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Development and evaluation of a miniaturized procedure for determining the bonding index: a novel prototype for solid dosage formulation development.

The purpose of this study was a comparative evaluation of miniaturized vs. University of Minnesota's (i.e., U of Minn. = Hiestand's) procedures for determining the tensile strength, indentation hardness, and bonding index (BI), one out of three Indices of Tableting Performance (ITP). Tableting properties of six direct compression placebo formulations were determined by using a compaction simulator and a Texture Analyser TA-XT2I, or by following the U of Minn. method, which included a specially designed triaxial compression device, a computer-controlled mechanical stress-strain analyzer, and a dynamic pendulum impact apparatus. Miniaturization of the procedures to determine the ITP, as well as the ability to differentiate between materials while operating compaction cycles more comparable to standard tablet production conditions, enabled proper evaluation of each material's inherent tableting properties. Indentation diameter calculated via an empirical equation appeared to correlate well with, and provided acceptable precision of accuracy to, the determination of indentation diameter via standard optical microscopy methods. The miniaturized and U of Minn. procedure exhibited a significant degree of correlation when comparing the BI. However, the tensile strength and indentation hardness values were somewhat different due to the use of triaxial decompression for the U of Minn. procedure vs. standard compaction profiling for the miniaturized procedure. The present direct compression placebo formulation data gathered from the miniaturized procedures and compared with the U of Minn. method for determining the ITP suggest that both techniques yield similar conclusions. However, discrimination of out-of-die compaction properties determined via the miniaturized procedures, such as tensile strength and indentation hardness, appeared to associate more precisely with changes in strain rate, thus allowing better discrimination of particle-particle interactions and ductile-to-brittle characteristics as a function of compaction speed and pressure.

Chemistry, Pharmaceutical↗

SPECT Imaging for Radioaerosol Deposition and Clearance Studies.

Planar gamma camera scintigraphy is well established for measuring the deposition and clearance of radioaerosols. Single photon emission computed tomography (SPECT) provides threedimensional (3D) reconstructions of the radioactivity distribution, thus avoiding the compression of 3D data into two-dimensional (2D) images and potentially offering superior assessment of aerosol deposition patterns. However, SPECT has traditionally been associated with long imaging times, making it unsuitable for measuring deposition and clearance of radioaerosols with fast clearance. Multi-detector SPECT systems can collect complete SPECT studies in <1 min, allowing both initial deposition and clearance over time to be assessed by dynamic SPECT. Simultaneous transmission measurement with an external source provides attenuation correction for absolute activity quantification as well as aiding in the definition of the lung volume of interest. A dynamic SPECT imaging protocol has been developed to allow fast imaging from the oropharynx to the abdomen using gamma cameras with limited axial field of views. This allows activity quantification not only in the lungs, but also in areas outside the thorax. However, fast dynamic SPECT imaging is technically and computationally more demanding and provides less scope for reducing the radioactivity administered to the subjects. It has been shown that dynamic SPECT, compared to planar imaging, is more sensitive in detecting changes in deposition as measured by the Penetration Index (PI). Thus, SPECT can better differentiate between large and small airways, which is important for lung regional analysis.

Administration, Inhalation↗

The magnitude and variability of design effects for community intervention studies.

Despite inadequate replication of treatment and comparison groups in community intervention studies, suitable estimates of variance can be obtained by multiplying the simple random sampling variance by a design effect, which can be estimated from other sources. To study the stability of these estimates, the authors performed a detailed investigation of the magnitude and sources of variability of design effects for age-adjusted mortality rates for selected causes of death separately for each of 44 US states. The authors made use of age-sex-race-county-specific data from the Compressed Mortality File generated by the National Center for Health Statistics. Design effects were calculated as the ratio of a cluster (county) sampling variance to the simple random sampling variance. The effects of sex, state, and year on the magnitude of the design effects were investigated by analysis of variance. Design effects were 2.33, 1.66, 1.24, 1.08, and 1.06 for ischemic heart disease, stroke, and cancers of the lung, breast, and colon, respectively. The largest source of variability was state; 35-70% of this variability could be attributed to the states' differing population sizes. The effect of sex was minimal. These results are relevant to the planning and analysis of community intervention studies.

Adolescent↗

Compression volume during mechanical ventilation: comparison of ventilators and tubing circuits.

