[PROBLEMS RELATIVE TO AIR POLLUTION OF WORK AREAS-FORMULATION AND EVALUATION OF THE MAXIMUM ACCEPTABLE CONCENTRATION FOR GAS AND TOXIC VAPORS].
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Air Pollution↗
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Results for “Problem Formulation”
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[Various problems of classification of ischemic heart disease and the formulation of its diagnosis].
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Angina Pectoris↗
More reliable protein NMR peak assignment via improved 2-interval scheduling.
Protein NMR peak assignment refers to the process of assigning a group of "spin systems" obtained experimentally to a protein sequence of amino acids. The automation of this process is still an unsolved and challenging problem in NMR protein structure determination. Recently, protein NMR peak assignment has been formulated as an interval scheduling problem (ISP), where a protein sequence P of amino acids is viewed as a discrete time interval I (the amino acids on P one-to-one correspond to the time units of I), each subset S of spin systems that are known to originate from consecutive amino acids from P is viewed as a "job" j(s), the preference of assigning S to a subsequence P of consecutive amino acids on P is viewed as the profit of executing job j(s) in the subinterval of I corresponding to P, and the goal is to maximize the total profit of executing the jobs (on a single machine) during I. The interval scheduling problem is max SNP-hard in general; but in the real practice of protein NMR peak assignment, each job j(s) usually requires at most 10 consecutive time units, and typically the jobs that require one or two consecutive time units are the most difficult to assign/schedule. In order to solve these most difficult assignments, we present an efficient 13/7-approximation algorithm for the special case of the interval scheduling problem where each job takes one or two consecutive time units. Combining this algorithm with a greedy filtering strategy for handling long jobs (i.e., jobs that need more than two consecutive time units), we obtain a new efficient heuristic for protein NMR peak assignment. Our experimental study shows that the new heuristic produces the best peak assignment in most of the cases, compared with the NMR peak assignment algorithms in the recent literature. The above algorithm is also the first approximation algorithm for a nontrivial case of the well-known interval scheduling problem that breaks the ratio 2 barrier.
Algorithms↗
Comparative bioavailability of oral sugar-coated and plain formulation of chloroquine phosphate marketed in Tanzania.
The bioavailability of chloroquine from a single oral dose (10 mg/kg body weight) of a sugar-coated (Dawaquin) and a plain formulation (Shellyquine) of chloroquine phosphate were compared in two groups of 10 volunteers each, following an overnight fast. Whole blood chloroquine concentrations were measured using high-performance liquid chromatography (HPLC) and bioavailability was determined by measuring area under the blood chloroquine concentration curve (AUC ng mL(-1) h) and the peak blood chloroquine concentration (Cpmax ng/mL). The AUC and Cpmax for Shellyquine were 4396.3 +/- 833 ng mL(-1) h and 162 +/- 14 ng/mL, respectively. The AUC and Cpmax for Dawaquin were 2060 +/- 339 ng mL(-1) h and 56.6 +/- 5.2 ng/mL, respectively. Shellyquine was significantly more bioavailable than Dawaquin (P<0.001). Although the Cpmax for Dawaquin was higher than the required therapeutic level for sensitive Plasmodium falciparum of 30 ng/mL, its blood levels may not guarantee a rapid clearance of parasites. The differences between the two formulations point to a problem in the quality of pharmaceuticals marketed in this country, whose extent need to be ascertained further. Failure of chloroquine phosphate in this country has already been declared by the Ministry of Health, and the potential contribution of poorly formulated products remains a subject of debate.
Administration, Oral↗
Postmenopausal hormone therapy and breast cancer: what is the problem?
