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PubMed2004

Hepatic tissue engineering for adjunct and temporary liver support: critical technologies.

The severe donor liver shortage, high cost, and complexity of orthotopic liver transplantation have prompted the search for alternative treatment strategies for end-stage liver disease, which would require less donor material, be cheaper, and less invasive. Hepatic tissue engineering encompasses several approaches to develop adjunct internal liver support methods, such as hepatocyte transplantation and implantable hepatocyte-based devices, as well as temporary extracorporeal liver support techniques, such as bioartificial liver assist devices. Many tissue engineered liver support systems have passed the "proof of principle" test in preclinical and clinical studies; however, they have not yet been found sufficiently reliably effective for routine clinical use. In this review we describe, from an engineering perspective, the progress and remaining challenges that must be resolved in order to develop the next generation of implantable and extracorporeal devices for adjunct or temporary liver assist.

Biomedical Technology↗
PubMed2004

Floating navigator echo (FNAV) for in-plane 2D translational motion estimation.

A modification of the classical navigator echo (NAV) technique is presented whereby both 2D translational motion components are computed from a single navigator line. Instead of acquiring the NAV at the center of the k-space, a kx line is acquired off-center in the phase-encoding (ky) direction as a floating NAV (FNAV). It is shown that the translational motion in both the readout and phase-encoding directions can be computed from this line. The algorithm used is described in detail and verified experimentally. The new technique can be readily implemented to replace classic NAV in MRI sequences, with little to no additional cost or complexity. The new method can help suppress 2D translational motion and provide more accurate motion estimates for other motion-suppression techniques, such as the diminishing variance algorithm.

Algorithms↗
PubMed2006

Parallel asynchronous particle swarm optimization.

The high computational cost of complex engineering optimization problems has motivated the development of parallel optimization algorithms. A recent example is the parallel particle swarm optimization (PSO) algorithm, which is valuable due to its global search capabilities. Unfortunately, because existing parallel implementations are synchronous (PSPSO), they do not make efficient use of computational resources when a load imbalance exists. In this study, we introduce a parallel asynchronous PSO (PAPSO) algorithm to enhance computational efficiency. The performance of the PAPSO algorithm was compared to that of a PSPSO algorithm in homogeneous and heterogeneous computing environments for small- to medium-scale analytical test problems and a medium-scale biomechanical test problem. For all problems, the robustness and convergence rate of PAPSO were comparable to those of PSPSO. However, the parallel performance of PAPSO was significantly better than that of PSPSO for heterogeneous computing environments or heterogeneous computational tasks. For example, PAPSO was 3.5 times faster than was PSPSO for the biomechanical test problem executed on a heterogeneous cluster with 20 processors. Overall, PAPSO exhibits excellent parallel performance when a large number of processors (more than about 15) is utilized and either (1) heterogeneity exists in the computational task or environment, or (2) the computation-to-communication time ratio is relatively small.

Journal Article↗
PubMed2005

High dose melphalan in the treatment of advanced neuroblastoma: results of a randomised trial (ENSG-1) by the European Neuroblastoma Study Group.

BACKGROUND: High dose myeloablative chemotherapy ("megatherapy"), with haematopoietic stem cell support, is now widely used to consolidate response to induction chemotherapy in patients with advanced neuroblastoma. PROCEDURE: In this study (European Neuroblastoma Study Group, ENSG1), the value of melphalan myeloablative "megatherapy" was evaluated in a randomised, multi-centre trial. Between 1982 and 1985, 167 children with stages IV and III neuroblastoma (123 stage IV > 1 year old at diagnosis and 44 stage III and stage IV from 6 to 12 months old at diagnosis) were treated with oncovin, cisplatin, epipodophyllotoxin, and cyclophosphamide (OPEC) induction chemotherapy every 3 weeks. After surgical excision of primary tumour, the 90 patients (69% of the total) who achieved complete response (CR) or good partial response (GPR) were eligible for randomisation either to high dose melphalan (180 mg per square meter) with autologous bone marrow support or to no further treatment. RESULTS: Sixty-five (72%) of eligible children were actually randomised and 21 of these patients were surviving at time of this analysis, with median follow-up from randomisation of 14.3 years. Five year event-free survival (EFS) was 38% (95% confidence interval (CI) 21-54%) in the melphalan-treated group and 27% (95% CI 12-42%) in the "no-melphalan" group. This difference was not statistically significant (P = 0.08, log rank test) but for the 48 randomised stage IV patients aged >1 year at diagnosis outcome was significantly better in the melphalan-treated group-5 year EFS 33% versus 17% (P = 0.01, log rank test). CONCLUSIONS: In this trial, high dose melphalan improved the length of EFS and overall survival of children with stage IV neuroblastoma >1 year of age who achieved CR or GPR after OPEC induction therapy and surgery. Multi-agent myeloablative regimens are now widely used as consolidation therapy for children with stage IV disease and in those with other disease stages when the MYCN gene copy number in tumour cells is amplified. Because they are more toxic, complex, and costly these combination megatherapy regimens should be compared with single agent melphalan in randomised clinical trials.

