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PubMed1993

Discovering sequence similarity by the algorithmic significance method.

The minimal-length encoding approach is applied to define concept of sequence similarity. A sequence is defined to be similar to another sequence or to a set of keywords if it can be encoded in a small number of bits by taking advantage of common subwords. Minimal-length encoding of a sequence is computed in linear time, using a data compression algorithm that is based on a dynamic programming strategy and the directed acyclic word graph data structure. No assumptions about common word ("k-tuple") length are made in advance, and common words of any length are considered. The newly proposed algorithmic significance method provides an exact upper bound on the probability that sequence similarity has occurred by chance, thus eliminating the need for any arbitrary choice of similarity thresholds. Preliminary experiments indicate that a small number of keywords can positively identify a DNA sequence, which is extremely relevant in the context of partial sequencing by hybridization.

Algorithms↗
PubMedDate not supplied

Entry of U.S. medical school graduates into family practice residencies: 1983-84.

This study is the third of a series from the American Academy of Family Physicians to report on the percentage of each medical school's graduates who enter family practice residency programs. Approximately 12.5% of the 15,739 graduates of United States medical schools between July 1982 and June 1983 were residents in family practice in December 1983. The Mountain and Pacific regions report the highest percentage of medical school graduates who were residents in family practice programs in December 1983; the New England and Middle Atlantic regions had the lowest percentages. Medical school graduates from publicly funded medical schools were twice as likely to be residents in family practice in December 1983 as were graduates from privately funded schools. The independent variable indicated by the presence of a family practice department in the medical school is the only variable which entered into a step-wise linear regression on a transformation of the dependent variable, percentage of graduates entering an FP residency program.

Family Practice↗
PubMedDate not supplied

[Rope pulley isokinetic system in shoulder rehabilitation--initial results].

AIM: Of this study was to evaluate the results of a shoulder rehabilitation program of different shoulder diseases, based on an isokinetie pulley system ("Moflex", Recotec/Bernina, Swiss). METHOD: In this prospective study 70 patients participated in a standardized rehabilitation program (instability: n = 19; rotator cuff disorders: n = 23; impingement syndrome without lesion: n = 16; others: n = 12; operative therapy: n = 47). The major aspect of the program was an isokinetic pulley system. RESULTS: Isokinetic training with the used device affords strict monitor-feedback to avoid critical torque values. Strength which was attained without relevant pain was almost linearly increased by a mean of 31% until the 20th day of rehabilitation, workload by 79%. At the end of the rehabilitation program the strength of the affected (mostly dominant) shoulder was 15% higher than in the unaffected shoulder; the respective workload values were almost equal. CONCLUSION: These first results demonstrate the value of the isokinetic pulley system in the rehabilitation of the investigated shoulder diseases. The equipment may be used already in an early postoperative state. First results of strength increases using an isokinetic pulley system in shoulder rehabilitation are presented.

Adult↗
PubMed2002

Novel trends in orphan market drug discovery: amyotrophic lateral sclerosis as a case study.

As new lead discovery technologies of high throughput screening and rational drug design have been incorporated into pharmaceutical and biotechnology drug discovery programs, researchers have focused on the applying these new technologies in diseases traditionally neglected by for-profit drug discovery efforts. This article reviews general trends in orphan disease lead discovery, identifies best practices of orphan market drug discovery and provides an overview of recent ALS lead discovery programs and drug development according to these metrics. Best practices in orphan market drug discovery embodied by programs like the NIH Anticonvulsant Screening Program include the (1) management of timelines and priorities, (2) engagement of for-profit partners, (3) creative application of technology, (4) collaboration, and (5) flexibility. Recent trends in ALS lead discovery have been shaped not only by the predominance of animal models of disease over in vitro models, but also by the successes and best practices of these earlier orphan market drug discovery programs. The ALS Treatment Initiative, the Johns Hopkins Center for ALS Research, the ALS Association, and the ALS Therapy Development Foundation have all initiated lead discovery programs in the past several years which seek to utilize existing experimental models of the disease and challenge assumptions about the linear nature of the lead discovery and development process. The compounds currently in clinical evaluation for ALS were identified as leads from a variety of sources, further reinforcing the transforming effect these new lead discovery programs have had on drug discovery and development in ALS. We conclude our review with an overview of the challenges and opportunities lead discovery in ALS currently faces, ultimately concluding that ALS lead discovery, and indeed orphan market drug discovery in general, would most benefit from more centralized lead discovery management, expanded national access to core facilities for lead discovery, and matrixed simultaneous screening of multiple compounds for multiple neglected diseases.

