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Pressure limited sustained off-resonance irradiation for collision-activated dissociation in fourier transform mass spectrometry.

A theoretical evaluation of the sustained off-resonance irradiation of ions (SORI) in the presence of a collisional buffer gas in a Fourier transform ion cyclotron resonance mass spectrometer is presented. It is shown that there is an optimal pressure for a given set of irradiation parameters corresponding to the most effective dissociation. Theoretical predictions are compared with experimental results for the dissociation of electrosprayed biopolymer ions and with previously accepted view of the SORI process.

Algorithms↗

Assessment of patients for orthognathic surgery.

Rapid advances in orthognathic surgery now allow the clinician to treat severe dentofacial deformities that were once only manageable by orthodontic camouflage. These cases were often compromised with unacceptable facial esthetics and unstable occlusal results. Over the past 25 years, there have been numerous improvements in technology and the surgical management of dentofacial deformities. These progressions now allow more predictable surgical outcomes, which ensure patient satisfaction. Not all patients are candidates for surgical treatment; therefore, patient assessment and selection remains paramount in the process of diagnosing and treatment planning for this type of irreversible treatment. The inclusion of patients in the decision-making process increases their awareness and acceptance of the final result. The past three decades indicate an increased usage of orthodontic treatment by both children and adults. Patient demographic profiles for severe occlusal and facial characteristics are presented in an effort to understand the epidemiological factors of malocclusion and predict the population's need for this service.

Adult↗

Mechanisms of muscle dedifferentiation during regeneration.

For many years people have known that amphibians have an amazing ability to regenerate lost body parts. In contrast humans have limited regeneration capacity and even simple wound healing results in scarring. Despite more than a century of scientific inquiry, this remarkable phenomenon remains poorly understood. Recent research has begun to provide insight into how this unique process that is now fully accepted to occur via the reversal of cell differentiation is executed at the molecular level. As more and more is known about regeneration and dedifferentiation we can begin to address the question: if given the right signals could mammals also regenerate body structures?

Animals↗

[Current techniques for primary flexor tendon repair].

Flexor tendon lacerations still represent a challenging problem to hand surgeons, particularly in zone 2. There has been a considerable improvement in therapeutic modalities during the past 30 years, following a better understanding of the tendon healing process. It is now universally accepted that flexor tendon repair must be performed in emergency, by mean of a direct primary suture, and followed by a immediate rehabilitation protocol. More recently, the benefits of early active motion has been demonstrated. Early axial loading of the repair enhances intrinsic callus formation, reduces peritendinous adhesion, and could attenuate the fragilization of the callus during the first three weeks. However, active motion generates a heavier stress on the repair. The initial resistance of the repair thus appeared to be the critical point. This has motivated a large number of investigations about the suture technique itself, with in vitro and in vivo evaluations. The results of these studies did precise the concept of "locking" and "grasping" sutures, and demonstrated the superiority of four strands sutures. These experimental results cannot be ignored by surgeons dealing with flexor tendon repairs.

Bony Callus↗

Biocatalysts for clean industrial products and processes.

Biocatalysis inherently offers the prospect of clean industrial processing and has become an accepted technology throughout most sectors. The convergence of biology and chemistry has enabled a plethora of industrial opportunities to be targeted, while discoveries in biodiversity and the impact of molecular biology and computational science are extending the range of natural and engineered biocatalysts that can be customised for clean industrial requirements.

Biodegradation, Environmental↗

Depressive syndromes in dementia.

