the function of biological specimens. However, high resolution structure determination is computationally intensive. This contribution analyzes the potential benefits of grid computing in this field, and draws the conclusion that there are excellent opportunities to take advantage of computational grids.
PREEMPTIVE JOB SCHEDULING POLICY FOR DISTRIBUTIVELY-OWNED WORKSTATION CLUSTERS
Authors: ABAWAJY JEMAL H.
Published: August 2004

Cluster computing has come to prominence as a cost-effective parallel processing tool for solving many complex computational problems. In this paper, we propose a new timesharing opportunistic scheduling policy to support remote batch job executions over networked clusters to be used in conjunction with the Condor Up-Down scheduling algorithm. We show that timesharing approaches can be used in an opportunistic setting to improve both mean job slowdowns and mean response times with little or no throughput reduction. We also show that the proposed algorithm achieves significant improvement in job response time and slowdown as compared to exiting approaches and some recently proposed new approaches.
A GEOMETRIC WAY TO OBTAIN DE-SITTER SUBSPACES PERPENDICULAR TO A FINITE SIZE EXTRA-DIMENSION IN CURVED 5D UNIVERSES
Authors: GUENDELMAN E. , RUCHVARGER H.
Published: August 2004

We define curved five-dimensional (5D) space–time from the embedding of 5D surfaces in a 6D flat space. Demanding that the 6D coordinates satisfy a separation of variables form and that the 5D metric is diagonal, we obtain that each curved 5D surface contains 4D hyperboloid de-Sitter subspaces with maximally symmetry SO (4,1). Therefore, we define a very special form for the curved 5D surface where the extra-dimension is perpendicular to the 4D hyperboloid de-Sitter spaces. By relating to a minimally coupled scalar field with a potential which depends on the extra-dimension only, the curved 5D surface's form is satisfied. A mechanism by means of which the extra-dimension can be of a finite size, is found. The borders of the finite extra-dimension are obtained when the scalar field potential goes to infinity for certain finite values of the scalar field. The geodesic lines' equations show that a particle cannot cross such borders.
CAUSALITY VIOLATION IN NONLOCAL QUANTUM FIELD THEORY
Authors: JAIN AMBAR , JOGLEKAR SATISH D.
Published: August 2004

We study the causality violation in the nonlocal ϕ4-theory (as formulated by Kleppe and Woodard) containing a finite mass scale Λ. Starting from the Bogoliubov–Shirkov criterion for causality, we construct and study combinations of S-matrix elements that signal violation of causality in the one-loop approximation. We find that the causality violation in the exclusive process ϕ+ϕ→ϕ+ϕ grows with energy, but the growth with energy, (for low to moderate energies) is suppressed to all orders compared to what one would expect purely from dimensional considerations. We however find that the causality violation in other processes such as ϕ+ϕ→ϕ+ϕ+ϕ+ϕ grows with energy as expected from dimensional considerations at low to moderate energies. For high enough energies comparable to the mass scale Λ, however, we find a rapid (exponential-like) growth in the degree of causality violation. We suggest a scenario, based on an earlier work, that will enable one to evade a large theoretical causality violation at high energies, should it be unobserved experimentally.
The Pricing of Instalments Receipts: New Zealand Evidence
Authors: Marsden Alastair , Poskitt Russell
Published: August 2004

We examine the pricing of instalments receipts ("IRs") issued on the New Zealand stock market that trade concurrently with the underlying shares. An IR is a security that has identical entitlements to dividends receipts as the holder of an ordinary share but allows the holder to acquire the ordinary share with fixed pre-scheduled payments spread over a period of time. Similar to Charupat and Prisman (2004) for IRs traded in the Canadian market, we find that IRs of secondary offerings in the New Zealand market trade at an economically significant premium in the immediate period following their initial issue. The premium then declines over time and becomes negative in the period prior to the final instalment payment date. Our study suggests the benefits of IRs are not unique to one institutional environment and that issuers can increase the demand for new securities by overcoming investors' borrowing restrictions.
The Share Price Responses and Determinants of Strategic Alliances in Taiwan's High-Tech Industry: A Quantile Regression Approach
Authors: Wang Ya-Hui , Wu Chien-Tai
Published: August 2004