Four ventilators (Puritan-Bennett MA-1 and MA-2, Emerson, and Bear I) and four commercially available disposable and nondisposable tubing circuits (Bennett nondisposable, Becton-Dickinson, Inspiron, and Life-line) were tested on a lung analog for differences in inspiratory-circuit compression volume. The compression ratio (Rc), equal to the gas volume compressed per cm H2O peak airway pressure, was calculated for each combination of ventilator and circuit at each of four compliance settings (0.15, 0.10, 0.05, 0.01 L/cm H2O) on the analog. Rc values ranged from 0.3 to 4.5 ml/cm H2O at the highest and lowest compliance settings, respectively, accounting for a reduction in delivered tidal volume of up to 20%. The Emerson ventilator with all tubing systems and the Bennett nondisposable circuit with each ventilator demonstrated slightly smaller compression volumes. Application of an inspiratory pause on the Bear I ventilator did not affect its compression characteristics. The clinical importance of compression volume and data from other ventilation systems are reviewed.

Humans↗

Long-term EEG monitoring: a clinical approach to electrophysiology.

Long-term electroencephalographic monitoring (LTM) is the capability of recording the EEG over long periods of time and not a specific duration. Prolonged EEG recording is used primarily for epilepsy monitoring, but LTM is also used in the intensive care unit, the operating room, and in the emergency department. The purpose of LTM is to expand the limited time sampling associated with shorter "routine" EEG recording. Audiovisual monitoring may also be used in conjunction with LTM to evaluate simultaneously a specific clinical behavior that may or may not be associated with EEG alteration. This is typically performed in a hospital setting for safety and ancillary testing purposes. LTM is used most frequently in the diagnosis and management of seizures and "spells," but has also gained wider application in the evaluation of sleep disorders, cerebrovascular disease, psychiatric conditions, and movement disorders. Computer-assisted LTM systems that process, analyze, compress, and store data digitally have become widely available in clinical practice both in the hospital as well as outside the hospital when the patient is ambulatory.

Diagnosis, Differential↗

Emergency magnetic resonance imaging of cervical spinal cord injuries: clinical correlation and prognosis.

OBJECTIVE: The goal of this study was to determine the prognostic and clinical value of magnetic resonance imaging (MRI) performed within hours after cervical spinal cord injuries in human patients. METHODS: Fifty-five patients with acute cervical vertebral column and spinal cord injuries underwent MRI as part of their initial treatment at the University of Michigan Medical Center. All images were obtained within 21 hours after injury (mean, 7.8 h) and were interpreted by an attending neuroradiologist who was blinded to the clinical status of the patients. Neurological function at presentation and in long-term follow-up examinations was compared with MRI characteristics assessed immediately after the injury. RESULTS: The presence and rostrocaudal length of intra-axial hematoma, the rostrocaudal length of spinal cord edema, the presence of spinal cord compression, and spinal cord compression by extra-axial hematoma were each significantly associated with poor neurological function at presentation and in long-term follow-up examinations. Although the best single predictor of long-term improvement in neurological function was the neurological function at presentation, four MRI characteristics, i.e., the presence of intra-axial hematoma, the extent of spinal cord hematoma, the extent of spinal cord edema, and spinal cord compression by extra-axial hematoma, provided significant additional prognostic information. MRI data demonstrated spinal cord compression for 27 of 55 patients (49%), leading to emergency surgery. Among patients who underwent imaging after restoration of normal vertebral alignment using closed cervical traction, 13 of 26 (50%) underwent emergency surgery for treatment of persistent, MRI-demonstrated, spinal cord compression. CONCLUSION: Emergency MRI after spinal cord injury provides accurate prognostic information regarding neurological function and aids in the diagnosis and treatment of persistent spinal cord compression after vertebral realignment.

Adolescent↗

Reduction of bone retropulsed into the spinal canal in thoracolumbar vertebral body compression burst fractures. A prospective randomized comparative study between Harrington rods and two transpedicular devices.