Antineoplastic Agents, Alkylating↗
PubMed2005

High accuracy prediction of beta-turns and their types using propensities and multiple alignments.

We have developed a method that predicts both the presence and the type of beta-turns, using a straightforward approach based on propensities and multiple alignments. The propensities were calculated classically, but the way to use them for prediction was completely new: starting from a tetrapeptide sequence on which one wants to evaluate the presence of a beta-turn, the propensity for a given residue is modified by taking into account all the residues present in the multiple alignment at this position. The evaluation of a score is then done by weighting these propensities by the use of Position-specific score matrices generated by PSI-BLAST. The introduction of secondary structure information predicted by PSIPRED or SSPRO2 as well as taking into account the flanking residues around the tetrapeptide improved the accuracy greatly. This latter evaluated on a database of 426 reference proteins (previously used on other studies) by a sevenfold crossvalidation gave very good results with a Matthews Correlation Coefficient (MCC) of 0.42 and an overall prediction accuracy of 74.8%; this places our method among the best ones. A jackknife test was also done, which gave results within the same range. This shows that it is possible to reach neural networks accuracy with considerably less computional cost and complexity. Furthermore, propensities remain excellent descriptors of amino acid tendencies to belong to beta-turns, which can be useful for peptide or protein engineering and design. For beta-turn type prediction, we reached the best accuracy ever published in terms of MCC (except for the irregular type IV) in the range of 0.25-0.30 for types I, II, and I' and 0.13-0.15 for types VIII, II', and IV. To our knowledge, our method is the only one available on the Web that predicts types I' and II'. The accuracy evaluated on two larger databases of 547 and 823 proteins was not improved significantly. All of this was implemented into a Web server called COUDES (French acronym for: Chercher Ou Une Deviation Existe Surement), which is available at the following URL: http://bioserv.rpbs.jussieu.fr/Coudes/index.html within the new bioinformatics platform RPBS.

Amino Acid Sequence↗
PubMed2003

A practical and user-friendly toxicity classification system with microbiotests for natural waters and wastewaters.

Various types of toxicity classification systems have been elaborated by scientists in different countries, with the aim of attributing a hazard score to polluted environments or toxic wastewaters or of ranking them in accordance with increasing levels of toxicity. All these systems are based on batteries of standard acute toxicity tests (several of them including chronic assays as well) and are therefore dependent on the culturing and maintenance of live stocks of test organisms. Most systems require performance of the bioassays on dilution series of the original samples, for subsequent calculation of L(E)C50 or threshold toxicity values. Given the complexity and costs of these toxicity measurements, they can only be applied in well-equipped and highly specialized laboratories, and none of the classification methods so far has found general acceptance at the international level. The development of microbiotests that are independent of continuous culturing of live organisms has stimulated international collaboration. Coordinated at Ghent University, Belgium, collaboration by research groups from 10 countries in central and eastern Europe resulted in an alternative toxicity classification system that was easier to apply and substantially more cost effective than any of the earlier methods. This new system was developed and applied in the framework of a cooperation agreement between the Flemish community in Belgium and central and eastern Europe. The toxicity classification system is based on a battery of (culture-independent) microbiotests and is particularly suited for routine monitoring. It indeed only requires testing on undiluted samples of natural waters or wastewaters discharged into the aquatic environment, except for wastewaters that demonstrate more than 50% effect. The scoring system ranks the waters or wastewaters in 5 classes of increasing hazard/toxicity, with calculation of a weight factor for the concerned hazard/toxicity class. The new classification system was applied during 2000 by the participating laboratories on samples of river water, groundwaters, drinking waters, mine waters, sediment pore waters, industrial effluents, soil leachates, and waste dump leachates and was found to be easy to apply and reliable.

