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Application of artificial neural networks (ANN) in the development of solid dosage forms.

The application of ANN in pharmaceutical development has been assessed using theoretical as well as typical pharmaceutical technology examples. The aim was to quantitatively describe the achieved data fitting and predicting abilities of the models developed with a view to using ANN in the development of solid dosage forms. The comparison between the ANN and a traditional statistical (i.e., response surface methodology, RSM) modeling technique was carried out using the squared correlation coefficient R2. Using a highly nonlinear arbitrary function the ANN models showed better fitting (R2 = 0.931 vs. R2 = 0.424) as well as predicting (R2 = 0.810 vs. R2 = 0.547) abilities. Experimental data from a tablet compression study were fitted using two types of ANN models (i.e., multilayer perceptrons and a hybrid network composed of a self-organising feature map joined to a multilayer perception). The achieved data fitting was comparable for the three methods (MLP R2 = 0.911, SOFM-MLP R2 = 0.850, and RSM R2 = 0.897). ANN methodology represents a promising modeling technique when applied to pharmaceutical technology data sets.

Algorithms↗

Automatic quality control for wavelet-based compression of volumetric medical images using distortion-constrained adaptive vector quantization.

The enormous data of volumetric medical images (VMI) bring a transmission and storage problem that can be solved by using a compression technique. For the lossy compression of a very long VMI sequence, automatically maintaining the diagnosis features in reconstructed images is essential. The proposed wavelet-based adaptive vector quantizer incorporates a distortion-constrained codebook replenishment (DCCR) mechanism to meet a user-defined quality demand in peak signal-to-noise ratio. Combining a codebook updating strategy and the well-known set partitioning in hierarchical trees (SPIHT) technique, the DCCR mechanism provides an excellent coding gain. Experimental results show that the proposed approach is superior to the pure SPIHT and the JPEG2000 algorithms in terms of coding performance. We also propose an iterative fast searching algorithm to find the desired signal quality along an energy-quality curve instead of a traditional rate-distortion curve. The algorithm performs the quality control quickly, smoothly, and reliably.

Algorithms↗

A model for acute, chronic, and delayed graded compression of the dog cauda equina. Presentation of the gross, microscopic, and vascular anatomy of the dog cauda equina and accuracy in pressure transmission of the compression model.

STUDY DESIGN: A new model for controlled, graded compression of the dog cauda equina was developed using the dog lumbar spine. The model was defined regarding macroscopic, microscopic, and vascular anatomy and regarding accuracy in pressure transmission. OBJECTIVES: The study was performed to develop a model for controlled, graded compression that would allow for acute, chronic, and delayed compression. SUMMARY OF BACKGROUND DATA: There has been an increasing interest for the reactions of the spinal nerve roots to mechanical deformation. The previously used models have had limitations regarding the duration and the onset of the compression and possibilities for a controlled variation of the compression pressure on chronically compressed nerve roots. METHODS: Macroscopic examination, light microscopy, and ink injection of the vasculature was used to assess the anatomic characteristics of the nerve tissue and the vasculature of the cauda equina in the dog lower lumbar spine. The relation between known pressures in the compression balloon used to compress the cauda equina and the pressure in the central thecal sac was assessed by measuring the pressure in an artificial thecal sac with a pressure transducer. RESULTS. The neural and vascular anatomy was found to have a close resemblance to the human cauda equina. The pressure in the thecal sac was within 5% of the pressure in the compression balloon at various pressures between 0-200 mm Hg. CONCLUSION: The presented model provides a good pressure transmission to the dog cauda equina, which has an anatomy that closely resembles the human cauda equina. The model may be well suited for physiologic studies of cauda equina compression. A double-balloon system may provide unique opportunities to induce chronic compression and delayed compression, i.e., additional compression after a certain time of chronic compression to resemble the changes in pressure that are characteristic for neurogenic claudication.

Animals↗

Palsy of the C5 nerve root after midsagittal-splitting laminoplasty of the cervical spine.

