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Use of out-of-hospital variables to predict severity of injury in pediatric patients involved in motor vehicle crashes.

STUDY OBJECTIVE: We sought to create a clinical decision rule, on the basis of variables available to out-of-hospital personnel, that could be used to accurately predict severe injury in pediatric patients involved in motor vehicle crashes as occupants. METHODS: We analyzed the National Automotive Sampling System database, a national probability sample, using pediatric patients up to 15 years old (occupants only) involved in motor vehicle crashes from January 1993 to December 1999. The National Automotive Sampling System database includes patients from regions throughout the country, weighted to represent a nationwide sample. Twelve out-of-hospital variables were used in classification and regression tree analysis to create a decision rule separating children with severe injuries (Injury Severity Score [ISS] > or =16) from those with minor injuries (ISS < 16). Misclassification costs and complexity parameters were selected to yield a decision tree with appropriate sensitivity and specificity for the identification of severely injured patients, while also being simple and practical for out-of-hospital use. Probability weights were used throughout the analysis to account for the sampling design and sampling weights. RESULTS: Using a sample size of 8,392 children, we constructed a decision rule using 3 out-of-hospital variables (Glasgow Coma Scale score, passenger space intrusion > or =6 in [> or =15 cm], and restraint use) to predict those patients with an ISS of 16 or more. Internal cross-validation was used to determine the sensitivity and specificity, yielding values of 92% and 73%, respectively, for the prediction of patients with an ISS of 16 or more. CONCLUSION: Out-of-hospital variables available to field personnel could be used to effectively triage pediatric motor vehicle crash patients using the decision rule developed here. Prospective trials would be needed to test this decision rule in actual use.

Accidents, Traffic↗

Age, cohort, and time development muddles: easy in practice, hard in theory.

The debate among developmental psychologists over how best to combine longitudinal and cross-sectional data sequences can be traced back at least four decades. During the 1970s, a variation of this theme received much attention: could the developmental influences of age, cohort, and time be unraveled by sufficiently ingenious application of combined data sequences? We believe discussion of this question has been needlessly parochial and confused. Substantive and methodological contributions from other disciplines have, until recently, been largely ignored by developmental psychologists. Moreover, the solutions debated by psychologists have generally been formulated in language that obscured, rather than explicated, the formal indeterminacy implicit in models of age, cohort, and time parameters. Methodologists have outlined formal solutions to problems of indeterminacy in the contexts of model identification and estimability theory. Sociologists have proposed solutions, based on explicitly theoretical assumptions, that permit model identification and unambiguous interpretation. We review these contributions, and suggest a hierarchy of solutions to the problem of age, cohort, and time indeterminacy.

Aging↗

Studies of a targeted risk reduction intervention through defined exercise (STRRIDE).

PURPOSE: The Studies of a Targeted Risk Reduction Intervention through Defined Exercise (STRRIDE) trial is a randomized controlled clinical trial designed to study the effects of exercise training regimens differing in dose (kcal.wk-1) and/or intensity (relative to peak VO2) on established cardiovascular risk factors and to investigate the peripheral biologic mechanisms through which chronic physical activity alters carbohydrate and lipid metabolism to result in improvements in these parameters of cardiovascular risk in humans. METHODS: We will recruit 384 subjects and randomly assign them to one of three exercise training regimens or to a sedentary control group. The recruiting goal is to attain a subject population that is 50% female and 30% ethnic minority. The overall strategy is to use graded exercise training regimens in moderately overweight subjects with impairments in insulin action and mild to moderate lipid abnormalities to investigate whether there are dose or intensity effects and whether adaptations in skeletal muscle (fiber type, metabolic capacity, and/or capillary surface area) account for improvements in insulin action and parameters of lipoprotein metabolism. We will study these variables before and after exercise training, and over the course of a 2-wk detraining period. The study sample size is chosen to power the study to examine differences in responses between subjects of different gender and ethnicity to exercise training with respect to the least sensitive parameter-skeletal muscle capillary density. RESULTS: The driving hypothesis is that improvements in cardiovascular risk parameters derived from habitual exercise are primarily mediated through adaptations occurring in skeletal muscle. CONCLUSION: Identification that amount and intensity of exercise matter for achieving general and specific health benefits and a better understanding of the peripheral mechanisms mediating the responses in carbohydrate and lipid metabolism to chronic physical activity will lead to better informed recommendations for those undertaking an exercise program to improve cardiovascular risk.