Amyotrophic Lateral Sclerosis↗
PubMed1996

Correction of 13C mass isotopomer distributions for natural stable isotope abundance.

Metabolism of singly or multiply 13C-labeled substrates leads to the production of molecules that contain 13C atoms at various positions. Molecules differing only in the number of isotopic atoms incorporated are referred to as mass isotopomers. The distribution of mass isotopomers of many molecules can be measured by gas chromatography/ mass spectrometry after chemical derivatization. Quantification of metabolite mass isotopomer abundance resulting from biological processes necessitates correction of the measured mass isotopomer distribution of the derivatized metabolite for contributions due to naturally occurring isotopes of its elements. This correction must take into account differences in the relative natural abundance distribution of each mass isotopomer (skewing). An IBM-compatible computer program was developed which (i) calculates the natural abundance mass isotopomer distribution of unlabeled and labeled standards given the molecular formula of the derivatized molecule or fragment ion, and (ii) calculates the natural abundance mass isotopomer distribution of the singly and multiply labeled molecule or fragment via non-linear fitting to the measured mass isotopomer distribution of the unlabeled molecule or fragment. The output of this program is used to correct measured mass isotopomer distributions for contributions from natural isotope abundances and to verify measured values for theoretical consistency. Differences between predicted and measured unlabeled and 13C-labeled isotopomer distributions for hydroxamate di-t-butyl-dimethylsilyl (di-TBDMS) derivatized pyruvate were measured. The program was applied to the mass isotopomer distribution of glucose labeled from [U-13C3]glycerol and of fatty acids labeled from [U-13C6]glucose and either [2-13C2] acetate or [U-13C2]acetate. In some of these cases, the measured mass isotopomer distributions corrected by the program were different from those corrected by the classical technique. Implications of these differences including those on the calculation of glucose production due to gluconeogenesis in isolated perfused rat liver are discussed.

Animals↗
PubMed1994

Patient dosimetry quality assurance program with a commercial diode system.

PURPOSE: To evaluate a commercial silicone diode dosimeter for a patient dosimetry quality assurance program. METHODS AND MATERIALS: The diode dosimeter was calibrated against an ion chamber and percentage depth dose, linearity, anisotropy, virtual source position, and field size factor studies were performed. Correction factors for lack of full scatter medium in the diode entrance and exit dose measurements were acquired. Dosimetry equations were proposed for calculation of dose delivered at isocenter. Diode dose accuracy and reproducibility were tested on phantom and on four patients. A patient dosimetry quality assurance program based on diode measured dose was instituted and patient dose data were collected. RESULTS: Diode measured percentage depth dose and field factors agreed to within 3% with those measured with an ion chamber. The diode exhibited less than 1.7% angular dose anisotropy and less than 0.5% nonlinearity up to 4 Gy. Diode dose measurements in phantom showed that the calculated doses differed from the prescribed dose by less than 1.5%; the diode exhibited a daily dose reproducibility of better than 0.2%. On four selected patients, the measured dose reproducibility was 1.5%; the average calculated doses were all within +/- 7% of the prescribed doses. For 33 of 40 patients treated with a 6 MV beam, measured doses were within +/- 7% of the prescribed doses. For 58 of 63 patients treated with an 18 MV beam, measured doses were within +/- 7% of the prescribed doses. For 11 out of 12 patients, a second repeat measurements yielded doses within +/- 7% of the prescribed doses. CONCLUSIONS: The proposed diode-based patient dosimetry quality assurance program with dose tolerance at +/- 7% is simple and feasible. It is capable of detecting certain serious treatment errors such as incorrect daily dose greater than 7%, incorrect wedge use, incorrect photon energy and patient setup errors involving some incorrect source-to-surface-distance vs. source-to-axis-distance treatments.

Anisotropy↗
PubMed2004

Acquisition of visuomanual skills and improvement of information processing capacities in 6- to 10-year-old children performing a 2D pointing task.