This article investigates share price responses to strategic alliances in Taiwan's high-tech industry from 1996 to 1999. We analyze the determinants of abnormal returns caused by strategic alliances using a quantile regression estimation procedure. Our empirical findings show that the wealth effect for a strategic alliance is positive, with no evidence of a wealth transfer between alliance partners. In addition, intra-industry alliances show significantly higher abnormal returns than inter-industry alliances. The horizontal and vertical alliances both have significantly positive abnormal returns, but the positive effect of vertical alliances primarily comes from downstream buyers. On the other hand, results from a quantile regression model show that the P/B ratio, director and supervisor shareholding ratios, and R&D ratio are important determinants of abnormal returns of strategic alliance announcements. Our empirical findings are consistent with the argument that the organizational flexibility offered by alliances is valuable to the high-tech industry which needs to cope with a fast-changing environment.
Statins but Not Angiotensin-Converting Enzyme Inhibitors Delay Progression of Aortic Stenosis
Authors: Rosenhek Raphael , Rader Florian , Loho Nicole , Gabriel Harald , Heger Maria , Klaar Ursula , Schemper Michael , Binder Thomas , Maurer Gerald , Baumgartner Helmut
Published: August 2004

Background—

Recently, statins and angiotensin-converting enzyme inhibitors (ACEIs) have been shown to slow aortic valve calcium accumulation. Although several studies also suggest that statins may reduce the hemodynamic progression of aortic stenosis (AS), no data are available for ACEIs or the combination of both.

Methods and Results—

A total of 211 consecutive patients (aged 70±10 years, 104 females) with native AS, defined by a peak velocity >2.5 m/s (valve area 0.84±0.23 cm
2
, mean gradient 42±19 mm Hg), with normal left ventricular function and no other significant valvular lesion who were examined between 2000 and 2002 and who had 2 echocardiograms separated by at least 6 months were included. Of these, 102 patients were treated with ACEIs, 50 patients received statins, and 32 patients received both. Hemodynamic progression of AS was assessed and related to medical treatment. Annualized increase in peak aortic jet velocity for the entire study group was 0.32±0.44 m · s
−1
· y
−1
. Progression was significantly lower in patients treated with statins (0.10±0.41 m · s
−1
· y
−1
) than in those who were not (0.39±0.42 m · s
−1
· y
−1
;
P
<0.0001). This effect was observed both in mild-to-moderate and severe AS. ACEI use, however, did not significantly affect hemodynamic progression (
P
=0.29). Furthermore, ACEIs had no additional effect on AS progression when given in combination with statins (0.11±0.42 versus 0.08±0.43 m · s
−1
· y
−1
for combination versus statin only;
P
=0.81). Cholesterol levels did not correlate with hemodynamic progression either in the group receiving statins or in the group that did not.

Conclusions—

ACEIs do not appear to slow AS progression. However, statins significantly reduce the hemodynamic progression of both mild-to-moderate and severe AS, an effect that may not be related to cholesterol lowering.
Subxiphoid Surgical Approach for Epicardial Catheter-Based Mapping and Ablation in Patients With Prior Cardiac Surgery or Difficult Pericardial Access
Authors: Soejima Kyoko , Couper Gregory , Cooper Joshua M. , Sapp John L. , Epstein Laurence M. , Stevenson William G.
Published: August 2004

Background—

Percutaneous epicardial mapping and ablation are successful in some patients with ventricular epicardial reentry circuits but may be impossible when pericardial adhesions are present, such as from prior cardiac surgery. The purpose of this study was to evaluate the feasibility of direct surgical exposure of the pericardial space to allow catheter epicardial mapping and ablation in the electrophysiology laboratory when percutaneous access is not feasible.

Methods and Results—

In 6 patients with prior cardiac surgery or failed percutaneous pericardial access, a subxiphoid pericardial window was attempted. In all 6 patients, manual lysis of adhesions exposed the epicardial surface of the heart through a small subxiphoid incision and allowed placement of an 8F sheath into the pericardial space under direct vision. Access to the diaphragmatic surface of the heart with ablation catheters was achieved in all patients, and catheter manipulation to the lateral and anterior walls was possible in 4 patients. Three-dimensional electroanatomic voltage maps revealed low-amplitude regions in the inferior or posterior left ventricular epicardium. A total of 16 ventricular tachycardias were induced, and 14 were abolished by radiofrequency ablation. Ablation was limited by intrapericardial defibrillator patches adherent to the likely target region in 2 patients. All patients had chest pain consistent with pericarditis early after the procedure that resolved within a few days. There were no other complications.

