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Ab initio prediction of thermodynamically feasible reaction directions from biochemical network stoichiometry.

Analysis of the stoichiometric structure of metabolic networks provides insights into the relationships between structure, function, and regulation of metabolic systems. Based on knowledge of only reaction stoichiometry, certain aspects of network functionality and robustness can be predicted. Current theories focus on breaking a metabolic network down into non-decomposable pathways able to operate in steady state. The physics underlying these theories is based on mass balance and the laws of thermodynamics. However, due to the inherent nonlinearity of the thermodynamic constraints on metabolic fluxes, computational analysis of large-scale biochemical systems can be expensive. In this study, it is shown how the feasible reaction directions may be determined by either computing the allowable ranges under the mass-balance and thermodynamic constraints or by analyzing the stoichiometric structure of the network. The computed reaction directions translate into a set of linear constraints necessary for thermodynamic feasibility. This set of necessary linear constraints is shown to be sufficient to guarantee feasibility in certain cases, thus translating the nonlinear thermodynamic constraints to linear. We show that for a reaction network of 44 internal reactions representing energy metabolism, the computed linear inequality constraints represent necessary and sufficient conditions for thermodynamic feasibility.

Cell Physiological Phenomena↗

[Feasibility and safety of intracoronary ultrasound. Experience of a single center].

BACKGROUND AND OBJECTIVES: Intracoronary ultrasound provides a number of advantages in the quantification and characterization of coronary stenoses with regard to contrast angiography. However, previous studies have reported a 3.5 to 11% complication rate, and a 10-30% failure rate in performing this technique. The purpose of the study is to analyze the feasibility of performing intracoronary ultrasound and the incidence of complications associated with the use of contemporary, state of the art equipment. MATERIAL AND METHODS: The feasibility of performing intracoronary ultrasound, analyzed as the percentage of successes and failures in performing the examination was reviewed, as well as the complication rate associated with the technique in all the procedures carried out between July 1, 1994 and February 29, 1996 in which intravascular ultrasound was attempted. Complications were categorized as related, non-related and uncertainly related to the ultrasound study. RESULTS: 239 vessels were studied with intravascular ultrasound in 209 procedures (74% interventional) performed on 139 patients. Ultrasound examination was feasible in all the diagnostic studies and in 96% of the interventional procedures. The major and minor procedural complication rate was 2.4 and 10.5% respectively. No major complication was related to the ultrasound examination. Three patients experienced minor complications (1.4%) related to the ultrasound study. All three complications occurred in baseline studies during interventional procedures. CONCLUSIONS: Intracoronary ultrasound is feasible and safe in the vast majority of the procedures. Improvements in smaller catheter size and design and larger operator expertise have significantly reduced the complication rate, particularly the most frequent coronary spasm so far. Complications are associated with baseline studies during interventional procedures and with less operator expertise.

Aged↗

An investigation into the feasibility of comparing three management options (augmentation, conservative and water) for nulliparae with dystocia in the first stage of labour.

OBJECTIVE: to evaluate the feasibility of a randomised controlled trial (RCT) examining the effect of three options (augmentation, conservative and water) for the management of dystocia in nulliparae. The main objectives were to explore the feasibility of trial procedures in the clinical environment, consent rates and acceptability of the management options to women, local incidence of dystocia in nulliparae and the size of the subsequent study. DESIGN: a two part study: a pilot, RCT with follow-up through to delivery with postnatal maternal surveys, and a case review of nulliparae with dystocia. SETTING: a large maternity unit in the South of England in May-July 1997 inclusive. PARTICIPANTS: nulliparae with dystocia in the first stage of labour who had an otherwise uncomplicated obstetric background. INTERVENTIONS: women in the pilot RCT received one of three management options: labouring in a waterbirth pool, conservative management or augmentation of labour, which is the standard management of women with dystocia condition in the Unit. FINDINGS: it is feasible to conduct an RCT of management of dystocia in the Unit. Seventy per cent (95% confidence interval 47% to 87%) of women approached agreed to participate. Conservative management was the least acceptable option to women and has been dropped from the subsequent trial. The audit provided some idea of possible differences in operative delivery and epidural rates depending on augmentation or not. A sample of 220 women should be large enough to detect moderate changes and will require a 2-year recruitment period. CONCLUSIONS: a subsequent trial is feasible and is now underway. It has the potential to provide information enabling women and practitioners to have a greater choice of care options in the presence of dystocia, or provide a good basis for an even larger trial.

