bluuebunny/crossref_metadata_2025 huggingface dataset:
Adaptation of the diaphragm and the vastus lateralis in mild-to-moderate COPD
Authors: Doucet M. , Debigaré R. , Joanisse D.R. , Côté C. , LeBlanc P. , Grégoire J. , Deslauriers J. , Vaillancourt R. , Maltais F.
Published: November 2004

The chronology of diaphragm and vastus lateralis adaptation in chronic obstructive pulmonary disease (COPD) has not been studied. The hypothesis of this study was that muscle changes would occur earlier in the diaphragm than in the vastus lateralis in COPD, a finding that would suggest that local factors would be more important than systemic factors in determining the muscle phenotypic expression, at least in mild-to-moderate disease.

The adaptation of the vastus lateralis and diaphragm muscles was evaluated in patients with mild-to-moderate COPD and in subjects with normal pulmonary function.

In both groups, the oxidative potential and the number of lipofuscin inclusions were higher in the diaphragm than in the vastus lateralis. Compared to control, the diaphragm in COPD had a higher oxidative capacity and a higher proportion of type I fibres, with a reciprocal decrease in type IIA fibres, while there was no difference in diaphragmatic cross sectional areas, capillarisation and lipofuscin inclusions. No significant differences were found in the vastus lateralis from both groups.

In conclusion, these data indicate that the diaphragm in controls and in chronic obstructive pulmonary disease has a higher oxidative potential than the vastus lateralis, and that muscle adaptation occurs earlier in the diaphragm than in the vastus lateralis in mild-to-moderate chronic obstructive pulmonary disease.
A prospective study of asthma incidence and its predictors: the RHINE study
Authors: Torén K. , Gislason T. , Omenaas E. , Jögi R. , Forsberg B. , Nyström L. , Olin A-C. , Svanes C. , Janson C.
Published: November 2004

The objective of this longitudinal study was to estimate the incidence rate of asthma, and to compare the incidence between subjects with or without baseline reporting of certain respiratory symptoms.

A follow-up of the random population samples in the European Respiratory Health Survey (ECRHS) in Sweden, Norway, Denmark, Iceland and Estonia was conducted in 1999–2001, in a population aged 30–54 yrs at follow-up (n=14,731). Asthma was defined as reporting either asthma or physician-diagnosed asthma, and a reported year when asthma symptoms were first noticed. Incidence rates, incidence rate ratios and hazard ratios were calculated with 95% confidence intervals.

The incidence rate of asthma was 2.2 cases per 1,000 person-yrs. The incidence was higher among females (2.9 cases·1,000 person-yrs−1) than among males (1.5 cases·1,000 person-yrs−1). When subjects with baseline reporting of wheezing were excluded, the incidence rate decreased to 1.7 cases·1,000 person-yrs−1, with a further decrease to 1.5 cases·1,000 person-yrs−1after exclusion of subjects with wheezing, nocturnal dyspnoea, chest tightness and cough. There was a strong association between onset of asthma and wheezing at baseline.

In this prospective, population-based study, the incidence rate of asthma in the whole population sample ranged 1.5–2.2·1,000 person-yrs−1, with a higher incidence range among females. The incidence was dependent on the extent to which subjects with respiratory symptoms were excluded from follow-up. Hence, for comparability between studies, the exclusion criteria in the follow-up population must be stated.
Influenza vaccination in asthmatic children: effects on quality of life and symptoms
Authors: Bueving H.J. , van der Wouden J.C. , Raat H. , Bernsen R.M.D. , de Jongste J.C. , van Suijlekom-Smit L.W.A. , Osterhaus A.D.M.E. , Rimmelzwaan G.F. , Mölken M. Rutten-van , Thomas S.
Published: November 2004

This study aimed to detect the effect of influenza vaccination on quality of life, symptomatology and spirometry in asthmatic children.

A randomised double-blind placebo-controlled trial in 696 (296 in 1999–2000 and 400 in 2000–2001) asthmatic children aged 6–18 yrs, which were vaccinated with either vaccine or placebo, was performed. Children participated for only one influenza season. They recorded symptoms in a diary and reported when symptom scores reached a predefined severity level. If this occurred research nurses visited them twice, first to take a pharyngeal swab and spirometry, and a week later to assess quality of life over the past illness week.

Compared with placebo, vaccination improved health-related quality of life in the weeks of illness related to influenza-positive swabs. However, no effect was found for respiratory symptoms recorded in the diaries during those weeks. Similarly, no differences were found for quality of life in all weeks of illness or for respiratory symptoms throughout the seasons.

Influenza vaccination was found to have a moderately beneficial effect on quality of life in influenza-positive weeks of illness in children with asthma.
Diagnosis and pharmacotherapy of severe acute respiratory syndrome: what have we learnt?
Authors: Tsang K.W. , Ooi G.C. , Ho P.L.
Published: November 2004

In 2003, the onset of severe acute respiratory syndrome (SARS) caused worldwide chaos. Although SARS was eradicated by isolation towards the end of 2003, sporadic cases have been reported in Singapore, Taiwan and mainland China.

In this review, SARS is discussed as a disease, as well as its diagnosis, management and pharmacotherapy.