Conclusions—

A direct surgical subxiphoid epicardial approach in the electrophysiology laboratory is feasible for patients with difficult pericardial access who require ablation of epicardial arrhythmia foci.
Effect of Baseline or Changes in Adrenergic Activity on Clinical Outcomes in the β-Blocker Evaluation of Survival Trial
Authors: Bristow M.R. , Krause-Steinrauf H. , Nuzzo R. , Liang Cheng-Seng , Lindenfeld J. , Lowes B.D. , Hattler B. , Abraham W.T. , Olson L. , Krueger S. , Thaneemit-Chen S. , Hare J.M. , Loeb H.S. , Domanski M.J. , Eichhorn E.J. , Zelis R. , Lavori P.
Published: August 2004

Background—

Adrenergic activation is thought to be an important determinant of outcome in subjects with chronic heart failure (CHF), but baseline or serial changes in adrenergic activity have not been previously investigated in a large patient sample treated with a powerful antiadrenergic agent.

Methods and Results—

Systemic venous norepinephrine was measured at baseline, 3 months, and 12 months in the β-Blocker Evaluation of Survival Trial (BEST), which compared placebo treatment with the β-blocker/sympatholytic agent bucindolol. Baseline norepinephrine level was associated with a progressive increase in rates of death or death plus CHF hospitalization that was independent of treatment group. On multivariate analysis, baseline norepinephrine was also a highly significant (
P
<0.001) independent predictor of death. In contrast, the relation of the change in norepinephrine at 3 months to subsequent clinical outcomes was complex and treatment group-dependent. In the placebo-treated group but not in the bucindolol-treated group, marked norepinephrine increase at 3 months was associated with increased subsequent risks of death or death plus CHF hospitalization. In the bucindolol-treated group but not in the placebo-treated group, the 1st quartile of marked norepinephrine reduction was associated with an increased mortality risk. A likelihood-based method indicated that 18% of the bucindolol group but only 1% of the placebo group were at an increased risk for death related to marked reduction in norepinephrine at 3 months.

Conclusions—

In BEST, a subset of patients treated with bucindolol had an increased risk of death as the result of sympatholysis, which compromised the efficacy of this third-generation β-blocker.
Synergistic Effect of Bone Marrow Mobilization and Vascular Endothelial Growth Factor-2 Gene Therapy in Myocardial Ischemia
Authors: Kawamoto Atsuhiko , Murayama Toshinori , Kusano Kengo , Ii Masaaki , Tkebuchava Tengiz , Shintani Satoshi , Iwakura Atsushi , Johnson Ingrid , von Samson Patrick , Hanley Allison , Gavin Mary , Curry Cindy , Silver Marcy , Ma Hong , Kearney Marianne , Losordo Douglas W.
Published: August 2004

Background—

We performed a series of investigations to test the hypothesis that combining angiogenic gene therapy and cytokine (CK)-induced endothelial progenitor cell mobilization would be superior to either strategy alone for treatment of chronic myocardial ischemia.

Methods and Results—

A swine model of chronic myocardial ischemia and a murine model of acute myocardial infarction were used in this study. In both models, animals were randomly assigned to 1 of 4 treatment groups: Combo group, intramyocardial vascular endothelial growth factor (VEGF)-2 gene transfer plus subcutaneous injection of CKs; VEGF-2, VEGF-2 gene transfer plus saline subcutaneously injected; CK, empty vector transfer plus CKs; and control, empty vector plus subcutaneous saline. Acute myocardial infarction was also induced in wild-type mice 4 weeks after bone marrow transplantation from enhanced green fluorescent protein transgenic mice to permit observation of bone marrow–derived cells in the myocardium after acute myocardial infarction. In chronic myocardial ischemia, combination therapy resulted in superior improvement in all indexes of perfusion and function compared with all other treatment groups. In the bone marrow transplant mice, double immunofluorescent staining revealed that the combination of CK-induced mobilization and local VEGF-2 gene transfer resulted in a significant increase in the number of bone marrow–derived cells incorporating into the neovasculature, indicating that recruitment and/or retention of bone marrow–derived progenitors was enhanced by mobilization and that local VEGF-2 gene transfer can provide signals for recruitment or incorporation of circulating progenitor cells.