STUDY DESIGN: The imaging characteristics of postoperative C5 nerve root palsy after midsagittal-splitting laminoplasty for cervical myelopathy, including those observed on plain radiography, computed tomography, and magnetic resonance imaging, were analyzed. OBJECTIVE: To investigate the imaging findings that predict occurrence of C5 nerve root palsy after midsagittal-splitting laminoplasty. SUMMARY OF BACKGROUND DATA: There have been several reports on imaging findings for postoperative nerve root palsy after open-door laminoplasty. However, there have been no detailed reports on imaging characteristics that predict the occurrence of nerve root palsy after midsagittal-splitting laminoplasty. METHODS: The study included 45 consecutive patients undergoing midsagittal-splitting laminoplasty with sufficient pre- and postoperative imaging examinations: 27 patients with cervical spondylotic myelopathy (CSM), 14 patients with ossification of the posterior longitudinal ligament (OPLL), and 4 patients with cervical disc herniation. Characteristics of pre- and postoperative plain radiographs, computed tomography scans, and magnetic resonance images were compared between the patients with and those without C5 nerve root palsy. RESULTS: Palsy of the C5 nerve root developed in 4 patients, and did not develop in 41 patients. Of the four patients with C5 nerve root palsy, one had CSM and the other three had OPLL. The incidence of C5 nerve root palsy involved 3 of 14 patients with OPLL patients (21.4%) and 1 of 31 patients without OPLL (3.2%) (P = 0.08). For both diseases, the patients with palsy tended to have increased postoperative cervical lordosis (P = 0.21). As for anterior compression on the spinal cord at C3, the P value for the comparison between the group with and the group without palsy was 0.07 for preoperative compression and 0.01 for postoperative compression. CONCLUSIONS: The preliminary data suggest that patients who have OPLL with marked anterior compression on spinal cord at C3 can be at risk for postoperative C5 nerve root palsy after midsagittal-splitting laminoplasty. Also, a postoperative increase in cervical lordosis may be the cause of postoperative nerve root palsy.

Adult↗

RLBWT-based LCP computation in compressed space for terabase-scale pangenome analysis.

MOTIVATION: Lossless full text indexes are utilized in a myriad of applications in bioinformatics. The continuously decreasing cost of generating biological data has resulted in the need to build full text indexes on biological datasets of increasing size. Many compressed full text indexes have been developed to address this problem. In particular, run-length Burrows-Wheeler transform (RLBWT) based compressed full text indexes have seen wide development and adoption. However, the construction of these RLBWT-based compressed full text indexes is still computationally expensive, sometimes prohibitively so, even for current dataset sizes. RESULTS: Therefore, we present algorithms for the construction of RLBWT-based compressed full text indexes and their supporting data structures in compressed space. The algorithms have a space complexity of O(r) words and run in O(n) time for repetitive datasets, where r is the number of runs in the BWT, n is the length of the text, and repetitive datasets implies nr∈Ω(log n). We provide the first algorithm to compute LCP-related information for repetitive datasets in optimal time and O(r) space, greatly reducing memory requirements. The key idea behind this algorithm is the utilization of r samples of the inverse suffix array at regular intervals. For example, on the Human Pangenome Reference Consortium Release 2 dataset, this reduces peak memory from 2135 GiB to 170 GiB (12.6x reduction) compared to the previous best method (pfp-thresholds). AVAILABILITY AND IMPLEMENTATION: The implementation is available at https://github.com/ucfcbb/TeraTools.

Algorithms↗

Mechanical and architectural bone adaptation in early stage experimental osteoarthritis.

The purpose of this study was to quantify mechanical and architectural changes to knee joint periarticular subchondral cancellous bone in early stage experimental osteoarthritis (OA). Unilateral anterior cruciate ligament transection (ACLX) was performed on 10 dogs that were assigned randomly to two groups: 3 weeks or 12 weeks post-ACLX. Cylindrical bone cores excised from the medial condyle of the distal femur after death were scanned using high-resolution microcomputed tomography (muCT) and subsequently failed under unconstrained uniaxial compression. The apparent-level elastic modulus was less in the ACLX femur compared with the contralateral control, and the decrease was significant (-45%; p < 0.05) by 12-weeks post-ACLX. A finite element (FE) analysis based on muCT data simulated the uniaxial compression tests on a specimen-by-specimen basis to determine tissue modulus. No change in tissue modulus was detected, and a single tissue modulus of 5100 MPa (95% CI, +/- 600 MPa) explained the apparent-level modulus changes observed in the disease-related bone adaptation. The three-dimensional (3D) connectivity was evaluated from the original muCT data to quantify architectural alterations in contrast to tissue alterations. Significantly increased connectivity (through plate perforations) occurred as early as 3 weeks post-ACLX and was as high as 127% by 12 weeks post-ACLX in the distal femur. These measured changes indicated that architectural adaptation predominated over tissue modulus changes affecting apparent-level elastic modulus in the early stage of experimental OA and suggests that to maintain normal cancellous bone after a traumatic injury, early intervention should focus on preventing the substantial architectural alterations.