Respiratory physicians and healthcare professionals have to be aware of advances in the understanding of the diagnosis and management of severe acute respiratory syndrome. More research is required in order to prepare for if this respiratory infection recurs, but there are concerns that adequate pharmaceutical support may be lacking for the development of a vaccine.
Lung cancer: clinical presentation and specialist referral time
Authors: Buccheri G. , Ferrigno D.
Published: November 2004

Many textbooks describe symptoms and signs of lung cancer but refer to old series of patients.

To update knowledge about lung cancer presentation, a study was carried out on 1,277 consecutive lung cancer patients, who were seen in a single Institution from January 1989 to October 2002. A set of 33 anthropometric, clinical, physical, laboratory, radiological, pathological and follow-up variables was prospectively recorded for all patients. In addition, information was obtained concerning symptoms of alarm (i.e.potential concern), times to specialist referral and the mix of symptoms at presentation. Patients were carefully followed-up and their subsequent clinical course was recorded.

Casual discovery with absence of symptoms occurred more frequently towards the end of the study period and the prevalence of chest pain became less common. No other time-dependent changes were found in the presenting symptoms. Delay in specialist referral was longer when presentation was provoked by cough or by the occurrence of systemic symptoms, such as weight loss, anorexia and asthenia. Referral delay was longer towards the end of the study, perhaps related to an increase in the number of elderly patients with co-morbidities. Both alarm and prevalence symptoms were strong predictors of the clinical outcome, as found in both univariate analysis (favourable: casual discovery and chest infection; unfavourable: chest pain, dyspnoea, systemic symptoms and symptoms of local or systemic dissemination) and in multivariate analysis (favourable: chest infection).

Early presentation of lung cancer is characterised by a specific symptomatic pattern. Knowledge of this pattern may help to improve the rate of early diagnosis.
Alveolar antioxidant status in patients with acute respiratory distress syndrome
Authors: Schmidt R. , Luboeinski T. , Markart P. , Ruppert C. , Daum C. , Grimminger F. , Seeger W. , Günther A.
Published: November 2004

In the acutely inflamed lung, oxidant stress occurs within the alveolar compartment. Under these conditions, the regulation of low molecular weight antioxidants in the epithelial lining fluid is poorly understood. Therefore, antioxidant levels were measured in the bronchoalveolar lavage fluid (BALF) of patients with acute respiratory distress syndrome (ARDS; n=40) and in healthy volunteers (n=20).

Reduced glutathione (GSH), oxidised glutathione (GSSG; enzymatic assay), retinol (vitamin A), α-tocopherol (vitamin E), ascorbic acid (vitamin C), uric acid (all by HPLC), plasmalogens (1-alkenyl-2-acyl phospholipids), polyunsaturated fatty acids (PUFA; both by gas–liquid chromatography), and F2-isoprostanes (ELISA) were quantified. All values are expressed as concentrations in cell-depleted BALF.

GSSG (ARDS: 0.13±0.02 µM; control: 0.03±0.01 µM; mean±sem) and F2-isoprostanes (ARDS: 78±10 pM; control: 26±5 pM) were increased in ARDS, thus indicating oxidant stress. GSH levels in patients did not change significantly, whereas concentrations of vitamins A and C, vitamin E (ARDS: 77±15 nM; control: 26±3 nM) and uric acid (ARDS: 11.8±2.2 µM; control: 0.7±0.0 µM) were significantly elevated in ARDS. PUFA of total lipids, which may act as sacrificial antioxidants, increased by a factor of ∼3 in patients, but plasmalogens showed a significant decrease.

In conclusion, low molecular weight antioxidants are elevated in the alveolar compartment of patients with acute respiratory distress syndrome. Further research is warranted to elucidate the molecular mechanisms underlying this finding.
Frontal brain lobe impairment in obstructive sleep apnoea: a proton MR spectroscopy study
Authors: Alchanatis M. , Deligiorgis N. , Zias N. , Amfilochiou A. , Gotsis E. , Karakatsani A. , Papadimitriou A.
Published: November 2004

Patients with obstructive sleep apnoea syndrome frequently have cognitive deficits, especially related to executive functions, which cannot be fully explained by daytime sleepiness and are partial irreversible after nasal continuous positive airway pressure treatment. The causal mechanism of these cognitive deficits is not yet known, but it has been proposed that they are associated with chemical and structural brain cell injury. The aim of this study was to investigate brain metabolism in patients with sleep apnoea syndrome.

Twenty-two patients with severe sleep apnoea and 10 healthy volunteers of comparable age were studied using single voxel proton magnetic resonance spectroscopy. Magnetic resonance spectra were obtained from prefrontal cortex, parieto-occipital and frontal periventricular white matter.

N-acetylaspartate-to-creatine and choline-to-creatine ratios were significantly lower in the frontal white matter of obstructive sleep apnoea patients when compared to controls. Absolute concentrations ofN-acetylaspartate and choline were also significantly reduced in the frontal white matter of patients with sleep apnoea.

Frontal lobe white matter lesions are known to be associated with cognitive executive dysfunction. The findings of this study may offer an explanation for the sometimes irreversible cognitive deficits associated with sleep apnoea.
Granulocyte markers in hypertonic and isotonic saline-induced sputum of asthmatic subjects
Authors: Cianchetti S. , Bacci E. , Ruocco L. , Bartoli M.L. , Ricci M. , Pavia T. , Dente F.L. , Di Franco A. , Vagaggini B. , Paggiaro P.L.
Published: November 2004

The aim of this study was to assess whether hyperosmolarity affects granulocyte mediator levels in induced sputum of asthmatic subjects.

