bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evolutionary programming as a platform for in silico metabolic engineering
Authors: Patil Kiran Raosaheb , Rocha Isabel , Förster Jochen , Nielsen Jens 
Published: December 2005

Abstract
Background
Through genetic engineering it is possible to introduce targeted genetic changes and hereby engineer the metabolism of microbial cells with the objective to obtain desirable phenotypes. However, owing to the complexity of metabolic networks, both in terms of structure and regulation, it is often difficult to predict the effects of genetic modifications on the resulting phenotype. Recently genome-scale metabolic models have been compiled for several different microorganisms where structural and stoichiometric complexity is inherently accounted for. New algorithms are being developed by using genome-scale metabolic models that enable identification of gene knockout strategies for obtaining improved phenotypes. However, the problem of finding optimal gene deletion strategy is combinatorial and consequently the computational time increases exponentially with the size of the problem, and it is therefore interesting to develop new faster algorithms.

Results
In this study we report an evolutionary programming based method to rapidly identify gene deletion strategies for optimization of a desired phenotypic objective function. We illustrate the proposed method for two important design parameters in industrial fermentations, one linear and other non-linear, by using a genome-scale model of the yeast Saccharomyces cerevisiae. Potential metabolic engineering targets for improved production of succinic acid, glycerol and vanillin are identified and underlying flux changes for the predicted mutants are discussed.

Conclusion
We show that evolutionary programming enables solving large gene knockout problems in relatively short computational time. The proposed algorithm also allows the optimization of non-linear objective functions or incorporation of non-linear constraints and additionally provides a family of close to optimal solutions. The identified metabolic engineering strategies suggest that non-intuitive genetic modifications span several different pathways and may be necessary for solving challenging metabolic engineering problems.
Chaperone use during intimate examinations in primary care: postal survey of family physicians
Authors: Price David H , Tracy C Shawn , Upshur Ross EG 
Published: December 2005

Abstract

Background
Physicians have long been advised to have a third party present during certain parts of a physical examination; however, little is known about the frequency of chaperone use for those specific intimate examinations regularly performed in primary care. We aimed to determine the frequency of chaperone use among family physicians across a variety of intimate physical examinations for both male and female patients, and also to identify the factors associated with chaperone use.

Methods
Questionnaires were mailed to a randomly selected sample of 500 Ontario members of the College of Family Physicians of Canada. Participants were asked about their use of chaperones when performing a variety of intimate examinations, namely female pelvic, breast, and rectal exams and male genital and rectal exams.

Results
276 of 500 were returned (56%), of which 257 were useable. Chaperones were more commonly used with female patients than with males (t = 9.09 [df = 249], p < 0.001), with the female pelvic exam being the most likely of the five exams to be attended by a chaperone (53%). As well, male physicians were more likely to use chaperones for examination of female patients than were female physicians for the examination of male patients. Logistic regression analyses identified two independent factors – sex of physician and availability of a nurse – that were significantly associated with chaperone use. For female pelvic exam, male physicians were significantly more likely to report using a chaperone (adjusted Odds Ratio [OR] 40.62, 95% confidence interval [CI] 16.91–97.52). Likewise, having a nurse available also significantly increased the likelihood of a chaperone being used (adjusted OR 6.92, 95% CI 2.74–17.46). This pattern of results was consistent across the other four exams. Approximately two-thirds of respondents reported using nurses as chaperones, 15% cited the use of other office staff, and 10% relied on the presence of a family member.

Conclusion
Clinical practice concerning the use of chaperones during intimate exams continues to be discordant with the recommendations of medical associations and medico-legal societies. Chaperones are used by only a minority of Ontario family physicians. Chaperone use is higher for examinations of female patients than of male patients and is highest for female pelvic exams. The availability of a nurse in the clinic to act as a chaperone is associated with more frequent use of chaperones.
Protocol for Project FACT: a randomised controlled trial on the effect of a walking program and vitamin B supplementation on the rate of cognitive decline and psychosocial wellbeing in older adults with mild cognitive impairment [ISRCTN19227688]
Authors: van Uffelen Jannique GZ , Hopman-Rock Marijke , Chin A Paw Marijke JM , van Mechelen Willem 
Published: December 2005

Abstract

Background
the prevalence of individuals with cognitive decline is increasing since the number of elderly adults is growing considerably. The literature provides promising results on the beneficial effect of exercise and vitamin supplementation on cognitive function both in cognitively healthy as well as in the demented elderly.