Observational studies provide evidence that breast cancer risk is increased with long-term oral use of postmenopausal estrogen replacement therapy (ET). Various large cohort studies have shown that the addition of a progestogen in combined hormone replacement therapy (EPT) increases this risk further. Prospective, randomized controlled trials have confirmed this for the continuous combined regimen. So, why not tell our patients, "Stop using ET and EPT, it is dangerous to your health!"? The answer is: there are too many problems to allow such an oversimplified, definite statement. What is the problem? There is more than one! The problems are as follows: In conclusion, we have a problem as we cannot formulate any general advice that holds for the majority of European postmenopausal women due to lack of consistency, lack of biological plausibility, and lack of relevance of randomized clinical trial data to our daily practical work. So, we have a problem and not a firm basis for undisputable statements.
Breast Neoplasms↗
ADHD: new pharmacological treatments on the horizon.
Attention-deficit/hyperactivity disorder (ADHD) is the most common neurobehavioral disorder affecting school-age children. In many cases, symptoms persist into adolescence and adulthood, causing significant lifelong impairments in academic, career, and social functioning. The stimulants methylphenidate and amphetamines have been used for decades as first-line therapy for the treatment of ADHD. Short-acting stimulant formulations control symptoms only for a few hours, creating the need for multiple daily doses of the medication. For school-age children, this necessitates administering medication during school hours, creating the potential for embarrassment and noncompliance. To offset these problems, longer acting stimulant formulations have been developed. Long-acting medications often control symptoms for up to 8 hours with only one daily dose of the medication, eliminating the need for in-school administration. Some long-acting stimulants are designed to control symptoms for up to 10 to 12 hours. Although stimulants are effective in most cases, some children are unable to tolerate these medications. Nonstimulant options are available for the treatment of ADHD and include atomoxetine, alpha-adrenergic agents, and antidepressants. Of these, atomoxetine is the only medication approved to treat ADHD. In spite of the number of medications available for the management of ADHD, treatment options with greater flexibility and reduced side effects are still desirable. A transdermal methylphenidate patch has recently been approved, and advances to existing stimulants currently under development include an amphetamine prodrug and a longer acting formulation of amphetamine. In addition, a number of nonstimulant entities, including guanfacine and modafinil, are under development for the treatment of ADHD.
Adrenergic Uptake Inhibitors↗
Interrupting drug therapy in the perioperative period.
Millions of patients undergo surgery each year and an increasing proportion of these patients are consuming therapeutic drugs. Drug therapy is often withheld in the immediate perioperative period and after major surgery, in particular, there is often a prolonged period of fasting. This may lead to withdrawal effects including recurrence or worsening of patients' disease symptomatology. These effects will occur during a period of physiological and pathophysiological stresses and render patients more vulnerable to drug withdrawal phenomena. Thus, patients may be exposed to greater and sometimes unnecessary risks in the perioperative period. There are relatively few studies that have investigated this problem. The ones that have, however, confirm that drug abstinence in the perioperative period is a relatively common phenomenon and one study has demonstrated an association between duration of drug abstinence and adverse outcomes. The pathophysiological effects of major surgery on gastrointestinal function, neuro-humoral and cytokine adaptive responses to surgical stress are under-appreciated. These responses can reduce the effectiveness of oral administration and exacerbate co-existing disease processes. These problems are compounded by a fragmented approach to perioperative drug therapy with no one group of healthcare professionals assuming responsibility for this aspect of care. This may in part be a consequence of the complexities of rationalising drug therapy in the perioperative period together with the lack of readily available and evidence based information strategies for individual drugs or drug classes. An additional problem relates to the formulations, inherent pharmacokinetics and limited routes of administration of many prescribed drugs. These can prevent a 'seamless' transition from preoperative to postoperative management. Consumers, health professionals, pharmaceutical companies and drug regulatory agencies must all play a part in rectifying this problem. There remains a need for further research to clarify the effects of abstinence on patient outcomes and also to identify optimum strategies to avoid unwanted drug abstinence.
Drug Administration Schedule↗
Fast and high precision algorithms for optimization in large-scale genomic problems.
