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A different type of cutting tool can be used to prepare fragments of stainless steel razor blades for microsurgery. The tool can be used to cut even flexible, extremely thin, unbreakable razor blades to any size, shape, or tip angle.
CONTEXT: Pneumococcal immunization rates for elderly and high-risk patients are only one third to one half the target rate of 60% established by the US Public Health Service. Limited or marginal literacy, which affects nearly 100 million Americans, especially the elderly, may contribute to these low rates of immunization. OBJECTIVE: To determine whether the use of a simple, low-literacy educational tool enhances patient-physician dialogue about pneumococcal vaccination and increases rates of immunization. DESIGN: A randomized controlled trial conducted between May and June of 1998. SETTING: Ambulatory care clinic of a 900-bed public teaching hospital serving a predominantly indigent, low-literate, African American, inner-city population. PARTICIPANTS: Of 433 patients who presented for routine primary care, had vaccine indications (age > or =65 years or chronic disease), and had not been previously vaccinated, 221 were randomly assigned to the intervention group and 212 to the control group. Of the total patient population (mean age, 63 years), 280 (64.7%) had less than a high school education, 401 (92.6%) were African American, and 300 (69.3%) were female. INTERVENTION: One-page, low-literacy (below fifth-grade level) educational handout encouraging patients to "ask your doctor about the pneumonia shot" vs a control group (1 -page, low-literacy educational handout conveying information about nutrition). MAIN OUTCOME MEASURES: Vaccination rates (documented by chart audit) of patients who received pneumococcal vaccination and rates of patients who self-reported having discussed vaccination with their physicians. RESULTS: Patients in the intervention group were 4 times more likely to have discussed the pneumococcal vaccine with their physicians than patients in the control group (87/221 [39.4%] vs 21/212 [9.9%]; relative risk [RR], 3.97 [95% confidence interval [CI], 2.71-5.83]), and were more than 5 times as likely to have received the pneumococcal vaccine than the control group (44/221 [19.9%] vs 8/212 [3.8%]; RR, 5.28 [95% CI, 2.80-9.93]). In a multivariate analysis controlling for race, sex, education, insurance status, age, level of physician training, health status, and vaccine indication, only assignment to the intervention group was statistically significantly related to the probability of being immunized or discussing the issue with their physicians (P<.001 for both trends). CONCLUSIONS: A simple, low-literacy educational tool increased pneumococcal vaccination rates and patient-physician discussions about the vaccine in an elderly, low-literate, indigent, minority population.
CONTEXT: The Framingham Heart Study helped to establish tools to assess coronary heart disease (CHD) risk, but the homogeneous nature of the Framingham population prevents simple extrapolation to other populations. Recalibration of Framingham functions could permit various regions of the world to adapt Framingham tools to local populations. OBJECTIVE: To evaluate the performance of the Framingham CHD risk functions, directly and after recalibration, in a large Chinese population, compared with the performance of the functions derived from the Chinese Multi-provincial Cohort Study (CMCS). DESIGN, SETTING, AND PARTICIPANTS: The CMCS cohort included 30 121 Chinese adults aged 35 to 64 years at baseline. Participants were recruited from 11 provinces and were followed up for new CHD events from 1992 to 2002. Participants in the Framingham Heart Study were 5251 white US residents of Framingham, Mass, who were 30 to 74 years old at baseline in 1971 to 1974 and followed up for 12 years. MAIN OUTCOME MEASURES: "Hard" CHD (coronary death and myocardial infarction) was used as the end point in comparisons of risk factors (age, blood pressure, smoking, diabetes, total cholesterol, and high-density lipoprotein cholesterol [HDL-C]) as evaluated by the CMCS functions, original Framingham functions, and recalibrated Framingham functions. RESULTS: The CMCS cohort had 191 hard CHD events and 625 total deaths vs 273 CHD events and 293 deaths, respectively, for