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At least 721 records · Page 40Linked to original sources

Oscillating blood droplets--implications for crime scene reconstruction.

Traditionally, the analysis of blood spatter on surfaces in the reconstruction of crime scenes relies on the assumption that blood droplets are spherical when they strike the surface. This paper explores the effects of their shape on the reconstruction of trajectories from their impact pattern, and reports a theoretical analysis of the lifetime of droplet oscillations. Oscillations damp quickly in blood droplets due to the viscosity. The analysis provides ranges of velocities and distances from the point of droplet projection within which it is unreliable to assume the droplets are spherical when they stain a surface. Non-spherical droplet stains predict incorrect positioning of the droplet projection point. Experimental data are presented to show that the estimates apply in practice.

Animals↗

Formation of the folding nucleus of an SH3 domain investigated by loosely coupled molecular dynamics simulations.

The experimentally well-established folding mechanism of the src-SH3 domain, and in particular the phi-value analysis of its transition state, represents a sort of testing table for computational investigations of protein folding. Here, parallel molecular dynamics simulations of the src-SH3 domain have been performed starting from denatured conformations. By rescuing and restarting only trajectories approaching the folding transition state, an ensemble of conformations was obtained with a completely structured central beta-sheet and a native-like packing of residues Ile-110, Ala-121, and Ile-132. An analysis of the trajectories shows that there are several pathways leading to the formation of the central beta-sheet whereas its two hairpins form in a different but consistent way.

Computer Simulation↗

Biological imaging of heavy charged-particle tracks.

The immunocytochemical response to DNA damage induced by low-energy bismuth and carbon ions was investigated in normal human fibroblasts. Inside the nuclei, the traversing charged particles lead to the accumulation of proteins related to DNA lesions and repair along the ion trajectories. Irradiation under a standard geometric setup with the beam direction perpendicular to the cell monolayer generates spots of these proteins as described previously for MRE11B (hMre11), CDKN1A (p21) and PCNA (Jakob et al., Int. J. Radiat. Biol. 78, 75-88, 2002). Here we present data obtained with a new irradiation geometry characterized by a small angle between the beam direction and the monolayer of cells. This new irradiation geometry leads to the formation of protein aggregates in the shape of streaks stretching over several micrometers in the x/y plane, thus facilitating the analysis of the fluorescence distributions along the particle trajectories. Measurements of fluorescence intensity along the ion tracks in double- and triple-stained samples revealed a strict spatial correlation for the occurrence of CDKN1A and MRE11B clusters. In addition, immunostained gamma-H2AX is used as a marker of double-strand breaks (DSBs) to visualize the localized induction of these lesions along the particle paths. A clear coincidence of CDKN1A and gamma-H2AX signals within the ion-induced streaks is observed. Also for PCNA, which mainly associates with lesions processed by excision repair, a strict colocalization with the MRE11B aggregations was found along the ion trajectories, despite the higher estimated yield of this type of lesions compared to DSBs. Strikingly similar patterns of protein clusters are generated not only for the various proteins studied but also using different ion species from carbon to bismuth, covering LET values ranging from about 300 to 13600 keV/microm and producing estimated DSB densities differing by a factor around 45. The patterns of protein clustering along the very heavy-ion trajectories appear far more heterogeneous than expected based on idealized DSB distributions arising from model calculations. The results suggest that additional factors like compaction or confined movement of chromatin are responsible for the observed clustering of proteins.

Bismuth↗

Generalized sensitivity functions in physiological system identification.

Parameters of physiological models are commonly associated in an input-output experiment with a specific pattern of the system response. This association is often made on an intuitive basis by traditional sensitivity analysis, i.e., by inspecting the variations of model output trajectories with respect to parameter variations. However, this approach provides limited information since, for instance, it ignores correlation among parameters. The aim of this study is to propose a new set of sensitivity functions, called the generalized sensitivity functions (GSF), for the analysis of input-output identification experiments. GSF are based on information theoretical criteria and provide, as compared to traditional sensitivity analysis, a more accurate picture on the information content of measured outputs on individual model parameters at different times. Case studies are presented on an input-output model and on two structural circulatory and respiratory models. GSF allow the definition of relevant time intervals for the identification of specific parameters and improve the understanding of the role played by specific model parameters in describing experimental data.

Animals↗

The application of latent curve analysis to testing developmental theories in intervention research.