There are several very difficult problems related to genetic or genomic analysis that belong to the field of discrete optimization in a set of all possible orders. With n elements (points, markers, clones, sequences, etc.), the number of all possible orders is n!/2 and only one of these is considered to be the true order. A classical formulation of a similar mathematical problem is the well-known traveling salesperson problem model (TSP). Genetic analogues of this problem include: ordering in multilocus genetic mapping, evolutionary tree reconstruction, building physical maps (contig assembling for overlapping clones and radiation hybrid mapping), and others. A novel, fast and reliable hybrid algorithm based on evolution strategy and guided local search discrete optimization was developed for TSP formulation of the multilocus mapping problems. High performance and high precision of the employed algorithm named guided evolution strategy (GES) allows verification of the obtained multilocus orders based on different computing-intensive approaches (e.g., bootstrap or jackknife) for detection and removing unreliable marker loci, hence, stabilizing the resulting paths. The efficiency of the proposed algorithm is demonstrated on standard TSP problems and on simulated data of multilocus genetic maps up to 1000 points per linkage group.
Algorithms↗
Optimal head related transfer functions for hearing and monaural localization in elevation: a signal processing design perspective.
Localization of sound sources by human listeners has been widely studied and theories and various models of the localization and hearing mechanism have been constructed. In the classical "duplex" theory, sound localization in azimuth is explained by interaural time or equivalently, phase differences at low frequencies, and by interaural amplitude differences at higher frequencies. Head related transfer functions (HRTF's) present a linear system approach to modeling localization by representing the direction-dependent transformation the sound undergoes at each ear. Localization in elevation is explained by directional differences in the HRTF's, which also explains monaural localization. We conjecture that the HRTF's evolved during the course of nature (due to the evolution of the shape and structure of the ear etc.) are optimal with respect to several physically realizable criteria. In this paper, we investigate the problem of defining the design constraints which when optimized yield a set of HRTF's for hearing and monaural vertical localization in an attempt to better understand, and if possible, duplicate nature's design. We pursue an engineer's design perspective and formulate a constrained optimization problem, where the desired set of HRTF's is optimized according to a cost function based on several criteria for localization, hearing and smoothness, and also by imposing physically realizable constraints on the HRTF's such as nonnegativity, energy etc. The value of the cost function for a candidate set of HRTF's is an indication of the similarity of that set of HRTF's with respect to the ideal solution (measured HRTF data). The final optimization results we present are similar to the actual HRTF's measured in human subjects, and the associated cost function values are found to be almost equal. This points to the fact that the optimization criteria defined are quite relevant. The significant outcome of this research is the identification of a relevant set of mathematical criteria that could be optimized in the human auditory system to facilitate good hearing and localization. These criteria along with the associated constraints represent the desirable characteristics of the HRTF's in an HRTF-based localization system, and could lead to a better understanding and modeling of the auditory system.
Algorithms↗
Hybrid formulation of the model-based non-rigid registration problem to improve accuracy and robustness.
We present a new algorithm to register 3D pre-operative Magnetic Resonance (MR) images with intra-operative MR images of the brain. This algorithm relies on a robust estimation of the deformation from a sparse set of measured displacements. We propose a new framework to compute iteratively the displacement field starting from an approximation formulation (minimizing the sum of a regularization term and a data error term) and converging toward an interpolation formulation (least square minimization of the data error term). The robustness of the algorithm is achieved through the introduction of an outliers rejection step in this gradual registration process. We ensure the validity of the deformation by the use of a biomechanical model of the brain specific to the patient, discretized with the finite element method. The algorithm has been tested on six cases of brain tumor resection, presenting a brain shift up to 13 mm.
Algorithms↗
A comparison of noninvasive reconstruction of epicardial versus transmembrane potentials in consideration of the null space.