STUDY DESIGN: This was a prospective, randomized study. OBJECTIVE: To compare the ability of three methods of internal fixation (Harrington rods, AO internal fixator, posterior segmental fixator) to obtain reduction of intracanal fragments in thoracolumbar vertebral compression burst fractures. SUMMARY OF BACKGROUND DATA: Sixty-seven acute thoracolumbar compression burst fractures of T12 or L1 were randomized into three groups that were treated using one of the three methods. Reduction was accomplished indirectly by distraction applied using the fixation device. METHODS: The spinal canal encroachment was calculated as a percentage of the estimated pre-injury value from serial transverse computed tomographic scans obtained on admission and immediately after surgery. RESULTS: The median preoperative sagittal encroachment of the spinal canal was 37% (range, 0-90%) of the normal diameter. All three methods of internal fixation produced a spinal canal clearance provided that the patient was operated on within 4 days after trauma. The median postoperative encroachment varied from 13% (range, 0-37%) to 22% (range, 0-37%), the best reduction being attained using Harrington rods and the poorest with the posterior segmental fixator. There was a suggestive statistical significance between these two. CONCLUSION: The differences in postoperative spinal canal encroachment and ability to obtain spinal canal clearance observed between the devices studied were small. There seems to be no reason to base the choice of the operative method in thoracolumbar fractures on any hypothetical differences in reductive power between Harrington rods and the AO internal fixator.

Adolescent↗

Rapid improvement of paraplegia caused by epidural involvements of Burkitt's lymphoma with chemotherapy.

STUDY DESIGN: Case report. OBJECTIVE: The authors present a case of atypical Burkitt's lymphoma with multiple epidural involvements. SUMMARY OF BACKGROUND DATA: Spinal cord compression in children is an emergency that requires urgent attention to minimize neurologic dysfunction. Although it is not life-threatening in most patients, cord compression can cause severe neurologic morbidity. MATERIALS AND METHODS: Because the patient showed rapid neurologic deterioration, we started chemotherapy and high-dose steroids without laminectomy or radiotherapy immediately after a tumor biopsy from the left mandible. RESULT: The combined therapies were very effective and his neurologic symptoms improved immediately. The epidural involved masses disappeared in imaging studies after the first course of chemotherapy including methylprednisolone (20 mg/kg per day for 3 consecutive days and gradually tapered off over 2 weeks), vincristine (1.5 mg/m2 per day), cyclophosphamide (2 g/m2 per day for 2 days) and pirarubicin (40 mg/m2 per day). After completing seven courses of chemotherapy, the patient is now fully ambulant. CONCLUSION: Considering the severe late effects of laminectomy and radiotherapy, chemotherapy should be considered as a first choice of treatment for spinal cord compression caused by malignant lymphoma.

Antineoplastic Combined Chemotherapy Protocols↗

Use of a wave reverberation technique to infer the density compression of shocked liquid deuterium to 75 GPa.

A novel approach was developed to probe density compression of liquid deuterium (L-D2) along the principal Hugoniot. Relative transit times of shock waves reverberating within the sample are shown to be sensitive to the compression due to the first shock. This technique has proven to be more sensitive than the conventional method of inferring density from the shock and mass velocity, at least in this high-pressure regime. Results in the range of 22-75 GPa indicate an approximately fourfold density compression, and provide data to differentiate between proposed theories for hydrogen and its isotopes.

Journal Article↗

Experimental demonstration of quantum source coding.

We report an experimental demonstration of Schumacher's quantum noiseless coding theorem. Our experiment employs a sequence of single photons, each of which represents three qubits in terms of eight spatial and polarization modes. We initially prepare each photon in one of a set of eight nonorthogonal code word states corresponding to the value of a block of three binary letters. We use quantum coding to compress this quantum data into a two-qubit quantum channel and then uncompress the two-qubit channel to restore the original data with a fidelity approaching the theoretical limit.

Journal Article↗

Vertebroplasty and kyphoplasty for treatment of painful osteoporotic compression fractures.

