bluuebunny/crossref_metadata_2025 huggingface dataset:
Transplant immunosuppressive agents in non‐transplant chronic autoimmune hepatitis: the Canadian association for the study of liver (CASL) experience with mycophenolate mofetil and tacrolimus
Authors: Chatur Nazira , Ramji Alnoor , Bain Vincent G. , Ma Mang M. , Marotta Paul J. , Ghent Cameron N. , Lilly Leslie B. , Heathcote E. Jenny , Deschenes Marc , Lee Samuel S. , Steinbrecher Urs P. , Yoshida Eric M.
Published: July 2005

Background: Conventional treatment of autoimmune hepatitis consists of either prednisone alone or in combination with azathioprine. Ten to 20% of patients do not respond to or are intolerant of this treatment. Novel drug treatments include immunosuppressive drugs such as tacrolimus (TAC), mycophenolate mofetil (MMF), methotrexate and cyclosporine. We describe a multi‐centre Canadian experience with MMF and TAC.

Objective: To study a multi‐centre patient population who had failed conventional therapy and were treated with non‐conventional medical therapy for autoimmune hepatitis and document response.

Methods: Members of the Canadian Association for the Study of Liver (CASL) obtained MMF from Hoffmann‐La Roche Ltd, as part of a compassionate release program, were contacted for standardized data on patients with AIH who received MMF or TAC. Response definitions based on aminotransferase changes were: Complete response (CR)‐sustained normalization, partial response (PR)‐improvement by greater than 50%, non‐response (NR)‐less than 50% improvement and relapse (RP)‐initial CR or PR followed by an increase in aminotransferases.

Results: A total of 16 patients were identified: six in Ontario, one in Quebec, five in Alberta and four in British Columbia. Three were treated with TAC, eleven with MMF and two with combination MMF and TAC. CR was observed in 50%, PR in 12.5%, RP in 25% and NR occurred in 12.5%. The CR for MMF without TAC was approximately 64%.

Conclusions: MMF is effective and well tolerated by patients with autoimmune hepatitis who do not respond to, or are intolerant of, conventional immunosuppressive agents.
Efficacy of zinc supplementation in preventing acute hepatitis in Long–Evans Cinnamon rats
Authors: Medici Valentina , Sturniolo Giacomo Carlo , Santon Alessandro , D'Incà Renata , Bortolami Marina , Cardin Romilda , Basso Daniela , Albergoni Vincenzo , Irato Paola
Published: July 2005

Objectives: Objectives: Long–Evans Cinnamon (LEC) rats are characterized by an abnormal hepatic deposition of copper (Cu) due to a lack of the Cu‐transporter P‐type adenosine triphosphatase: accordingly, the strain is a good animal model of Wilson's disease. The effect of oral zinc (Zn) acetate treatment on the development of acute hepatitis and the biochemical parameters of Cu‐induced liver damage was studied in 5‐week‐old LEC rats (n=52).

Methods: Rats receiving 50 or 80 mg/ml/day Zn acetate by gavage and control rats receiving a daily dose of glucose solution 0.02 g/ml by gastric intubation were killed at 1, 2 or 8 weeks after the start of treatment.

Results: Treatment with Zn acetate resulted in the prevention of acute hepatitis: 10 of the 13 untreated rats developed signs and symptoms compatible with acute hepatitis between the 6th and 7th week of treatment. Tissue metallothionein (MT) significantly increased in the treated rats and positively correlated with Zn concentrations within the liver. Control rats had a significantly higher iron concentration in the liver and kidneys compared with supplemented rats, after both short‐ and long‐term experiments. 8‐hydroxy‐2′‐deoxyguanosine amounts were significantly lower in untreated rats.

Conclusions: Zn acetate prevents acute hepatitis, by increasing tissue MT concentrations, reducing Cu absorption and interfering with Fe metabolism.
Intracellular localization of NS3 and C proteins in chronic hepatitis C
Authors: Kasprzak Aldona , Seidel Jolanta , Biczysko Wiesława , Wysocki Jacek , Spachacz Rafał , Zabel Maciej
Published: July 2005

Background: The cellular localization of hepatitis C virus (HCV) proteins in chronic hepatitis C remains a debatable issue. Aim of the studies included cellular and subcellular localization of two HCV proteins, NS3 and C protein, in liver biopsies from 20 children with chronic hepatitis C employing commercially available monoclonal antibodies and a semiquantitative technique of the proteins expression. In the studies advantage was taken of (Strept)avidin‐biotin peroxidase complex and ImmunoMax technique.

Results: The cytoplasmic localization of both proteins dominated over nuclear localization. The total amount of NS3 protein exceeded that of C protein. At the ultrastructural level, we observed both proteins in endoplasmic reticulum membranes and mitochondria, but small amount of both proteins was seen also in cell nuclei. The amount of either protein did not correlate with liver histology in our patients. No correlation could be disclosed between content of both proteins and HCV RNA levels in serum. Content of NS3 demonstrated negative correlation with activity of alanine transaminase.