We compare two source formulations for the electrocardiographic forward problem in consideration of their implications for regularizing the ill-posed inverse problem. The established epicardial potential source model is compared with a bidomain-theory-based transmembrane potential source formulation. The epicardial source approach is extended to the whole heart surface including the endocardial surfaces. We introduce the concept of the numerical null and signal space to draw attention to the problems associated with the nonuniqueness of the inverse solution and show that reconstruction of null-space components is an important issue for physiologically meaningful inverse solutions. Both formulations were tested with simulated data generated with an anisotropic heart model and with clinically measured data of two patients. A linear and a recently proposed quasi-linear inverse algorithm were applied for reconstructions of the epicardial and transmembrane potential, respectively. A direct comparison of both formulations was performed in terms of computed activation times. We found the transmembrane potential-based formulation is a more promising source formulation as stronger regularization by incorporation of biophysical a priori information is permitted.
Adult↗
Psychiatric decision-making by medical students.
Analysis of medical students' formulations and replies to clinical problems indicates difficulty in deciding on the nature and organization of treatment. A programme describing a problem-solving approach was devised, and students taught in this way were shown to be significantly more able to formulate organized treatment plans with more precise aims. It is suggested that problem-solving methods are likely to be much more effective than conventional teaching of psychiatry.
Decision Making↗
Risk assessment in the formulation of anaesthesia safety standards.
Risk assessment involves identifying hazards and then estimating their chance of occurrence and their severity. Risk management involves the cost-effective reduction of risk to levels perceived to be acceptable to society; risk levels set by experts may not be accepted, as perceived risk is strongly influenced by the nature of the adverse outcome and the context in which it was incurred. An understanding of the psychology of risk perception may lessen the negative impact of disasters and may better prepare the victims and their relatives. In formulating the international anaesthesia safety standards an attempt was made to base decisions on sound risk assessment and management principles. A review of the literature revealed that the hazards which posed most risks to patients were hypoxic gas mixtures, gas flow, circuit, endotracheal tube, airway and ventilation problems. These constituted one to two thirds of all incidents during anaesthesia, and account for most causes of brain damage that are dealt with by medical insurance companies. The size of the settlements provides evidence that these are viewed as very serious problems. Minimum standards were formulated with this information in mind; in recommending a sequence for equipment purchases great emphasis was placed on preventing the patient from breathing hypoxic gas mixtures, and on continuous monitoring of the adequacy of the airway, ventilation, the circulation and tissue oxygenation.
Anesthesia↗
Optimal segmentation of pupillometric images for estimating pupil shape parameters.
The problem of determining the pupil morphological parameters from pupillometric data is considered. These characteristics are of great interest for non-invasive early diagnosis of the central nervous system response to environmental stimuli of different nature, in subjects suffering some typical diseases such as diabetes, Alzheimer disease, schizophrenia, drug and alcohol addiction. Pupil geometrical features such as diameter, area, centroid coordinates, are estimated by a procedure based on an image segmentation algorithm. It exploits the level set formulation of the variational problem related to the segmentation. A discrete set up of this problem that admits a unique optimal solution is proposed: an arbitrary initial curve is evolved towards the optimal segmentation boundary by a difference equation; therefore no numerical approximation schemes are needed, as required in the equivalent continuum formulation usually adopted in the relevant literature.
Algorithms↗
Three-dimensional finite element computer model of the forward problem of electrocardiology.
This study analyses forward problem of electrocardiology. Premature beats originated from subepicardial layer of myocardium were simulated in order to analyse their shape dependence on the site of origin. The equation governing the propagation of the electrical wave through human thorax together with transition and boundary conditions is derived under the clearly stated simplifying assumptions. The weak formulation of the forward problem of electrocardiology is introduced, too. The Galerkin method as a convenient tool for looking for the numerical solution is mentioned and its practical implementation--finite element method--then used in order to obtain numerical results. The obtained results were presented in the form of isopotential maps and compared with actually measured body surface isopotential maps of the depolarization phase. The parameters of the model were then optimalized in accordance with the measured data. In spite of the lack of quantitative data the model has proved that the presented method was able to be used for the simulation studies of ventricular ectopic beats. It was shown that only a small difference between the site of beat origin can be well distinguished on the simulated body surface maps. (Fig. 3, Ref. 3.)