Framingham. For most risk factor categories, the relative risks for CHD were similar for Chinese and Framingham participants, with a few exceptions (ie, age, total cholesterol of 200-239 mg/dL [5.18-6.19 mmol/L], and HDL-C less than 35 mg/dL [0.91 mmol/L] in men; smoking in women). The discrimination using the Framingham functions in the CMCS cohort was similar to the CMCS functions: the area under the receiver operating characteristic curve was 0.705 for men and 0.742 for women using the Framingham functions vs 0.736 for men and 0.759 for women using the CMCS functions. However, the original Framingham functions systematically overestimated the absolute CHD risk in the CMCS cohort. For example, in the 10th risk decile in men, the predicted rate of CHD death was 20% vs an actual rate of 3%. Recalibration of the Framingham functions using the mean values of risk factors and mean CHD incidence rates of the CMCS cohort substantially improved the performance of the Framingham functions in the CMCS cohort. CONCLUSIONS: The original Framingham functions overestimated the risk of CHD for CMCS participants. Recalibration of the Framingham functions improved the estimates and demonstrated that the Framingham model is useful in the Chinese population. For regions that have no established cohort, recalibration using CHD rates and risk factors may be an effective method to develop CHD risk prediction algorithms suited for local practice.
A newly developed desktop microtomograph was used to evaluate whether it is suitable for visualizing the three-dimensional (3D) morphology of the mouse inner ear (at a micrometer level) and whether it is applicable as a fast screening tool to detect hereditary abnormalities in this organ. To this end, the epistatic circler, a mutant mouse showing abnormal circling behaviour, was used as a model. The inner ears were dissected out, formaldehyde-fixed, and scanned at maximal resolution along the longitudinal axis. After segmentation, stacks of tomographic images were used for 3D reconstruction of the bony labyrinth. Finally, the obtained data were correlated with subsequent conventional histological examination. The spatial resolution (8 microm) achieved by this instrument, was found to be far superior to that obtained by conventional computer tomography (CT) and magnetic resonance (MR)-imaging equipment. The technique provides detailed tomographic images of the bony labyrinths and enables an adequate 3D reconstruction of the inner ear structures in this small mammal. In addition, it allows a screening for pathologic specimens prior to the more time- and labour-consuming histological techniques, which are still essential to gather information at a (sub)cellular level. This imaging technique can be regarded as a valuable tool in future research on hereditary inner ear abnormalities.
BACKGROUND: Patients with head and neck cancer may face decisions between surgery or radiation (with or without chemotherapy) which involve significant trade-offs in functional outcomes. This preliminary investigation is designed to examine patients' priorities among the effects of treatments for head and neck cancer. METHODS: A new instrument designed to allow patients to rank personal priorities among 12 treatment effects was developed and tested. A cross section of patients (19) from pretreatment and posttreatment time periods and 23 controls participated. RESULTS: Preliminary findings indicate high individual variability, with some differences between groups according to treatment time. Differences between patients and controls are evident. We report test-retest reliability and the limitations of this new tool. CONCLUSIONS: The data suggest that measures of health state values should be conducted with patients rather than healthy volunteers. Patients' priorities may be influenced by treatment and some values may be more susceptible to change with experience of treatment effects. This new tool may provide insight into how patients' prioritize the anticipated and experienced effects of treatment for head and neck cancers.
White-fronted capuchins were observed to use leaves as cups to retrieve water from tree cavities. On multiple occasions several individuals performed this behavior. Thus, these capuchins engage in habitual tool use, as defined by McGrew's classificatory scheme of tool using behavior.