Conclusions—

Mobilization of endothelial progenitor cells with cytokines potentiates VEGF-2 gene therapy for myocardial ischemia and enhances bone marrow cell incorporation into ischemic myocardium.
Asperger syndrome from childhood into adulthood
Authors: Berney Tom
Published: August 2004

Asperger syndrome, a form of autism with normal ability and normal syntactical speech, is associated with a variety of comorbid psychiatric disorders. The disorder is well known to child psychiatry, and we are beginning to recognise the extent of its impact in adulthood. The article reviews the diagnosis and assessment of Asperger syndrome and its links with a wide range of psychiatric issues, including mental disorder, offending and mental capacity. It also describes the broader, non-psychiatric management of Asperger syndrome itself, which includes social and occupational support and education, before touching on the implications the disorder has for our services.
Treating unhappiness – society needs palliative psychopharmacology
Authors: Charlton Bruce G. , McKenzie Kwame
Published: August 2004

The hospice movement has shown that, even when underlying pathologies are incurable, there may be considerable scope for providing symptomatic relief through optimal use of pharmacological agents. Symptomatic palliative treatment has revolutionised terminal care, especially the management of severe pain. Could this principle equally be applied to the treatment of low-grade misery and everyday unhappiness?
Changes in distributed neural circuitry function in patients with first-episode schizophrenia
Authors: Mendrek A. , Laurens K. R. , Kiehl K. A. , Ngan E. T. C. , Stip E. , Liddle P. F.
Published: August 2004

Background

A number of functional brain abnormalities have been reported in schizophrenia, but it remains to be determined which of them represent trait and state markers of the illness.

Aims

To delineate regional brain dysfunctions that remain stable and those that fluctuate during the course of schizophrenia.

Method

A cohort of patients with first-episode schizophrenia and a matched group of control participants underwent functional magnetic resonance imaging on two occasions 6–8 weeks apart during performance of a working memory task. The patients' disease was in partial remission at the second scan.

Results

Relative to control participants, the function of the left dorsolateral prefrontal cortex, left thalamus and right cerebellum remained disturbed in the people with schizophrenia, whereas the dysfunction of the right dorsolateral prefrontal cortex, right thalamus, left cerebellum and cingulate gyrus normalised, with significant reduction in symptoms.

Conclusions

These results suggest that dysfunction of the left fronto-thalamo-cerebellar circuitry is a relatively stable characteristic of schizophrenia, whereas disturbance of the right circuitry and cingulate gyrus is predominantly a state-related phenomenon.
Ethnicity, social deprivation and psychological distress in adolescents
Authors: Stansfeld Stephen A. , Haines Mary M. , Head Jenny A. , Bhui Kamaldeep , Viner Russell , Taylor Stephanie J. C. , Hillier Sheila , Klineberg Emily , Booy Robert
Published: August 2004

Background

In adults the prevalence of psychological distress varies in different ethnic groups, and this has been explained by differences in socio-economic status. Is this also the case in adolescents?

Aims

To examine whether ethnic differences in prevalence of psychological distress in adolescents are associated with social deprivation.

Method

A cross-sectional questionnaire survey was used to assess 2790 male and female pupils, aged 11–14 years, from a representative sample of 28 east London secondary schools.

Results

Rates of psychological distress were similar to rates in UK national samples in boys and girls. Bangladeshi pupils, although highly socially disadvantaged, had a lower risk of psychological distress (OR=0.63, 95% CI 0.4–0.9). Non-UK White girls had higher rates of depressive symptoms (OR=1.54, 95% C11.1–2.2).

Conclusions

High rates of depressive symptoms in non-UK White girls may be related to recent migration. Low rates of psychological distress in Bangladeshi pupils in this sample relative to White pupils, despite socio-economic disadvantage, could be associated with cultural protective factors that require further investigation.
Preventing crime by people with schizophrenic disorders: the role of psychiatric services
Authors: Hodgins S. , Müller-Isberner R.
Published: August 2004

Background

Knowledge of when and how to implement treatments to prevent criminal offending among people with schizophrenia is urgently needed.