Adult↗

Hemodynamic assessment of critically ill patients using echocardiography Doppler.

PURPOSE OF REVIEW: The evaluation of hemodynamic status in critically ill patients is a leading recommended indication of transesophageal echocardiography in the intensive care unit. Advantages and diagnostic yield of transesophageal echocardiography in this setting are particularly relevant when considering limitations and questioned prognostic impact of pulmonary artery catheterization. RECENT FINDINGS: Recent clinical studies have been performed to validate and assess the value of transesophageal echocardiography in determining cardiac output, cardiac preload dependence, right ventricular function, and left ventricular filling pressure. In addition, diagnostic capacity and therapeutic impact of transesophageal echocardiography have been widely reported in various intensive care unit settings. SUMMARY: Transesophageal echocardiography appears well suited for the determination of cardiac index and to track its variations after therapeutic interventions. Although repeated measurements of left ventricular end-diastolic dimension allows to accurately track preload variations, a single determination is not reliable to predict fluid responsiveness in intensive care unit patients. Identification of preload dependence in hemodynamically unstable patients currently tends to rely mainly on dynamic parameters that use cardiopulmonary interactions under mechanical ventilation. Transesophageal echocardiography also allows to adequately assess right ventricular function and left ventricular filling pressure using combined Doppler modalities. Adequate education and training of intensivists and anesthesiologists is crucial to further develop the use of transesophageal echocardiography in the intensive care unit setting. Despite the absence of randomized controlled studies documenting transesophageal echocardiography benefits on patient outcome, present evidence and experience strongly recommend a larger use of echocardiography Doppler for a comprehensive functional hemodynamic assessment of critically ill patients with circulatory failure.

Blood Pressure↗

On modeling center of foot pressure distortion through a medium.

The center of foot pressure (COP) is a commonly used output measure of the postural control system as it is indicative of the systems stability. A dense piece of foam, i.e., a sponge, can be used to emulate random environmental conditions that distort the ground reaction forces received and interpreted by the cutaneous sensors in the feet; thus introducing uncertainty into the control system. In this paper, the density and size of the sponge was selected such that a subject's weight did not cause full compression. In general, the COP is measured from the bottom of the sponge. As the sponge is used to distort ground reaction forces, it is reasonable then to assume that the COP signal would also be distorted. The use of other sensory information to identify state of balance, and compute necessary balance adjustments, is therefore required. In addition to a sponge, many different types of specialized footwear and inserts are used for people with peripheral neuropathy, such as diabetics. However, it is difficult to design diabetic footwear without a better understanding of the mechanical and physiological effects that different surfaces typical of outdoor terrains, such as a sponge, which cannot be predicted without the sense of the foot, have on balance. Therefore, the goal of this study was to investigate the change of the COP signal from the top and bottom of the sponge. Portable force sensing mats from Vista Medical were used to obtain the COP from the top and bottom of the sponge. The COP measured on the bottom of the sponge is not the same as the COP measured on the top, particularly in the medial-lateral direction. Several linear and nonlinear models were used to identify the unknown plant; i.e., the sponge. Overall, the nonlinear neural network method had superior performance when compared with the linear models. Thus, the results indicate that the signals from the top and bottom of the sponge are in fact different, and furthermore, they are nonlinearly related. A nonlinear mathematical model is proposed which describes COP distortion through a medium such as a sponge. Although the values for the model parameters determined were for a particular sponge, this study suggests that a neural network plant identification model may be applied to any medium other than the sponge; the information can then be used to determine how the balance control model is affected given the sensory information received.