A technique is established for the role of intracellular proteins to be eliminated and thereby gives information about their specific role in signal transduction within cells. Rat pancreatic islets as well as INS-1 cells (an insulin secreting cell line) were electrically permeabilized in order to introduce high molecular weight compounds. Optimized conditions were five exposures with 15-s intervals, tau = 200 ms, an electric field of 1.36 kV per 0.4 cm in a specific permeabilization buffer at a calculated Ca++ concentration of 5 x 10(-8) M. In electroporation control experiments the spectrophotometrically measured uptake of the cell membrane-impermeable propidium iodide, FITC-labelled dextran (MW approximately 4000) and FITC-labelled antibodies (MW approximately 150,000) was established as being 81.5 +/- 5.0, 82.7 +/- 3.0 and 81.0 +/- 1.0 per cent of maximum, respectively. These data were corroborated qualitatively by visualizing microscopically the fluorescence of the FITC-labelled compounds in islets as well as in INS-1 cells. The cells appear to reseal since control experiments indicated a short-lived outflow of lactate dehydrogenase (MW of 140,000 which is similar to that of antibodies) and of insulin for the first 15-20 min. After electroporation the cells were functionally intact, i.e. responded to the stimulus carbachol (CCh). Only 18.0 +/- 10.1 per cent of cells had not resealed after 2 h (propidium iodide uptake measured at various time intervals after electroporation). As was shown recently the effect of specific compounds such as CCh and CCK8 on insulin release was eliminated selectively by antibodies against specific G proteins thus proving this method to be a valuable tool. In conclusion, adding antibodies to electrically permeabilized cells is a valuable tool for eliminating a specific cell function in order to elucidate the specific role of intracellular compounds. This method can probably be used for testing the specific role of other proteins in cell functions.
The feasibility, utility and reliability of the Zung Self-Rating Depression Scale (ZSDS) was examined in a large sample of ambulatory cancer patients. This tool and a brief 11-item version of the ZSDS (excluding nine items concerning somatic symptoms), which was developed during the course of the survey, were used to estimate the prevalence of self-reported depressive symptoms. Patient characteristics that may be associated with an increased risk of clinically significant depressive symptoms were also explored. Twenty-five ambulatory oncology clinics affiliated with Community Cancer Care, Inc. enrolled and surveyed 1109 subjects. The alpha coefficients for the ZSDS (0.84) and the Brief ZSDS (0.84) indicated high levels of internal consistency. The overall prevalence of clinically significant depressive symptoms as defined by the ZSDS was 35.9% and by the Brief ZSDS was 31.1%. The ZSDS and the Brief ZSDS were highly correlated (r = 0.92). The medical and demographic variables most associated with clinically significant depressive symptoms were more advanced stage of disease at time of diagnosis, lung cancer as primary tumor type, higher ECOG rating (greater degree of physical disability), and having been prescribed antidepressant medications. The high prevalence of depressive symptoms observed in this study is consistent with rates found in other studies of self-report depression instruments in cancer patients. The initial indicators of internal consistency and validity suggest that the Zung SDS or the brief version may be useful screening tools to identify depressive symptoms in oncology patients.
There is a considerable need to develop comprehensive, systematic mechanisms to analyze the vast number of proteins that orchestrate various cellular functions and to identify proteins associated with disease or that are affected by pharmacological agents. Two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) continues to be relied upon to analyze protein constituents of cells and tissues. We have developed a Laboratory Information Processing System (LIPS) as a computer-based tool for capturing quantitative and qualitative changes in thousands of proteins detected in 2-D gels of various types. Protein databases have been developed to serve as a repository for data processing of the basic and derived data and of findings derived from different studies. There have been remarkable advances both in database technology as well as in the computer hardware that have benefited our effort at mining protein data from 2-D gels. We here review our current efforts aimed at improving the performance and features of our 2-D related protein databases, with particular emphasis on the tools we utilize for database mining via a systematic analysis of information known as post-planned analysis.