Aims

To identify opportunities for interventions to prevent offending among men with schizophrenic disorders by tracking their histories of offending and admissions to hospital.

Method

We examined 232 men with schizophrenic disorders discharged from forensic and general psychiatric hospitals. Data were collected from participants, family members and official records.

Results

More than three-quarters (77.8%) of the forensic patients had previously been admitted to general psychiatric services; 24.3% of the general psychiatric patients had a criminal record. Offences had been committed by 39.8% of the forensic patients and 10.8% of the general psychiatric patients before their first admission to general psychiatry, and after their first admission these 59 patients committed 195 non-violent and 59 violent offences. Subsequently, 49 of them committed serious violent offences that led to forensic hospital admission. The offenders were distinguished by a pervasive and stable pattern of antisocial behaviour evident from at least mid-adolescence.

Conclusions

General psychiatry requires resources in order to prevent criminal offending among a subgroup of patients with schizophrenic disorders.
What British psychiatrists read
Authors: Jones Teresa , Hanney Stephen , Buxton Martin , Burns Tom
Published: August 2004

Background

The role of journals in disseminating research to clinicians is increasingly debated. Current measures of esteem for journals (e.g. impact factors) may not indicate clinical penetration.

Aims

To assess the perceived importance of different mental health journals to psychiatrists' clinical practice and compare this with impact factors.

Method

Random samples of psychiatrists providing child and adolescent, adults of working age and old age services chose up to ten journals read or consulted with regard to their clinical work, ranking the top three. For these journals, comparisons were made with impact factors and importance as outlets for UK psychiatry research.

Results

A total of 560 questionnaires were completed (47%). Two membership journals (the British Journal of Psychiatry and the BMJ) were most read and highest ranked. Associations between impact factors, clinicians' ratings and importance as outlets for psychiatry papers varied.

Conclusions

The results could lead to reconsideration of the importance of some journals. Academic assessments of the status of journals should not be assumed to reflect their influence on clinicians.
Focus on psychiatry in Egypt
Authors: Okasha A.
Published: August 2004

Mental disorders have been recognised in Egypt for millennia; 5000 years ago, they were considered to be physical ailments of the heart or uterus, as described in the Ebers and Kahun papyri (Okasha, 2001). These disorders carried no stigma, as there was no demarcation then between psyche and soma. In the 14th century – 600 years before similar institutions were founded in Europe – the first psychiatric unit was established, in Kalaoon Hospital in Cairo.
Psychiatry in the future
Authors: Marks Isaac
Published: August 2004

A hundred and fifty years ago, physical disease was known to be widespread but was usually untreated. Anxiety and depression is now like that. Up to a fifth of the entire population are affected, of whom 84% were untreated in a UK community survey (Bebbington et al, 2000). ‘Developed’ countries are underdeveloped when it comes to treating anxiety and depressive disorders, even though effective treatment is available in the form of brief cognitive–behavioural therapy. In the UK, waiting times for such therapy can be as long as 2 years. Routine therapy outcomes are rarely reported. The delivery and monitoring and also teaching of therapy still largely conform to a 19th century model, and could be advanced by greater use of information technology. Such technology could catalyse a model of community care delivered mainly in the home, by enhancing access to effective self-help, audit of outcome and professional training.
Audit of disposal of clinically confidential information
Authors: Dietrich Craige , Khan Zahir , Warner James
Published: August 2004

Aims and Method

We conducted a 3-cycle audit of disposal of clinically sensitive information in a mental health unit, in order to identify and reduce potential breaches in patients' confidentiality. Material from waste bins in administrative areas of a mental health unit was examined every evening during each period of the audit.

Results

The first search, conducted over a 3-week period, yielded 11 documents containing highly-sensitive information about patients. After feedback to staff and improvement of shredding facilities, no sensitive information was found during the follow-up 3-week survey, 3 months later. However, a third survey 2 years later found 24 highly-sensitive items after one week, despite shredding facilities being maintained.