BACKGROUND: Depressive syndromes in dementia are common, treatment is challenging and controlled intervention studies are small in number. The goal of this paper is to review known information about the etiology, epidemiology and treatment of these syndromes, as summarized at the recent Canadian Consensus Conference on Dementia. METHODS: A number of Medline searches were performed (most recently updated in October 2000) using the subject categories dementia and depression, or apathy or emotional lability and other relevant articles were also reviewed. The background article was edited and amended at the Consensus Conference on Dementia. Final recommendations appearing in the summary article by Patterson et al were accepted by the group consensus process. Clinical discussion and informational updates were added for the current text by the authors. RESULTS: Depressive syndromes, ranging in severity from isolated symptoms to full depressive disorders, increase in dementia. While clear-cut depressive disorder is increased in this population, sub-syndromal disorders are even more common and cause considerable distress. Antidepressant treatment may improve the quality of life in depressed, demented people, although it is less successful than in those without cognitive impairment and carries more risk of iatrogenic effects. CONCLUSIONS: Physicians should be alert to the presence of depressive syndromes in dementia. Depressive illness should be treated and, when necessary, referral should be made to an appropriate specialist. Treatment must minimize iatrogenic effects. Although there is some support for treatment of syndromes that do not meet criteria for depressive disorder or dysthymia, the first line of intervention in these situations should involve nonpharmacological approaches.

Aged↗

DNA sequence recognition by the antitumor drug ditercalinium.

The antitumor drug ditercalinium is a rare example of a noncovalent DNA-binding ligand that forms bisintercalation complexes via the major groove of the double helix. Previous structural studies have revealed that the two connected pyridocarbazolium chromophores intercalate into DNA with the positively charged bis(ethylpiperidinium) linking chain oriented to the wide groove side of the helix. Although the interaction of ditercalinium with short oligonucleotides containing 4-6 contiguous GC base pairs has been examined in detail by biophysical and theoretical approaches, the sequence preference for ditercalinium binding to long DNA fragments that offer a wide variety of binding sites has been investigated only superficially. Here we have investigated both sequence preferences and possible molecular determinants of selectivity in the binding of ditercalinium to DNA, primarily using methods based upon DNase I footprinting. A range of multisite DNA substrates, including several natural restriction fragments and different PCR-generated fragments containing unconventional bases (2,6-diaminopurine, inosine, uridine, 5-fluoro- and 5-methylcytosine, 7-deazaguanine, 7-deazaadenine, and N(7)-cyanoboranoguanine), have been employed to show that ditercalinium selectively recognizes certain GC-rich sequences in DNA and to identify some of the factors which affect its DNA-binding sequence selectivity. Specifically, the footprinting data have revealed that the 2-amino group on the purines or the 5-methyl group on the pyrimidines is not essential for the formation of ditercalinium-DNA complexes whereas the major groove-oriented N(7) of guanine does appear as a key element in the molecular recognition process. The loss of N(7) at guanines but not adenines is sufficient to practically abolish sequence-selective binding of ditercalinium to DNA. Thus, as expected for a major groove binding drug, the N(7) of guanine is normally required for effective complex formation with GC base pairs, but interestingly the substitution of the N(7) with a relatively bulky cyanoborane group does not markedly affect the sequence recognition process. Therefore, the hydrogen bond accepting capability at N(7) of guanines is not sufficient to explain the GC-selective drug-DNA association, and the implications of these findings are considered.

Antineoplastic Agents↗

Evaluation of exploration and monitoring methods for verification of natural attenuation using the virtual aquifer approach.

Though natural attenuation (NA) is increasingly considered as a remediation technology, the methods for proper identification and quantification of NA are still under discussion. Here the "Virtual Aquifer" approach is used to demonstrate problems which may arise during measurement of concentrations in observation wells and for interpolation of locally measured concentrations in contaminated heterogeneous aquifers. The misinterpretation of measured concentrations complicates the identification and quantification of natural attenuation processes. The "Virtual Aquifer" approach accepts the plume simulated with a numerical model for a heterogeneous aquifer as "virtual reality". This virtual plume is investigated in the model with conventional methods like observations wells. The results of the investigation can be compared to the virtual "reality", evaluating the monitoring method. Locally determined concentrations are interpolated using various interpolation methods and different monitoring set-ups. The interpolation results are compared to the simulated plume to evaluate the quality of interpolation. This evaluation is not possible in nature, since concentrations in a heterogeneous aquifer are never known in detail.