The continual threat of chemical and biological warfare has prompted the need for unambiguous analytical methods for the confirmation of agent exposure. In this paper, we have investigated the use of matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-ToF/MS) as a diagnostic tool for this purpose. Mass spectral studies of the interaction of sulfur mustard (bis-(2-chloroethyl) sulfide, HD) with hemoglobin and metallothioneine were conducted. In vitro experiments with purified proteins were performed, using both HD and chloroethylethyl sulfide (CEES), in an effort to determine the extent of alkylation and occurrence of HD cross-linking using the MALDI-ToF/MS technique. In a typical experiment, 50 ml of 5 mM HD in acetonitrile was added to an equal volume of 0.5 mM hemoglobin in deionized water followed by vortexing and incubation at room temperature. After 24 h, the samples were analyzed by MALDI-ToF/MS. Mass spectral results indicated the presence of at least two distinct alkylation adducts for both HD and CEES experiments. These results demonstrate that MALDI-ToF/MS is a useful analytical technique to investigate the interaction of HD with biomolecules and may be employed potentially as a diagnostic tool for the confirmation of exposure to chemical warfare agents.
BACKGROUND: There has been a recent trend to encourage routine outcome measurement and needs assessment as an aid to decision making in clinical practice and patient care. Standardised instruments have been developed which measure clinical symptoms of disorders such as schizophrenia, wider health related quality of life and patients' needs. Such measures might usefully be applied to aid the recognition of psychosocial problems and to monitor the course of patients' progress over time in terms of disease severity and associated deficits in health related quality of life. They might also be used to help clinicians to make decisions about treatment and to assess subsequent therapeutic impact. Such an approach is not, however, without cost and the actual benefit of the adoption of routine outcome and needs assessment in the day-to-day care of those with schizophrenia remains unclear. OBJECTIVES: To establish the value of the routine administration of outcome measures and needs assessment tools and the feedback they provide in improving the management and outcome of patients with schizophrenia and related disorders. SEARCH STRATEGY: The reviewers undertook electronic searches of the British Nursing Index (1994 to Sept 1999), the Cochrane Library (Issue 2, 2002), the Cochrane Schizophrenia Group Trials Register (2002), EMBASE (1980-2002), MEDLINE (1966-2002), and PsycLIT (1887-2002), together with hand searches of key journals. References of all identified studies were searched for further trials, and the reviewers contacted authors of trials. SELECTION CRITERIA: Randomised controlled trials comparing the feedback of routine standardised outcome measurement and needs assessment, to routine care for those with schizophrenia. DATA COLLECTION AND ANALYSIS: Reviewers evaluated data independently. Studies which randomised clinicians or clinical teams (rather than individual patients) were considered to be the most robust. However only those which took account of potential clustering effects were considered further. Where possible and appropriate, risk ratios (RR) and their 95% confidence intervals (CI) were calculated. For continuous data Weighted Mean Differences (WMD) were calculated. Data were inspected for heterogeneity. MAIN RESULTS: No randomised data were found which addressed the specified objectives. One unpublished and one ongoing trial was identified. REVIEWER'S CONCLUSIONS: The routine use of outcomes measures and needs assessment tools is, as yet, unsupported by high quality evidence of clinical and cost effectiveness. Clinicians, patients and policy makers alike may wish to see randomised evidence before this strategy is routinely adopted.
The identification of individual protein species within an organism's proteome has been optimised by increasing the information produced from mass spectral analysis through the chemical derivatisation of tryptic peptides and the development of new software tools. Peptide fragments are subjected to two forms of derivatisation. First, lysine residues are converted to homoarginine moieties by guanidination. This procedure has two advantages, first, it usually identifies the C-terminal amino acid of the tryptic peptide and also greatly increases the total information content of the mass spectrum by improving the signal response of C-terminal lysine fragments. Second, an Edman-type phenylthiocarbamoyl (PTC) modification is carried out on the N-terminal amino acid. The renders the first peptide bond highly susceptible to cleavage during mass spectrometry (MS) analysis and consequently allows the ready identification of the N-terminal residue. The utility of the procedure has been demonstrated by developing novel bioinformatic tools to exploit the additional mass spectral data in the identification of proteome proteins from the yeast Saccharomyces cerevisiae. With this combination of novel chemistry and bioinformatics, it should be possible to identify unambiguously any yeast protein spot or band from either two-dimensional or one-dimensional electropheretograms.