Clinical Implications

Changes in behaviour identified in this audit appear to be due to education rather than improved facilities. All staff involved in patient care need to maintain awareness of the need for safe disposal of confidential material.
A note on the lilypond model
Authors: Cotar Codina , Volkov Stanislav
Published: August 2004

We consider some generalizations of the germ-grain growing model studied by Daley, Mallows and Shepp (2000). In this model, a realization of a Poisson process on a line with points Xi is fixed. At time zero, simultaneously at each Xi, a circle (grain) starts growing at the same speed. It grows until it touches another grain, and then it stops. The question is whether the point zero is eventually covered by some circle. In our note we expand this model in the following three directions. We study: a one-sided growth model with a fixed number of circles; a grain-growth model on a regular tree; and a grain-growth model on a line with non-Poisson distributed centres of the circles.
On boundary estimation
Authors: Cuevas Antonio , Rodríguez-Casal Alberto
Published: August 2004

We consider the problem of estimating the boundary of a compact set S ⊂ ℝd from a random sample of points taken from S. We use the Devroye-Wise estimator which is a union of balls centred at the sample points with a common radius (the smoothing parameter in this problem). A universal consistency result, with respect to the Hausdorff metric, is proved and convergence rates are also obtained under broad intuitive conditions of a geometrical character. In particular, a shape condition on S, which we call expandability, plays an important role in our results. The simple structure of the considered estimator presents some practical advantages (for example, the computational identification of the boundary is very easy) and makes this problem quite close to some basic issues in stochastic geometry.
Technology diffusion by learning from neighbours
Authors: Chatterjee Kalyan , Xu Susan H.
Published: August 2004

In this paper, we consider a model of social learning in a population of myopic, memoryless agents. The agents are placed at integer points on an infinite line. Each time period, they perform experiments with one of two technologies, then each observes the outcomes and technology choices of the two adjacent agents as well as his own outcome. Two learning rules are considered; it is shown that under the first, where an agent changes his technology only if he has had a failure (a bad outcome), the society converges with probability 1 to the better technology. In the other, where agents switch on the basis of the neighbourhood averages, convergence occurs if the better technology is sufficiently better. The results provide a surprisingly optimistic conclusion about the diffusion of the better technology through imitation, even under the assumption of extremely boundedly rational agents.
Why do these quite different best-choice problems have the same solutions?
Authors: Samuels Stephen M.
Published: August 2004

The full-information best-choice problem, as posed by Gilbert and Mosteller in 1966, asks us to find a stopping rule which maximizes the probability of selecting the largest of a sequence of n i.i.d. standard uniform random variables. Porosiński, in 1987, replaced a fixed n by a random N, uniform on {1,2,…,n} and independent of the observations. A partial-information problem, imbedded in a 1980 paper of Petruccelli, keeps n fixed but allows us to observe only the sequence of ranges (max - min), as well as whether or not the current observation is largest so far. Recently, Porosiński compared the solutions to his and Petruccelli's problems and found that the two problems have identical optimal rules as well as risks that are asymptotically equal. His discovery prompts the question: why? This paper gives a good explanation of the equivalence of the optimal rules. But even under the lens of a planar Poisson process model, it leaves the equivalence of the asymptotic risks as somewhat of a mystery. Meanwhile, two other problems have been shown to have the same limiting risks: the full-information problem with the (suboptimal) Porosiński-Petruccelli stopping rule, and the full-information ‘duration of holding the best’ problem of Ferguson, Hardwick and Tamaki, which turns out to be nothing but the Porosiński problem in disguise.
Importance sampling on coalescent histories. I
Authors: De Iorio Maria , Griffiths Robert C.
Published: August 2004

Stephens and Donnelly (2000) constructed an efficient sequential importance-sampling proposal distribution on coalescent histories of a sample of genes for computing the likelihood of a type configuration of genes in the sample. In the current paper a characterization of their importance-sampling proposal distribution is given in terms of the diffusion-process generator describing the distribution of the population gene frequencies. This characterization leads to a new technique for constructing importance-sampling algorithms in a much more general framework when the distribution of population gene frequencies follows a diffusion process, by approximating the generator of the process.
Importance sampling on coalescent histories. II: Subdivided population models
Authors: De Iorio Maria , Griffiths Robert C.
Published: August 2004