PURPOSE: To review the pathophysiology of osteoporosis and describe vertebroplasty and kyphoplasty, which are minimally invasive procedures to treat the pain associated with vertebral compression fractures (VCFs). DATA SOURCES: Extensive literature review of osteoporosis, vertebroplasty, and kyphoplasty supplemented by case study and clinical experience in the minimally invasive interventional neuroradiology interventions. CONCLUSIONS: Osteoporosis is a progressive debilitating process that destroys the cancellous bone, weakening the overall integrity and stability of the bone. The loss of bone mass places the individual at increased risk for vertebral body, hip, and wrist fractures. In the past, there was no treatment option to repair vertebral body deformity or instability after osteoporotic VCFs. Management solely relied on the use of nonsteroidal anti-inflammatory drugs, narcotics, muscle relaxants, and/or orthotic bracing to provide pain relief. VCFs alter the stability of the vertebral body and column, and the lack of stabilization can lead to chronic pain syndrome, immobility, pulmonary compromise, progression of spinal deformity, increase in the risk for additional VCFs, and increase in the risk for comorbidities and mortality related to immobility. IMPLICATIONS FOR PRACTICE: Vertebroplasty and kyphoplasty are minimally invasive procedures aimed at pain control, stabilization of the vertebral body, and with kyphoplasty, the ability to provide some correction of deformity with partial restoration of vertebral body height. Providing pain control and stabilization of the vertebral column improves mobility, thus decreasing the potential risks associated with immobility.

Aged↗

Application of the Tsai-Wu quadratic multiaxial failure criterion to bovine trabecular bone.

As a first step toward development of a multiaxial failure criterion for human trabecular bone, the Tsai-Wu quadratic failure criterion was modified as a function of apparent density and applied to bovine tibial trabecular bone. Previous data from uniaxial compressive, tensile, and torsion tests (n = 139 total) were combined with those from new triaxial tests (n = 17) to calibrate and then verify the criterion. Combinations of axial compression and radial pressure were used to produce the triaxial compressive stress states. All tests were performed with minimal end artifacts in the principal material coordinate system of the trabecular network. Results indicated that the stress interaction term F12 exhibited a strong nonlinear dependence on apparent density (r2 > 0.99), ranging from -0.126 MPa-2 at low densities (0.29 g/cm3) to 0.005 MPa-2 at high densities (0.63 g/cm3). After calibration and when used to predict behavior of new-specimens without any curve-fitting, the Tsai-Wu criterion had a mean (+/- SD) error of -32.6 +/- 10.6 percent. Except for the highest density triaxial specimens, most (15/17 specimens) failed at axial stresses close to their predicted uniaxial values, and some reinforcement for transverse loading was observed. We conclude that the Tsai-Wu quadratic criterion, as formulated here, is at best only a reasonable predictor of the multiaxial failure behavior of trabecular bone, and further work is required before it can be confidently applied to human bone.

Animals↗

Firearm suicide among older men.

Data from the Compressed Mortality File for the years 1979 to 1991 were analyzed to determine epidemiologic trends in the rates of suicide by firearms among three age groups of white and black men age 65 and older (65 to 74 years, 75 to 84 years, and 85 years and older). In 1991, among men age 65 and older, firearms accounted for 80 percent of all suicides. Firearm suicide rates increased significantly over time among white men in all three age groups, especially those age 75 and older, and among black men between the ages of 75 and 84. Clinicians should regularly conduct a firearm-availability history with elderly men who are depressed or suicidal.

Age Factors↗

Income inequality and mortality in US counties: does minority racial concentration matter?

UNLABELLED: This study examined (1) the relationship between income inequality and mortality among all counties in the contiguous United States to ascertain whether the relationships found for states and metropolitan areas extend to smaller geographic units and (2) the influence of minority racial concentration on the inequality-mortality linkage. METHODS: This county-level ecologic analysis used data from the Compressed Mortality Files and the US Census. Weighted least squares regression models of age-, sex-, and race-adjusted county mortality rates were estimated to examine the additive and interactive effects of income inequality and minority racial concentration. RESULTS: Higher income inequality at the county level was significantly associated with higher total mortality. Higher minority racial concentration also was significantly related to higher mortality and interacted with income inequality. CONCLUSIONS: The relationship between income inequality and mortality is robust for counties in the United States. Minority concentration interacts with income inequality, resulting in higher mortality in counties with low inequality and a high percentage of Blacks than in counties with high inequality and a high percentage of Blacks.

Black or African American↗

Beyond average protein secondary structure content prediction using FTIR spectroscopy.