Baths↗

Assessing commercial feasibility: a practical and ethical prerequisite for human clinical testing.

This article proposes that an assessment of commercial feasibility should be integrated as a prerequisite for human clinical testing to improve the quality and relevance of materials being investigated, as an ethical aspect for human subject protection, and as a means of improving accountability where clinical development is funded on promises of successful translational research. A commercial feasibility analysis is not currently required to justify human clinical testing, but is assumed to have been conducted by industry participants, and use of public funds for clinical trials should be defensible in the same manner. Plant-made vaccines (PMVs) are offered in this discussion as a model for evaluating the relevance of commercial feasibility before human clinical testing. PMVs have been proposed as a potential solution for global health, based on a vision of immunizing the world against many infectious diseases. Such a vision depends on translating current knowledge in plant science and immunology into a potent vaccine that can be readily manufactured and distributed to those in need. But new biologics such as PMVs may fail to be manufactured due to financial or logistical reasons--particularly for orphan diseases without sufficient revenue incentive for industry investment--regardless of the effectiveness which might be demonstrated in human clinical testing. Moreover, all potential instruments of global health depend on translational agents well beyond the lab in order to reach those in need. A model compromising five criteria for commercial feasibility is suggested for inclusion by regulators and ethics review boards as part of the review process prior to approval of human clinical testing. Use of this model may help to facilitate safe and appropriate translational research and bring more immediate benefits to those in need.

Biotechnology↗

Feasibility of using kangaroo (skin-to-skin) care with colicky infants.

Infant colic affects about 20% of all infants and the cause remains elusive. Healthcare providers typically view infant colic as a minor inconvenience that is harmless to the thriving infant and will go away with time; however, parents view caring for a colicky infant as a crisis situation. The purpose of this feasibility study conducted via the internet was to examine the feasibility of implementing kangaroo care at the beginning of colicky episodes. Mothers of colicky infants began the study by completing the on-line Infant Colic Scale and recording in a baseline state-of-arousal diary for 3 days. Next, they implemented kangaroo care at the beginning of as many episodes of colic as possible for 2 weeks while recording in a second state-of-arousal diary. Then, they stopped kangaroo care for 2 days while continuing to record in the second state-of-arousal diary, and lastly they were asked how kangaroo care worked for them.Seventy-five parents of colicky infants consented to participate in this study; however, only five of them actually did. Three of these completed only the baseline state-of-arousal diary, and two completed all parts of the study. This dropout rate showed that conducting such an intervention via the internet is not a feasible approach. Because kangaroo care for infants with colic is a promising intervention and because there are no other effective treatments for most of these infants, another feasibility study is warranted using different methods. Then if results are promising, a larger clinical trial should be conducted.

Adult↗

Feasibility and tolerability of sequential doxorubicin/paclitaxel followed by cyclophosphamide, methotrexate, and fluorouracil and its effects on tumor response as preoperative therapy.

PURPOSE: The European Cooperative Trial in Operable breast cancer (ECTO) randomly tested whether efficacy of adjuvant doxorubicin followed by i.v. cyclophosphamide, methotrexate, and fluorouracil (CMF; doxorubicin-->CMF, arm A) could be improved by adding paclitaxel (doxorubicin/paclitaxel-->CMF) as adjuvant (arm B) or primary systemic therapy (PST, arm C). We report here feasibility, tolerability, locoregional antitumor activity, and breast conservation rate. METHODS: A total of 1,355 women entered the study. Feasibility and safety were compared in arm A versus arms B plus C. Surgical findings were compared in arms A plus B versus arm C. RESULTS: Grade 3 or 4 National Cancer Institute toxicities were low (<5%) in all arms. Neuropathy was more frequent in the paclitaxel-containing arms (grade 2, 20.5% versus 5.0%; grade 3, 1.3% versus 0.2%). At 31 months of follow-up, asymptomatic drop of left ventricular ejection fraction was similar in all arms, whereas symptomatic cardiotoxicity was recorded in three patients (0.5%) in A and in three patients (0.3%) in B plus C. PST induced clinical complete plus partial remission in 78%, with an in-breast pathologic complete response rate of 23% and an in-breast plus axilla pathologic complete response rate of 20%. In the multivariate analysis, only estrogen receptor (ER) status was significantly associated with pathologic complete response (odds ratio for ER negative, 5.77; 95% confidence interval, 3.49-9.52; P<0.0001). PTS induced a significant axillary downstaging (P<0.001), and breast sparing surgery was feasible in 65% versus 34% (P<0.001). CONCLUSIONS: Doxorubicin/paclitaxel-->CMF is feasible, safe, and well tolerated. Given as PST, it is markedly active, allowing for breast-sparing surgery in a large fraction of patients.