Conclusion: In conclusion, the new aspect in present studies involved localization of C and NS3 proteins at the levels of light and electron microscopy in children. For the first time also intramitochondrial localization of NS3 protein was demonstrated.
Relationship between Lens culinaris agglutinin‐reactive α‐fetoprotein and pathologic features of hepatocellular carcinoma
Authors: Tada Toshifumi , Kumada Takashi , Toyoda Hidenori , Kiriyama Seiki , Sone Yasuhiro , Tanikawa Makoto , Hisanaga Yasuhiro , Kitabatake Shusuke , Kuzuya Teiji , Nonogaki Koji , Shimizu Junichi , Yamaguchi Akihiro , Isogai Masatoshi , Kaneoka Yuji , Washizu Junji , Satomura Shinji
Published: July 2005

Abstract: Aim: We investigated pathological features of Lens culinaris agglutinin‐reactive α‐fetoprotein (AFP‐L3)‐positive hepatocellular carcinoma (HCC) in order to seek a pathological basis of poor prognosis of HCC patients with elevated AFP‐L3.

Methods: A total of 111 patients with HCC ≤5 cm in diameter who underwent hepatic resection were studied. Serum AFP‐L3 concentration was measured within a month prior to surgery by lectin‐affinity electrophoresis coupled with antibody‐affinity blotting, and expressed as AFP‐L3 percentage of total AFP. AFP‐L3 of 10% or higher was judged to be positive. Pathologic features of resected HCC specimens were evaluated and classified concerning growth pattern (expansive or infiltrative growth), capsule formation, capsule infiltration, septal formation, portal vein invasion, hepatic vein invasion, bile duct invasion, and intrahepatic metastasis. These macroscopic and microscopic findings were compared between AFP‐L3‐positive and negative HCC specimens.

Results: Thirty‐three (29.7%) were positive for AFP‐L3. The prevalence of HCC with infiltrative growth, with capsule infiltration, with septum formation, with portal vein invasion, and with hepatic vein invasion was significantly higher in AFP‐L3‐positive group (P=0.0121, 0.0290, 0.0442, 0.0314, and 0.0433, respectively). These pathologic features reportedly indicate the progression of the tumor.

Conclusions: AFP‐L3‐positive HCC had several pathologic features of progressed state of HCC, which accounted for the AFP‐L3 as an indicator of poor prognosis of HCC.
Effect of diphenyl dimethyl bicarboxylate on concanavalin A‐induced liver injury in mice
Authors: Gao Mei , Zhang Jianjun , Liu Gengtao
Published: July 2005

Abstract: Diphenyl dimethyl bicarboxylate (DDB) is a hepatoprotectant and used in the treatment of chronic viral hepatitis patients in China. The aim of the present paper was to investigate the effect of DDB on liver injury mediated by immune response in concanavalin A (Con A)‐treated mice. A dose of Con A 30 mg/kg was injected via the tailvein to induce liver injury in mice. Serum alanine transaminase (ALT), aspartate aminotransferase (AST), total bile acid (TBA), total bilirubin (TBIL) and tumor necrosis factor α (TNF‐α) level as well as liver TNF‐α mRNA expression were determined. The following results were obtained: (1) Prior oral administration of DDB 150 mg/kg markedly reduced the elevated serum ALT, TBA and TBIL levels, and the liver lesions in Con A‐treated mice; (2) DDB significantly inhibited the elevation of serum TNF‐α and liver TNF‐α mRNA expression 2 h after Con A injection; (3) DDB significantly inhibited hepatocyte nuclear DNA fragmentation 12 h after Con A injection; (4) DDB dose‐dependently prevented the direct DNA damage induced by CuSO4–Phen–Vit C–H2O2 system in vitro, and the ex vivo experiment also showed that the administration of DDB reduced the susceptibility of mouse liver nuclei DNA to CuSO4–Phen—Vit C–H2O2 system. These results suggest that DDB could directly protect hepatocyte DNA from oxidative damage, and inhibit TNF‐α mRNA expression in liver tissue, which resulted in prevention of liver damage induced by Con A in mice.
Adiponectin levels among patients with chronic hepatitis B and C infections and in response to IFN‐α therapy
Authors: Lu Jin‐Ying , Chuang Lee‐Ming , Yang Wei‐Shiung , Tai Tong‐Yuan , Lai Ming‐Yang , Chen Pei‐Jer , Kao Jia‐Horng , Lee Cha‐Ze , Lee Hsuan‐Shu
Published: July 2005

Abstract: Aims: The study was designed to survey the change of adiponectin levels before and after interferon‐α (IFN‐α) therapy in patients with chronic hepatitis B and C infections.

Methods: Twenty‐one biopsy‐proved patients with chronic hepatitis B (10 cases) and hepatitis C (11 cases) were given IFN‐α for a total of 24 weeks. Fasting plasma glucose, insulin and adiponectin levels were obtained before and 12 weeks after completion of IFN‐α therapy. Insulin suppression test was conducted before and within 1 week after IFN‐α therapy.

Results: The change of adiponectin levels differed significantly between responders (eight cases) and non‐responders (13 cases) to IFN‐α treatment (−4.8±2.2 vs. 0.5±1.0 μg/ml, P=0.03). After adjusting for age, gender and change in body mass index, the study found the change of adiponectin levels still significantly related to the response to IFN‐α (P=0.04). When hepatitis B virus (HBV) and hepatitis C virus (HCV)‐infected patients were separately analyzed, the adiponectin levels reported a trend to decrease in HCV responders (11.9±3.2 vs. 10.8±3.0 μg/ml, P=0.02, n=4) and HBV responders (17.7±4.1 vs. 9.2±1.0 μg/ml, P=0.10, n=4). In addition, a significant decrease of steady‐state plasma glucose in insulin suppression test was noted in responders (13.6±1.8–11.7±1.2 mmol/l, P=0.03), but not in non‐responders (12.3±1.1–11.0±1.0 mmol/l, P=0.20), after IFN‐α therapy.