The effectiveness of a prevention or intervention program has traditionally been assessed using time-specific comparisons of mean levels between the treatment and the control groups. However, many times the behavior targeted by the intervention is naturally developing over time, and the goal of the treatment is to alter this natural or normative developmental trajectory. Examining time-specific mean levels can be both limiting and potentially misleading when the behavior of interest is developing systematically over time. It is argued here that there are both theoretical and statistical advantages associated with recasting intervention treatment effects in terms of normative and altered developmental trajectories. The recently developed technique of latent curve (LC) analysis is reviewed and extended to a true experimental design setting in which subjects are randomly assigned to a treatment intervention or a control condition. LC models are applied to both artificially generated and real intervention data sets to evaluate the efficacy of an intervention program. Not only do the LC models provide a more comprehensive understanding of the treatment and control group developmental processes compared to more traditional fixed-effects models, but LC models have greater statistical power to detect a given treatment effect. Finally, the LC models are modified to allow for the computation of specific power estimates under a variety of conditions and assumptions that can provide much needed information for the planning and design of more powerful but cost-efficient intervention programs for the future.

Case-Control Studies↗

Specificity of practice in a ball interception task.

Learning of an aiming task has been shown to be specific to the sources of afferent information available during practice. However, this has not been the case when a one-hand ball-catching task has been used. The goal of the present study was to determine the cause of these conflicting results. Participants practiced an interception task in either a normal vision condition or a ball-only condition. They were all then transferred to the ball-only condition, using either the same ball trajectories as in acquisition or different ones. Being transferred from a normal vision condition to a ball-only condition resulted in a significant increase in spatial interception errors, thus supporting the specificity of practice hypothesis. Using new ball trajectories in transfer caused a significant increase in error for all participants. The pattern of errors observed when new ball trajectories were used suggests that participants had difficulty correlating information about the location of their arm via proprioception and a combination of retinal and extra-retinal information about the ball trajectory.

Analysis of Variance↗

[A new model for the study of filarial physiopathology: Molinema dessetae in its definitive natural host, Proechimys oris. 1].

The filarial rodent model Molinema dessetae/Proechimys oris, recently adapted in the laboratory allows studies on the host/parasite relationships. Development of filarial worm was described elsewhere, and the model standardized. Biological, parasitological data and antifilarial drug response were determined. Natural models can seldom be used in laboratory; in non natural models many informations on the host-parasite relationships are lost and pathological studies can only be fragmentary and punctual. With inbred Proechimys oris we have the possibility to investigate with a natural filarial model. Three rodent groups have been studied for over a period of one year. The first group comprises eleven parasite free animals; the second one, eight rodents infected once by L3, and the last with eight rodents regularly re-infected during the period of experiment. Several biological parameters were considered: weight, total red and white blood cell counts, haemoglobinemia, mean cell volume, differential leucocyte count, blood urea nitrogen, total serum proteins and electrophoretic pattern, endogenous creatinine clearance, circulating immune complexes. On the whole, more than 19,700 biological data were obtained and several multivariate statistical analysis were necessary for a valid interpretation. The Principal Component Analysis (ACP) shows in each infected rodent distinct trajectories related either with the age of the host or with the filarial infection itself. Three graphic methods were used: individual graphics of each rodent, graphics of each rodent group and, individual and group statistical center of gravity. At the end of the experiments, the rodents were autopsied and a detailed histological study of the whole body was made. Different lesions and stages of inflammatory processes found were analysed and classified as follows: granulomatous nodule with eosinophilic and neutrophilic polymorphs; foreign-body granulomatous nodule; sclerocicatricial nodule; mononucleate cell infiltrate. Secondary pathological alterations, such as irritative lesions and blocage of lymph and blood vessels, were found. A comprehensive study of all our qualitative histological results was performed by a second multivariate analysis: the Correspondence Analysis (AFC). This analysis confirmed the heterogeneity of each Proechimys infected and multi-infected groups. The cross checking between the ACP and AFC allows the separation of two physiopathological filarial groups; the first group (A) is characterized by moderate biological variations and the absence of hepatosplenic lesions.(ABSTRACT TRUNCATED AT 400 WORDS)

Aedes↗

Cross sections and ion kinetic energy analysis for the electron impact ionization of acetylene.

Using a Nier-type electron impact ion source in combination with a double focusing two sector field mass spectrometer, partial cross sections for electron impact ionization of acetylene are measured for electron energies up to 1000 eV. Discrimination factors for ions are determined using the deflection field method in combination with a three-dimensional ion trajectory simulation of ions produced in the ion source. Analysis of the ion yield curves obtained by scanning the deflectors allows the assignment of ions with the same mass-to-charge ratio to specific production channels on the basis of their different kinetic energy distributions. This analysis also allows to determine, besides kinetic energy distributions of fragment ions, partial cross sections differential in kinetic energy. Moreover a charge separation reaction, the Coulomb explosion of the doubly charged parent ions C2H2++ into the fragment ions C2H+ and H+, is investigated and its mean kinetic energy release (KER=3.88 eV) is deduced.