Methods/Design
the design is a two-by-two factorial randomised controlled trial. The study population consists of independently living elderly, between 70 and 80 years old, with mild cognitive impairment (MCI). In the RCT the effect of two interventions, a walking program and vitamin supplementation, is examined. The walking program (WP) is a group-based program aimed at improving cardiovascular endurance; frequency two lessons a week; lesson duration one hour; program duration one year. Non-walking groups receive a placebo activity program (PAP) (i.e. low intensive non-aerobic group exercises, like stretching) with the same frequency, lesson and program duration. Vitamin supplementation consists of a single daily vitamin supplement containing 50 mg B6, 5 mg folic acid and 0,4 mg B12 for one year. Subjects not receiving vitamin supplements are daily taking an identically looking placebo pill, also for a year. Participants are randomised to four groups 1) WP and vitamin supplements; 2) WP and placebo supplements; 3) PAP and vitamin supplements; 4) PAP and placebo supplements. Primary outcome measures are measures of cognitive function. Secondary outcomes include psychosocial wellbeing, physical activity, cardiovascular endurance and blood vitamin levels.

Discussion
no large intervention study has been conducted yet on the effect of physical activity and vitamin supplementation in a population-based sample of adults with MCI. The objective of the present article is to describe the design of a randomised controlled trial examining the effect of a walking program and vitamin B supplementation on the rate of cognitive decline in older adults with MCI.
A randomised controlled trial of the effects of albendazole in pregnancy on maternal responses to mycobacterial antigens and infant responses to bacille Calmette-Guérin (BCG) immunisation [ISRCTN32849447]
Authors: Elliott Alison M , Namujju Proscovia B , Mawa Patrice A , Quigley Maria A , Nampijja Margaret , Nkurunziza Peter M , Belisle John T , Muwanga Moses , Whitworth James AG ,   the "Mother and Baby" study team
Published: December 2005

AbstractBackgroundMaternal schistosomiasis and filariasis have been shown to influence infant responses to neonatal bacille Calmette-Guérin (BCG) immunisation but the effects of maternal hookworm, and of de-worming in pregnancy, are unknown.MethodsIn Entebbe, Uganda, we conducted a randomised, double-blind, placebo-controlled trial of a single dose of 400 mg of albendazole in the second trimester of pregnancy. Neonates received BCG. Interferon-gamma (IFN-γ) and interleukin (IL)-5 responses to a mycobacterial antigen (crude culture filtrate proteins (CFP) ofMycobacterium tuberculosis) were measured in a whole blood assay. We analysed results for binary variables using χ2tests and logistic regression. We analysed continuous variables using Wilcoxon's tests.ResultsMaternal hookworm was associated with reduced maternal IFN-γ responses to CFP (adjusted odds ratio for IFN-γ > median response: 0.14 (95% confidence interval 0.02–0.83, p = 0.021). Conversely, maternal hookworm was associated with subsequent increased IFN-γ responses in their one-year-old infants (adjusted OR 17.65 (1.20–258.66; p = 0.013)). Maternal albendazole tended to reduce these effects.ConclusionUntreated hookworm infection in pregnancy was associated with reduced maternal IFN-γ responses to mycobacterial antigens, but increased responses in their infants one year after BCG immunisation. The mechanisms of these effects, and their implications for protective immunity remain, to be determined.
Cloxacillin versus vancomycin for presumed late-onset sepsis in the Neonatal Intensive Care Unit and the impact upon outcome of coagulase negative staphylococcal bacteremia: a retrospective cohort study
Authors: Lawrence Sarah L , Roth Virginia , Slinger Robert , Toye Baldwin , Gaboury Isabelle , Lemyre Brigitte 
Published: December 2005