De Iorio and Griffiths (2004) developed a new method of constructing sequential importance-sampling proposal distributions on coalescent histories of a sample of genes for computing the likelihood of a type configuration of genes in the sample by simulation. The method is based on approximating the diffusion-process generator describing the distribution of population gene frequencies, leading to an approximate sample distribution and finally to importance-sampling proposal distributions. This paper applies that method to construct an importance-sampling algorithm for computing the likelihood of samples of genes in subdivided population models. The importance-sampling technique of Stephens and Donnelly (2000) is thus extended to models with a Markov chain mutation mechanism between gene types and migration of genes between subpopulations. An algorithm for computing the likelihood of a sample configuration of genes from a subdivided population in an infinitely-many-alleles model of mutation is derived, extending Ewens's (1972) sampling formula in a single population. Likelihood calculation and ancestral inference in gene trees constructed from DNA sequences under the infinitely-many-sites model are also studied. The Griffiths-Tavaré method of likelihood calculation in gene trees of Bahlo and Griffiths (2000) is improved for subdivided populations.
Poisson approximation for some point processes in reliability
Authors: Gravereaux Jean-Bernard , Ledoux James
Published: August 2004

In this paper, we consider a failure point process related to the Markovian arrival process defined by Neuts. We show that it converges in distribution to a homogeneous Poisson process. This convergence takes place in the context of rare occurrences of failures. We also provide a convergence rate of the convergence in total variation of this point process using an approach developed by Kabanov, Liptser and Shiryaev for the doubly stochastic Poisson process driven by a finite Markov process.
Tail asymptotics for processor-sharing queues
Authors: Guillemin Fabrice , Robert Philippe , Zwart Bert
Published: August 2004

The basic queueing system considered in this paper is the M/G/1 processor-sharing queue with or without impatience and with finite or infinite capacity. Under some mild assumptions, a criterion for the validity of the reduced-service-rate approximation is established when service times are heavy tailed. This result is applied to various models based on M/G/1 processor-sharing queues.
Estimation of the offspring mean in a supercritical or near-critical size-dependent branching process
Authors: Lalam N. , Jacob C.
Published: August 2004

We consider a single-type supercritical or near-critical size-dependent branching process {Nn}n such that the offspring mean converges to a limit m ≥ 1 with a rate of convergence of order as the population size Nn grows to ∞ and the variance may vary at the rate where −1 ≤ β < 1. The offspring mean m(N) = m + μN-α + o(N-α) depends on an unknown parameter θ0 belonging either to the asymptotic model (θ0 = m) or to the transient model (θ0 = μ). We estimate θ0 on the nonextinction set from the observations {Nh,…,Nn} by using the conditional least-squares method weighted by (where γ ∈ ℝ) in the approximate model mθ,ν̂n(·), where ν̂n is any estimation of the parameter of the nuisance part (O(N-α) if θ0 = m and o(N-α) if θ0 = μ). We study the strong consistency of the estimator of θ0 as γ varies, with either h or n - h remaining constant as n → ∞. We use either a minimum-contrast method or a Taylor approximation of the first derivative of the contrast. The main condition for obtaining strong consistency concerns the asymptotic behavior of the process. We also give the asymptotic distribution of the estimator by using a central-limit theorem for random sums and we show that the best rate of convergence is attained when γ = 1 + β.
Modelling the PCR amplification process by a size-dependent branching process and estimation of the efficiency
Authors: Lalam N. , Jacob C. , Jagers P.
Published: August 2004

We propose a stochastic modelling of the PCR amplification process by a size-dependent branching process starting as a supercritical Bienaymé-Galton-Watson transient phase and then having a saturation near-critical size-dependent phase. This model allows us to estimate the probability of replication of a DNA molecule at each cycle of a single PCR trajectory with a very good accuracy.
Numerical inversion for Laplace transforms of functions with discontinuities
Authors: Sakurai T.
Published: August 2004

We analyse the role of Euler summation in a numerical inversion algorithm for Laplace transforms due to Abate and Whitt called the EULER algorithm. Euler summation is shown to accelerate convergence of a slowly converging truncated Fourier series; an explicit bound for the approximation error is derived that generalizes a result given by O'Cinneide. An enhanced inversion algorithm called EULER-GPS is developed using a new variant of Euler summation. The algorithm EULER-GPS makes it possible to accurately invert transforms of functions with discontinuities at arbitrary locations. The effectiveness of the algorithm is verified through numerical experiments. Besides numerical transform inversion, the enhanced algorithm is applicable to a wide range of other problems where the goal is to recover point values of a piecewise-smooth function from the Fourier series.