Tire traces: discrimination and classification of pyrolysis-GC/MS profiles

Tire traces can be observed on several crime scenes as vehicles are often used by criminals. The tread abrasion on the road, while braking or skidding, leads to the production of small rubber particles which can be collected for comparison purposes. This research focused on the statistical comparison of Py-GC/MS profiles of tire traces and tire treads. The optimisation of the analytical method was carried out using experimental designs. The aim was to determine the best pyrolysis parameters regarding the repeatability of the results. Thus, the pyrolysis factor effect could also be calculated. The pyrolysis temperature was found to be five time more important than time. Finally, a pyrolysis at 650 °C during 15 s was selected. Ten tires of different manufacturers and models were used for this study. Several samples were collected on each tire, and several replicates were carried out to study the variability within each tire (intravariability). More than eighty compounds were integrated for each analysis and the variability study showed that more than 75% presented a relative standard deviation (RSD) below 5% for the ten tires, thus supporting a low intravariability. The variability between the ten tires (intervariability) presented higher values and the ten most variant compounds had a RSD value above 13%, supporting their high potential of discrimination between the tires tested. Principal Component Analysis (PCA) was able to fully discriminate the ten tires with the help of the first three principal components. The ten tires were finally used to perform braking tests on a racetrack with a vehicle equipped with an anti-lock braking system. The resulting tire traces were adequately collected using sheets of white gelatine. As for tires, the intravariability for the traces was found to be lower than the intervariability. Clustering methods were carried out and the Ward's method based on the squared Euclidean distance was able to correctly group all of the tire traces replicates in the same cluster than the replicates of their corresponding tire. Blind tests on traces were performed and were correctly assigned to their tire source. These results support the hypothesis that the tested tires, of different manufacturers and models, can be discriminated by a statistical comparison of their chemical profiles. The traces were found to be not differentiable from their source but differentiable from all the other tires present in the subset. The results are promising and will be extended on a larger sample set.

On-line desorption of dried blood spot: A novel approach for the direct LC/MS analysis of micro-whole blood samples.

The aim of this work is to present a new concept, called on-line desorption of dried blood spots (on-line DBS), allowing the direct analysis of a dried blood spot coupled to liquid chromatography mass spectrometry device (LC/MS). The system is based on an inox cell which can receive a blood sample (10 microL) previously spotted on a filter paper. The cell is then integrated into LC/MS system where the analytes are desorbed out of the paper towards a column switching system ensuring the purification and separation of the compounds before their detection on a single quadrupole MS coupled to atmospheric pressure chemical ionisation (APCI) source. The described procedure implies that no pretreatment is necessary in spite the analysis is based on whole blood sample. To ensure the applicability of the concept, saquinavir, imipramine, and verapamil were chosen. Despite the use of a small sampling volume and a single quadrupole detector, on-line DBS allowed the analyses of these three compounds over their therapeutic concentrations from 50 to 500 ng/mL for imipramine and verapamil and from 100 to 1000 ng/mL for saquinavir. Moreover, the method showed good repeatability with relative standard deviation (RSD) lower than 15% based on two levels of concentration (low and high). Function responses were found to be linear over the therapeutic concentration for each compound and were used to determine the concentrations of real patient samples for saquinavir. Comparison of the founded values with those of a validated method used routinely in a reference laboratory showed a good correlation between the two methods. Moreover, good selectivity was observed ensuring that no endogenous or chemical components interfered with the quantitation of the analytes. This work demonstrates the feasibility and applicability of the on-line DBS procedure for bioanalysis.

Development and validation of a gas chromatography-negative chemical ionization tandem mass spectrometry method for the determination of ethyl glucuronide in hair and its application to forensic toxicology.

Ethyl glucuronide (EtG) is a minor and direct metabolite of ethanol. EtG is incorporated into the growing hair allowing retrospective investigation of chronic alcohol abuse. In this study, we report the development and the validation of a method using gas chromatography-negative chemical ionization tandem mass spectrometry (GC-NCI-MS/MS) for the quantification of EtG in hair. EtG was extracted from about 30 mg of hair by aqueous incubation and purified by solid-phase extraction (SPE) using mixed mode extraction cartridges followed by derivation with perfluoropentanoic anhydride (PFPA). The analysis was performed in the selected reaction monitoring (SRM) mode using the transitions m/z 347-->163 (for the quantification) and m/z 347-->119 (for the identification) for EtG, and m/z 352-->163 for EtG-d(5) used as internal standard. For validation, we prepared quality controls (QC) using hair samples taken post mortem from 2 subjects with a known history of alcoholism. These samples were confirmed by a proficiency test with 7 participating laboratories. The assay linearity of EtG was confirmed over the range from 8.4 to 259.4 pg/mg hair, with a coefficient of determination (r(2)) above 0.999. The limit of detection (LOD) was estimated with 3.0 pg/mg. The lower limit of quantification (LLOQ) of the method was fixed at 8.4 pg/mg. Repeatability and intermediate precision (relative standard deviation, RSD%), tested at 4 QC levels, were less than 13.2%. The analytical method was applied to several hair samples obtained from autopsy cases with a history of alcoholism and/or lesions caused by alcohol. EtG concentrations in hair ranged from 60 to 820 pg/mg hair.