AbstractBackgroundCoagulase negative staphylococcus (CONS) is the main cause of late-onset sepsis in Neonatal Intensive Care Units (NICU). Although CONS rarely causes fulminant sepsis, vancomycin is frequently used as empiric therapy. Indiscriminate use of vancomycin has been linked to the emergence of vancomycin resistant organisms. The objective of this study was to compare duration of CONS sepsis and mortality before and after implementation of a policy of selective vancomycin use and compare use of vancomycin between the 2 time periods.MethodsA retrospective study was conducted of infants ≥4 days old, experiencing signs of sepsis with a first positive blood culture for CONS, during two 12-month periods. Late-onset sepsis was treated empirically with vancomycin and gentamicin during period 1, and cloxacillin and gentamicin during period 2. The confidence interval method was used to assess non-inferiority of the outcomes between the two study groups.ResultsThere were 45 episodes of CONS sepsis during period 1 and 37 during period 2. Duration of sepsis was similar between periods (hazard ratio of 1.00, 95%CI: 0.64, 1.57). One death during period 2 was possibly related to CONS sepsis versus none in period 1. Vancomycin was used in 97.8% of episodes in period 1 versus 81.1% of episodes in period 2.ConclusionAlthough we failed to show non-inferiority of duration of sepsis in the cloxacillin and gentamicin group compared to the vancomycin and gentamicin group, duration of sepsis was clinically similar. Restricting vancomycin for confirmed cases of CONS sepsis resistant to oxacillin appears effective and safe, and significantly reduces vancomycin use in the NICU.
An automated, broad-based, near real-time public health surveillance system using presentations to hospital Emergency Departments in New South Wales, Australia
Authors: Muscatello David J , Churches Tim , Kaldor Jill , Zheng Wei , Chiu Clayton , Correll Patricia , Jorm Louisa 
Published: December 2005

AbstractBackgroundIn a climate of concern over bioterrorism threats and emergent diseases, public health authorities are trialling more timely surveillance systems. The 2003 Rugby World Cup (RWC) provided an opportunity to test the viability of a near real-time syndromic surveillance system in metropolitan Sydney, Australia. We describe the development and early results of this largely automated system that used data routinely collected in Emergency Departments (EDs).MethodsTwelve of 49 EDs in the Sydney metropolitan area automatically transmitted surveillance data from their existing information systems to a central database in near real-time. Information captured for each ED visit included patient demographic details, presenting problem and nursing assessment entered as free-text at triage time, physician-assigned provisional diagnosis codes, and status at departure from the ED. Both diagnoses from the EDs and triage text were used to assign syndrome categories. The text information was automatically classified into one or more of 26 syndrome categories using automated "naïve Bayes" text categorisation techniques. Automated processes were used to analyse both diagnosis and free text-based syndrome data and to produce web-based statistical summaries for daily review. An adjusted cumulative sum (cusum) was used to assess the statistical significance of trends.ResultsDuring the RWC the system did not identify any major public health threats associated with the tournament, mass gatherings or the influx of visitors. This was consistent with evidence from other sources, although two known outbreaks were already in progress before the tournament. Limited baseline in early monitoring prevented the system from automatically identifying these ongoing outbreaks. Data capture was invisible to clinical staff in EDs and did not add to their workload.ConclusionWe have demonstrated the feasibility and potential utility of syndromic surveillance using routinely collected data from ED information systems. Key features of our system are its nil impact on clinical staff, and its use of statistical methods to assign syndrome categories based on clinical free text information. The system is ongoing, and has expanded to cover 30 EDs. Results of formal evaluations of both the technical efficiency and the public health impacts of the system will be described subsequently.
Comparison of foot orthoses made by podiatrists, pedorthists and orthotists regarding plantar pressure reduction in The Netherlands
Authors: Guldemond Nick A , Leffers Pieter , Schaper Nicolaas C , Sanders Antal P , Nieman Fred HM , Walenkamp Geert HIM 
Published: December 2005