Aged↗

FEASIBLE (II): Its use in an actual PACS evaluation study.

The software package FEASIBLE is a tool for carrying out observer performance studies. The structure, background and possibilities of the program are described in paper I of this series. Observer performance studies can be used to evaluate the diagnostic quality of Picture Archiving and Communication System (PACS) components. This paper summarizes the general features of such an evaluation. It states the specific characteristics of a diagnostic evaluation of a prototype PACS. The examples of the use of FEASIBLE presented here originate from the study that has recently been conducted within the Dutch PACS project, a cooperation between the BAZIS project IMAGIS (IMAGe Information System), the Utrecht University Hospital and Philips Medical Systems. Furthermore, this paper demonstrates how FEASIBLE is used to carry out an observer performance study. It is shown step-by-step how experiments on the evaluation of PACS components can be executed in an easy, reliable and quick way, by means of the FEASIBLE package.

Evaluation Studies as Topic↗

Japan, Indonesia to investigate condom plant feasibility.

The Japanese government has begun investigations on the possibility of constructing a condom manufacturing plant in Indonesia in response to a request by the Indonesian government. Indonesia, which hopes to reduce its birthrate as of 1971 by 1/2 by 1990, asked for Japanese assistance in building a condom plant based on the expectation that demand for this contraceptive method, although quite low at present, will increase rapidly in the near future with stepped-up motivation campaigns. As a 1st step in the investigation, the Japan International Cooperation Agency (JICA) sent a study team of family planning experts headed by Family Planning Federation of Japan Chairman Dr. Hidebumi Kubo and including JOICFP International Division Director MR. Tameyoshi Katagiri to Indonesia from March 15-24. During its visit, the JICA team held discussions with representatives of BKKBN (the National Family Planning Coordinating Board) including its Chairman and Minister of Health Dr. Suwardjono and reached agreement on the scope and schedule of work toward determining the feasibility of building and operating a condom plant in Indonesia. In defining the scope of work and the schedule, the JICA team and the BKKBN representatives decided on specific issues to be investigated in the feasibility study to be carried out by JICA and scheduled to be completed by the end of October of this year. To be included in the feasibility study are: estimation of future domestic demand for condoms, examination of the domestic supply of latex capacity, chemicals and packaging materials, and collection of information on infrastructure relating to water, energy, transportation, etc. Actual data collection for the study is expected to begin in late May or early June. Dr. Kubo and Mr. Katagiri, upon returning to Japan, reported great enthusiasm for the project in Indonesia and expressed the hope that the plant construction will be feasible so that the country's family planning program can be given a boost and the cooperative relationship between Indonesia and Japan deepened.

Asia↗

Feasibility of using patient navigation to improve identification of hereditary cancer syndromes in newly diagnosed patients with colorectal cancer.

PURPOSE: Germline genetic testing to identify hereditary cancer syndromes in patients newly diagnosed with colorectal cancer (CRC) carries substantial benefits. We examined the feasibility of using patient navigation, an evidence-based approach to reduce structural barriers to recommended care, to improve test completion by increasing pretest counseling attendance. METHODS: We conducted key informant interviews with representatives from organizations providing cancer care to CRC patients. Interviews included questions derived from the Consolidated Framework for Implementation Research, which delineates barriers and facilitators to implementing evidence-based practices. We used an inductive-deductive coding approach to identify themes related to program feasibility. RESULTS: We interviewed 19 participants across 13 organizations. Key feasibility barriers included funding to implement and sustain a navigation program, staffing and supervising the navigator role, health information technology needs, gaining administrators' buy-in, and evolving genetic service delivery models. Participants suggested multiple strategies to address implementation barriers, but most would prefer other approaches to improve genetic test completion over implementing a genomics-focused patient navigation program. CONCLUSION: Stakeholders across a range of health care organizations saw limited value in improving the identification of hereditary CRC syndromes by implementing a program designed to increase pretest genetic counseling attendance. The need to scale up genetic testing has shifted interest toward delivery models better integrated in established care pathways, requiring fewer resources and providing broader reach.