Ocular distribution, spectrum of activity, and in vivo viral neutralization of a fully humanized anti-herpes simplex virus IgG Fab fragment following topical application.

Herpes simplex ocular infection is a major cause of corneal blindness. Local antiviral treatments exist but are associated with corneal toxicity, and resistance has become an issue. We evaluated the biodistribution and efficacy of a humanized anti-herpes simplex virus (anti-HSV) IgG FAb fragment (AC-8; 53 kDa) following repeated topical administration. AC-8 was found in the corneal epithelium, anterior stroma, subepithelial stromal cells, and retinal glial cells, with preferential entry through the ocular limbus. AC-8 was active against 13 different strains of HSV-1, with 50% and 90% mean effective concentrations (MEC(50) and MEC(90), respectively) ranging from 0.03 to 0.13 μg/ml, indicating broad-spectrum activity. The in vivo efficacy of AC-8 was evaluated in a mouse model of herpes-induced ocular disease. Treatment with low-dose AC-8 (1 mg/ml) slightly reduced the ocular disease scores. A greater reduction of the disease scores was observed in the 10-mg/ml AC-8-treated group, but not as much as with trifluridine (TFT). AC-8 treatment reduced viral titers but less than trifluridine. AC-8 did not display any toxicity to the cornea or other structures in the eye. In summary, topical instillation of an anti-HSV FAb can be used on both intact and ulcerated corneas. It is well tolerated and does not alter reepithelialization. Further studies to improve the antiviral effect are needed for AC-8 to be considered for therapeutic use.

Measuring the relative effect of factors affecting species distribution model predictions

1. Species distribution models are increasingly used to address conservation questions, so their predictive capacity requires careful evaluation. Previous studies have shown how individual factors used in model construction can affect prediction. Although some factors probably have negligible effects compared to others, their relative effects are largely unknown. 2. We introduce a general "virtual ecologist" framework to study the relative importance of factors involved in the construction of species distribution models. 3. We illustrate the framework by examining the relative importance of five key factors-a missing covariate, spatial autocorrelation due to a dispersal process in presences/absences, sample size, sampling design and modeling technique-in a real study framework based on plants in a mountain landscape at regional scale, and show that, for the parameter values considered here, most of the variation in prediction accuracy is due to sample size and modeling technique. Contrary to repeatedly reported concerns, spatial autocorrelation has only comparatively small effects. 4. This study shows the importance of using a nested statistical framework to evaluate the relative effects of factors that may affect species distribution models.

Complex syntax in autism spectrum disorders: a study of relative clauses.

BACKGROUND: The few studies that have evaluated syntax in autism spectrum disorder (ASD) have yielded conflicting findings: some suggest that once matched on mental age, ASD and typically developing controls do not differ for grammar, while others report that morphosyntactic deficits are independent of cognitive skills in ASD. There is a need for a better understanding of syntax in ASD and its relation to, or dissociation from, nonverbal abilities. AIMS: Syntax in ASD was assessed by evaluating subject and object relative clause comprehension in adolescents and adults diagnosed with ASD with a performance IQ within the normal range, and with or without a history of language delay. METHODS & PROCEDURES: Twenty-eight participants with ASD (mean age 21.8) and 28 age-matched controls (mean age 22.07) were required to point to a character designated by relative clauses that varied in syntactic complexity. OUTCOMES & RESULTS: Scores indicate that participants with ASD regardless of the language development history perform significantly worse than age-matched controls with object relative clauses. In addition, participants with ASD with a history of language delay (diagnosed with high-functioning autism in the DSM-IV-TR) perform worse on subject relatives than ASD participants without language delay (diagnosed with Asperger syndrome in the DSM-IV-TR), suggesting that these two groups do not have equivalent linguistic abilities. Performance IQ has a positive impact on the success of the task for the population with ASD. CONCLUSIONS & IMPLICATIONS: This study reveals subtle grammatical difficulties remaining in adult individuals with ASD within normal IQ range as compared with age-matched peers. Even in the absence of a history of language delay in childhood, the results suggest that a slight deficit may nevertheless be present and go undetected by standardized language assessments. Both groups with and without language delay have a similar global performance on relative clause comprehension; however, the study also indicates that the participants with reported language delay show more difficulty with subject relatives than the participants without language delay, suggesting the presence of differences in linguistic abilities between these subgroups of ASD.