Conclusions: IFN‐α resulted in a decrease of serum adiponectin levels but an improvement of insulin resistance in responders to the treatment. The result contradicts previous concept of the relationship between insulin resistance and adiponectin levels. Whether and how the augmented immune response, which was supposed to result from the disappearance or the profound down‐regulation of the virus or viral antigens in responders to IFN‐α treatment, contributes to the lowering of adiponectin levels needs to be further investigated.
Successful treatment of hepatitis C reinfection with interferon‐α2b and ribavirin after liver transplantation
Authors: Yedibela Süleyman , Schuppan Detlef , Müller Volker , Schellerer Vera , Tannapfel Andrea , Hohenberger Werner , Meyer Thomas
Published: July 2005

Abstract: Introduction: Recurrence of hepatitis C virus (HCV) infection after orthotopic liver transplantation (OLT) is a virtually universal occurrence, and a significant proportion of patients develop chronic hepatitis and cirrhosis. The aim of this study was to evaluate the safety and efficacy of interferon (IFN)‐α2b plus ribavirin (RIBA) in the treatment of recurrent HCV after OLT over the long term.

Material and methods: Fifteen patients with recurrent HCV infection (positive serum HCV RNA, elevated serum aminotransferases, histological activity) were started on IFN‐α2b (3–6 million units administered subcutaneously three times a week) plus RIBA (800–1200 mg/day) 18±5 months after OLT. HCV RNA was determined 1, 3, 6, 9, 12 and 18 months after initiation of treatment. Liver biopsy was performed before and after therapy. The patients were followed up for a mean of 33±5 months.

Results: Thirteen patients (87%) were treated for at least 6 months and nine patients (60%) for 12 months. After 3 months, 11 patients (73%) were free from HCV RNA (<50 copies/ml); the virological end‐of‐treatment response was 67%. Five patients (33%) remained HCV RNA‐negative 6 months posttreatment (sustained response (SR)). During the follow‐up period, four patients (27%) died of liver failure, recurrent HCV after virological response, or HCC. The histological activity index improved significantly for both inflammatory activity and fibrosis, from 8.8 to 4.7 and from 7.3 to 4.8, respectively. In none of the patients were signs of rejection observed.

Conclusion: Combination therapy with IFN and RIBA in transplanted patients with chronic hepatitis C is an effective treatment that results in a high virological SR rate. It is well tolerated and leads to an improvement in histological outcome.
Growth hormone and connective tissue in exercise
Authors: Doessing S. , Kjaer M.
Published: July 2005

Over the last few years, growth hormone (GH) has become increasingly popular as doping within different sports. However, the precise mechanisms behind the ergogenic (performance enhancing) effects of GH in athletes are still being debated. Besides a well‐documented stimulatory effect of GH on carbohydrate and fatty acid metabolism, and a possible anabolic effect on myofibrillar muscle protein, we suggest a role for GH as an anabolic agent in connective tissue in human skeletal muscle and tendon. Given the importance of the connective tissue for the function of skeletal muscle and tendon, a strengthening effect of GH on connective tissue could fit with the ergogenic effect of GH experienced by athletes.

This review examines the endogenous secretion of GH and its mediators in relation to exercise. Furthermore, we consider the effect of endogenous GH and administered recombinant human GH (rhGH) on both myofibrillar and connective tissue protein synthesis, thus offering an alternative explanation for the ergogenic effect of GH. Finally, we suggest a possible therapeutic role for rhGH in clinical management of the frequently suffered injuries in the connective tissue.
Gene expression and matrix turnover in overused and damaged tendons
Authors: Riley G. P.
Published: July 2005

Chronic, painful conditions affecting tendons, frequently known as tendinopathy, are very common types of sporting injury. The tendon extracellular matrix is substantially altered in tendinopathy, and these changes are thought to precede and underlie the clinical condition. The tendon cell response to repeated minor injuries or “overuse” is thought to be a major factor in the development of tendinopathy. Changes in matrix turnover may also be effected by the cellular response to physical load, altering the balance of matrix turnover and changing the structure and composition of the tendon. Matrix turnover is relatively high in tendons exposed to high mechanical demands, such as the supraspinatus and Achilles, and this is thought to represent either a repair or tissue maintenance function. Metalloproteinases are a large family of enzymes capable of degrading all of the tendon matrix components, and these are thought to play a major role in the degradation of matrix during development, adaptation and repair. It is proposed that some metalloproteinase enzymes are required for the health of the tendon, and others may be damaging, leading to degeneration of the tissue. Further research is required to investigate how these enzyme activities are regulated in tendon and altered in tendinopathy. A profile of all the metalloproteinases expressed and active in healthy and degenerate tendon is required and may lead to the development of new drug therapies for these common and debilitating sports injuries.
Assessing the prevalence of dental caries among elementary school children in North Korea: a cross‐sectional survey in the Kangwon province
Authors: Goe Leon C , Baysac Mary Anne S , Todd Knox H , Linton John A
Published: July 2005

Objectives:  The lack of epidemiological studies has made it difficult to assess the extent of public health problems in North Korea. In the absence of empirical data, less intrusive study designs acceptable to the North Korean government could be developed to gauge the public's health. To this end we developed a basic oral health survey in order to assess the prevalence of untreated dental caries among children.