Biodegradation, Environmental↗

Estimating social adjustment following spinal trauma--II: Population trends and effects of compensation on adjustment.

Adaptation to, or acceptance of, acquired spinal cord injury is accepted as an essentially longitudinal process. Changes in an individual's social, financial and domestic positions in turn affect issues concerning quality of life and self-image. The responses of 302 individuals with spinal cord injury in the United Kingdom and United States of America are presented to produce individual profiles of social adjustment. The differences between the UK and USA groups are presented, together with a combined analysis which addresses, in particular, the effects which being involved in litigation has on the process of social adjustment. Individual data concerning social adjustment, provided through a scale developed by the authors, and the utility of graphical presentation of the data is also presented. Such presentation has been found to have particular importance in clinical interview, situations by providing a framework for further exploration of individual adjustment difficulties, and in legal settings.

Adult↗

Immunoaffinity extraction in veterinary residue analysis--a regulatory viewpoint.

The utility of immunoaffinity chromatography (IAC) for the purification of veterinary drug residues from extracts of foods of animal origin is widely acknowledged. However owing to the unique nature of the specific antibody reagent used when synthesising an immunosorbent, certain reassurances are needed before an IAC process can be considered an acceptable stage in a routine analytical method. European Community legislation requires applicants for Maximum Residue Limits or national Marketing Authorization for veterinary medicinal products, used in food producing animals, to provide a routine analytical method in accordance with Volume VI of the Rules Governing Medicinal Products in the European Community. In order to ensure the continued supply of immunosorbent material, applicants wishing to use IAC sample clean-up procedures should consider generating the following data: a standard operating procedure (SOP) for antibody production (or cell-line maintenance in the case of monoclonal antibodies), a specifications document of antibody characterisation, an SOP for immunosorbent synthesis, validation of immunosorbent operating conditions and an assessment of its performance criteria. This paper aims to introduce analysts to the technique of IAC and to suggest how those areas of concern highlighted above may be addressed.

Animals↗

Monitoring the care of lung cancer patients: linking audit and care pathways.

Clinical audit plays an important role in monitoring the provision of care for patients whatever their condition. Care pathways define the steps and expected course of events in the care of patients with a specific clinical problem over a set time scale. This paper describes a study undertaken in a multisite cancer unit to develop a tool for monitoring the progress of lung cancer patients through a care pathway and auditing key standards within the pathway. Important issues associated with the development of this tool are highlighted. The process of developing this tool involved the following steps: a review of the literature dealing with the management of lung cancer patients; interviews with key personnel in primary, secondary, tertiary and palliative care; development of a paper-based series of forms representing key steps in the patient's care pathway; 3-month trial of the paper-based tool; analysis of completion rates and interviews with form users to evaluate effectiveness; and recommendations for creating an electronic record using the experience and lessons learned from the paper version. The paper forms developed through this multistage process were found to be acceptable to users and have the potential to provide accurate information at key points for audit throughout the patient's time within the health-care system for their lung cancer condition. The flexibility of this methodology allows it to be adapted readily to a variety of clinical situations and conditions.

Cancer Care Facilities↗

Osteoarthritic cartilage fibrillation is associated with a decrease in chondrocyte adhesion to fibronectin.

OBJECTIVE: Cartilage destruction in osteoarthritis (OA) is generally accepted as a failed repair process. Cell adhesion is implicated in tissue repair. Therefore, adhesion of OA chondrocytes to extracellular matrix proteins was investigated. DESIGN: Using chondrocytes from human OA femoral head cartilage, adhesion to fibronectin and type II collagen of cells from distinct areas showing an intact cartilage surface or a fibrillated cartilage surface was studied. Modulation of chondrocyte adhesion by both protein kinase C (PKC) inhibitors and glucosamine sulfate (GS) was also investigated. RESULTS: A significant (P < 0.05) decrease in adhesion to fibronectin of chondrocytes from fibrillated cartilage, relative to those from grossly normal OA cartilage, was demonstrated. Adhesion to type II collagen was not modified by the chondrocyte origins (either from normal or fibrillated OA cartilage). Adhesion to fibronectin of cells from grossly intact cartilage was decreased by the addition of PKC and calmodulin-dependent kinase inhibitors, W7 and sphingosine, to the cell culture. Adhesion to fibronectin of chondrocytes from fibrillated cartilage was significantly (P < 0.05) increased after glucosamine sulfate treatment. CONCLUSION: Fibrillation of cartilage from OA femoral head is associated with a defective adhesion of chondrocytes to fibronectin. The process is suggested to be dependent of PKC and/or calmodulin-dependent kinases and potentially reversible. Conceivably, it could play a role in OA cartilage destruction.