Adaptation, Physiological↗

Advantages of Artificial Neural Networks (ANNs) as alternative modelling technique for data sets showing non-linear relationships using data from a galenical study on a solid dosage form.

Artificial Neural Networks (ANN) methodology was used to assess experimental data from a tablet compression study showing highly non-linear relationships (i.e. measurements of ejection forces) and compared to classical modelling technique (i.e. Response Surface Methodology, RSM). These kinds of relationships are known to be difficult to model using classical methods. The aim of this investigation was to quantitatively describe the achieved degree of data fitting and predicting abilities of the developed models. The comparison between the ANN and RSM was carried out both graphically and numerically. For comparing the goodness of fit, all data were used, whereas for the goodness of prediction the data were split into a learning and a validation data set. Better results were achieved for the model using ANN methodology with regard to data fitting and predicting ability. All determined ejection properties were mainly influenced by the concentration of magnesium stearate and silica aerogel, whereas the other factors showed very much lower effects. Important relationships could be recognised from the ANN model only, whereas the RSM model ignored them. The ANN methodology represents a useful alternative to classical modelling techniques when applied to variable data sets presenting non-linear relationships.

Chemistry, Pharmaceutical↗

Improvement of statistical potentials and threading score functions using information maximization.

We show that statistical potentials and threading score functions, derived from finite data sets, are informatic functions, and that their performance depends on the manner in which data are classified and compressed. The choice of sequence and structural parameters affects estimates of the conditional probabilities P(C|S), the quantification of the effect of sequence S on conformation C, and determines the amount of information extracted from the data set, as measured by information gain. The mathematical link between information gain and mean conformational energy, established in this work using the local backbone potential as model, demonstrates that manipulation of descriptive parameters also alters the "energy" values assigned to native conformation and to decoy structures in the test pool, and consequently, the performance of such statistical potential functions in fold recognition exercises. We show that sequence and structural partitions that maximize information gain also minimize the mean energy of the ensemble of native conformations. Moreover, we establish an informatic basis for the placement of the native score within an energy spectrum given by the decoy pool in a threading exercise. We discover that, among all informatic quantities, information gain is the best predictor of threading success, even better than the standard Z-score. Consequently, the choices of sequence and structural descriptors, extent of compression, and levels of discretization that maximize information gain must also produce the best potential functions. Strategies to optimize these parameters with respect to information extraction are therefore relevant to building better statistical potentials. Last, we demonstrate that the backbone torsion potential, defined by the trimer sequence, can be an effective tool in greatly reducing the set of possible conformations from a vast decoy pool.

Amino Acid Sequence↗

Quality of cardiopulmonary resuscitation during out-of-hospital cardiac arrest.

CONTEXT: Cardiopulmonary resuscitation (CPR) guidelines recommend target values for compressions, ventilations, and CPR-free intervals allowed for rhythm analysis and defibrillation. There is little information on adherence to these guidelines during advanced cardiac life support in the field. OBJECTIVE: To measure the quality of out-of-hospital CPR performed by ambulance personnel, as measured by adherence to CPR guidelines. DESIGN AND SETTING: Case series of 176 adult patients with out-of-hospital cardiac arrest treated by paramedics and nurse anesthetists in Stockholm, Sweden, London, England, and Akershus, Norway, between March 2002 and October 2003. The defibrillators recorded chest compressions via a sternal pad fitted with an accelerometer and ventilations by changes in thoracic impedance between the defibrillator pads, in addition to standard event and electrocardiographic recordings. MAIN OUTCOME MEASURE: Adherence to international guidelines for CPR. RESULTS: Chest compressions were not given 48% (95% CI, 45%-51%) of the time without spontaneous circulation; this percentage was 38% (95% CI, 36%-41%) when subtracting the time necessary for electrocardiographic analysis and defibrillation. Combining these data with a mean compression rate of 121/min (95% CI, 118-124/min) when compressions were given resulted in a mean compression rate of 64/min (95% CI, 61-67/min). Mean compression depth was 34 mm (95% CI, 33-35 mm), 28% (95% CI, 24%-32%) of the compressions had a depth of 38 mm to 51 mm (guidelines recommendation), and the compression part of the duty cycle was 42% (95% CI, 41%-42%). A mean of 11 (95% CI, 11-12) ventilations were given per minute. Sixty-one patients (35%) had return of spontaneous circulation, and 5 of 6 patients discharged alive from the hospital had normal neurological outcomes. CONCLUSIONS: In this study of CPR during out-of-hospital cardiac arrest, chest compressions were not delivered half of the time, and most compressions were too shallow. Electrocardiographic analysis and defibrillation accounted for only small parts of intervals without chest compressions.