Journal Article↗

Can principal components yield a dimension reduced description of protein dynamics on long time scales?

The suitability of principal component analysis (PCA) to yield slow collective coordinates for use within a dimension reduced description of conformational motions in proteins is evaluated. Two proteins are considered, T4 lysozyme and crambin. We present a quantitative evaluation of the convergence of conformational coordinates obtained with principal component analysis. Detailed analyses of (>200 ns) molecular dynamics trajectories and crystallographic data suggests that simulations of a few nanoseconds should generally provide a stable and statistically reliable definition of the essential and near constraints subspaces. Moreover, a systematic assessment of the density of states of the dynamics of all principal components showed that for an optimal separation of time scales it is crucial to include also side chain atoms in the PCA.

Algorithms↗

Trajectory tracking of piezoelectric positioning stages using a dynamic sliding-mode control.

Trajectory tracking performance of a piezoelectric positioning stage almost depends on whether the tracking controller can effectively compensate the inherent hysteresis phenomenon. In this paper, a dynamic sliding-mode control (DSMC) with backstepping is proposed for the trajectory tracking of the piezoelectric positioning stage, which is suitable for a component of scanning microscopes. An equivalent model developed from a linear motion dynamics with addition of the hysteresis nonlinearity and strain-dependent function first is proposed to approximately represent the dynamics of motion of a one-dimensional piezoelectric positioning stage. Then, based on the equivalent model, the DSMC with an asymptotical sliding surface is proposed for the trajectory tracking control of the piezoelectric positioning stage. Moreover, the analysis of stability can be completed by mathematics, and the convergence rate of the tracking error can be governed by the choice of the control parameter values. Using the DSMC to trajectory tracking control, the piezoelectric positioning stage becomes more suitable for practical applications, especially with the need of various trajectories tracking in microscopy. To validate the proposed control scheme, a computer-based controller and a piezoelectric positioning stage with a capacitive displacement sensor are implemented. Experimental results illustrate the feasibility of the proposed controller for trajectory tracking applications.

Journal Article↗

[Application and evaluation of the VICON system in gait analysis].

By employing the VICON system, segment angular displacement, velocity and acceleration of the lower limbs were achieved from an Above-Knee (A/K) Amputee using a constant friction prosthesis during the swing phase of the gait cycle. By applying computer for data analysis and inputing anthropometric data of the (A/K) Amputee, kinematic trajectory and a stick diagram of lower limbs were obtained. The data were then compared with those obtained from normal subjects. The results showed that the VICON system can provide quantitative analysis of several important parameters in the gait cycle and that it is very helpful in the evaluation and rehabilitation training of abnormal gait.

Adult↗

Comparing trajectories of cognitive functioning in treatment-resistant and non-resistant depression: a multicentre linear mixed-effects analysis.

BACKGROUND: Impaired cognitive functioning is a severe symptom in major depressive disorder (MDD). Recent evidence suggests it may be a central characteristic in its treatment resistant form (TRD), potentially constituting a clinical marker for treatment resistance and a target amenable to intervention. To date, cognitive functioning in TRD remains poorly understood and longitudinal investigations are scarce. METHODS: This observational prospective cohort study, including 320 patients diagnosed with MDD from the multicentre PROMPT study, examined differences in cognitive functioning between 118 TRD and 202 non-TRD patients over a period of twelve weeks in a real-world setting, using linear mixed modelling. Patients that failed to respond to at least two prior antidepressants trials at baseline were classified as TRD. RESULTS: TRD patients showed significantly poorer baseline performances than non-TRD patients in attention/processing speed (β = -0.45; 95%CI[-0.70, -0.19]; FDR-p = 0.003) and verbal memory (β = -0.45; 95%CI[-0.72, -0.18]; FDR-p = 0.003). Significant time × group interactions were observed in motor speed and verbal fluency tasks. Post-hoc-analyses revealed stagnation in TRD patients and significant improvement in non-TRD patients. Across all other tasks improvement was observed in both groups, and random effects showed large heterogeneity between patients, indicating notable individual differences in cognitive performances. CONCLUSIONS: The results suggest distinct recovery patters between non-TRD and TRD patients, and diminished functioning in TRD patients at the domain level. However, intact and diminished performances likely occur in both groups, warranting further investigation of cognitive heterogeneity. These short-term findings highlight the need for more comprehensive longitudinal research on cognition in TRD.