AbstractBackgroundThere is a need for evidence of clinical effectiveness of foot orthosis therapy. This study evaluated the effect of foot orthoses made by ten podiatrists, ten pedorthists and eleven orthotists on plantar pressure and walking convenience for three patients with metatarsalgia. Aims were to assess differences and variability between and within the disciplines. The relationship between the importance of pressure reduction and the effect on peak pressure was also evaluated.MethodsEach therapist examined all three patients and was asked to rate the 'importance of pressure reduction' through a visual analogue scale. The orthoses were evaluated twice in two sessions while the patient walked on a treadmill. Plantar pressures were recorded with an in-sole measuring system. Patients scored walking convenience per orthosis. The effects of the orthoses on peak pressure reduction were calculated for the whole plantar surface of the forefoot and six regions: big toe and metatarsal one to five.ResultsWithin each discipline there was an extensive variation in construction of the orthoses and achieved peak pressure reductions. Pedorthists and orthotists achieved greater maximal peak pressure reductions calculated over the whole forefoot than podiatrists: 960, 1020 and 750 kPa, respectively (p < .001). This was also true for the effect in the regions with the highest baseline peak pressures and walking convenience rated by patients A and B. There was a weak relationship between the 'importance of pressure reduction' and the achieved pressure reduction for orthotists, but no relationship for podiatrists and pedorthotists.ConclusionThe large variation for various aspects of foot orthoses therapy raises questions about a consistent use of concepts for pressures management within the professional groups.
An indirect enzyme-linked immunosorbent assay for rapid and quantitative assessment of Type III virulence phenotypes of Pseudomonas aeruginosa isolates
Authors: Li Li , Ledizet Michel , Kar Kalipada , Koski Raymond A , Kazmierczak Barbara I 
Published: December 2005

Abstract

Background
The presence of a Type III secretion system in clinical isolates of Pseudomonas aeruginosa is associated with severe disease and poor outcomes in infections caused by this pathogen. We describe an indirect enzyme-linked immunosorbent assay that rapidly and quantitatively detects two exotoxins, ExoU and ExoT, and two structural components, PopD and PcrV, of the P. aeruginosa Type III secretion system after in-vitro growth in a calcium-free minimal medium.

Methods
We used this assay to characterize the Type III secretion phenotype of 74 clinical isolates of P. aeruginosa. Findings were compared with results of standard immunoblotting and correlated with Type III secretion-dependent virulence of isolates toward cultured epithelial cells.

Results
Results of the ELISA assay were concordant with immunoblot detection of the secreted antigens for 73 of 74 isolates. The Type III secretion phenotype assessed by this immunoassay predicted bacterial virulence toward epithelial cells in vitro for all but five of the clinical isolates.

Conclusion
The availability of an ELISA assay for rapid detection of Type III secreted virulence factors will facilitate large clinical studies to examine whether the Type III secretion phenotype of a P. aeruginosa isolate predicts the course of clinical disease in a patient and should be taken into account in determining optimal treatment strategies for infected patients.
The diagnostic value of biomarkers (SteatoTest) for the prediction of liver steatosis
Authors: Poynard Thierry , Ratziu Vlad , Naveau Sylvie , Thabut Dominique , Charlotte Frederic , Messous Djamila , Capron Dominique , Abella Annie , Massard Julien , Ngo Yen , Munteanu Mona , Mercadier Anne , Manns Michael , Albrecht Janice 
Published: December 2005

Abstract

Background
Biopsy is the usual gold standard for liver steatosis assessment. The aim of this study was to identify a panel of biomarkers (SteatoTest), with sufficient predictive values, for the non-invasive diagnosis of steatosis in patients with or without chronic liver disease. Biomarkers and panels were assessed in a training group of consecutive patients with chronic hepatitis C and B, alcoholic liver disease, and non-alcoholic fatty liver disease, and were validated in two independent groups including a prospective one. Steatosis was blindly assessed by using a previously validated scoring system.