The aim of this study was to investigate motor performance and visuomanual control through the analysis of Fitts' law in 6-, 8-, and 10-year-old children and adults performing a constrained two-dimensional pointing task. Participants were required to point and click on targets appearing on a laptop computer screen with a standard computer mouse. Three sizes of targets were used to create different indexes of difficulty. Analysis first showed linear visuomanual abilities to perform bi-dimensional pointing movements. It appears that developmental motor performance changes are due to combined enhanced programming processes and online feedback processing. Immature visuomanual control of 10-year-old children could be explained by higher cognitive requirements related to the task. As predicted by Fitts' law, movement time linearly decreases with the enlargement of target width. Moreover, a regression analysis of movement time on index of difficulty (ID) clearly showed significant differences for cognitive processing capacities with age: increasing ID effects are more dramatic in younger children performing computer mouse pointing movements.

Adult↗
PubMed1991

A mathematical study of simple exponential modelling in biochemical processes.

This paper discusses the application of simple exponential functions for analyses of complex biochemical processes such as transport phenomena in a mammalian system. The main aim is to identify these exponential function models using various curve fitting techniques. The experimental data used is based on transport of a radio-active tracer 32P (Radio-phosphorus) from a central compartment of blood plasma to subsidiary organ compartments in insulin-treated diabetic rats. The data has been analysed with a view to fitting exponential functions. A graphical method of exponential peeling and six (I to VI) computer programs based on iterative methods for solving single, as well as, multiple exponential functions have been used. The method of exponential peeling has also been compared with the least squares method for simple linear regression. The sum of two exponential functions has been found to be the most preferred Goodness of Fit by the computer programs. This model indicates that the transport of 32P in blood plasma in rats is governed by two major metabolic parameters. Further interpretations of the fitted equations are discussed.

Animals↗
PubMed1999

Encouraging schools to promote health: impact of the Western Australian School Health Project (1992-1995).

The Western Australian School Health (WASH) Project, a school health promotion intervention operating over a four-year period (1992-1995), provided a comprehensive, year-long intervention to help successive groups of schools develop health promotion programs. The WASH Project worked with self-selected school communities and used community development strategies to support participating schools in identifying and responding to health concerns relevant to their students. This paper reports the school impact results of the WASH Project. School impact data involved 24 variables categorized into two areas: school organizational factors supportive of health promotion, and school health promotion factors. Two methods of analysis were used: logistic regression indicating the direction of change, and linear regression indicating the magnitude of change. Results demonstrated that schools successfully made organizational changes, such as the allocation of additional time, personnel, and monetary resources, to support health promotion.

Adolescent↗
PubMed2005

Estimation of linear mixed models with a mixture of distribution for the random effects.

The aim of this paper is to propose an algorithm to estimate linear mixed model when random effect distribution is a mixture of Gaussians. This heterogeneous linear mixed model relaxes the classical Gaussian assumption for the random effects and, when used for longitudinal data, can highlight distinct patterns of evolution. The observed likelihood is maximized using a Marquardt algorithm instead of the EM algorithm which is frequently used for mixture models. Indeed, the EM algorithm is computationally expensive and does not provide good convergence criteria nor direct estimates of the variance of the parameters. The proposed method also allows to classify subjects according to the estimated profiles by computing posterior probabilities of belonging to each component. The use of heterogeneous linear mixed model is illustrated through a study of the different patterns of cognitive evolution in the elderly. HETMIXLIN is a free Fortran90 program available on the web site: http://www.isped.u-bordeaux2.fr.

Aged↗
PubMed1998

Pombe: a gene-finding and exon-intron structure prediction system for fission yeast.

A special program developed by the authors, called Pombe, identifies protein coding regions in the Schizosaccharomyces pombe genome. Linear discriminant analysis was applied to predict 5'-terminal, internal, 3'-terminal exons (coding-exon) and introns. The accuracy of the prediction was tested by cross verifications. The sensitivity, specificity and correlation coefficient for the internal exon prediction were 98.5%, 99.9% and 98.3% respectively at the nucleotide level. Open reading frames were studied and used to predict intron-less genes: 99.0% of such genes were identified with correct stopping sites. The gene structure was determined by dynamic programming and the prediction achieved 97.0% correlation coefficient at the nucleotide level. The program is available at http:(/)/clio.cshl.org/genefinder.