Aged↗

JPEG2000 and dissemination of cultural heritage over the Internet.

By applying the latest technologies in image compression for managing the storage of massive image data within cultural heritage databases and by exploiting the universality of the Internet we are now able not only to effectively digitize, record and preserve, but also to promote the dissemination of cultural heritage. In this work we present an application of the latest image compression standard JPEG2000 in managing and browsing image databases, focusing on the image transmission aspect rather than database management and indexing. We combine the technologies of JPEG2000 image compression with client-server socket connections and client browser plug-in, as to provide with an all-in-one package for remote browsing of JPEG2000 compressed image databases, suitable for the effective dissemination of cultural heritage.

Abstracting and Indexing↗

A special theory of biphasic mixtures and experimental results for human annulus fibrosus tested in confined compression.

A finite deformation mixture theory is used to quantify the mechanical properties of the annulus fibrosus using experimental data obtained from a confined compression protocol. Certain constitutive assumptions are introduced to derive a special mixture of an elastic solid and an inviscid fluid, and the constraint of intrinsic incompressibility is introduced in a manner that is consistent with results obtained for the special theory. Thirty-two annulus fibrosus specimens oriented in axial (n = 16) and radial (n = 16) directions were obtained from the middle-lateral portion of intact intervertebral discs from human lumbar spines and tested in a stress-relaxation protocol. Material constants are determined by fitting the theory to experimental data representing the equilibrium stress versus stretch and the surface stress time history curves. No significant differences in material constants due to orientation existed, but significant differences existed due to the choice of theory used to fit the data. In comparison with earlier studies with healthy annular tissue, we report a lower aggregate modulus and a higher initial permeability constant. These differences are explained by the choice of reference configuration for the experimental studies.

Biomechanical Phenomena↗

Effects of intermittent pneumatic compression on venous haemodynamics and fibrinolytic activity.

Pneumatic intermittent compression is an effective method to prevent postoperative venous thromboembolism. Its efficacy has been ascribed to both a haemodynamic action (increase of blood flow velocity) and a stimulation of endogenous fibrinolytic activity [via the production of tissue-type plasminogen activator (t-PA) by the vascular endothelium]. The relative contribution of these two effects is still debated. In a randomized, cross-over study in ten healthy volunteers, we compared the haemodynamic and fibrinolytic effects of two different pneumatic intermittent compression devices: a classical, low-pressure, whole-leg boots system, and a novel, high-pressure, plantar compression system. The study was performed at rest, to compare haemodynamics and fibrinolytic activity modifications, and under induced venous leg stasis, in order to compare the two compression systems in experimental conditions mimicking laparoscopic surgery. Our data show that (1) a pneumatic compression device that exerts its compression on the plantar venous plexus only induced an increase of venous blood peak velocity and flow in the common femoral vein that is very similar to that induced by the classical whole-leg boots compression system; (2) the venous stasis induced by an external pressure mimicking the conditions of laparoscopic surgery further increased the absolute velocity and flow increase, with the two intermittent compression systems tested; (3) no changes of t-PA or plasminogen activator-inhibitor 1 antigens were observed with either pneumatic compression device. In conclusion, the present study indicates that the antithrombotic effect of mechanical prophylaxis is probably mainly due to its ability to increase venous peak velocity and flow, especially under venous stasis conditions.

Adult↗

Limitations of bandwidth compression hearing aids applied to the voiced portion of speech.

Numerous speech processing techniques have been applied to assist hearing-impaired subjects with extreme high-frequency hearing losses who can be helped only to a limited degree with conventional hearing aids. The results of providing this class of deaf subjects with a speech encoding hearing aid, which is able to reproduce intelligible speech for their particular needs, have generally been disappointing. There are at least four problems related to bandwidth compression applied to the voiced portion of speech: (1) the problem of pitch extraction in real time; (2) pitch extraction under realistic listening conditions, i.e. when competing speech and noise sources are present; (3) an insufficient data base for successful compression of voiced speech; and (4) the introduction of undesirable spectral energies in the bandwidth-compressed signal, due to the compression process itself. Experiments seem to indicate that voiced speech segments bandwidth limited to f = 1000 Hz, even at a loss of higher formant frequencies, is in most instances superior in intelligibility compared to bandwidth-compressed voiced speech segments of the same bandwidth, even if pitch can be extracted with no error. With the added complexity of real-time pitch extraction which has to function in actual listening conditions, it is doubtful that a speech encoding hearing aid, based on bandwidth compression on the voiced portion of speech, could be successfully implemented. However, if bandwidth compression is applied to the unvoiced portions of speech only, the above limitations can be overcome (1).