Animals↗
PubMed1996

Unsolved problems in early breast cancer detection: focus on the underserved.

In the last decade, numerous research and programmatic efforts have attempted to improve cancer screening practices among women from diverse race/ethnic backgrounds on the assumption that observed differences in breast cancer survival were largely due to differences in early detection practices. Recent data from the 1992 National Health Interview Survey and a 1992 survey in San Francisco Bay Area multiethnic communities indicate that rates of self-reported breast cancer screening tests among African American, Hispanic, and white women no longer differ significantly. However, there are large, persistent socioeconomic differences as reflected in educational and income levels, the recency of immigration, and English language proficiency. This emphasizes the continuing need for interventions tailored specifically for the underserved, with the racial, ethnic, and cultural composition of the intended audience informing educational messages and strategies. However, effective research interventions are complex and costly throughout the spectrum of outreach, inreach, and follow-up. Thus the generalizability of these strategies to under-founded providers and agencies in low-income communities may be limited. Therefore, as ongoing research continues to refine strategies, the application of effective community-based intervention should seek out potential partnerships with programs that provide the critical access to services. Cancer control scientists are well positioned to advocate for community-based infrastructures that facilitate translation of research into practice.

Adult↗
PubMed2000

Design of an electrical impedance tomography phantom using active elements.

The architecture of a novel phantom for electrical impedance tomography (EIT) is proposed. The design employs active elements, which include multiplying digital to analogue converters (MDAC), so that the impedance distribution in the phantom may be varied dynamically using computer control. The phantom is designed to assist in the validation of an EIT system under test. A number of published layouts for passive phantoms are analysed, and the requirements for an active element are specified for the most applicable of these. The use of active elements throughout a phantom imposes significant costs because of the need for each active element to operate independently. This proposal limits the cost and complexity by employing active elements in a restricted region of the phantom. Currently available technology, principally due to the limited analogue bandwidth of the MDAC, precludes the construction of a fully capable phantom from active elements. However, a design is specified that would enable its future development to cover the frequency range from 10 kHz to 1 MHz.

Electric Impedance↗
PubMed1994

Chronic illness of the temporomandibular joints as experienced by support-group members.

PURPOSE: For temporomandibular disorders, the clinical situation is one of considerable etiologic, diagnostic, and therapeutic uncertainty. Using interview data, this report describes this condition and the search for care from the perspective of sufferers who are support-group members. PARTICIPANTS AND METHODS: Thirty-two individuals participated; all were members of a support group for individuals with long-term problems attributed to the temporomandibular joints and/or the surrounding masticatory muscles. Using a structured, open-ended interview format, this study investigated how individuals understand and give meaning to their symptoms, their patterns of care seeking, and the consequences of the illness on their lives. The participants also completed several structured questionnaires. RESULTS: For these support-group members, symptoms extended beyond the jaw and surrounding area, with extensive musculoskeletal involvement and resulting dysfunctions that have far-reaching consequences for the sufferers' lives. Primary care physicians are often consulted, especially early in the illness history. They also provide ongoing care and are asked for guidance when patients seek specialized treatment. A striking aspect of the findings from the interviews is the complex and costly pattern of health care seeking. This extended search for effective treatment is examined with reference to culturally based understanding, shared by patients and clinicians, about the nature of illness.

Adult↗
PubMed1978

Influence of elevated pulmonary vascular resistance on the relationship between central venous pressure and pulmonary artery occluded pressure following cardiopulmonary bypass.

This study has demonstrated that CVP measurement is an unreliable index of left ventricular filling pressure in unselected patients undergoing A-C bypass procedures. The influence of altered PVR on the disparity between right and left ventricular filling pressures is not of prime importance. The inconsistent relationship between CVP and PAo is primarily a result of ventricular dysfunction and not altered PVR. This suggests that following A-C bypass surgery patients cannot be grouped with respect to altered PVR as the variable which determines whether CVP will be a reliable guide to changes in left atrial pressure. Routine use of Swan-Ganz catheters would improve the precision of monitoring and fluid administration in all patients following CPB. However, it would also increase the cost and complexity of routine care and add a very low incidence of complications to all patients having cardiac surgery. At present, we monitor high risk patients from the time of surgery and advocate early insertion of Swan-Ganz catheters in low risk patients if they are not responding to appropriate management.