Computer Simulation↗
[Formulation of a capsule preparation with high active ingredient content using re-crystallized drug compound].
Richter Gedeon Company aimed to manufacture and launch a generic product, that's original is already on market in Hungary. The goal of a generic development is to produce an essentially similar product to the original one. It seems to be simple and routine work, but during the formulation a couple of problems have to be solved. Our active agent was voluminous therefore we could not fill the whole quantity of the active, even without any excipients. In addition the flow property of the powder mixture were very bad, and it may cause inaccurate capsule filling and significant differences in the weight of the filled capsules. During the formulation we managed to assure the appropriate physical properties of the agent by re-crystallisation. We changed the excipients used in the first trials. Chemically these were the same, but with different physical features.
Capsules↗
Human exposure assessment in the near field of GSM base-station antennas using a hybrid finite element/method of moments technique.
A hybrid finite-element method (FEM)/method of moments (MoM) technique is employed for specific absorption rate (SAR) calculations in a human phantom in the near field of a typical group special mobile (GSM) base-station antenna. The MoM is used to model the metallic surfaces and wires of the base-station antenna, and the FEM is used to model the heterogeneous human phantom. The advantages of each of these frequency domain techniques are, thus, exploited, leading to a highly efficient and robust numerical method for addressing this type of bioelectromagnetic problem. The basic mathematical formulation of the hybrid technique is presented. This is followed by a discussion of important implementation details-in particular, the linear algebra routines for sparse, complex FEM matrices combined with dense MoM matrices. The implementation is validated by comparing results to MoM (surface equivalence principle implementation) and finite-difference time-domain (FDTD) solutions of human exposure problems. A comparison of the computational efficiency of the different techniques is presented. The FEM/MoM implementation is then used for whole-body and critical-organ SAR calculations in a phantom at different positions in the near field of a base-station antenna. This problem cannot, in general, be solved using the MoM or FDTD due to computational limitations. This paper shows that the specific hybrid FEM/MoM implementation is an efficient numerical tool for accurate assessment of human exposure in the near field of base-station antennas.
Cell Phone↗
Probing the performance limits of the Escherichia coli metabolic network subject to gene additions or deletions.
An optimization-based procedure for studying the response of metabolic networks after gene knockouts or additions is introduced and applied to a linear flux balance analysis (FBA) Escherichia coli model. Both the gene addition problem of optimally selecting which foreign genes to recombine into E. coli, as well as the gene deletion problem of removing a given number of existing ones, are formulated as mixed-integer optimization problems using binary 0-1 variables. The developed modeling and optimization framework is tested by investigating the effect of gene deletions on biomass production and addressing the maximum theoretical production of the 20 amino acids for aerobic growth on glucose and acetate substrates. In the gene deletion study, the smallest gene set necessary to achieve maximum biomass production in E. coli is determined for aerobic growth on glucose. The subsequent gene knockout analysis indicates that biomass production decreases monotonically, rendering the metabolic network incapable of growth after only 18 gene deletions. In the gene addition study, the E. coli flux balance model is augmented with 3,400 non-E. coli reactions from the KEGG database to form a multispecies model. This model is referred to as the Universal model. This study reveals that the maximum theoretical production of six amino acids could be improved by the addition of only one or two genes to the native amino acid production pathway of E. coli, even though the model could choose from 3,400 foreign reaction candidates. Specifically, manipulation of the arginine production pathway showed the most promise with 8.75% and 9.05% predicted increases with the addition of genes for growth on glucose and acetate, respectively. The mechanism of all suggested enhancements is either by: 1) improving the energy efficiency and/or 2) increasing the carbon conversion efficiency of the production route.
Aerobiosis↗