A total of 32 mild-to-moderate asthmatics, who inhaled either hypertonic (HS; 4.5% NaCl) or isotonic (IS; 0.9% NaCl) solutions for 15 min, were studied. Selected sputum was used for analysis. Eosinophil cationic protein (ECP), eosinophil protein X (EPX), myeloperoxidase (MPO) and free neutrophil elastase (NE) were measured in sputum supernatant.

Sample weight, total and differential cell counts, as well as viability and squamous cell percentage were no different after the two tests. No significant differences in ECP, EPX, MPO or NE levels were observed between HS- and IS-induced sputum. Repeatability of the two tests was good for macrophages, neutrophils, eosinophils, ECP, EPX and NE, but not for lymphocytes and MPO.

In conclusion, hyperosmolarity does not affect sputum cell counts and the levels of most granulocyte degranulation markers examined in this study, confirming that both hypertonic and isotonic solutions can be reliably used to induce sputum in asthmatics.
Treatment of exercise-induced asthma with beclomethasone dipropionate in children with asthma
Authors: Petersen R. , Agertoft L. , Pedersen S.
Published: November 2004

A new hydrofluoroalkane-beclomethasone dipropionate (HFA-BDP) aerosol markedly increases drug delivery to the airways. Therefore, even low doses of HFA-BDP should be effective, and the present study assesses this.

A randomised, double-blind, crossover study was used to compare the effect of placebo, HFA-BDP 50 µg or 100 µg givenq.d.(QVARTMAutohalerTM; 3M Pharmaceuticals, St. Paul, MN, USA) on exercise-induced bronchoconstriction and exhaled nitric oxide (eNO). After a 14-day run-in, 25 children (5–14 yrs old) entered three 4-week treatment periods, separated by a 1-week washout. After each period, the fall in forced expiratory volume in one second (FEV1), after an exercise test, and eNO were measured.

Significant treatment effects with no carry-over or period effects were seen for both eNO and maximum fall in FEV1after exercise. Differences were seen between placebo (fall in FEV1=27.9%; eNO=14.4 parts per billion (ppb)) and either dose of HFA-BDP, but not between the two active doses (50 µg: fall in FEV1=20.8%, eNO=9.3 ppb; 100 µg: fall in FEV1=20.9%, eNO=8.9 ppb).

In conclusion, lowq.d.doses of hydrofluoroalkane-beclomethasone dipropionate reduced exhaled nitric oxide and exercise-induced bronchoconstriction. Further studies are needed to assess whetherq.d.administration of beclomethasone dipropionate is as effective asb.i.d.administration.
Pramipexole in unipolar and bipolar depression
Authors: Whiskey Eromona , Taylor David
Published: November 2004

Aims and Method

To review the evidence for this use of pramipexole in the treatment of unipolar and bipolar depression, a literature search on Embase and Medline was conducted in December 2003. The search was updated in July 2004. The reference sections of retrieved papers were searched for further relevant references.

Results

There are limited data on the clinical use of pramipexole in affective disorders. Only two double-blind trials in bipolar depression and one in unipolar depression were retrieved. Most information is in the form of case reports and open studies. No dose-response relationships have been established and a wide range of doses has been employed in the reports.

Clinical Implications

In view of the fact that the evidence for the use of pramipexole is still limited at the time of writing, its routine clinical use cannot be recommended. The data appear promising, but further research is required to determine its role in affective disorders.
Psychiatry as a career choice compared with other specialties: A survey of medical students
Authors: Rajagopal Sundararajan , Rehill Kamaljit Singh , Godfrey Emma
Published: November 2004

Aims and Method

The aim of this study was to determine the attitudes of medical students in the UK towards different specialties as career options and to ascertain the position of psychiatry among these specialties. Students belonging to a London medical school completed a questionnaire.

Results

Among the 301 students who completed the survey, psychiatry was the least popular clinical specialty. The study revealed that the students had a number of misconceptions about psychiatry. A family history of mental illness was significantly associated with choosing psychiatry as a career.

Clinical Implications

Considering the unpopularity of the specialty, it is likely that recruitment of psychiatrists will continue to be a major problem for the foreseeable future. Measures need to be taken to dispel the misconceptions about psychiatry.
Audit of the use of psychotropic medication for challenging behaviour in a community learning disability service
Authors: Marshall Tom
Published: November 2004

Aims and Method

The aims of the study were to identify patients in a community learning disability service receiving psychotropic medication for challenging behaviour, to examine prescribing practice and to compare this against local consensus standards. Local consensus standards were agreed by the consultants and the notes were reviewed by the author.

Results

A total of 102 patients were identified as receiving psychotropic medication for challenging behaviour (26.7% of notes examined). The most common additional diagnoses were autism (29%) and epilepsy (28%). The average duration of treatment was 5.3 years, and multiple drugs were used in 34% of these patients. Antipsychotics were the most commonly used drugs (96% of patients). There was rarely a detailed description of the challenging behaviour. There was little regular monitoring of side-effects or warning about potential side-effects when the medication was started.