Aged↗

Judgement of the quality of bowel preparation at screening flexible sigmoidoscopy is associated with variability in adenoma detection rates.

BACKGROUND AND STUDY AIMS: Adenoma detection rates (ADRs) at screening flexible sigmoidoscopy are known to vary between endoscopists. Variability in the technique used and in the quality of bowel preparation may explain this. The aim of this study was to establish whether there is a relationship between the grading of bowel preparation and the ADR. MATERIALS AND METHODS: The relationship between the ADR and assessment of bowel preparation was examined using the full United Kingdom Flexible Sigmoidoscopy Screening Trial data set (n = 38 601). The consistency of the bowel preparation classification was then investigated by six experienced endoscopists (video scorers), who examined 260 flexible sigmoidoscopy cases - 20 from each of the 13 trial endoscopists. RESULTS: Overall, the ADR was significantly higher in flexible sigmoidoscopy examinations with excellent or good bowel preparation ( P = 0.02). However, endoscopists with a higher ADR coded a smaller proportion of their examinations as having excellent/good preparation ( P = 0.002). Video scorers agreed with the trial endoscopists' definition of bowel preparation in 48.9 % of the readings, but they scored the quality of preparation as poorer than the trial endoscopists in 36.4 % and 40.6 %, respectively, in the intermediate-performance group (10 % < ADR < 14 %) and lower-performance group (ADR </= 10 %) in comparison with only 12.9 % in the high-performance group (ADR > or =14 %). There was a significant linear trend between the proportion scored as having poor bowel preparation and the ADR ( P < 0.001), varying from 2.7 % in the higher-performance ADR group to 13.4 % in the lower-performance group. CONCLUSIONS: Endoscopists with a higher ADR are more likely to be critical of the quality of bowel preparation. Training in judgement processes such as non-acceptance of suboptimal bowel preparation is required in order to ensure universally high standards in screening procedures.

Adenoma↗

[Motor grammar of the spinal cord--status and revision].

Modern neurophysiological research, mainly in the second third of this century, has led to a set of widely accepted findings on the basic processes and rules of interactions between bodily periphery and the spinal level, which may be called a kind of elementary "grammar" of the spinal cord. As far as these apply to motor control functions, they are expressed here in condensed form as ten "paragraphs", which until recently belonged to the conventional standard teaching of neurophysiology. Each paragraph is then critically reviewed, supplemented and revised, as far as necessary, based on research progress in the last thirty years. The review deals with: Alpha motoneurones and their motor units; the muscle spindle with its sensory and motor structures, and its efferent controls by gamma and beta neurones; the spinal connections and effects of the afferents from primary and secondary spindle endings; properties and spinal effects of the Golgi tendon organs; new aspects of the flexor reflex afferents (FRA), of recurrent Renshaw feedback, and of presynaptic inhibition. The last paragraph stresses the importance of supraspinal controls of the spinal moto- and interneurones.

Afferent Pathways↗

[Integration of psychosocial services into the management of the child with cancer].