This paper demonstrates that secondary structure information beyond purely protein secondary structure content can be predicted from FTIR (Fourier transform infrared spectroscopy) spectra of proteins with a high degree of accuracy. Both neural networks and adaptive neuro-fuzzy inference systems (ANFISs) were employed to predict helix/sheet segment information. The best results were achieved using ANFISs with fuzzy subtractive clustering based on normalised, compressed amide I data with an average SEP (standard error of prediction, root mean of squared errors) of 1.51. Predictions for average helix/sheet length based merely on the amide I band maximum position in combination with the full-width at half-height resulted in a comparable average SEP of 1.62. This suggests the importance of information on the position and width of the amide I band maximum for the prediction of helix/sheet segment information. Finally, the most promising pattern recognition approaches found in this study were applied to a protein with an as yet unknown x-ray structure: native a1-antichymotrypsin (a1-ACT).

Algorithms↗

Studies on the compressibility of wax matrix granules of acetaminophen and their admixtures with various tableting bases.

Matrix granules of acetaminophen have been formed by a melt granulation process whereby the acetaminophen powder was triturated with the melted wax--goat wax, glyceryl monostearate or carnuba wax. The compressibility of the matrix granules and their admixture, with diluent granules (lactose, alpha-cellulose or microcrystalline cellulose) was investigated. The granules were compressed to tablets at a constant load (30 arbitrary units on the load scale) of a manesty single punch machine. Resulting tablets were evaluated for tensile strength (T) and disintegration times (DT). Granule flow was determined by measuring their angle of repose when allowed to fall freely on a level surface. Matrix granules prepared by melt granulation with goat wax or glyceryl monostearate were too sticky and therefore did not flow at all. They were also poorly compressible (T values = 0.20MN/m2). Inclusion of the diluent remarkably improved granule flow property and compressibility. The T values of the tablets (measure of compressibility) increased from about 0.24 to 0.65 MN/m2 during increase in diluent (lactose) content from 20 to 80 %w/w. Microcrystalline cellulose and alpha-cellulose were more effective than lactose in promoting compressibility of the granules. By contrast the matrix granules formed with carnuba wax were free flowing (angle of repose, 18.60). Addition of the diluent further improved flowability slightly. The matrix granules (without a diluent) were readily compressible (T value, 1.79MN/m2). Addition of the diluent (80%w/w) reduced T values (MN/m2) slightly to 1.32 (lactose), 1.48 (alpha-cellulose) and 1.74 (microcrystalline cellulose). Tablets of the matrix granules only, disintegrated rapidly within 3 minutes. DT was further reduced to <30 s by addition of any of the diluents. The indication is that the inclusion of the diluents studied can be used to improve the compressibility of the otherwise poorly compressible matrix granules. Based on the flowability, compressibility, and disintegration data, carnuba wax proved most promising in the melt granulation of the test drug for sustained release applications.

Acetaminophen↗

[Current events about echography in 2006: position of the ultrasound functional imaging for the early evaluation of targeted therapeutics].

The early and functional evaluation of new treatments in oncology is a main goal. At present, technical advances in Doppler ultrasonography allow the detection of neovascularization for superficial and deep malignant tumours in order to evaluate the efficiency of new treatments such as antiangiogenic molecules. Contrast agents injection improves the efficiency of this technique and developments of perfusion softwares optimize this detection. Slow flows in tumour microvessels can be detected. Treatment response can be early predicted based on changes in the vascularization before volume modification. The availability of quantification softwares operating from the raw data before their compression for video display affords one and objective quantification of the contrast agent uptake.

Antineoplastic Agents↗

[The mechanism of fatigue fracture of the ribs].

To elucidate the mechanism of fatigue-rib-fracture, 8 rib-fractured cases were investigated. In assuming the M. serratus anterior (MSA) as the major cause from the anatomical muscle route, EMG was taken, and three-dimensional resultant forces from the muscles around the shoulder of a fresh cadaver were estimated. Most fractures were found in the sixth or seventh ribs, with a tendency to occur along the posterolateral segment. Biomechanical analysis revealed 12 and 62 kg forces applied on the scapulo-thoracic joint and gleno-humeral joint respectively by adding 90 degrees-anterior-elevation under no load. The maximum muscle-force of MSA occurring at 90 degrees-anterior-elevation was 1.2 kg in the sixth serratus in our study. These data were supported by the results with EMG. The stress on the ribs were calculated by two-dimensional finite element method, using the data. The maximum compressive stress on one rib was 4.75 kg/mm2 when 13.0 kg of MSA-force was added. In considering the limit of fatigue endurance of bones, these results suggest that muscle-force which causes fatigue fracture of ribs arises from lifting an object weighing more than 20 kg.

Adolescent↗