Methods:  A cross‐sectional survey of 854 elementary school students was conducted in the city of Wonsan, North Korea. Students were screened and classified into one of three states of oral health: no caries, minor caries or severe dental caries. Verbal surveys were concurrently administered on children to collect basic information on oral health behaviours and demographic characteristics. Statistical analyses were performed to determine if any variables were significant predictors of oral health status category.

Results:  Among the 854 students screened, we found 255 students with no caries (29.9%), 316 students with minor caries (37.0%), and 283 students with severe caries (33.1%). The majority of students (70.1%) screened had dental caries. Almost all of the students (98.5%) claimed to brush their teeth daily and 71.2% of students visited a dentist in the past year. There were no significant predictors of oral health status.

Conclusions:  The oral health of children in Wonsan, North Korea is comparable if not slightly better than the oral health status of children of similar age in countries with similar Social‐Economic Status (SES). Basic oral health screens are useful to produce a snapshot of general oral health status among children in North Korea and may provide insight as to the general health of these children.
Probing the existence of the Epeak–Eiso correlation in long gamma ray bursts
Authors: Ghirlanda Giancarlo , Ghisellini Gabriele , Firmani Claudio
Published: July 2005

We probe the existence of the Epeak–Eiso correlation in long gamma-ray bursts (GRBs) using a sample of 442 BATSE bursts with known Epeak and with redshift estimated through the lag–luminosity correlation. This sample confirms that the rest-frame peak energy is correlated with the isotropic equivalent energy. The distribution of the scatter of the points around the best-fitting line is similar to that obtained with the 27 bursts with spectroscopic redshifts. We interpret the scatter in the Epeak–Eiso plane as due to the opening angle distribution of GRB jets. By assuming that the collimation corrected energy correlates with Epeak we can derive the observed distribution of the jet opening angles, which turns out to be lognormal with a peak value of .
The connection between shear and star formation in spiral galaxies
Authors: Seigar Marc S.
Published: July 2005

We present a sample of 33 galaxies for which we have calculated (i) the average rate of shear from published rotation curves, (ii) the far-infrared luminosity from IRAS fluxes, and (iii) the Ks-band luminosity from the Two Micron All Sky Survey (2MASS). We show that a correlation exists between the shear rate and the ratio of the far-infrared to Ks-band luminosity. This ratio is essentially a measure of the star formation rate per unit mass, or the specific star formation rate. From this correlation we show that a critical shear rate exists, above which star formation would turn off in the discs of spiral galaxies. Using the correlation between shear rate and spiral arm pitch angle, this shear rate corresponds to the lowest pitch angles typically measured in near-infrared images of spiral galaxies.
Evaporation and condensation of H I clouds in thermally bistable interstellar media: semi-analytic description of isobaric dynamics of curved interfaces
Authors: Nagashima Masahiro , Koyama Hiroshi , Inutsuka Shu-ichiro
Published: July 2005

We analyse the evaporation and condensation of spherical and cylindrical H i clouds of the cold neutral medium surrounded by the warm neutral medium. Because the interstellar medium including those two phases is well described as a thermally bistable fluid, it is useful to apply pattern formation theories to the dynamics of the interface between the two phases. Assuming isobaric evolution of fluids and a simple polynomial form of the heat-loss function, we show the curvature effects of the interface. We find that approximate solutions for spherical clouds are in good agreement with numerically obtained solutions. We extend our analysis to general curved interfaces taking into account the curvature effects explicitly. We find that the curvature effects always stabilize curved interfaces under assumptions such as isobaric evolution that we adopt in this Letter.
Parameter space studies for the self-gravity interfacial instability
Authors: Hueckstaedt R. M. , Peterson A. H. , Hunter J. H.
Published: July 2005

Hydrodynamic instabilities play an important role in determining the morphology and evolution of astronomical entities. Any interface of discontinuous density is subject to instabilities, including Rayleigh–Taylor, Kelvin–Helmholtz, and a recently discovered instability driven by self-gravity. In an ongoing computational study, we seek to validate the linear theory developed for the self-gravity-driven interfacial instability and examine its non-linear behaviour. Here, we present the results from hydrodynamic simulations designed to expand the parameter space and investigate the effects of perturbation strength, Atwood number and compressibility.
Lens galaxy environments and anomalous flux ratios in gravitational lenses
Authors: Oguri Masamune
Published: July 2005

The fraction of substructures required to account for anomalous flux ratios in gravitational lens systems appears to be higher than that predicted in the standard cold dark matter cosmology. We present a possible alternative route to anomalous flux ratios from lens galaxy environments. We consider compound lens systems where a lens galaxy lies in a group or cluster, and estimate the contribution of substructures in the group/cluster to the fraction using an analytic model of substructures. We find that the contribution becomes dominant when the impact parameter of the lens is less than ∼30 per cent of the virial radius of the group/cluster. This indicates that environmental effects can partly explain the high incidence of anomalous flux ratios.
Multimodel Ranking and Inference in Ground Water Modeling
Authors: Poeter Eileen , Anderson David
Published: July 2005