The integration of colleagues from psychosocial occupations into the traditional team of doctors and nurses demands a holistic treatment concept, the general desire for interdisciplinary action, and readiness for patience in the process of mutual learning. The acceptance of the psychosocial services by the patient and his/her family is frequently determined by the acceptance by physicians and nurses. The members of the psychosocial team are confronted with the following tasks.: 1. Developing a trustful relationship with the patient and his/her parents, 2. Setting up a history of family dynamics, 3. Practical assistance in matters of hospital routines, 4. Assistance in the emotional aspects of coping with the disease, 5. Rendering support to a patient and his/her family at death, 6. Leading and moderating groups of parents who live with so called "residual fear" or are mourning a child. Colleagues of the psychosocial team, who have to be able to cope with these existentially demanding tasks within a relationship to patients and their families over an extended period of time should have sufficient professional identity, adequate professional competence, and a certain foundation of life experience.

Child↗

Comparison of efficiency and bias of free energies computed by exponential averaging, the Bennett acceptance ratio, and thermodynamic integration.

Recent work has demonstrated the Bennett acceptance ratio method is the best asymptotically unbiased method for determining the equilibrium free energy between two end states given work distributions collected from either equilibrium and nonequilibrium data. However, it is still not clear what the practical advantage of this acceptance ratio method is over other common methods in atomistic simulations. In this study, we first review theoretical estimates of the bias and variance of exponential averaging (EXP), thermodynamic integration (TI), and the Bennett acceptance ratio (BAR). In the process, we present a new simple scheme for computing the variance and bias of many estimators, and demonstrate the connections between BAR and the weighted histogram analysis method. Next, a series of analytically solvable toy problems is examined to shed more light on the relative performance in terms of the bias and efficiency of these three methods. Interestingly, it is impossible to conclusively identify a "best" method for calculating the free energy, as each of the three methods performs more efficiently than the others in at least one situation examined in these toy problems. Finally, sample problems of the insertion/deletion of both a Lennard-Jones particle and a much larger molecule in TIP3P water are examined by these three methods. In all tests of atomistic systems, free energies obtained with BAR have significantly lower bias and smaller variance than when using EXP or TI, especially when the overlap in phase space between end states is small. For example, BAR can extract as much information from multiple fast, far-from-equilibrium simulations as from fewer simulations near equilibrium, which EXP cannot. Although TI and sometimes even EXP can be somewhat more efficient in idealized toy problems, in the realistic atomistic situations tested in this paper, BAR is significantly more efficient than all other methods.

Bias↗

The effect of fibronectin coating on endothelial cell kinetics in polytetrafluoroethylene grafts.

Despite the proven experimental success of endothelial cell seeding of prosthetic vascular grafts, the process has not been widely accepted for clinical use because of its complexity and the need for a relatively large length of autologous vein to provide the requisite number of cells. Using autologous endothelial cells radiolabeled with indium 111-oxine, we studied the effect of fibronectin coating of polytetrafluoroethylene grafts in a canine carotid interposition model on initial endothelial cell adherence and subsequent cell retention for up to 72 hours following restoration of blood flow. Since the number of harvested endothelial cells varied widely depending on the diameter and length of available vein, cellular adherence was best expressed as a percentage of the original cell harvest. More than twice as many (46.7% vs. 19.8%) endothelial cells initially adhered to fibronectin-coated grafts compared with uncoated control grafts. Fibronectin did not appear to influence the loss of cells within the first 30 minutes following restoration of blood flow. However, over the next 24 hours, it clearly reduced the mean cell loss from 3.7%/hr to 2.2%/hr and resulted in a sixfold increase (21.3% vs. 3.4%) in the number of retained cells at the end of a 24-hour period. When the endothelial cell preclot was performed with a solution of culture medium 199, as opposed to heparinized whole blood, there was no significant difference in endothelial cell retention.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Role of cerebral endothelium in brain oedema.

The view that cerebral endothelial cells represent the cellular basis of the blood-brain barrier has been generally accepted. The regulation of transport processes operating in the cerebral endothelial cells is currently of great interest. Our knowledge of these regulatory mechanisms is briefly reviewed here with special regard to the molecular processes involved in the formation of brain oedema and emphasis on new therapeutic means for its prevention.

Brain↗