The investigation of emerging contaminant issues is a proactive effort in environmental analysis. As a part of this effort, sewage effluent is of current analytical interest because of the presence of pharmaceuticals and their metabolites and personal care products. The environmental impact of these components is still under investigation but their constant perfusion into receiving waters and their potential effect on biota is of concern. This paper examines a tool for the characterization of sewage effluent using capillary electrophoresis-laser induced fluorescence (CE-LIF) with a frequency-doubled laser operated in the ultraviolet (UV). Fluorescent acidic analytes are targeted because they present special problems for techniques such as gas chromatography-mass spectrometry (GC-MS) but are readily accessible to CE-LIF. As an example of the application of this tool, salicylic acid is determined near the 100 ng/L (7 x 10(-10) M) level in sewage effluent. Salicylic acid is a metabolite of various analgesics. Relatively stable in the environment, it is a common contaminant of municipal sewage systems. Salicylic acid was recovered from freshly collected samples of the effluent by liquid-liquid extraction. Confirmation of identity was by electron ionization GC-MS after conversion of the salicylic acid to the methyl ester by means of trimethylsilyldiazomethane. CE-LIF in the UV has revealed more than 50 individual peaks in the extract and a background response that suggests a large and indeterminate number of additional compounds are present. These data together with complementary techniques provide information on the complexity and components in these effluent streams.
OBJECTIVE: To develop, validate, and determine the measurement characteristics of a quantitative tool for assessing the severity of muscle involvement in children with idiopathic inflammatory myopathies. METHODS: The Childhood Myositis Assessment Scale (CMAS) was developed from 2 existing observational functional assessment tools to assess muscle function in the areas of strength and endurance across a wide range of ability and ages. The 14 ordinal items included were chosen to assess primarily axial and proximal muscle groups and are ranked with standard performance and scoring methods. Following the development of the CMAS, a training video and written instructions were developed and reviewed by the physicians participating in this study. Subsequently, utilizing a randomized block design, 12 physicians independently scored 10 children (9 with dermatomyositis, 1 with polymyositis; ages 4-15 years) twice in one day (morning and afternoon) on the CMAS. A pediatric physical therapist performed quantitative manual muscle strength testing (MMT) twice on each child (morning and afternoon), including the neck, trunk, and proximal and distal extremity muscle groups. RESULTS: The CMAS has a potential range of 0-51, with higher scores indicating greater muscle strength and endurance. The observed mean for the 10 patients was 36.4 (median 44, SD 14.1, observed range 5-51). The total score for the CMAS correlated with the physician's global assessment (by visual analog scale) of disease activity, the MMT score, serum creatine kinase level, and the Juvenile Arthritis Functional Assessment Report score. The score on the CMAS was not correlated with patient age. Interrater reliability (Kendall's coefficient of concordance) ranged from 0.77 to 1.0 for individual items (all P < 0.001), and overall, it was 0.95 (P < 0.001). Intrarater reliability for the individual physicians was measured by correlation of the CMAS scores for each patient on 2 separate evaluations and ranged from 0.97 to 0.99, with an overall correlation for all physicians of 0.98 (all P < 0.001). CONCLUSION: The CMAS demonstrated an acceptable range of observed scores, excellent convergent validity, and excellent inter- and intrarater reliability. The CMAS is validated to quantitatively assess muscle function in the areas of strength and endurance in children with idiopathic inflammatory myopathies. It can be used in routine clinical care as well as therapeutic trials.
FindPept (http://www.expasy.org/tools/findpept.html) is a software tool designed to identify the origin of peptide masses obtained by peptide mass fingerprinting which are not matched by existing protein identification tools. It identifies masses resulting from unspecific proteolytic cleavage, missed cleavage, protease autolysis or keratin contaminants. It also takes into account post-translational modifications derived from the annotation of the SWISS-PROT database or supplied by the user, and chemical modifications of peptides. Based on a number of experimental examples, we show that the commonly held rules for the specificity of tryptic cleavage are an oversimplification, mainly because of effects of neighboring residues, experimental conditions, and contaminants present in the enzyme sample.