Uncertainty of hydrogeologic conditions makes it important to consider alternative plausible models in an effort to evaluate the character of a ground water system, maintain parsimony, and make predictions with reasonable definition of their uncertainty. When multiple models are considered, data collection and analysis focus on evaluation of which model(s) is(are) most supported by the data. Generally, more than one model provides a similar acceptable fit to the observations; thus, inference should be made from multiple models. Kullback‐Leibler (K‐L) information provides a rigorous foundation for model inference that is simple to compute, is easy to interpret, selects parsimonious models, and provides a more realistic measure of precision than evaluation of any one model or evaluation based on other commonly referenced model selection criteria. These alternative criteria strive to identify the true (or quasi‐true) model, assume it is represented by one of the models in the set, and given their preference for parsimony regardless of the available number of observations the selected model may be underfit. This is in sharp contrast to the K‐L information approach, where models are considered to be approximations to reality, and it is expected that more details of the system will be revealed when more data are available. We provide a simple, computer‐generated example to illustrate the procedure for multimodel inference based on K‐L information and present arguments, based on statistical underpinnings that have been overlooked with time, that its theoretical basis renders it preferable to other approaches.
School Tobacco Policies in a Tobacco‐Growing State
Authors: Hahn Ellen J. , Rayens Mary Kay , Rasnake Rob , York Nancy , Okoli Chizimuzo T.C. , Riker Carol A.
Published: July 2005

Abstract: This study examined factors associated with tobacco‐free policies and tobacco cessation in schools serving children in grades 6 to 12 in a tobacco‐growing state using a cross‐sectional telephone survey of school administrators from public and private middle and high schools (N = 691), representing 117 of the 120 Kentucky counties. Trained health department staff contacted 1028 schools; 691 (67%) participated in a phone survey, which lasted an average of 19 minutes. Variables of interest were indoor and outdoor smoking policies, fund‐raising in Bingo halls, provision of cessation and prevention programs, owning or leasing a tobacco base, if the school received money from tobacco companies, type of school (public vs private), and school setting (urban vs rural). Only 20% of Kentucky schools reported comprehensive tobacco‐free policies. Urban area schools were nearly twice as likely to have a tobacco‐free campus than rural schools. Schools that did fund‐raising in smoky Bingo halls were 30% less likely to have tobacco‐free school policies. While few schools had a tobacco affiliation, those that received money from tobacco companies or grew tobacco were nearly 3 times as likely to provide cessation resources, compared to schools without tobacco affiliation. Rural schools were less likely to be tobacco free and provide cessation services. School‐related, off‐campus, extracurricular events might be considered as an element of tobacco‐free school policy. Schools with tobacco affiliation may provide more cessation resources due to the increased prevalence of tobacco use in these areas. (J Sch Health. 2005;75(6):219–225)
Do junior doctors know where to insert chest drains safely?
Authors: Griffiths J R , Roberts N
Published: July 2005

Background

The safe insertion of a chest drain is a skill doctors across specialties require. Incorrect placement can lead to significant morbidity and even mortality.

Methods

This audit surveyed junior doctors working in a teaching hospital about their specialty and level of experience with intercostal drains. They were then asked to mark on a photograph where they would insert a chest drain for a pneumothorax in a non-emergency situation.

Results

Of the 55 junior doctors surveyed, 45% were outside the safe area of chest drain insertion as defined by the British Thoracic Society. The most common error was a choice of insertion site too low (24%).

Conclusions

In this audit 45% of juniors surveyed would have placed a chest drain outside the safe triangle recommended by the British Thoracic Society. The common mistake of a choice of insertion site too low should be discussed in postgraduate teaching programmes.
Clinical associations of Dupuytren’s disease
Authors: Hart M G , Hooper G
Published: July 2005

Dupuytren’s disease (DD) is a common progressive fibrotic condition affecting the palmar and digital fascia. Although its management is undertaken by hand surgeons, it is commonly seen by other doctors as an incidental finding. In many cases it is believed to be associated with other medical conditions, although the evidence for such associations is not always clear. This review considers the evidence behind these associations and discusses the aetiology of DD. By doing so, it is hoped that this review will permit a better understanding of the relevance of DD as a clinical sign.
It is time to test low level laser therapy in Great Britain
Authors: Moshkovska T , Mayberry J
Published: July 2005

Low level laser therapy (LLLT) has been used in Eastern Europe and Asia for the treatment of a wide range of conditions for many years. Its continued acceptance in these populations reflects the efficacy with which it is regarded both by clinicians and their patients. Although there have been a substantial number of reports on its clinical benefit and some practitioners have used the technique in North America and Australasia it has yet to be subjected to detailed assessment through randomised clinical trials. The purpose of this review is to stimulate interest in the technique and to encourage rigorous research into its potential value.
Co-morbidity in general practice
Authors: Saltman D C , Sayer G P , Whicker S D
Published: July 2005

Background

Co-morbidity, or the presence of more than one clinical condition, is gaining increased attention in epidemiological and health services research. However, the clinical relevance of co-morbidity has yet to be defined. In general practice, few studies have been conducted into co-morbidity, either at a single health care encounter, an episode of care, or for a defined time period.

Aims

To describe the major co-morbidity cluster profiles recorded by general practitioners. Another aim of this study is to describe the common clusters of co-prescribing.

Methods and results

Twelve month data from patients attending 156 GPs from 95 practices around a six month period of January to June 2003 were analysed. This represented 840 961 encounters from about 200 000 individual patients at these participating practices. Co-morbidity and co-prescribing cluster profiles are represented by problems managed and reasons for prescribing for the top 10 presentations and top 10 prescribed drugs in the study period.