Auditory Perception↗

Wavelet compression of ECG signals by the set partitioning in hierarchical trees algorithm.

A wavelet electrocardiogram (ECG) data codec based on the set partitioning in hierarchical trees (SPIHT) compression algorithm is proposed in this paper. The SPIHT algorithm [1] has achieved notable success in still image coding. We modified the algorithm for the one-dimensional case and applied it to compression of ECG data. Experiments on selected records from the MIT-BIH arrhythmia database revealed that the proposed codec is significantly more efficient in compression and in computation than previously proposed ECG compression schemes. The coder also attains exact bit rate control and generates a bit stream progressive in quality or rate.

Algorithms↗

Realtime transfer of live video images in parallel with three-dimensional modelling of the surgical field in computer-assisted telesurgery.

We have carried out three-dimensional, computer-assisted, functional endoscopic sinus telesurgery. Surgeons at different locations up to 300 km apart could not only see and transfer video images but also transfer three-dimensional computer models and manipulate them in realtime during surgery. Two different approaches were used. In the first telesurgery procedure we used M-JPEG compression and transmitted the data using fibre optic connections (ATM OC-3) at a bandwidth of 155 Mbit/s. In the second telesurgery procedure video images were transmitted over four E1 digital lines, amounting to about 8 Mbit/s of bandwidth, with better compression standards, such as MPEG1 and 2. We found that MPEG2 video compression produced the best picture quality for the operating field and endoscopic cameras. For conferencing and consultation between two or more connected sites during the surgery, we used JPEG and MPEG1 video compression with audio. The main feature of our three-dimensional telesurgery was the use of three-dimensional modelling of the operative field. This is important for emergency surgical interventions. We do not advocate that inexperienced surgeons operate on patients, not even with the guidance of a remote surgeon. However, three-dimensional telesurgery may become very valuable for experienced surgeons in the future.

Adult↗

Use of epidural corticosteroids in low back pain.

OBJECTIVE: To review the literature regarding the safety and efficacy of epidural corticosteroid injections in the treatment of low back pain (LBP) of various etiologies. DATA SOURCES: A MEDLINE search (1966-February 1999) of English-language literature pertaining to the use of epidural corticosteroids in LBP was performed. Additional literature was obtained from reference lists of pertinent articles identified through the search. STUDY SELECTION AND DATA EXTRACTION: All articles were considered for the review. The clinical trials included are those that enrolled a larger patient population and were primarily controlled clinical trials. The authors selected pertinent information for further discussion. DATA SYNTHESIS: Nerve root compression and inflammation are thought to be factors contributing to LBP. Corticosteroids act to decrease inflammation and may be of benefit in relieving LBP, especially if administered directly to the affected area via the epidural route. However, data on the efficacy of various corticosteroid agents administered via this route are limited. In addition, there have been reports of significant adverse reactions, thought to be due primarily to the preservative components in the corticosteroid preparations. Therefore, the role of these agents in the therapy of LBP remains to be determined. CONCLUSIONS: Based on the studies reviewed, epidural corticosteroids may be an effective treatment for LBP. Their use is warranted in patients who have failed conservative therapy. Although they contain preservatives, it appears that these agents are relatively safe and do not cause significant neurotoxicities.

Adrenal Cortex Hormones↗

Real-time near-infrared monitoring of content uniformity, moisture content, compact density, tensile strength, and Young's modulus of roller compacted powder blends.

A method for real-time in-line near-infrared (NIR) monitoring of roller compaction is reported. Multivariate analysis using partial least square projections to latent structures (PLS) was used to relate the spectral data with key compact attributes: content uniformity, moisture content, relative density, tensile strength, and Young's modulus. NIR calibration curves were generated using the spectral data collected on simulated ribbons, that is, tablets prepared under uni-axial compression, and tested on the data collected on another set of simulated ribbons and by monitoring the ribbons as they exited the roller compactor. For all compact attributes, the NIR predicted values agreed well with the values measured using a reference method.

Acetaminophen↗