Adult↗

Working with the confocal scanning UV-laser microscope: specific DNA localization at high sensitivity and multiple-parameter fluorescence.

The use of fast-staining DNA-specific dyes such as DAPI or Hoechst 33342/33258 has been a major problem for confocal scanning laser microscopy (CSLM) studies of intranuclear chromatin organization. Moreover, the availability of a confocal ultraviolet scanning laser microscope configuration, which allows an excitation at wavelengths of 364 nm as well as 488, 514 and 543 nm, is a prerequisite for single as well as multiple fluorescence parameter studies, especially if these studies are concerned with the precise localization of intranuclear signals. Here we report the characteristics and application of a CSLM, which was adapted for UV-excitation and therefore enables comparison of the spatial distribution of several types of signals within one preparation. In addition to multiple-parameter studies, we have also investigated the sensitivity of the system with regard to the identification of the double-stranded DNA of lampbrush chromosome loops in germinal vesicles of amphibian oocytes.

Animals↗

Ultrasonic characterization of biological tissues.

Ultrasonic imaging has become increasingly important as a diagnostic tool in medicine because it is noninvasive and it can provide valuable information otherwise unattainable. However, at present, clinical interpretation of an ultrasonic image still mostly relies on recognition of boundaries and positional relationship of anatomical structures and a subjective analysis of the distribution or texture of echo amplitudes. Other potentially useful information carried back by the echoes is completely discarded. The aim of ultrasonic tissue characterization research is to develop methods to extract additional information from the returned echoes so that tissue pathology or abnormality can be reliably identifed and severity of the pathology objectively assessed with quantitative criteria. A number of ultrasonic parameters including acoustic velocity, impedance, attentuation and scattering, have been utilized in attempting to achieve this goal. In this paper, recent progress in this research will be discussed and relevant results presented.

Acoustics↗

Concordance evaluation of coronary risk scores: implications for cardiovascular risk screening.

OBJECTIVE: To assess the similarities and differences in predicted high-risk individuals identified by different cardiovascular risk calculation algorithms Research design and methods: A representative population of 10000 individuals was modelled in a computer using baseline data from the National Health Survey for England. The effects of biological groups identified by each calculator depend on the variation in each major model parameters were then applied to each hypothetical individual. The predictive capacities of 3 different risk identification systems based on computer calculation (the Framingham algorithm), or on tabular methods (the Sheffield tables and the General Rule to Enable Atheroma Treatment) were evaluated. RESULTS: All three models predict that similar numbers would receive treatment with 2.9 and 10% receiving treatment at 30 and 15% 10 year risk thresholds, respectively. However, concordance is limited as 0.3 or 6.8% are positive on all three systems; 1.6 or 9.7% on any two calculators at the 30 and 15% thresholds, respectively. The risk baseline assumptions in each model. CONCLUSION: Care needs to be taken with applying risk calculators to populations different from which they were derived. Any cardiovascular risk scoring system needs to be thoroughly evaluated against epidemiological data before it is introduced and also needs to be updated in line with changing trends in risk factors.

Algorithms↗

New strategies for the treatment of acute myelogenous leukemia: differentiation induction--present use and future possibilities.