Conclusions

By analysing the 10 most prevalent problems and 10 most prevalent drugs prescribed in consultations in a community sample, other co-morbidities that are particular to general practice, for example hypertension and lipid disorders, can be uncovered. Whether these clusters are causally related or occur by chance requires further analysis.
Approach to the patient with epilepsy in the outpatient department
Authors: Hadjikoutis S , Smith P E M
Published: July 2005

Epilepsy is common and serious (prevalence 750 per 100 000) and has an impact upon employment, education, and driving. The diagnosis requires a detailed history including witness account. Clinicians must distinguish seizures particularly from syncope and psychogenic attacks. Electroencephalography and magnetic resonance brain scanning help to identify causes and classification of epilepsy, but alone rarely provide the diagnosis. Antiepileptic drug treatment is required long term and is potentially hazardous; patients should start treatment only after informed discussion with an epilepsy specialist. Patients require reliable written information, particularly the driving regulations, and the impact of seizures on employment, education, and leisure. Women must understand the potential drug teratogenic effects. Certain patient groups benefit from targeted epilepsy services, for example, learning disabled, children, teenagers, and elderly. People with epilepsy require long term specialist follow up. Although this is currently provided in mainly in secondary care (including nurse led clinics), improved liaison with primary care should enable improved access to epilepsy services. Epilepsy care should be multidisciplinary and long term, linking primary and secondary care, and empowering patients towards improved management of their condition.
Functional abdominal pain
Authors: Matthews P J , Aziz Q
Published: July 2005

Functional abdominal pain or functional abdominal pain syndrome (FAPS) is an uncommon functional gut disorder characterised by chronic or recurrent abdominal pain attributed to the gut but poorly related to gut function. It is associated with abnormal illness behaviour and patients show psychological morbidity that is often minimised or denied in an attempt to discover an organic cause for symptoms. Thus the conventional biomedical approach to the management of such patients is unhelpful and a person’s symptom experience is more usefully investigated using a biopsychosocial evaluation, which necessarily entails a multidisciplinary system of healthcare provision. Currently the pathophysiology of the disorder is poorly understood but is most likely to involve a dysfunction of central pain mechanisms either in terms of attentional bias, for example, hypervigilance or a failure of central pain modulation/inhibition. Although modern neurophysiological investigation of patients is promising and may provide important insights into the pathophysiology of FAPS, current clinical management relies on an effective physician-patient relationship in which limits on clinical investigation are set and achievable treatment goals tailored to the patient’s needs are pursued.
Disease progression and adverse events in patients listed for elective percutaneous coronary intervention
Authors: Talwar S , Karpha M , Thomas R , Vurwerk C , Cox I C , Burrell C J , Motwani J G , Gilbert T J , Haywood G A
Published: July 2005

Objective

To record disease progression and the timing of adverse events in patients on a waiting list for elective percutaneous coronary intervention (PCI).

Design

Observational prospective study.

Settings

A UK tertiary cardiothoracic centre, at a time when waiting lists for PCI were up to 18 months.

Patients

145 patients (116 men, median age 59.5 years) placed on an elective waiting list for PCI between October 1998 and September 1999.

Main outcome measures

Adverse events recorded were death, myocardial infarction, need for urgent hospital admission because of unstable angina, and need for emergency revascularisation while waiting for PCI.

Results

During a median follow up of 10 months (range 1–18 months), nine (6.2%) patients experienced an adverse event. Eight (5.52%) patients were admitted with unstable angina as emergencies. One was admitted with a myocardial infarction. Twenty nine (20.0%) patients had significant disease progression at the time of the repeat angiogram before PCI. In 10 (7%), disease had progressed so that PCI was no longer feasible and patients were referred for coronary artery bypass graft. Sixteen (11%) were removed from the PCI waiting list because of almost complete resolution of their anginal symptoms.

Conclusion

Adverse coronary events and clinically significant disease progression occur commonly in patients waiting for PCI. Despite the presence of severe coronary lesions, myocardial infarction was rare and no patients died while on the waiting list. Resolution of anginal symptoms was also comparatively common. The pathophysiology of disease progression frequently necessitates a change in the treatment of patients waiting for PCI.
THE DESIGN PRINCIPLES AND ALGORITHMS OF A WEIGHTED GRAMMAR LIBRARY
Authors: ALLAUZEN CYRIL , MOHRI MEHRYAR , ROARK BRIAN
Published: July 2005

We present the software design principles, algorithms, and utilities of a general weighted grammar library, the GRM Library, that can be used in a variety of applications in text, speech, and biosequence processing. Several of the algorithms and utilities of this library are described, including in some cases their pseudocodes and pointers to their use in applications. The algorithms and the utilities were designed to support a wide variety of semirings and the representation and use of large grammars and automata of several hundred million rules or transitions.
UNSOLVABILITY LEVELS OF OPERATION PROBLEMS FOR SUBCLASSES OF CONTEXT-FREE LANGUAGES
Authors: BORDIHN HENNING , HOLZER MARKUS , KUTRIB MARTIN
Published: July 2005

We investigate the operation problem for linear and deterministic context-free languages: Fix an operation on formal languages. Given linear (deterministic, respectively) context-free languages, is the application of this operation to the given languages still a linear (deterministic, respectively) context-free language? Besides the classical operations, for which the linear and deterministic context-free languages are not closed, we also consider the recently introduced root and power operation. We show non-semi-decidability, to be more precise, we show completeness for the second level of the arithmetic hierarchy for all of the aforementioned operations, except for the power operation, if the underlying alphabet contains at least two letters. The result for the power operation solves an open problem stated in Theoret. Comput. Sci.314 (2004) 445–449.
BRUTE FORCE DETERMINIZATION OF NFAs BY MEANS OF STATE COVERS
Authors: CHAMPARNAUD J.-M. , COULON F. , PARANTHOËN T.
Published: July 2005