Algorithms↗
PubMedDate not supplied

Negative effect of stress of in vitro fertilization program on quality of semen.

There are controversial data on the effects of stress on semen quality during treatment for infertility. We have compared the parameters of semen obtained from 84 patients on the day of the ovocyte pick-up during an in vitro fertilization and embryo transfer program (IVF) with those of semen collected from the same patients on the day of admission to the program (up to 3 months earlier). Abnormal semen has been found in 2 of the 84 patients on the day of admission and in 11 on the day of IVF. There were no improvements in semen quality of any patient at the second test. All except two parameters evaluated objectively by the Hamilton-Thorn Motility analyzer were significantly worse (p < 0.001) on the day of IVF, the exceptions were the percentage with moderate or slow motility and the Linear Index. These data indicate that the emotional stress to a subject enrolled in an IVF program negatively affects the quality of semen. Some suggestions are made for improved management of these patients.

Adult↗
PubMed1988

Helix geometry in proteins.

In this report we describe a general survey of all helices found in 57 of the known protein crystal structures, together with a detailed analysis of 48 alpha-helices found in 16 of the structures that are determined to high resolution. The survey of all helices reveals a total of 291 alpha-helices, 71 3(10)-helices and no examples of pi-helices. The conformations of the observed helices are significantly different from the "ideal" linear structures. The mean phi, psi angles for the alpha- and 3(10)-helices found in proteins are, respectively, (-62 degrees, -41 degrees) and (-71 degrees, -18 degrees). A computer program, HBEND, is used to characterize and to quantify the different types of helix distortion. alpha-Helices are classified as regular or irregular, linear, curved or kinked. Of the 48 alpha-helices analysed, only 15% are considered to be linear; 17% are kinked, and 58% are curved. The curvature of helices is caused by differences in the peptide hydrogen bonding on opposite faces of the helix, reflecting carbonyl-solvent/side-chain interactions for the exposed residues, and packing constraints for residues involved in the hydrophobic core. Kinked helices arise either as a result of included proline residues, or because of conflicting requirements for the optimal packing of the helix side-chains. In alpha-helices where there are kinks caused by proline residues, we show that the angle of kink is relatively constant (approximately 26 degrees), and that there is minimal disruption of the helix hydrogen bonding. The proline residues responsible for the kinks are highly conserved, suggesting that these distortions may be structurally/functionally important.

Amino Acid Sequence↗
PubMed2001

Using segmented linear regression models with unknown change points to analyze strategy shifts in cognitive tasks.

Some years ago, Beem (1993, 1995) described a program for fitting two regression lines with an unknown change point (Segcurve). He suggested that such models are useful for the analysis of a variety of phenomena and gave an example of an application to the study of strategy shifts in a mental rotation task. This technique has also proven to be very fruitful for investigating strategy use and strategy shifts in other cognitive tasks. Recently, Beem (1999) developed SegcurvN, which fits n regression lines with (n - 1) unknown change points. In the present article we present this new technique and demonstrate the usefulness of a three-phase segmented linear regression model for the identification of strategies and strategy shifts in cognitive tasks by applying it to data from a numerosity judgment experiment. The advantages and shortcomings of this technique are evaluated.

Attention↗
PubMed2006

Management of environmental health issues for the 2004 Athens Olympic Games: is enhanced integrated environmental health surveillance needed in every day routine operation?

BACKGROUND: Management of environmental health issues is an integral part of public health systems. An active integrated environmental health surveillance and response system was developed for the Athens Olympics to monitor and prevent exposure to environmental hazards. The potential for permanent implementation of the program was examined. METHODS: The environmental health surveillance and response system included standardization, computerization and electronic transmission of data concerning environmental inspections of 17 site categories (restaurants, swimming pools etc) of public health interest, drinking and recreational water examinations and suggested corrective actions. The Olympic Planning Unit integrated and centrally managed data from 13 public health agencies, recommended, supervised and coordinated prompt corrective actions. Methods used to test the effectiveness of the program were the assessment of water quality test and inspection results trends over time using linear regression and epidemiological surveillance findings. RESULTS: Between January 2003 and September the 30th, 2004, 196 inspectors conducted 8562 inspections, collected 5024 water samples and recommended 17 027 corrective actions. In 10 cruise ships used as floating hotels inspectors conducted 10 full inspections, 2 re-inspections, and 27 follow-up inspections. Unsatisfactory inspection results (r = 0.44, p < 0.0001) and positive water quality tests (r = 0.39, p < 0.001) presented an overall decrease trend over time. In August, 2003, an outbreak of salmonellosis was linked to a hotel restaurant which accommodated athletes during a test event. CONCLUSION: Lessons learned for future events include timely implementation and installation of communication processes, and rapid and coordinated response to unsatisfactory inspection results. Routine national programs need to adopt enhanced environmental health surveillance aimed at public health decision-making, but with a different perspective.