Humans↗

Hamming distance geometry of a protein conformational space: application to the clustering of a 4-ns molecular dynamics trajectory of the HIV-1 integrase catalytic core.

Protein structures can be encoded into binary sequences (Gabarro-Arpa et al., Comput Chem 2000;24:693-698) these are used to define a Hamming distance in conformational space: the distance between two different molecular conformations is the number of different bits in their sequences. Each bit in the sequence arises from a partition of conformational space in two halves. Thus, the information encoded in the binary sequences is also used to characterize the regions of conformational space visited by the system. We apply this distance and their associated geometric structures to the clustering and analysis of conformations sampled during a 4-ns molecular dynamics simulation of the HIV-1 integrase catalytic core. The cluster analysis of the simulation shows a division of the trajectory into two segments of 2.6 and 1.4 ns length, which are qualitatively different: the data points to the fact that equilibration is only reached at the end of the first segment. The Hamming distance is compared also to the r.m.s. deviation measure. The analysis of the cases studied so far shows that under the same conditions the two measures behave quite differently, and that the Hamming distance appears to be more robust than the r.m.s. deviation.

Algorithms↗

Quantification of left ventricular modification in weightlessness conditions from the spatio-temporal analysis of 2D echocardiographic images.

Two-dimensional echocardiography (2DE) performed during flights with a parabolic trajectory to simulate weightlessness provides a unique means to study left ventricular (LV) modifications to prevent post-flight orthostatic intolerance in astronauts. However, conventional analysis of 2DE is based on manual tracings and depends on experience. Accordingly, the aim was objectively to quantify, from 2DE images, the LV modifications related to different gravity levels, by applying a semi-automated level-set border detection technique. The algorithm validation was performed by the comparison of manual tracing results, obtained by two independent observers with 20 images, with the semi-automated measurements. To quantify LV modifications, three consecutive cardiac cycles were analysed for each gravity phase (1 Gz, 1.8 Gz, 0 Gz). The level-set procedure was applied frame-by-frame to detect the LV endocardial contours and obtain LV area against time curves, from which end-diastolic (EDA) and end-systolic (ESA) areas were computed and averaged to compensate for respiratory variations. Linear regression (y = 0.91x + 1.47, r = 0.99, SEE:0.80cm2) and Bland-Altman analysis (bias = -0.58 cm2, 95% limits of agreement= +/- 2.14cm2) showed excellent correlation between the semi-automatic and manually traced values. Inter-observer variability was 5.4%, and the inter-technique variability was 4.1%. Modifications in LV dimensions during the parabola were found: compared with 1 Gz values, EDA and ESA were significantly reduced at 1.8 Gz by 8.8 +/- 5.5% and 12.1 +/- 10.1%, respectively, whereas, during 0 Gz, EDA and ESA increased by 13.3 +/- 7.3% and 11.6 +/- 5.1%, respectively, owing to abrupt changes in venous return. The proposed method resulted in fast and reliable estimations of LV dimensions, whose changes caused by different gravity conditions were objectively quantified.

Adult↗

The long-term outcomes of drug use by methadone maintenance patients.

The aim of the study is to predict long-term outcomes of methadone maintenance (MM), other than continued heroin use, on the basis of drug use occurring early in MM treatment. In previous research, the weak association of initial drug use during MM with measures of rehabilitation status may be due to the use of measures that do not differentiate trends in different types of drug use. In the present study, 222 patients who completed 6 months of MM were assessed at program intake, evaluated for opiates and cocaine in the first 6 months of treatment, and given a follow-up assessment 2 years after treatment entry. The intake status of the patients was assessed using the Addiction Severity Index. Opiate and cocaine use during the first 6 months of MM was assessed by urine toxicology. Outcomes were assessed using a structured interview and official criminal records at follow-up. Cluster analysis of urine toxicologies during treatment identified 3 trajectory classes of MM patients: (A) variably high levels of opiate use, but consistently low cocaine use; (B) low and diminishing opiate and cocaine use; and (C) consistently high cocaine use, with diminishing opiate use. In an 18-month period, after these trends were observed, Cluster C had significantly more criminal charges than Cluster B had (3 times as many), but not significantly more than those of Cluster A. Clusters A and B did not differ significantly in criminal charges. Regardless of cluster membership, subjects with increasing levels of cocaine use in the first 6 months of MM had more hospitalizations for drug and alcohol problems during the follow-up period than subjects without increasing levels of cocaine use had. The results provide evidence of negative sequelae of cocaine use during MM that underscore the importance of clinical efforts to reduce levels of cocaine and other nonopiate drug use by MM patients.