Finite automata determinization is a critical operation for numerous practical applications such as regular expression search. Algorithms have to deal with the possible blow up of determinization. There exist solutions to control the space and time complexity like the so called "on the fly" determinization. Another solution consists in performing brute force determinization, which is robust and technically fast, although a priori its space complexity constitutes a weakness. However, one can reduce this complexity by perfoming a partial brute force determinization. This paper provides optimizations that consist in detecting classes of unreachable states and transitions of the subset automaton, which leads in average to an exponential reduction of the complexity of brute force and partial brute force determinization.
AN AUTOMATA APPROACH TO MATCH GAPPED SEQUENCE TAGS AGAINST PROTEIN DATABASE
Authors: HAN YONGHUA , MA BIN , ZHANG KAIZHONG
Published: July 2005

In Biochemistry, tandem mass spectrometry (MS/MS) is the most common method for peptide and protein identifications. One computational method to get a peptide sequence from the MS/MS data is called de novo sequencing, which is becoming more and more important in this area. However De novo sequencing usually can only confidently determine partial sequences, while the undetermined parts are represented by "mass gaps". We call such a partially determined sequence a gapped sequence tag. When a gapped sequence tag is searched in a database for protein identification, the determined parts should match the database sequence exactly, while each mass gap should match a substring of amino acids whose masses add up to the value of the mass gap. In such a case, the standard string matching algorithm does not work any more. In this paper, we present a new efficient algorithm to find the matches of gapped sequence tags in a protein database.
THE GENERALIZATION OF GENERALIZED AUTOMATA: EXPRESSION AUTOMATA
Authors: HAN YO-SUB , WOOD DERICK
Published: July 2005

We explore expression automata with respect to determinism and minimization. We define determinism of expression automata using prefix-freeness. This approach is, to some extent, similar to that of Giammarresi and Montalbano's definition of deterministic generalized automata. We prove that deterministic expression automata languages are a proper subfamily of the regular languages. We close by defining the minimization of deterministic expression automata.
STATE COMPLEXITY OF CONCATENATION AND COMPLEMENTATION
Authors: JIRÁSEK JOZEF , JIRÁSKOVÁ GALINA , SZABARI ALEXANDER
Published: July 2005

We investigate the state complexity of concatenation and the nondeterministic state complexity of complementation of regular languages. We show that the upper bounds on the state complexity of concatenation are also tight in the case that the first automaton has more than one accepting state. In the case of nondeterministic state complexity of complementation, we show that the entire range of complexities, up to the known upper bound can be produced.
STATE COMPLEXITY AND THE MONOID OF TRANSFORMATIONS OF A FINITE SET
Authors: KRAWETZ BRYAN , LAWRENCE JOHN , SHALLIT JEFFREY
Published: July 2005

In this paper we consider the state complexity of an operation on formal languages, root(L). This naturally entails the discussion of the monoid of transformations of a finite set. We obtain good upper and lower bounds on the state complexity of root(L) over alphabets of all sizes. As well, we present an application of these results to the problem of 2DFA-DFA conversion.
APPROXIMATING DEPENDENCY GRAMMARS THROUGH INTERSECTION OF STAR-FREE REGULAR LANGUAGES
Authors: YLI-JYRÄ ANSSI
Published: July 2005

The paper formulates the Hays and Gaifman dependency grammar (HGDG) in terms of constraints on a string based encoding of dependency trees and develops an approach to obtain a regular approximation for these grammars. Our encoding of dependency trees uses brackets in a novel fashion: pairs of brackets indicate dependencies between pairs of positions rather than boundaries of phrases. This leads to several advantages: (i) HGDG rules over the balanced bracketing can be expressed using regular languages. (ii) A new homomorphic representation for context-free languages is obtained. (iii) A star-free regular approximation for the original projective dependency grammar is obtained by limiting the number of stacked dependencies. (iv) By relaxing certain constraints, the encoding can be extended to non-projective dependency trees and graphs, (v) strong generative power of HGDGs can now be characterized through sets of bracketed strings.
ONLINE SCHEDULING OF UNIT JOBS WITH BOUNDED IMPORTANCE RATIO
Authors: FUNG STANLEY P. Y. , CHIN FRANCIS Y. L. , SHEN HONG
Published: July 2005

We consider the following online scheduling problem. We are given a set of jobs, each having an integral release time and deadline, unit processing length, and a nonnegative real weight. In each time unit one job is to be scheduled, and the objective is to maximize the total value (weight) obtained by scheduling the jobs. This problem arises in the scheduling of packets in network switches supporting quality-of-service (QoS). Previous algorithms for this problem are 2-competitive.