A differentiation block and an accumulation of immature myeloid cells characterize acute myelogenous leukemia (AML). However, native AML cells usually show some morphological signs of differentiation that allow a classification into different subsets, and further differentiation may be induced by exposure to various soluble mediators, for example, all-trans retinoic acid (ATRA) and several cytokines. Combination therapy with ATRA and chemotherapy should now be regarded as the standard treatment of the acute promyelocytic leukemia (APL) variant of AML. Although several agents can also induce leukemic cell differentiation for other AML subgroups, in vitro studies as well as clinical data have demonstrated that these agents often have heterogeneous effects on the leukemic progenitors. This makes the clinical impact of differentiation induction therapy for individual patients difficult to predict. However, differentiation induction should be regarded as a promising therapeutic approach, especially as a part of immunotherapy or in combination with intensive chemotherapy to increase the susceptibility of AML blasts to drug-induced apoptosis. Although the morphology-based French-American-British classification was used to identify APL as an AML subset that required a special treatment, it seems unlikely that this classification alone can be used to identify new subsets of AML patients with special therapeutic requirements. Future studies on differentiation induction in AML should therefore focus on A) the identification of therapeutic agents with more predictable effects; B) the use of clinical and laboratory parameters to define new subsets of AML patients in which differentiation induction has a predictable and beneficial effect, and C) the characterization of how AML blast sensitivity to drug-induced apoptosis is altered by differentiation induction.

Apoptosis↗

Evaluation of the CFP-substrate-YFP system for protease studies: advantages and limitations.

A protease can be defined as an enzyme capable of hydrolyzing peptide bonds. Thus, characterization of a protease involves identification of target peptide sequences, measurement of activities toward these sequences, and determination of kinetic parameters. Biological protease substrates based on fluorescent protein pairs, which allow for use of fluorescence resonance energy transfer (FRET), have been recently developed for in vivo protease activity detection and represent a very interesting alternative to chemical substrates for in vitro protease characterization. Here, we analyze a FRET system consisting of cyan and yellow fluorescent proteins (CFP and YFP, respectively), which are fused by a peptide linker serving as protease substrate. Conditions for CFP-YFP fusion protein production in Escherichia coli and purification of proteins were optimized. FRET between CFP and YFP was found to be optimum at a pH between 5.5 and 10.0, at low concentrations of salt and a temperature superior to 25 degrees C. For efficient FRET to occur, the peptide linker between CFP and YFP can measure up to 25 amino acids. The CFP-substrate-YFP system demonstrated a high degree of resistance to nonspecific proteolysis, making it suitable for enzyme kinetic analysis. As with chemical substrates, substrate specificity of CFP-substrate-YFP proteins was tested towards different proteases and kcat/Km values were calculated.

Enzyme Activation↗

Sentinel node status and tumor characteristics: a study of 234 invasive breast carcinomas.

CONTEXT: Axillary lymph node status is the most important prognostic factor in patients with breast cancer. Tumor size and lymph node status, the most reliable pathologic bases of the tumor staging system, are practical parameters for estimating survival status. With the advent of lymphatic mapping and sentinel node (SN) identification, there is potential for a more efficient and sensitive evaluation of the axillary lymph node status. OBJECTIVE: To correlate SN status with tumor size, grade, and lymphovascular invasion. DESIGN: We examined 234 patients with unifocal breast carcinomas measuring 25 mm or less as detected by preoperative ultrasound during the period May 1998 through December 2002. Sentinel nodes were examined by frozen section and paraffin section as per protocol. RESULTS: Of the 234 patients, SN was identified in 221 (94.5%). An average of 1.38 SNs were examined per patient. Seventy-seven of 221 patients were SN positive on paraffin section. Sixty-six (85.7%) of these 77 cases could be correctly diagnosed as positive for metastatic carcinoma on frozen section. Two cases reported as positive on paraffin section were reported as suspicious on frozen section. Logistic regression indicated that tumor size, grade, and lymphovascular invasion were all significantly associated with SN status (P < .001). CONCLUSIONS: Tumor size, grade, and lymphovascular invasion were significantly associated with SN status in unifocal invasive breast carcinoma.

Axilla↗

[Angiography with spiral computerized tomography in the study of aneurysms of the visceral arteries. Techniques and results].