Humans↗

New muscle power test in neuromuscular disease. Feasibility and reliability.

We studied the feasibility, reliability, and reproducibility of an "all-out" 30-second cycling or arm cranking test of muscle power and muscle endurance (the Wingate Anaerobic Test) in 66 girls and boys aged 5 to 18 years old who had cerebral palsy or a myopathy. The arm and leg tests, given in duplicate, were feasible in 94% and 61% of subjects, respectively. Reliability coefficients exceeded .95 in patients with spastic cerebral palsy and myopathies and were somewhat lower in those with athetotic cerebral palsy. Means and SDs were similar in both trials. We conclude that the Wingate Anaerobic Test is feasible, highly reliable, and reproducible in these patients.

Adolescent↗

Modified type IV-V radical hysterectomy with systematic pelvic and aortic lymphadenectomy in the treatment of patients with stage III cervical carcinoma. Feasibility, technique, and clinical results.

BACKGROUND: Due to the high prevalence of perioperative major morbidity and the difficulties in achieving surgical disease free margins, surgery has had no role in the treatment of patients with Stage III cervical carcinoma. METHODS: Forty-two women with International Federation of Gynecology and Obstetrics (FIGO) Stage III cervical carcinoma responding to platinum-based neoadjuvant chemotherapy underwent the maximum surgical effort, comprised of a modified type IV-V radical hysterectomy (37 patients) or anterior pelvectomy (5 patients) with systematic pelvic and aortic lymphadenectomy. Feasibility, modifications of surgical technique, and pathologic and clinical data were analyzed. RESULTS: Surgery was feasible in all 42 patients intraoperatively selected. Disease free margins were achieved in all but one patient. The median operating time was 390 minutes, and the median estimated blood loss was 800 mL. In the last series of patients, these figures declined to 320 minutes and 600 mL, respectively. Major morbidity consisted of severe intraoperative hemorrhage in two patients, pulmonary embolism in four, ureteral fistula in three, and laparocele in three. The number of lymph nodes removed ranged from 30 to 117 with a median of 56. The mean lengths of vagina and lateral parametrium resected were 55 and 48 mm, respectively. Despite perioperative chemotherapy, lymph node metastasis was present in 36% of patients, parametrial disease in 38%, and vaginal disease in 45%. After a median follow-up of 53 months, the 5-year overall and disease-free survival rates of radically operated patients were 70% and 58%, respectively. CONCLUSIONS: Thanks to improved surgical technique and perioperative care, extended radical surgery appears to be feasible with acceptable morbidity in chemosensitive women with Stage III cervical carcinoma and may constitute a valid alternative to radiotherapy in these patients.

Adenocarcinoma↗

The feasibility of electronic tracking devices in dementia: a telephone survey and case series.

BACKGROUND: Patients with dementia who go out unaccompanied are at risk of accidents or getting lost. It is not known whether they could benefit from electronic tracking devices or whether such devices are practically feasible. METHOD: The likely demand for an electronic tracking device was assessed by means of a telephone survey of a convenience sample of 99 carers. The practical feasibility of a tracking system was assessed in 24 patients with dementia. RESULTS: The telephone survey suggested that 20% of patients were at continuing risk of traffic accidents and 45% were at continuing risk of getting lost. About 7% could have benefited from using the device at the time of survey and a further 11% could have benefited at an earlier point in their illness. In the feasibility study, only nine patients consistently used the device. In two patients, it was successfully used in a search. One patient was injured by a passing vehicle when he had got lost out of range of the device. A major barrier to using the device was recognizing the risk of getting lost before it happened. CONCLUSION: Significant numbers of patients are at risk. Electronic tracking devices may occasionally be useful in carefully selected cases.

Accidents, Traffic↗

Feasibility of mobile provision of health services: a study of child monitoring centres in The Netherlands.