Nest distribution varies with dispersal method and familiarity-mediated aggression for two sympatric ants

Dispersal mechanisms and competition together play a key role in the spatial distribution of a population. Species that disperse via fission are likely to experience high levels of localized competitive pressure from conspecifics relative to species that disperse in other ways. Although fission dispersal occurs in many species, its ecological and behavioural effects remain unclear. We compared foraging effort, nest spatial distribution and aggression of two sympatric ant species that differ in reproductive dispersal: Streblognathus peetersi, which disperse by group fission, and Plectroctena mandibularis, which disperse by solitary wingless queens. We found that although both species share space and have similar foraging strategies, they differ in nest distribution and aggressive behaviour. The spatial distribution of S. peetersi nests was extremely aggregated, and workers were less aggressive towards conspecifics from nearby nests than towards distant conspecifics and all heterospecific workers. By contrast, the spatial distribution of P. mandibularis nests was overdispersed, and workers were equally aggressive towards conspecific and heterospecific competitors regardless of nest distance. Finally, laboratory experiments showed that familiarity led to the positive relationship between aggression and nest distance in S. peetersi. While unfamiliar individuals were initially aggressive, the level of aggression decreased within 1 h of contact, and continued to decrease over 24 h. Furthermore, individuals from near nests that were not aggressive could be induced to aggression after prolonged isolation. Overall, these results suggest that low aggression mediated by familiarity could provide benefits for a species with fission reproduction and an aggregated spatial distribution.

Differential expression of peroxisome proliferator-activated receptors (PPARs): tissue distribution of PPAR-alpha, -beta, and -gamma in the adult rat.

Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear hormone receptor superfamily that can be activated by various xenobiotics and natural fatty acids. These transcription factors primarily regulate genes involved in lipid metabolism and also play a role in adipocyte differentiation. We present the expression patterns of the PPAR subtypes in the adult rat, determined by in situ hybridization using specific probes for PPAR-alpha, -beta and -gamma, and by immunohistochemistry using a polyclonal antibody that recognizes the three rat PPAR subtypes. In numerous cell types from either ectodermal, mesodermal, or endodermal origin, PPARs are coexpressed, with relative levels varying between them from one cell type to the other. PPAR-alpha is highly expressed in hepatocytes, cardiomyocytes, enterocytes, and the proximal tubule cells of kidney. PPAR-beta is expressed ubiquitously and often at higher levels than PPAR-alpha and -gamma. PPAR-gamma is expressed predominantly in adipose tissue and the immune system. Our results suggest new potential directions to investigate the functions of the different PPAR subtypes.

Does lamotrigine use in pregnancy increase orofacial cleft risk relative to other malformations?

OBJECTIVE: To investigate whether first trimester exposure to lamotrigine (LTG) monotherapy is specifically associated with an increased risk of orofacial clefts (OCs) relative to other malformations, in response to a signal regarding increased OC risk. METHODS: Population-based case-control study with malformed controls based on EUROCAT congenital anomaly registers. The study population covered 3.9 million births from 19 registries 1995-2005. Registrations included congenital anomaly among livebirths, stillbirths, and terminations of pregnancy following prenatal diagnosis. Cases were 5,511 nonsyndromic OC registrations, of whom 4,571 were isolated, 1,969 were cleft palate (CP), and 1,532 were isolated CP. Controls were 80,052 nonchromosomal, non-OC registrations. We compared first trimester LTG and antiepileptic drug (AED) use vs nonepileptic non-AED use, for mono and polytherapy, adjusting for maternal age. An additional exploratory analysis compared the observed and expected distribution of malformation types associated with LTG use. RESULTS: There were 72 LTG exposed (40 mono- and 32 polytherapy) registrations. The ORs for LTG monotherapy vs no AED use were 0.67 (95% CI 0.10-2.34) for OC relative to other malformations, 0.80 (95% CI 0.11-2.85) for isolated OC, 0.79 (95% CI 0.03-4.35) for CP, and 1.01 (95% CI 0.03-5.57) for isolated CP. ORs for any AED use vs no AED use were 1.43 (95% CI 1.03-1.93) for OC, 1.21 (95% CI 0.82-1.72) for isolated OC, 2.37 (95% CI 1.54-3.43) for CP, and 1.86 (95% CI 1.07-2.94) for isolated CP. The distribution of other nonchromosomal malformation types with LTG exposure was similar to non-AED exposed. CONCLUSION: We find no evidence of a specific increased risk of isolated orofacial clefts relative to other malformations due to lamotrigine (LTG) monotherapy. Our study is not designed to assess whether there is a generalized increased risk of malformations with LTG exposure.

A fatal overdose of cocaine associated with coingestion of marijuana, buprenorphine, and fluoxetine. Body fluid and tissue distribution of cocaine and its metabolites determined by hydrophilic interaction chromatography-mass spectrometry(HILIC-MS).