Clinical Implications

Challenging behaviour is a common cause of multiple prescribing in learning disability patients, and is often long-term in the absence of a strong evidence base. Other specialties use medication to control disturbed behaviour, particularly in people with dementia or personality disorder, so this audit may also be of interest to old age, adult and forensic psychiatrists.
Experience of stigma among Chinese mental health patients in Hong Kong
Authors: Chung K. F. , Wong M. C.
Published: November 2004

Aims and Method

The study was intended to rectify the lack of data on how Chinese people experience the stigma of mental illness. A questionnaire on perceived stigmatisation, experiences of rejection and ways of coping with stigma was completed by 193 persons attending a psychiatric out-patient clinic in Hong Kong.

Results

Most of the participants were aware of the stigma associated with mental illness, but experiences of rejection were relatively less frequent. Eleven per cent of the respondents indicated that they were neglected by health care professionals and 8% had been avoided by family members. The most frequently reported coping method was maintaining secrecy about the illness.

Clinical Implications

In China, people with mental health problems experience stigma in various degrees. However, some of the people surveyed expressed feelings of relief that others were supportive and sympathetic towards their illness. Mental health professionals should maintain optimism in helping their patients to cope with the stigma.
What if Santa died? Childhood myths and development
Authors: Breen Lynda
Published: November 2004

Disenchantment with Santa Claus is a rite of passage that usually signals the adoption of an adult-defined reality. The ethics of the custom, which has been described as misleading, have recently been debated and there are suggestions that it is less well maintained than in previous years. This short article explores some of the sociocognitive benefits of promoting the Santa Claus tale and its associated customs. Sociological theories suggest benefits in family bonding and pro-social behaviour, including sharing. Cognitive theories describe enhanced fantastical thinking, expansion of the internal object world and purposeful play. Children may draw parallels between Santa Claus and God, although there is no current evidence that finding out he does not exist impairs their subsequent capacity for religious faith. Whether or not the fable is a threat to the child's trust is to be decided by each parent. On balance, the tale of Santa Claus is a powerful tool that may serve to nurture social and cognitive development, particularly in a technological society where children mature earlier.
Epidermal Growth Factor Receptor (EGFR) Status in Primary Colorectal Tumors Does Not Correlate With EGFR Expression in Related Metastatic Sites: Implications for Treatment With EGFR-Targeted Monoclonal Antibodies
Authors: Scartozzi Mario , Bearzi Italo , Berardi Rossana , Mandolesi Alessandra , Fabris Guidalberto , Cascinu Stefano
Published: November 2004

Purpose

We hypothesized that the detection of epidermal growth factor receptor (EGFR) expression performed in primary tumors for treatment with EGFR-targeted monoclonal antibodies could not always correlate with EGFR status in metastatic sites, thus making cancer cells in these sites resistant to therapy. The aim of our study was to correlate EGFR expression on primary tumors and related metastases in order to find out whether assessing EGFR status on primary cancer is to be considered an effective tool for planning treatment with EGFR-targeted antibodies.

Patients and Methods

We retrospectively evaluated EGFR immunohistochemistry from primary tumors and related metastatic sites in 99 colorectal cancer patients. The site of primary tumor was colon in 77 patients (78%) and rectum in 22 patients (22%). Metastatic sites analyzed were liver in 84 patients (81%), lung in 13 patients (13%), bone in one patient (1%), and brain in five patients (5%). EGFR status was defined as positive if the percentage of malignant cells stained was ≥ 1%.

Results

EGFR status was positive in 53 primary tumors (53%). In 19 primary tumors expressing EGFR (36%), the corresponding metastatic site was found negative, whereas it was found positive in seven metastases (15%) from EGFR-negative primary cancers. The difference between these two groups of patients (ie, EGFR-positive to EGFR-negative v EGFR-negative to EGFR-positive) was statistically significant (P = .036).

Conclusion

Our results suggest that the detection of the EGFR in primary colorectal cancer could be inadequate for planning therapy with EGFR-targeted monoclonal antibodies in a considerable proportion of both EGFR-positive and -negative primary tumors (36% and 15%, respectively).
Quality of Life in Patients With Colorectal Cancer 1 Year After Diagnosis Compared With the General Population: A Population-Based Study
Authors: Arndt Volker , Merx Henrike , Stegmaier Christa , Ziegler Hartwig , Brenner Hermann
Published: November 2004

Purpose

Quality of life (QOL) has become an important outcome measure for patients with cancer, but long-term results from population-based studies are rare. The objective of our study was to identify specific limitations of QOL in survivors of colorectal cancer in comparison with men and women from the general population 1 year after diagnosis when acute treatment effects are expected to have declined.

Patients and Methods

QOL was assessed 1 year after diagnosis in a population-based cohort of 439 patients with colorectal cancer from Saarland (Germany) using the EORTC-QLC30 questionnaire. Specific functional and symptom QOL scores were compared with published reference data from the general population.

Results

Of 439 patients, 378 of them survived the first year after tumor diagnosis (86.1%). Of these, 309 returned the questionnaire (response rate, 81.7%). Compared with the general population, colorectal cancer patients scored their physical, role, cognitive, and global health functioning only slightly worse. More severe limitations were observed for the emotional and social functioning scales and for the symptom subscales of fatigue, dyspnea, insomnia, constipation, diarrhea, and financial difficulties. The differences regarding functional and symptom scores were predominantly found in younger age groups whereas older cancer patients and controls rated their health and QOL similarly.