Cluster Analysis↗

Childhood behavioral profiles leading to adolescent conduct disorder: risk trajectories for boys and girls.

OBJECTIVE: To examine the link between childhood behavioral dimensions and adolescent conduct disorder (CD) among a large sample of boys and girls monitored longitudinally. METHOD: Teachers rated the behaviors of 1,569 children every year between kindergarten and grade 6. On the basis of these seven yearly ratings, groups of children who followed distinct trajectories on three behavioral dimensions--hyperactivity, fearfulness, and helpfulness--were identified with a semiparametric statistical analysis. Children were then categorized into one of eight behavioral profiles, representing different combinations of the trajectories. Logistic regressions were used to estimate the relation between the profiles and CD in adolescence (mean = 15.7 years). RESULTS: Boys had a significant risk for CD if they were hyperactive (odds ratio [OR] = 4.27; 95% confidence interval [CI], 1.8-10.16); hyperactive and unhelpful (OR = 2.83; CI, 1.07-7.46); or hyperactive, fearless, and unhelpful (OR = 3.93; CI, 1.27-12.17). Girls had a significant risk for CD only if they were both hyperactive and unhelpful (OR = 4.61; CI, 1.31-16.24). More boys than girls exhibited profiles of risk and met criteria for CD in adolescence. CONCLUSIONS: Sex-specific childhood behavioral profiles that represented risk for CD in adolescence were identified. There were sex differences in the prevalence of the childhood profiles representing risk for CD.

Adolescent↗

Shrinkage estimation for functional principal component scores with application to the population kinetics of plasma folate.

We present the application of a nonparametric method to performing functional principal component analysis for functional curve data that consist of measurements of a random trajectory for a sample of subjects. This design typically consists of an irregular grid of time points on which repeated measurements are taken for a number of subjects. We introduce shrinkage estimates for the functional principal component scores that serve as the random effects in the model. Scatterplot smoothing methods are used to estimate the mean function and covariance surface of this model. We propose improved estimation in the neighborhood of and at the diagonal of the covariance surface, where the measurement errors are reflected. The presence of additive measurement errors motivates shrinkage estimates for the functional principal component scores. Shrinkage estimates are developed through best linear prediction and in a generalized version, aiming at minimizing one-curve-leave-out prediction error. The estimation of individual trajectories combines data obtained from that individual as well as all other individuals. We apply our methods to new data regarding the analysis of the level of 14C-folate in plasma as a function of time since dosing of healthy adults with a small tracer dose of 14C-folic acid. A time transformation was incorporated to handle design irregularity concerning the time points on which the measurements were taken. The proposed methodology, incorporating shrinkage and data-adaptive features, is seen to be well suited for describing population kinetics of 14C-folate-specific activity and random effects, and can also be applied to other functional data analysis problems.

Adult↗

Cost-effectiveness analysis of fecal occult blood screening for colorectal cancer.

OBJECTIVES: Clinical trials have demonstrated that fecal occult blood screening for colorectal cancer can significantly reduce mortality. However, to be deemed a priority from a public health policy perspective, any new program must prove itself to be cost-effective. The objective of this study was to assess the cost-effectiveness of screening for colorectal cancer using a fecal occult blood screening test, the Hemoccult-II, in a cohort of 100,000 asymptomatic individuals 50-74 years of age. METHODS: A decision analysis model using a Markov approach simulates the trajectory of the cohort allocated either to screening or no screening over a 20-year period through several health states. Clinical and economic data used in the model came from the Burgundy trial, French population-based studies, and Registry data. RESULTS: Modeling biennial screening versus the absence of screening over a 20-year period resulted in a 17.7 percent mortality reduction and a discounted incremental cost-effectiveness ratio of 3357 Euro per life-year gained among individuals 50-74 years of age. Sensitivity analyses performed on epidemiological and economic data showed the strong impact on the results of colonoscopy cost, of compliance to screening, and of specificity of the screening test. CONCLUSIONS: Cost-effectiveness estimates and sensitivity analyses suggest that biennial screening for colorectal cancer with fecal occult blood test could be recommended from the age of 50 until 74. Our findings support the attempts to introduce large-scale population screening programs.

Aged↗