In the Netherlands children up to the age of 4 years are regularly monitored. Several demographic and economic developments have led to the idea of using mobile child monitoring centres. Mobile units are expected to be flexible, effective and efficient but little information is available about the implications for the organization, the clients and other third parties involved. This paper outlines an approach for assessing the feasibility of mobile child monitoring centres. The focus is on the area Midden-Gelderland in the Netherlands and the implications of alternative options are compared on the basis of feasibility criteria or performance measures. The implementation of mobile units for child monitoring appears to be feasible with respect to most performance measures but there are also disadvantages. The approach taken proved to be a valuable exercise since it provided detailed information on all implications. It was decided that the mobile units would not be purchased but that some child monitoring centres could be closed without replacing them.

Benchmarking↗

Conservative treatment feasibility with induction chemotherapy, surgery, and radiotherapy for patients with breast carcinoma larger than 3 cm.

BACKGROUND: The traditional surgical treatment for operable breast carcinoma larger than 3 cm is mastectomy. To avoid mutilating surgery, the authors administered primary chemotherapy to 158 patients with operable nonmetastatic large breast carcinoma with a TNM classification of T2 greater than 3 cm and T3 with a lymph node status of N0-N1. Conservative treatment was proposed for patients responding to the chemotherapy and whose tumor was reduced to 3 cm or less. The purpose of the study was to evaluate the feasibility and treatment results of this strategy. METHODS: The mean patient age was 50.4 years. Eighty-two patients had T2 carcinomas greater than 3 cm, and 76 had T3 carcinoma. Fifty-four tumors were classified as lymph node status N0, and 104 as N1. Mean tumor size was 5.6 cm. Patients were treated with three courses of the NVCF regimen (mitoxantrone, vindesin, cyclophosphamide, and 5-fluorouracil) or the EVCF regimen, in which mitoxantrone was replaced by epirubicin every 4 weeks, and then administered with a radiosurgical combination. RESULTS: The overall response rate to induction chemotherapy was 60.8% with 20.2% complete tumor regression. Twenty-one percent of the patients experienced grade 3 or 4 chemotherapy toxic effects, which were all acceptable and reversible. Breast-conserving treatment was feasible in 48.7% of patients (77 of 158). Forty-five patients (28.5%) were treated with a radiosurgical combination (tumorectomy plus radiation therapy), whereas 32 (20.2%) were treated with radiotherapy alone (external irradiation and brachytherapy). Other patients were treated with mastectomy. Age, tumor stage, histology, hormonal status, and hormonal receptor rate had no influence on the frequency of the observed regressions. Isolated recurrences occurred in 11 patients, 6 who were treated conservatively and 5 who were treated with mastectomy. Metastatic relapses were observed in 38 patients (14.6% in the chemotherapy responders and 38.7% in the nonresponders) (P < 0.02). Five-year actuarial survival was 73.2% and was significantly higher for responders to the induction treatment. CONCLUSION: These preliminary results suggest that primary chemotherapy and radiosurgical breast-conserving treatment is feasible and is an alternative to mastectomy for patients with large operable breast carcinoma who are responders to the induction treatment. The long term benefit of this strategy must be evaluated in well designed controlled trials.

Antineoplastic Combined Chemotherapy Protocols↗

Feasibility and efficacy of high dose conformal radiotherapy for patients with locally advanced pancreatic carcinoma.

BACKGROUND: The feasibility and efficacy of high dose conformal radiotherapy were examined in the treatment of patients with locally advanced, unresectable pancreatic carcinoma. METHODS: Forty-four patients with pathologically confirmed, unresectable pancreatic adenocarcinoma without distant metastases were treated in a Phase II study. The patients received three-dimensional, planned, high dose conformal radiotherapy (70-72 grays). Toxicity was scored according to the World Health Organization criteria. Follow-up time ranged from 7 months to 25 months (median, 9 months). RESULTS: The treatment was feasible. Forty-one patients received the intended total dose. Treatment was never stopped because of toxicity. Acute toxicity was mainly Grade 1 and Grade 2 (in 70% and 57% of patients, respectively), whereas Grade 3 toxicity was seen in 9% of patients. One fatal event occurred that was not treatment related. Late Grade 3 and Grade 4 gastrointestinal toxicity was seen in 3 patients and 2 patients, respectively. Late (Grade 5) gastrointestinal bleeding was observed in 3 patients, 2 of whom had local tumor progression. At 3 months, reduction in tumor size was seen in 27% of patients, stable disease was seen in 20% of patients, and local disease progression was seen in 40% of patients. Ultimately, local disease progression was observed in 44% of patients. No true partial or complete responses were documented. The median survival from the time of diagnosis was 11 months (10 months from the start of radiotherapy). Seventeen of 25 patients (68%) experienced pain relief. CONCLUSIONS: High dose conformal radiotherapy for the treatment of patients with locally advanced pancreatic carcinoma is feasible with acceptable toxicity. In case of pain, it can offer palliation. The efficacy of the treatment in terms of prolongation of life is not proven. Distant metastases remain the major problem.