Conclusion

Deficits in emotional and social functioning and specific limitations like fatigue, dyspnea, insomnia, constipation, diarrhea, and financial difficulties are main factors hampering the QOL among colorectal cancer patients and seem to affect predominantly younger patients.
European Intergroup Studies (MMT4-89 and MMT4-91) on Childhood Metastatic Rhabdomyosarcoma: Final Results and Analysis of Prognostic Factors
Authors: Carli M. , Colombatti R. , Oberlin O. , Bisogno G. , Treuner J. , Koscielniak E. , Tridello G. , Garaventa A. , Pinkerton R. , Stevens M.
Published: November 2004

Purpose

Final results are presented from two consecutive European studies for patients with metastatic rhabdomyosarcoma (RMS) to identify prognostic variables and determine the value of high-dose chemotherapy (HDCT) in complete remission.

Patients and Methods

A total of 174 patients aged 3 months to 18 years participated. From 1989 to 1991, patients received four cycles of intensive multiagent chemotherapy. From 1991 to 1995, patients achieving complete remission received consolidation with HDCT. All received local therapy (surgery, radiation therapy) according to response.

Results

At a median follow-up of 8 years, 5-year overall survival (OS) and event-free survival (EFS) for the whole group were 24% and 20%, respectively. No statistical difference was found between HDCT and standard chemotherapy (5-year OS, 36% v 27%; EFS 29% v 23%). Univariate analysis identified primary tumor in parameningeal, extremity, or other sites; age younger than 1 year and older than 10 years; bone or bone marrow metastases; multiple metastases; and multiple sites of metastases as unfavorable prognostic factors for OS and EFS. Multivariate analysis identified unfavorable site, bone or bone marrow involvement, and unfavorable age as independently unfavorable factors. Two subgroups were identified. Those with fewer than two unfavorable factors had 5-year EFS and OS of 40% and 47%, respectively. Patients with ≥ two unfavorable factors had 5-year EFS and OS of 7.5% and 9%, respectively.

Conclusion

A minority of patients with metastatic RMS have better survival than overall results for this population suggest. Those in the highest risk group have such poor survival that they are candidates for first-line novel therapies. There is no evidence that consolidation with HDCT improves outcome.
Short-Term Efficacy of Methylphenidate: A Randomized, Double-Blind, Placebo-Controlled Trial Among Survivors of Childhood Cancer
Authors: Mulhern Raymond K. , Khan Raja B. , Kaplan Stuart , Helton Susan , Christensen Robbin , Bonner Melanie , Brown Ronald , Xiong Xiaoping , Wu Sengjie , Gururangan Sridharan , Reddick Wilburn E.
Published: November 2004

Purpose

Children surviving acute lymphoblastic leukemia (ALL) and malignant brain tumors (BTs) have a higher incidence of attention and learning problems in school than do their healthy peers. The present study tests the hypothesis that the psychostimulant methylphenidate (MPH) improves cognitive and social functioning among these patients.

Patients and Methods

We report on 83 long-term survivors of ALL and BT identified as having attentional deficits on behavioral testing and parent or teacher report, and problems with academic achievement. The 47 male and 36 female patients ranged from 0.6 to 14.3 years (median, 5.4 years) of age at diagnosis and 6.7 to 17.9 years (median, 11.9 years) of age at participation. The patients (40 ALL, 43 BT) participated in a randomized, double-blind, 3-week home cross-over trial of placebo (bid), low-dose MPH (0.3 mg/kg; maximum dose, 10 mg bid), and moderate-dose MPH (0.6 mg/kg; maximum dose, 20 mg bid). The primary end points were weekly teacher and parent reports on the Conners’ Rating Scales and Social Skills Rating System.

Results

Compared to placebo, significant improvement with MPH was reported by teachers and parents on the Conners’ Rating Scales and by teachers on the Social Skills Rating System. However, no consistent advantage of moderate dose over low dose was observed. Of those participating, 66 (79.5%) of the 83 patients continued on best clinical management.

Conclusion

Treatment with MPH can at least temporarily reduce some attentional and social deficits among survivors of childhood ALL and BT. Long-term follow-up will reveal those subsets of patients who are more likely to benefit from MPH.
Path reversal, islands, and the gapped alignment of random sequences
Authors: Spouge John L.
Published: November 2004

In bioinformatics, the notion of an ‘island’ enhances the efficient simulation of gapped local alignment statistics. This paper generalizes several results relevant to gapless local alignment statistics from one to higher dimensions, with a particular eye to applications in gapped alignment statistics. For example, reversal of paths (rather than of discrete time) generalizes a distributional equality, from queueing theory, between the Lindley (local sum) and maximum processes. Systematic investigation of an ‘ownership’ relationship among vertices in ℤ2 formalizes the notion of an island as a set of vertices having a common owner. Predictably, islands possess some stochastic ordering and spatial averaging properties. Moreover, however, the average number of vertices in a subcritical stationary island is 1, generalizing a theorem of Kac about stationary point processes. The generalization leads to alternative ways of simulating some island statistics.
Poisson approximation for (k1,k2)-events via the Stein-Chen method
Authors: Vellaisamy P.
Published: November 2004