Blood Pressure↗
PubMedDate not supplied

Reduction of neural damage in irreversible cerebral ischemia by calcium antagonists.

Because of the complexity and cost of clinical investigations and the virtual lack of pharmacological leads, drugs for the treatment of strokes have to be tested extensively in animal models closely mimicking the human disorder. With the recent introduction of in vivo NMR imaging (MRI) and spectroscopy (MRS), it is now possible to evaluate the consequences of strokes and to monitor the effects of therapeutic interventions in animals with the same methodology as in humans. The appearance and evolution of brain infarcts in spontaneously hypertensive rats (SHR), after occlusion of the middle cerebral artery (MCA), were detected with MRI. In coronal sections through the rat brain, regions with increased MRI signal started to become discernible after 6 h and turned out to be largely necrotic already after 24 h, as revealed by histology. The location (fronto-parietal cortex, caudate-putamen) and total infarct size, as determined from MR images or histology, were highly reproducible. Posttreatment with the dihydropyridine calcium antagonist isradipine (PN 200-110), at a daily dose of 3 X 0.3 mg/kg sc, reduced the total infarct size by 30-40%, determined by quantitative MRI and confirmed by histology. Biochemical markers of necrosis, such as the increased brain wet wt, the levels of sodium, potassium, dopamine, and noradrenaline, were changed toward normal values. The functional consequences of these morphological effects of isradipine were reflected by the parallel improvement of a neurological score. Follow-up observations made by MRI and histology indicated that the morphological differences between treated and control animals were still present to the same extent after 2 wk and, therefore, seem to be permanent. In order to elucidate the putative mechanisms involved, the influence of calcium antagonists on cerebral blood flow (CBF) and high energy phosphates (HEPs) was investigated. CBF was measured quantitatively with [14C] iodoantipyrine in MCA-occluded SHRs. Although isradipine had no effect on CBF in the contralateral hemisphere, at a dose reducing infarct size, it increased the reduced blood flow in the lesioned hemisphere toward normal values. HEPs (PCr and ATP) as well as inorganic phosphate (Pi) and intracellular pH were measured noninvasively in the rat brain by 31P MRS using a surface coil. Under normal conditions, calcium antagonists had no effect on these parameters.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed2005

QTL analysis of seed yield components in red clover (Trifolium pratense L.).

Cultivars of red clover (Trifolium pratense L.), an important forage crop in temperate regions, are often characterised by an unsatisfactory level of seed yield, leading to high production costs. This complex trait is influenced by many components and negatively correlated with other important traits, such as forage yield or persistence. Therefore, seed yield has proven to be difficult to improve. Thus, the objectives of this study were to assess association among seed yield components and to provide the basis for identifying molecular markers linked to QTLs for seed yield components to assist breeding for improved red clover cultivars. A total of 42 SSR and 216 AFLP loci were used to construct a molecular linkage map with a total map length of 444.2 cM and an average distance between loci of 1.7 cM. A total of 38 QTLs were identified for eight seed yield components. The traits seed number per plant, seed yield per head, seed number per head, head number per plant and percent seed set were highly correlated with seed yield per plant, and QTLs for several of these traits were often detected in the same genome region. Head number per plant may present a particularly useful character for the improvement of seed yield since it can easily be determined before seed maturity. In addition, two genome regions containing four or five QTLs for different seed yield components, respectively, were identified representing candidate regions for further characterisation of QTLs. This study revealed several key components which may facilitate further improvement of seed yield. The QTLs identified represent an important first step towards marker-assisted breeding in red clover.

Analysis of Variance↗
PubMed2000

[CRIGOS: development of a compact robot for image-guided orthopedic surgery].