Careful descriptions of dysmorphic features have led to the delineation of hundreds of specific syndromes and patterns of congenital anomalies. The defining of unusual behavior had largely been neglected by clinical geneticists until the study of the natural history of microdeletions revealed that each has unique and characteristic behavior(s). In this study, a simple tool to describe behavior is presented that is to be used in the genetics clinic as part of routine evaluation. The form is meant to simplify recording and does not require the formal training needed for psychological assessments. It is hoped that routine recording of behavior among individuals seen in the genetics clinic will lead to better recognition of unusual behavior among individuals with known conditions, as well as the recognition of conditions characterized only by unusual behavior. Better description of behavioral patterns should lead to the ascertainment of homogeneous groups of affected individuals with abnormalities in the functional pathways that generate patterns of reaction. The genetic and biochemical basis for these patterns of reaction (abnormal behavior) should then be available for both natural history and molecular studies. The tool consists of 12 categories of behavioral features that can be assessed by the medical geneticist. The list was built to allow the observation of as many behavioral aspects as possible, but to keep it to a practical size and to use those features that are simple to describe and quantitate. We expect that its use will produce a rich source of behavioral profiles and will eventually contribute to the better understanding of unusual behavior.
We conducted an exploratory investigation in an area where nut-cracking by wild capuchin monkeys is common knowledge among local residents. In addition to observing male and female capuchin monkeys using stones to pound open nuts on stone "anvils," we surveyed the surrounding area and found physical evidence that monkeys cracked nuts on rock outcrops, boulders, and logs (collectively termed anvils). Anvils, which were identified by numerous shallow depressions on the upper surface, the presence of palm shells and debris, and the presence of loose stones of an appropriate size to pound nuts, were present even on the tops of mesas. The stones used to crack nuts can weigh >1 kg, and are remarkably heavy for monkeys that weigh <4 kg. The abundance of shell remains and depressions in the anvil surface at numerous anvil sites indicate that nut-cracking activity is common and long-enduring. Many of the stones found on anvils (presumably used to pound nuts) are river pebbles that are not present in the local area we surveyed (except on or near the anvils); therefore, we surmise that they were transported to the anvil sites. Ecologically and behaviorally, nut-cracking by capuchins appears to have strong parallels to nut-cracking by wild chimpanzees. The presence of abundant anvil sites, limited alternative food resources, abundance of palms, and the habit of the palms in this region to produce fruit at ground level all likely contribute to the monkeys' routine exploitation of palm nuts via cracking them with stones. This discovery provides a new reference point for discussions regarding the evolution of tool use and material culture in primates. Routine tool use to exploit keystone food resources is not restricted to living great apes and ancestral hominids.
Nondietary function is an important concern in the study of the human dentition and its role in adaptation. The purpose of the present investigation is to describe and interpret a pattern of dental wear in the anterior dentition of precontact hunter-gatherers that inhabited the western Great Basin. These data are discussed in light of ethnographic documentation as a means by which the archaeological record is linked with associated behavior of the representative populations. A series of 171 dentitions from a group of archaeological localities was examined. Of 1,931 teeth observed, 16 of these showed narrow (0.4-2.0 mm) transverse grooves located on the midocclusal surfaces of anterior teeth. The grooves were restricted in occurrence to five older adult males. Documentation of prehistoric and historic western Great Basin aboriginal populations indicates an adaptation that involves use of plant materials in the production of a variety of utilitarian objects, such as fish nets, basketry, funerary bags, fowling bags, and rope. In postcontact contexts, the anterior dentition has been shown to play an important role in the preparation of materials used for the production of this equipment. It seems most likely, then, that the grooves observed herein resulted directly from the use of the dentition as part of the tool assemblage for the production of other tools.