Consider a sequence of independent Bernoulli trials with success probabilityp. LetN(n;k1,k2) denote the number of times thatk1failures are followed byk2successes among the firstnBernoulli trials. We employ the Stein-Chen method to obtain a total variation upper bound for the rate of convergence ofN(n;k1,k2) to a suitable Poisson random variable. As a special case, the corresponding limit theorem is established. Similar results are obtained forNk3(n;k1,k2), the number of times thatk1failures followed byk2successes occurk3times successively innBernoulli trials. The bounds obtained are generally sharper than, and improve upon, some of the already known results. Finally, the technique is adapted to obtain Poisson approximation results for the occurrences of the above-mentioned events under Markov-dependent trials.
The behavior of multivariate maxima of moving maxima processes
Authors: Zhang Zhengjun , Smith Richard L.
Published: November 2004

In the characterization of multivariate extremal indices of multivariate stationary processes, multivariate maxima of moving maxima processes, or M4 processes for short, have been introduced by Smith and Weissman. Central to the introduction of M4 processes is that the extreme observations of multivariate stationary processes may be characterized in terms of a limiting max-stable process under quite general conditions, and that a max-stable process can be arbitrarily closely approximated by an M4 process. In this paper, we derive some additional basic probabilistic properties for a finite class of M4 processes, each of which contains finite-range clustered moving patterns, called signature patterns, when extreme events occur. We use these properties to construct statistical estimation schemes for model parameters.
Scale functions of Lévy processes and busy periods of finite-capacity M/GI/1 queues
Authors: Dube Parijat , Guillemin Fabrice , Mazumdar Ravi R.
Published: November 2004

In this paper we use the exit time theory for Lévy processes to derive new closed-form results for the busy period distribution of finite-capacity fluid M/G/1 queues. Based on this result, we then obtain the busy period distribution for finite-capacity queues with on–off inputs when the off times are exponentially distributed.
M/GI/1 queues with services of both positive and negative customers
Authors: Zhu Yijun , Zhang Zhe George
Published: November 2004

We consider an M/GI/1 queue with two types of customers, positive and negative, which cancel each other out. The server provides service to either a positive customer or a negative customer. In such a system, the queue length can be either positive or negative and an arrival either joins the queue, if it is of the same sign, or instantaneously removes a customer of the opposite sign at the end of the queue or in service. This study is a generalization of Gelenbe's original concept of a queue with negative customers, where only positive customers need services and negative customers arriving at an empty system are lost or need no service. In this paper, we derive the transient and the stationary probability distributions for the major performance measures in terms of generating functions and Laplace transforms. It has been shown that the previous results for the system with negative arrivals of zero service time are special cases of our model. In addition, we obtain the stationary waiting time distribution of this system in terms of a Laplace transform.
The spectral gap and perturbation bounds for reversible continuous-time Markov chains
Authors: Mitrophanov A. Yu.
Published: November 2004

We show that, for reversible continuous-time Markov chains, the closeness of the nonzero eigenvalues of the generator to zero provides complete information about the sensitivity of the distribution vector to perturbations of the generator. Our results hold for both the transient and the stationary states.
The Kelly system maximizes median fortune
Authors: Ethier S. N.
Published: November 2004

It is well known that the Kelly system of proportional betting, which maximizes the long-term geometric rate of growth of the gambler's fortune, minimizes the expected time required to reach a specified goal. Less well known is the fact that it maximizes the median of the gambler's fortune. This was pointed out by the author in a 1988 paper, but only under asymptotic assumptions that might cause one to question its applicability. Here we show that the result is true more generally, and argue that this is a desirable property of the Kelly system.
Specialist clinics in remote Australian Aboriginal communities: where rock art meets rocket science
Authors: Gruen Russell , Bailie Ross
Published: November 2004

People in remote Aboriginal communities in the Northern Territory have greater morbidity and mortality than other Australians, but face considerable barriers when accessing hospital-based specialist services. The Specialist Outreach Service, which began in 1997, was a novel policy initiative to improve access by providing a regular multidisciplinary visiting specialist services to remote communities. It led to two interesting juxtapositions: that of “state of the art” specialist services alongside under-resourced primary care in remote and relatively traditional Aboriginal communities; and that of attempts to develop an evidence base for the effectiveness of outreach, while meeting the short-term evaluative requirements of policy-makers.

In this essay, first we describe the development of the service in the Northern Territory and its initial process evaluation. Through a Cochrane systematic review we then summarise the published research on the effectiveness of specialist outreach in improving access to tertiary and hospital-based care. Finally we describe the findings of an observational population-based study of the use of specialist services and the impact of outreach to three remote communities over 11 years.

Specialist outreach improves access to specialist care and may lessen the demand for both outpatient and inpatient hospital care. Specialist outreach is, however, dependent on well-functioning primary care. According to the way in which outreach is conducted and the service is organised, it can either support primary care or it can hinder primary care and, as a result, reduce its own effectiveness.
Pricing of general practice in Australia: some recent proposals to reform Medicare
Authors: Jones Glenn , Savage Elizabeth , Hall Jane
Published: November 2004

In the Australian Medicare system, general practitioners (GPs) are paid on a fee-for-service basis. A practitioner can choose to bill the government directly (termed bulk billing) and receive 85% of a regulated fee as full payment. Bulk billed consultations are free to the patient. However, GPs are free to charge above the regulated fee. The patient can then claim a rebate from the government but only the equivalent of 85% of the regulated Medicare fee. Such co-payments for GP consultations cannot be covered by private health insurance.