Accident Prevention↗
PubMed1996

Comparison of low-volume, Draize and in vitro eye irritation test data. I. Hydroalcoholic formulations.

The first phase in a series of investigations of the relationship between low-volume eye test (LVET) data, Draize eye irritation test data, and comparable data from 25 in vitro assay protocols is presented. These investigations utilize Draize eye test and in vitro assay data generated previously as part of the Cosmetic, Toiletry and Fragrance Association (CTFA) Evaluation of Alternatives Program. LVET data were generated de novo using the same 10 representative hydroalcoholic personal-care formulations. The linear correlation between maximum average score (MAS) as determined by the Draize test and the LVET (LVET-MAS) was 0.93. Comparison of in vitro assay performance with that of the LVET was determined by statistical analysis of the relationship between LVET-MAS and in vitro endpoint. As in the CTFA program, regression modelling is the primary means of enabling such a comparison. The objective is to predict LVET-MAS for a given test material (and to place upper and lower prediction interval bounds in the range in which the LVET-MAS is anticipated to fall with high probability) conditional on observing an in vitro assay score for that material. The degree of confidence in prediction is quantified in terms of the relative widths of prediction intervals constructed about the fitted regression curves. Four assays [EYTEX MPA (membrane partition assay), HET-CAM (hen's egg test-chorioallantoic membrane HET-CAM) I, neutral red release and HET-CAM II] were shown to have the greatest agreement with the LVET. These assays were also among those with low discordance rates relative to the Draize test. Prediction of LVET-MAS values from experimentally determined in vitro scores was more accurate for hydroalcoholic formulations with lower rather than higher irritancy potential.

Animal Testing Alternatives↗
PubMed2006

Operon prediction using both genome-specific and general genomic information.

We have carried out a systematic analysis of the contribution of a set of selected features that include three new features to the accuracy of operon prediction. Our analyses have led to a number of new insights about operon prediction, including that (i) different features have different levels of discerning power when used on adjacent gene pairs with different ranges of intergenic distance, (ii) certain features are universally useful for operon prediction while others are more genome-specific and (iii) the prediction reliability of operons is dependent on intergenic distances. Based on these new insights, our newly developed operon-prediction program achieves more accurate operon prediction than the previous ones, and it uses features that are most readily available from genomic sequences. Our prediction results indicate that our (non-linear) decision tree-based classifier can predict operons in a prokaryotic genome very accurately when a substantial number of operons in the genome are already known. For example, the prediction accuracy of our program can reach 90.2 and 93.7% on Bacillus subtilis and Escherichia coli genomes, respectively. When no such information is available, our (linear) logistic function-based classifier can reach the prediction accuracy at 84.6 and 83.3% for E.coli and B.subtilis, respectively.

Bacillus subtilis↗
PubMed1984

Programming time as a function of number of movement parts and changes in movement direction.

The question of whether changes seen in simple reaction time (SRT) as a function of response complexity (i.e., number of movement parts) should be considered as differences in the time needed to centrally program a motor response was addressed. Using a large-scale tapping response, 14 subjects contacted from one to five targets positioned in a straight line, while a second group of 14 subjects executed 90 degrees changes in direction in striking the targets. Results revealed that mean SRT and mean premotor time increased linearly as the number of movement parts increased, regardless of whether changes in movement direction had to be programmed, with the greatest increase occurring between one-, and two-part responses. Increases in motor time were not sufficient to account for the sizeable SRT effect. These findings support the position of increased central programming time for more complex responses, and also help establish some of the boundaries of the complexity effect.

Journal Article↗

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