Adenocarcinoma↗

Assessing the feasibility of retrospective cohort studies.

While most epidemiologic cohort studies are preceded by some sort of feasibility study, details of such prior investigations are rarely reported. Yet it is during such feasibility studies that critical decisions are made, such as site selection and definition of exposure. Here we present the details on one such feasibility study, conducted to determine the possibility of a cohort mortality study of workers exposed to ethylene oxide. Issues discussed include methods for estimating sample size and power, for estimating levels of exposure, and for assessing the adequacy of personnel records.

Data Collection↗

Direct stenting with a combined intravascular ultrasound-coronary stent delivery platform: a feasibility trial.

IVUS is considered as the most accurate tool for the assessment of optimal stent deployment. Direct stenting has shown to be a safe, efficient, and resource-saving procedure in selected patients. In a prospective 1-month feasibility trial, a new combined IVUS-coronary stent delivery platform (Josonics Flex, Jomed, Helsingborn, Sweden) was evaluated during direct stenting in consecutive patients considered eligible for direct stenting. The feasibility endpoint was successful stent deployment without any clinical adverse event, while the efficacy endpoint was strategic adaptation according to standard IVUS criteria for optimal stent deployment at the intermediate phase (after a result considered angiographically optimal) and at the end of the intervention (after optimization according to IVUS standards). A total of 16 patients were successfully treated with this device without any major clinical complication. At the intermediate phase, optimal stent deployment was achieved in four patients only, while at the end only one patient had nonoptimal IVUS stent deployment. In particular, the minimal in-stent cross-section area increased from 6.3 +/- 1.2 to 8.3 +/- 2.5 mm(2). These preliminary data demonstrate the feasibility of direct stenting with a combined IVUS-stent catheter in selected patients and confirm the results from larger randomized trials on the impact of IVUS on strategic adaptations during coronary stent placement.

Adult↗

Feasibility and safety of transbrachial approach for patients with severe carotid artery stenosis undergoing stenting.

Although sporadic successful cases using the transradial approach (TRA) for carotid stenting have been reported, the safety and feasibility of carotid stenting using either TRA or a transbrachial approach (TBA) have not been fully investigated. Recently, we have developed a safe and feasible method of TRA for cerebrovascular angiographic studies. This study investigated whether a TBA approach using a 7-French (F) Kimny guiding catheter for carotid stenting is safe and feasible for patients with severe carotid stenosis. Thirteen patients were enrolled into this study (age range, 63-78 years). Seven of these 13 patients had severe peripheral vascular disease. A retrograde-engagement technique, involving looping 6-F Kimny guiding catheter, was utilized for carotid angiographic study. For carotid stenting, the 6-F Kimny guiding catheter was replaced with a 7-F Kimny guiding catheter, and the procedure was performed as the follows. First, an extra-support wire was inserted into the middle portion of external carotid artery (ECA). Second, a 0.035-inch Teflon wire was advanced into the common carotid artery. Then, the 6-F guiding catheter was exchanged for a 7-F Kimny guiding catheter. Third, if the first and second steps did not provide adequate support for exchanging the guiding catheter, a PercuSurge GuardWire was inserted into the ECA, followed by distal balloon inflation for an anchoring support. FilterWire EX was used in 9 patients and PercuSurge GuardWire in 4 patients to protect from distal embolization during the procedure. The procedure was successful in all patients. No neurological or vascular bleeding complications were observed and all patients were discharged uneventfully. The TBA for carotid stenting was safe and effective, providing a last resort for patients unsuited to femoral arterial access and surgical intervention.

Aged↗