INTRODUCTION: The aneurysms of visceral vessels are characterized by few or no symptoms and the diagnosis is often occasional. We investigated the usefulness of CT angiography in the diagnosis and preoperative assessment of this condition. MATERIALS AND METHODS: From January 1993 to March 1998, twenty-five patients (aged 32-69 years) with 28 aneurysms underwent CT angiography before and after contrast agent injection to study lesion number, site, size, neck, intraluminal thrombosis and wall calcifications. Data from axial images were postprocessed on an external work-station to obtain CT angiograms. CT angiography findings were analyzed with a double blinded method by 2 radiologists comparing CT angiography with digital subtraction angiography images and evaluating the information obtained from Multiplanar (MPR), Maximum Intensity Projection (MIP) and Shaded Surface Display (SSD) reconstructions. Surgical findings were available for 10 patients. RESULTS: There was complete agreement between CT angiography and digital subtraction angiography in the identification of all lesions; the correlation rate was 94.42% for lesion location, 89.28% for lesion size, 85.71% for detection of endoluminal thrombosis and 82.14% for identification of wall calcifications. Axial and MPR images were useful in the assessment of ali parameters, while MIP images accurately demonstrated wall calcifications and the lesion relationships with adjacent structures. No additional information was obtained from SSD reconstructions. CONCLUSIONS: In our experience CT angiography can replace digital subtraction angiography in the diagnosis and preoperative work-up of visceral vessels aneurysms. CT angiography was superior to digital angiography in the evaluation of the lesion exact dimensions in cases with large thrombotic component and diffuse wall calcifications.

Adult↗

Laboratory scaledown of protein purification processes involving fractional precipitation and centrifugal recovery.

The ability to predict the performance of large-scale processes is central to the rapid development of successful operations at the pilot and industrial scale. In this article, we examine the operation, at laboratory scale, of precipitation reactors and centrifuges for protein precipitate recovery and dewatering and how they might best mimic large-scale reactors and centrifuges, in this case, a pilot-scale batch stirred-tank reactor and a multichamber-bowl centrifuge. Novel approaches to bench-top centrifuge operation are provided, in particular with a view to delivery of material for subsequent high-resolution purification, which would be obtained at full pilot scale. Results are presented in terms of properties of the protein precipitates, the fraction of solids recovered, and the extent of dewatering achieved. Good agreement was obtained at bench scale (a 1000-fold scale down factor) for all of these parameters for pilot-scale, batch-feed operation. In addition, the methodology developed allows identification of the extent of break-up that occurs in continuous-feed centrifuges when processing shear-sensitive materials such as the protein precipitates studied here.

Alcohol Dehydrogenase↗

Cancer vaccines: an old idea comes of age.

Cancer vaccines are at the forefront of novel, targeted approaches to cancer treatment. Low toxicity, the potential for circumventing drug cross-resistance, and the potential for persistence of the antitumor effect due to immunologic memory represent a mandate for accelerated clinical development. Advances in molecular immunology have suggested approaches for overcoming the formidable mechanisms of immune tolerance that are pre-established in cancer patients, and many have already been tested in preclinical models. Also, early studies revealed that not all tumor antigens are created equal, and identifying those capable of eliciting immune-mediated tumor rejection is essential to the development of effective recombinant cancer vaccines. While early trials have generally resulted in disappointing clinical outcomes, they have yielded insight into the critical parameters for the design of cancer vaccine trials and provided powerful reagents for tumor antigen identification. By utilizing the lessons learned from the research laboratory and these early clinical trials, informative second generation vaccine trials should have a high likelihood of success. Clinical protocols that consider how best to incorporate therapeutic cancer vaccines into the current standard of care should allow cancer vaccines to take their place alongside traditional cancer treatment modalities in oncology practice.

Animals↗

Abdominal ultrasonography in inheredited diseases of carbohydrate metabolism.