In the ten years following the introduction of Medicare in 1984, the bulk billing rate for GP consultations steadily increased to 84%. Since then the rate has fallen to below 68%. In April 2003 the Minister for Health announced a reform package under the title A Fairer Medicare which aimed, among other things, to increase the availability of bulk billing for some patients. A key feature of the proposal involved changes to the way that GPs are reimbursed. Following political opposition that would have prevented it passing both houses of the federal parliament, a revised version, MedicarePlus, was released in November 2003. This paper describes the factors influencing a GP's choice to bulk bill and examines the two proposals, in this context.
Equity of access to elective surgery: reflections from NZ clinicians
Authors: Mcleod Deborah , Dew Kevin , Morgan Sonya , Dowell Anthony , Cumming Jackie , Cormack Donna , Mckinlay Eileen , Love Tom
Published: November 2004

Objectives

To explore factors potentially influencing equitable access to elective surgery in New Zealand by describing clinicians’ perceptions of equity and the factors they consider when prioritising patients for elective surgery.

Methods

A qualitative study in selected New Zealand localities. A purposive sample of 49 general practitioners, specialists and registrars were interviewed. Data were analysed thematically.

Results

General practitioners described unequal opportunities for patients to access primary and secondary care and, in particular, private sector elective surgery. They felt that socio-economically disadvantaged patients were less able to advocate for themselves and were more vulnerable to being lost to the elective surgical booking system as well as being less able to access private care. Both GPs and secondary care clinicians described situations where they would personally advocate for individual patients to improve their access. Advocacy was related to clinicians’ perceptions of the “value” that patients would receive from the surgery and patients” needs for public sector funding.

Conclusions

The structure of the health system contributes to inequities in access to elective care in New Zealand. Subjective decision making by clinicians has the potential to advantage or disadvantage patients through the weighting clinicians place on socio-demographic factors when making rationing decisions. Review of the potential structural barriers to equitable access, further public debate and guidance for clinicians on the relative importance of socio-demographic factors in deciding access to rationed services are required for allocation of services to be fair.
Comparison of private for-profit with private community-governed not-for-profit primary care services in New Zealand
Authors: Crampton Peter , Davis Peter , Lay-Yee Roy , Raymont Antony , Forrest Christopher , Starfield Barbara
Published: November 2004

Objective

To compare the characteristics of patients, their disease patterns, and the investigation and referral patterns in private community-governed not-for-profit and private for-profit primary care practices in New Zealand.

Methods

Observational study using a representative survey of visits to general practitioners in New Zealand. Practices were categorised according to their ownership: private for-profit or private community-governed not-for-profit. Patient socio-demographic characteristics, treated prevalence and other characteristics of presenting problems, morbidity burden, numbers of investigations and referral patterns were compared.

Results

Compared with for-profit practices, community-governed not-for-profit practices served a younger, largely non-European population, nearly three-quarters of whom had a means-tested benefit card (community services card), 10.5% of whom were not fluent in English, and the majority of whom lived in the 20% of areas ranked as the most deprived (by the NZDep2001 index of socio-economic deprivation). Patients visiting not-for-profit practices were diagnosed with more problems, including higher rates of asthma, diabetes and skin infections, but lower rates of chest infections. The duration of visits was also significantly longer. No differences were observed in the average number of laboratory tests ordered. The odds of specialist referral were higher in for-profit patients when confounding variables were controlled for.

Conclusions

Community-governed not-for-profit practices in New Zealand serve a poor, largely non-European population who present with somewhat different rates of various problems compared with patients at for-profit practices. The study highlights for communities, policy-makers and purchasers the importance of community-governed not-for-profit practices in meeting the needs of low-income and minority population groups.
Hematopoietic cytokines as tumor markers
Authors: Mroczko Barbara , Szmitkowski Maciej
Published: November 2004

Stem cell factor (SCF), interleukin 3 (IL-3), granulocyte-macrophage-colony stimulating factor (GM-CSF), granulocyte-colony stimulating factor (G-CSF) and macrophage-colony stimulating factor (M-CSF) are members of a group of glycoproteins called hematopoietic cytokines (HCs). These cytokines regulate the growth and differentiation of hematopoietic progenitor cells and functionally activate mature neutrophils or macrophages. The effect of HCs is not limited to bone marrow cells. Some studies have shown that HCs can also stimulate the proliferation of non-hematopoietic cells. The receptors for HCs have been detected in cancer cell lines, and stimulation of HCs receptors induced proliferation of tumor cells. Moreover, some investigations have shown HC mRNA expression in these cell lines and recent studies have demonstrated that HCs can stimulate tumor progression. Several cells of malignant tumors have been observed to secrete large amounts of HCs and increased concentrations of HCs have been found in the sera of cancer patients. There are a number of situations in which the measurement of HCs may provide clinically useful information, particularly regarding prognosis and response to treatment. In this paper we discuss the results of studies that have examined the potential use of HCs as tumor markers.
The apoB/apoA-I ratio is better than the cholesterol ratios to estimate the balance between plasma proatherogenic and antiatherogenic lipoproteins and to predict coronary risk
Authors: Walldius Göran , Jungner Ingmar , Aastveit Are H. , Holme Ingar , Furberg Curt D. , Sniderman Allan D.
Published: November 2004