Results
310 patients were included in the training group; 434 in three validation groups; and 140 in a control group. SteatoTest was constructed using a combination of the 6 components of FibroTest-ActiTest plus body mass index, serum cholesterol, triglycerides, and glucose adjusted for age and gender. SteatoTest area under the ROC curves was 0.79 (SE = 0.03) in the training group; 0.80 (0.04) in validation group 1; 0.86 (0.03) in validation group 2; and 0.72 (0.05) in the validation group 3 – all significantly higher than the standard markers: γ-glutamyl-transpeptidase or alanine aminotransferase. The median SteatoTest value was 0.13 in fasting controls; 0.16 in non-fasting controls; 0.31 in patients without steatosis; 0.39 in grade 1 steatosis (0–5%); 0.58 in grade 2 (6–32%); and 0.74 in grade 3–4 (33–100%). For the diagnosis of grade 2–4 steatosis, the sensitivity of SteatoTest at the 0.30 cut-off was 0.91, 0.98, 1.00 and 0.85 and the specificity at the 0.70 cut-off was 0.89, 0.83, 0.92, 1.00, for the training and three validation groups, respectively.

Conclusion
SteatoTest is a simple and non-invasive quantitative estimate of liver steatosis and may reduce the need for liver biopsy, particularly in patients with metabolic risk factor.
Dynamic 3D echocardiography in virtual reality
Authors: van den Bosch Annemien E , Koning Anton HJ , Meijboom Folkert J , McGhie Jackie S , Simoons Maarten L , van der Spek Peter J , Bogers Ad JJC 
Published: December 2005

Abstract

Background
This pilot study was performed to evaluate whether virtual reality is applicable for three-dimensional echocardiography and if three-dimensional echocardiographic 'holograms' have the potential to become a clinically useful tool.

Methods
Three-dimensional echocardiographic data sets from 2 normal subjects and from 4 patients with a mitral valve pathological condition were included in the study. The three-dimensional data sets were acquired with the Philips Sonos 7500 echo-system and transferred to the BARCO (Barco N.V., Kortrijk, Belgium) I-space. Ten independent observers assessed the 6 three-dimensional data sets with and without mitral valve pathology. After 10 minutes' instruction in the I-Space, all of the observers could use the virtual pointer that is necessary to create cut planes in the hologram.

Results
The 10 independent observers correctly assessed the normal and pathological mitral valve in the holograms (analysis time approximately 10 minutes).

Conclusion
this report shows that dynamic holographic imaging of three-dimensional echocardiographic data is feasible. However, the applicability and use-fullness of this technology in clinical practice is still limited.
Discontinuation of treatment of schizophrenic patients is driven by poor symptom response: a pooled post-hoc analysis of four atypical antipsychotic drugs
Authors: Liu-Seifert Hong , Adams David H , Kinon Bruce J 
Published: December 2005

Abstract

Background
Stopping antipsychotic treatment can interrupt improvement and exacerbate the illness. The reasons for discontinuing treatment during controlled clinical trials were analyzed to explore this phenomenon.

Methods
A post-hoc, pooled analysis was made of 4 randomized, double-blind clinical trials, 24–28 weeks in duration, involving 1627 patients with schizophrenia or a related disorder. Analyses combined all the atypical antipsychotic treatment groups in the studies.

Results
The majority of patients (53%) stopped their treatment at an early stage. Poor psychiatric response along with worsening symptoms was the most frequently given reason for discontinuing the course (36%), which was substantially more common than discontinuation due to poor tolerability of the medication (12%). This phenomenon was corroborated by less improvement in patients who discontinued treatment compared with those who completed, based on the PANSS total scores. Discontinuation due to poor response was, apparently, more predominantly linked to patient perception than to physicians' conclusions alone (80% vs. 20%). Discontinuation due to patient perception of poor response appeared to occur particularly early in the course of treatment. Patients who discontinued due to poor toleration of the medication responded in a more comparable manner with completers.

Conclusion
Discontinuing treatment may lead to exacerbation of symptoms, undermining therapeutic progress. In these studies, poor response to treatment and worsening of underlying psychiatric symptoms, and to a lesser extent, intolerability to medication were the primary contributors to treatment being discontinued. Our findings suggest that adherence may be enhanced by effective symptom control, as objectively measured and as subjectively perceived. Such strategies may improve patients' willingness to undertake long-term therapy and increase the likelihood of a better prognosis.