PURPOSE: To determine the usefulness of abdominal sonography in inherited diseases of carbohydrate metabolism. MATERIALS AND METHODS: Thirty patients (age range, 4 months to 27 years) with glycogen storage diseases, galactosemia, disorders of fructose metabolism were studied with sonography. Echogenicity of the liver, sonographic dimensions of liver, kidneys and spleen were evaluated. Plasma blood parameters (ALT, AST, total cholesterol, triglycerides) were determined. RESULTS: Liver was enlarged in 21/22 patients (95.4%) with glycogen storage diseases, in both subjects with disorders of fructose metabolism, and in 2/6 patients (33.3%) with galactosemia. Hepatic echogenicity was increased in 20/22 patients (90.9%) with glycogen storage diseases, and in the subject with hereditary fructose intolerance. Patients with galactosemia did not show increased liver echogenicity. Both kidneys were enlarged in 8/17 patients (47.0%) with glycogen storage disease type I. Subjects with increased hepatic echogenicity exhibited higher plasma concentrations of any blood parameter than the others with normal echogenicity (p<0.05). CONCLUSIONS: Sonography can be useful in identification of inherited diseases of carbohydrate metabolism even if further examinations are necessary for an ultimate diagnosis.

Adolescent↗

A probabilistic model for identifying protein names and their name boundaries.

This paper proposes a method for identifying protein names in biomedical texts with an emphasis on detecting protein name boundaries. We use a probabilistic model which exploits several surface clues characterizing protein names and incorporates word classes for generalization. In contrast to previously proposed methods, our approach does not rely on natural language processing tools such as part-of-speech taggers and syntactic parsers, so as to reduce processing overhead and the potential number of probabilistic parameters to be estimated. A notion of certainty is also proposed to improve precision for identification. We implemented a protein name identification system based on our proposed method, and evaluated the system on real-world biomedical texts in conjunction with the previous work. The results showed that overall our system performs comparably to the state-of-the-art protein name identification system and that higher performance is achieved for compound names. In addition, it is demonstrated that our system can further improve precision by restricting the system output to those names with high certainties.

Artificial Intelligence↗

A proposed classification of changes in the electrocardiogram in acute myocardial infarction.

Concepts regarding the aetiology and significance of changes in the electrocardiogram in acute myocardial infarction (AMI) have been changing and modified substantially in recent years. Today, the electrocardiogram must be analysed in the light of our current knowledge. When interpreting it, one must consider all the new information that electrocardiography (including electrical field monitoring by means of body surface mapping) employing sophisticated technology can provide. Optimal electrocardiographic information and its classification in AMI require detailed evaluation of the electrocardiogram characterizing all alterations in waves, ST segment denivelizations as well as their combinations, distribution and duration. The authors propose a new classification of alterations in the electrocardiogram in AMI which takes into account also the dynamics of electrocardiographic alterations, formerly a standard parameter. Future research and, most importantly, clinical practice will show whether this electrocardiographic classification allows identification of relatively homogeneous (in terms of clinical status and prognosis) groups of patients with AMI.

Electrocardiography↗

Rapid surveys in support of district health information systems: an experience from Uganda.

The role of rapid health assessment in generating data other than routine reporting for a multi-element primary health care information system is presented. Rapid surveys, based on the adaptation of the WHO/EPI cluster survey methodology, may generate reliable and valid results useful for the support of a managerial PHC information system. However, because of the limitations inherent to the method, so far, only few studies have investigated more than few PHC related issues. The experience of a household rapid survey conducted in Arua District, Uganda, using a modified EPI cluster survey methodology, is reported. Rapid appraisal methods were used to prioritize the information requirement and to identify the survey items. Fully supervised teams of primary school teachers were used as interviewers. Data processing, check and analysis were speeded up by a lap-top computer, in spite of problems of erratic power. Within a 10-day time span between the start of the survey and the publishing of results, data on health services' utilization, health seeking behaviour, coverage of PHC services, including immunization, and anthropometric data on the nutritional status of under-five children were obtained. Standard errors and 95% confidence intervals were calculated taking into account the variability of the parameters under investigation and true design effects were computed. The findings were utilized for the identification of health priorities and the monitoring of effectiveness of programmes, as well as to validate routine reporting. The methodological package was built up looking at the local context, so that it could become an operational tool for the district health management team.

Adolescent↗