Background: The apolipoprotein B (apoB)/apoA-I ratio represents the balance of proatherogenic and antiatherogenic lipoproteins. The purpose of this study was to determine whether the apoB/apoA-I ratio was superior to any of the cholesterol ratios – total cholesterol/high-density lipoprotein cholesterol (TC/HDL-C), low-density lipoprotein cholesterol (LDL-C)/HDL-C and non-HDL-C/HDL-C – in predicting the risk of coronary disease. Moreover, we examined whether any lipids, lipoproteins or cholesterol ratios add significant predictive information beyond that provided by the apoB/apoA-I ratio.

Methods: Plasma lipids, lipoproteins, apoB, and apoA-I were measured in 69,030 men and 57,168 women above 40years of age. After a mean follow-up of 98months, 1183 men and 560 women had died from a myocardial infarction in this prospective apolipoprotein-related mortality risk (AMORIS) study.

Results: High apoB and a high apoB/apoA-I ratio were strongly related to increased coronary risk, while high apoA-I was inversely related to risk. The apoB/apoA-I ratio was superior to any of the cholesterol ratios in predicting risk. This advantage was most pronounced in subjects with LDL-C levels <3.6mmol/l. Addition of lipids, lipoproteins or any cholesterol ratio to apoB/apoA-I in risk models did not further improve the strong predictive value of apoB/apoA-I.

Conclusions: These results indicate that the apoB/apoA-I ratio is at present the best single lipoprotein-related variable to quantitate coronary risk. Given the additional advantages apolipoproteins possess – fasting samples are not required, apoB/apoA-I is a better index of the adequacy of statin therapy than LDL-C, and the measurement of apoB and apoA-I are standardized, whereas LDL-C and HDL-C are not – there would appear to be considerable advantage to integrating apolipoproteins into clinical practice.
Determination of asymmetric dimethylarginine (ADMA) using a novel ELISA assay
Authors: Schulze Friedrich , Wesemann Reinhard , Schwedhelm Edzard , Sydow Karsten , Albsmeier Jennifer , Cooke John P. , Böger Rainer H.
Published: November 2004

Asymmetric dimethylarginine (ADMA) is an endogenous competitive inhibitor of nitric oxide synthase (NOS). Elevated ADMA plasma levels have been reported in connection with diseases associated with an impaired endothelial L-arginine-NO pathway and endothelial dysfunction, such as atherosclerosis, hypercholesterolemia, chronic heart failure, diabetes mellitus, and hypertension. NO production by NOS is decreased due to elevated ADMA levels. In fact, there is increasing interest in determination of ADMA levels in samples of various origins. The aim of this work was to develop a precise and easy immunoassay in contrast to the existing methods, such as HPLC, liquid chromatography-mass spectrometry (LC-MS) and gas chromatography (GC)-MS. We determined cross-reactivity in our immunoassay of 1.2% for symmetric dimethylarginine and <0.02% for L-arginine. The limit of quantitation was 0.05μmol/l. We found good correlation of the values measured when we compared our assay with LC-tandem MS (n=29; r=0.984; p<0.0001). We determined ADMA levels in human serum and plasma, mouse and rat plasma, and cell culture supernatant. For human plasma we found a mean of 0.65μmol/l in healthy subjects. In the plasma of mice and rats we found mean concentrations of 1.05 and 1.09μmol/l, respectively.
HDL and clinical and biochemical correlates in Italian non-smoker women
Authors: Bigazzi Federico , Pino Beatrice Dal , Forastiere Francesco , Pistelli Riccardo , Rossi Giuseppe , Simoni Marzia , Baldacci Sandra , Viegi Giovanni , Bionda Alberto , Sampietro Tiziana
Published: November 2004

High-density lipoprotein (HDL)-cholesterol levels, inversely related to the risk of myocardial infarction, are determined by genetic and environmental factors. The aim of this study was to evaluate the prevalence of low and high HDL plasma levels and the influence of environmental factors and lipid profile in an Italian non-smoker female population. HDL, apolipoprotein A-I, apolipoproteins, lipids and estrogen plasma levels were measured in a population of 1471 women with a mean age of 45±14years. HDL values ≤35mg/dl were noted in 11.2% of the subjects, showing 2.4% coronary heart disease (CHD) prevalence. The 90th percentile was characterized by HDL levels ≥66mg/dl and the absence of coronary atherosclerosis. Total cholesterol, apolipoprotein B and triglycerides (r=−0.31, p<0.0001) were the main determinants of HDL levels; apolipoprotein E, estrogen use, body mass index (BMI), alcohol consumption and age showed a weaker correlation. Apolipoprotein A-I concentration was influenced more notably by estrogen use, total cholesterol and apolipoprotein E; levels of triglycerides, apolipoprotein B, BMI, age and alcohol consumption are less important. The parameters considered here, taken together, explain HDL and apolipoprotein A-I variability of approximately 31% and 24%, respectively. A surprisingly high prevalence of very low (≤35mg/dl) and high (≥66mg/dl) HDL levels in Italian women further confirms the importance of studies on the HDL distribution in different population groups.