In this paper, we present a medical robot system dedicated to support the surgeon during challenging tasks within orthopedic interventions. The main goal of this work is to develop a system as technically simple as the surgical requirements allow to keep its cost and complexity to a minimum. Therefore, we primarily focus on calibrated X-ray imaging for image acquisition, an easy registration procedure and robotic execution using a positioning device with simple parallel kinematics. Examples of different orthopedic interventions using the compact robot system for image-guided orthopedic surgery (CRIGOS) are presented, as well as various modes of execution of the device.

Arthroplasty, Replacement, Knee↗
PubMed1998

Immunotherapy of cancer with dendritic-cell-based vaccines.

Animal studies have shown that vaccination with genetically modified tumor cells or with dendritic cells (DC) pulsed with tumor antigens are potent strategies to elicit protective immunity in tumor-bearing animals, more potent than "conventional" strategies that have been tested in clinical settings with limited success. While both vaccination strategies are forms of cell therapy requiring complex and costly ex vivo manipulations of the patient's cells, current protocols using dendritic cells are considerably simpler and would be more widely available. Vaccination with defined tumor antigens presented by DC has obvious appeal. However, in view of the expected emergence of antigen-loss variants as well as natural immunovariation, effective vaccine formulations must contain mixtures of commonly, if not universally, expressed tumor antigens. When, or even if, such common tumor antigens will be identified cannot be, predicted, however. Thus, for the foreseeable future, vaccination with total-tumor-derived material as source of tumor antigens may be preferable to using defined tumor antigens. Vaccination with undefined tumor-derived antigens will be limited, however, by the availability of sufficient tumor tissue for antigen preparation. Because the mRNA content of single cells can be amplified, tumor mRNA, or corresponding cDNA libraries, offer an unlimited source of tumor antigens. DC transfected with tumor RNA were shown to engender potent antitumor immunity in animal studies. Thus, immunotherapy using autologous DC loaded with unfractionated tumor-derived antigens in the form of RNA emerges as a potentially powerful and broadly useful vaccination strategy for cancer patients.

Animals↗
PubMed2004

Surgical mortality score: risk management tool for auditing surgical performance.

Existing methods of risk adjustment in surgical audit are complex and costly. The present study aimed to develop a simple risk stratification score for mortality and a robust audit tool using the existing resources of the hospital Patient Administration System (PAS) database. This was an observational study for all patients undergoing surgical procedures over a two-year period, at a London university hospital. Logistic regression analysis was used to determine predictive factors of in-hospital mortality, the study outcome. Odds ratios were used as weights in the derivation of a simple risk-stratification model-the Surgical Mortality Score (SMS). Observed-to-expected mortality risk ratios were calculated for application of the SMS model in surgical audit. There were 11,089 eligible cases, under five surgical specialties (maxillofacial, orthopedic, renal transplant/dialysis, general, and neurosurgery). Incomplete data were 3.7% of the total, with no evidence of systematic underreporting. The SMS model was well calibrated [Hosmer-Lemeshow C-statistic: development set (3.432, p = 0.33), validation set (6.359, p = 0.10) with a high discriminant ability (ROC areas: development set [0.837, S.E.=0.013] validation set [0.816, S.E. = 0.016]). Subgroup analyses confirmed that the model can be used by the individual specialties for both elective and emergency cases. The SMS is an accurate risk- stratification model derived from existing database resources. It is simple to apply as a risk-management, screening tool to detect aberrations from expected surgical outcomes and to assist in surgical audit.

Adult↗
PubMed1998

Positron emission tomography as a diagnostic tool in oncology.

Early diagnosis in oncology is important for treatment by surgical intervention, which generally has the highest curative potential. For higher stages of disease involvement, initiation of rapid treatment is indicated to provide the patient with the optimal therapy regimen. Although this may not improve the prognosis, it will maintain the quality of life. Anatomic imaging modalities, such as CT, MR imaging, and US, are clinically important high-resolution imaging techniques that are well suited to reveal structural abnormalities. However, the differentiation of lesions as being benign or malignant is still problematic. Metabolic imaging modalities in nuclear medicine (NM), i.e., single photon emission computed tomography (SPECT) and positron emission tomography (PET), can reveal biochemical parameters of the lesions such as glucose, oxygen, or amino acid metabolism, or measure the receptor density status. These parameters may allow a completely new clinical perspective in the management and understanding of diseases such as cancer. Although PET has been around since the early 1960s, it has only recently emerged as a powerful diagnostic tool in oncology. Society has great difficulty accepting this clinical imaging modality because of its high cost and complexity. Current applications of PET in oncology have been in characterizing lesions, differentiating recurrent disease from treatment effects, staging tumors, evaluating the extent of disease, and therapy monitoring. Here, the role of PET in diagnosis, staging, and restaging of cancer is reviewed and compared with the other tumor imaging modalities. We cover articles published in the past 3 years. We utilize the typical radiology format, in which the contribution in each body area is reviewed (topographic orientation), instead of the more organ-based approach used in internal medicine.