In this paper we propose a new algorithm that achieves an improved competitive ratio when the importance ratio is bounded. Specifically, for job weights within the range [1..B], our algorithm is 2 - 1/(⌈ lg B⌉ + 2)-competitive, and the bound is tight.
LANGUAGE FAMILIES DEFINED BY A CILIATE BIO-OPERATION: HIERARCHIES AND DECISION PROBLEMS
Authors: DASSOW JÜRGEN , HOLZER MARKUS
Published: July 2005

We formalize the hairpin inverted repeat excision, which is known in ciliate genetics as an operation on words and languages by defining [Formula: see text] as the set of all words xαyRαRz where w = xαyαRz and the pointer α is in P. We extend this concept to language families which results in families [Formula: see text]. For [Formula: see text] and [Formula: see text] be the families of finite, regular, context-free, context-sensitive or recursively enumerable language, respectively, we determine the hierarchy of the families [Formula: see text] and compare these families with those of the Chomsky hierarchy. Furthermore, we present the status of decidability of the membership problem, emptiness problem and finiteness problem for the families [Formula: see text].
ON VARIOUS NOTIONS OF PARALLELISM IN P SYSTEMS
Authors: IBARRA OSCAR H. , YEN HSU-CHUN , DANG ZHE
Published: July 2005

We consider the following definition (different from the standard definition in the literature) of "maximal parallelism" in the application of evolution rules in a P system G: Let R = {r1, …rk} be the set of (distinct) rules in the system. G operates in maximally parallel mode if at each step of the computation, a maximal subset of R is applied, and at most one instance of any rule is used at every step (thus at most k rules are applicable at any step). We refer to this system as a maximally parallel system. We look at the computing power of P systems under three semantics of parallelism. For a positive integer n ≤ k, define:

n-Max-Parallel: At each step, nondeterministically select a maximal subset of at most n rules in R to apply (this implies that no larger subset is applicable).

≤ n-Parallel: At each step, nondeterministically select any subset of at most n rules in R to apply.

n-Parallel: At each step, nondeterministically select any subset of exactly n rules in R to apply.

In all three cases, if any rule in the subset selected is not applicable, then the whole subset is not applicable. When n = 1, the three semantics reduce to the Sequential mode.

We focus on two popular models of P systems: multi-membrane catalytic systems and communicating P systems. We show that for these systems, n-Max-Parallel mode is strictly more powerful than any of the following three modes: Sequential, ≤ n-Parallel, or n-Parallel. For example, it follows from the result in [9] that a maximally parallel communicating P system is universal for n = 2. However, under the three limited modes of parallelism, the system is equivalent to a vector addition system, which is known to only define a recursive set. These generalize and refine the results for the case of 1-membrane systems recently reported in [3]. Some of the present results are rather surprising. For example, we show that a Sequential 1-membrane communicating P system can only generate a semilinear set, whereas with k membranes, it is equivalent to a vector addition system for any k ≥ 2 (thus the hierarchy collapses at 2 membranes - a rare collapsing result for nonuniversal P systems). We also give another proof (using vector addition systems) of the known result [8] that a 1-membrane catalytic system with only 3 catalysts and (non-prioritized) catalytic rules operating under 3-Max-Parallel mode can simulate any 2-counter machine M. Unlike in [8], our catalytic system needs only a fixed number of noncatalysts, independent of M.

A simple cooperative system (SCO) is a P system where the only rules allowed are of the form a → v or of the form aa → v, where a is a symbol and v is a (possibly null) string of symbols not containing a. We show that a 9-Max-Parallel 1-membrane SCO is universal.
RELATING TREE SERIES TRANSDUCERS AND WEIGHTED TREE AUTOMATA
Authors: MALETTI ANDREAS
Published: July 2005

Bottom-up tree series transducers (tst) over the semiring [Formula: see text] are implemented with the help of bottom-up weighted tree automata (wta) over an extension of [Formula: see text]. Therefore bottom-up [Formula: see text]-weighted tree automata ([Formula: see text]-wta) with [Formula: see text] a distributive Ω-algebra are introduced. A [Formula: see text]-wta is essentially a wta but uses as transition weight an operation symbol of the Ω-algebra [Formula: see text] instead of a semiring element. The given tst is implemented with the help of a [Formula: see text]-wta, essentially showing that [Formula: see text]-wta are a joint generalization of tst (using IO-substitution) and wta. Then a semiring and a wta are constructed such that the wta computes a formal representation of the semantics of the [Formula: see text]-wta. The applicability of the obtained presentation result is demonstrated by deriving a pumping lemma for deterministic finite [Formula: see text]-wta from a known pumping lemma for deterministic finite wta. Finally, it is observed that the known decidability results for emptiness cannot be applied to obtain decidability of emptiness for finite [Formula: see text]-wta. Thus with help of a weaker version of the derived pumping lemma, decidability of the emptiness problem for finite [Formula: see text]-wta is shown under mild conditions on [Formula: see text].
AN NP-COMPLETE FRAGMENT OF LTL
Authors: MUSCHOLL ANCA , WALUKIEWICZ IGOR
Published: July 2005

A fragment of linear time temporal logic (LTL) is presented. It is proved that the satisfiability problem for this fragment is NP-complete. The fragment is larger than previously known NP-complete fragments. It is obtained by prohibiting the use of until operator and requiring to use only next operators indexed by a letter.
INFINITE ITERATED FUNCTION SYSTEMS IN CANTOR SPACE AND THE HAUSDORFF MEASURE OF ω-POWER LANGUAGES
Authors: STAIGER LUDWIG
Published: July 2005

We use means of formal language theory to estimate the Hausdorff measure of sets of a certain shape in Cantor space. These sets are closely related to infinite iterated function systems in fractal geometry.

Our results are used to provide a series of simple examples for the non-coincidence of limit sets and attractors for infinite iterated function systems.