Biomarkers, Tumor↗
PubMed2003

Rasmussen's model of human behavior in laparoscopy training.

AIMS: Compared to aviation, where virtual reality (VR) training has been standardized and simulators have proven their benefits, the objectives, needs, and means of VR training in minimally invasive surgery (MIS) still have to be established. The aim of the study presented is to introduce Rasmussen's model of human behavior as a practical framework for the definition of the training objectives, needs, and means in MIS. METHODS: Rasmussen distinguishes three levels of human behavior: skill-, rule-, and knowledge-based behaviour. The training needs of a laparoscopic novice can be determined by identifying the specific skill-, rule-, and knowledge-based behavior that is required for performing safe laparoscopy. Future objectives of VR laparoscopy trainers should address all three levels of behavior. RESULTS: Although most commercially available simulators for laparoscopy aim at training skill-based behavior, especially the training of knowledge-based behavior during complications in surgery will improve safety levels. However, the cost and complexity of a training means increases when the training objectives proceed from the training of skill-based behavior to the training of complex knowledge-based behavior. CONCLUSION: In aviation, human behavior models have been used successfully to integrate the training of skill-, rule-, and knowledge-based behavior in a full flight simulator. Understanding surgeon behavior is one of the first steps towards a future full-scale laparoscopy simulator.

Algorithms↗
PubMed2000

New tools in diagnosing catheter-related infections.

Clinical criteria alone are insufficient to allow a diagnosis of intravascular catheter-related sepsis (CRS). A definite diagnosis of CRS usually requires removal of the catheter for quantitative catheter tip culture. However, only about 15-25% of central venous catheters (CVC) removed because infection is suspected actually prove to be infected, and the diagnosis is always retrospective. Other diagnostic tests, such as differential quantitative blood cultures from samples taken simultaneously from the catheter and a peripheral vein, have been proposed to avoid unjustified removal of the catheter and the potential risks associated with the placement of a new catheter at a new site: a central-to-peripheral blood culture colony count ratio of 5:1 to 10:1 is considered indicative of CRS. Despite its high specificity, the latter diagnostic technique is not routinely used in clinical practice because of its complexity and cost. The measurement of the differential time to positivity between hub blood (taken from the catheter port) and peripheral blood cultures might be a reliable tool facilitating the diagnosis of CRS in situ. In an in vitro study, we found a strong relationship between the inoculum size of various microorganisms and the time to positivity of cultures. When the times to positivity of cultures of blood taken simultaneously from central and peripheral veins in patients with and without CRS were examined, we found that earlier positivity of central vs peripheral vein blood cultures was highly correlated with CRS. Using a cut-off value of +120 min, the "differential time to positivity" of the paired blood samples, defined as time to positivity of the peripheral blood minus that of the hub blood culture, had 91% specificity and 94% sensitivity for the diagnosis of CRS. This method may be coupled with other techniques that have high negative predictive value, such as skin cultures at the catheter exit site. This diagnostic test can be proposed for routine clinical practice in most hospitals using automatic devices for blood cultures positivity detection. Endoluminal brushing of the catheter is considered sensitive and specific for the diagnosis of CRS, but the risk of embolisation or subsequent bacteraemia should be considered. Gram staining and the acridine-orange leucocyte cytospin test on through-catheter blood culture have been proposed for rapid diagnosis of CRS without catheter removal. The technique, which requires 100 microl catheter blood and the use of light and ultraviolet microscopy, is considered simple, rapid (30 min) and inexpensive. In conclusion, diagnostic tools such as paired blood cultures or Gram staining and the acridine-orange leucocyte cytospin test should allow a diagnosis of CRS without catheter removal in cancer patients.

Algorithms↗