Chromatographic separation of highly polar basic drugs with ideal ionspray mass spectrometry volatile mobile phases is a difficult challenge. A new quantification procedure was developed using hydrophilic interaction chromatography-mass spectrometry with turbo-ionspray ionization in the positive mode. After addition of deuterated internal standards and simple clean-up liquid extraction, the dried extracts were reconstituted in 500 microL pure acetonitrile and 5 microL was directly injected onto a Waters Atlantis HILIC 150- x 2.1-mm, 3-microm column. Chromatographic separations of cocaine, seven metabolites, and anhydroecgonine were obtained by linear gradient-elution with decreasing high concentrations of acetonitrile (80-56% in 18 min). This high proportion of organic solvent makes it easier to be coupled with MS. The eluent was buffered with 2 mM ammonium acetate at pH 4.5. Except for m-hydroxy-benzoylecgonine, the within-day and between-day precisions at 20, 100, and 500 ng/mL were below 7 and 19.1%, respectively. Accuracy was also below +/- 13.5% at all tested concentrations. The limit of quantification was 5 ng/mL (%Diff < 16.1, %RSD < 4.3) and the limit of detection below 0.5 ng/mL. This method was successfully applied to a fatal overdose. In Switzerland, cocaine abuse has dramatically increased in the last few years. A 45-year-old man, a known HIV-positive drug user, was found dead at home. According to relatives, cocaine was self-injected about 10 times during the evening before death. A low amount of cocaine (0.45 mg) was detected in the bloody fluid taken from a syringe discovered near the corpse. Besides injection marks, no significant lesions were detected during the forensic autopsy. Toxicological investigations showed high cocaine concentrations in all body fluids and tissues. The peripheral blood concentrations of cocaine, benzoylecgonine, and methylecgonine were 5.0, 10.4, and 4.1 mg/L, respectively. The brain concentrations of cocaine, benzoylecgonine, and methylecgonine were 21.2, 3.8, and 3.3 mg/kg, respectively. The highest concentrations of norcocaine (about 1 mg/L) were measured in bile and urine. Very high levels of cocaine were determined in hair (160 ng/mg), indicating chronic cocaine use. A low concentration of anhydroecgonine methylester was also found in urine (0.65 mg/L) suggesting recent cocaine inhalation. Therapeutic blood concentrations of fluoxetine (0.15 mg/L) and buprenorphine (0.1 microg/L) were also discovered. A relatively high concentration of Delta(9)-THC was measured both in peripheral blood (8.2 microg/L) and brain cortex (13.5 microg/kg), suggesting that the victim was under the influence of cannabis at the time of death. In addition, fluoxetine might have enhanced the toxic effects of cocaine because of its weak pro-arrhythmogenic properties. Likewise, combination of cannabinoids and cocaine might have increase detrimental cardiovascular effects. Altogether, these results indicate a lethal cocaine overdose with a minor contribution of fluoxetine and cannabinoids.

Comparison of plantar pressure distribution in adolescent runners at low vs. high running velocity.

This study aimed to compare foot plantar pressure distribution while jogging and running in highly trained adolescent runners. Eleven participants performed two constant-velocity running trials either at jogging (11.2 ± 0.9 km/h) or running (17.8 ± 1.4 km/h) pace on a treadmill. Contact area (CA in cm(2)), maximum force (F(max) in N), peak pressure (PP in kPa), contact time (CT in ms), and relative load (force time integral in each individual region divided by the force time integral for the total plantar foot surface, in %) were measured in nine regions of the right foot using an in-shoe plantar pressure device. Under the whole foot, CA, F(max) and PP were lower in jogging than in running (-1.2% [p<0.05], -12.3% [p<0.001] and -15.1% [p<0.01] respectively) whereas CT was higher (+20.1%; p<0.001). Interestingly, we found an increase in relative load under the medial and central forefoot regions while jogging (+6.7% and +3.7%, respectively; [p<0.05]), while the relative load under the lesser toes (-8.4%; p<0.05) was reduced. In order to prevent overloading of the metatarsals in adolescent runners, excessive mileage at jogging pace should be avoided.

Inferring ultraviolet anatomical exposure patterns while distinguishing the relative contribution of radiation components

Exposure to solar ultraviolet (UV) radiation is the main causative factor for skin cancer. UV exposure depends on environmental and individual factors, but individual exposure data remain scarce. While ground UV irradiance is monitored via different techniques, it is difficult to translate such observations into human UV exposure or dose because of confounding factors. A multi-disciplinary collaboration developed a model predicting the dose and distribution of UV exposure on the basis of ground irradiation and morphological data. Standard 3D computer graphics techniques were adapted to develop a simulation tool that estimates solar exposure of a virtual manikin depicted as a triangle mesh surface. The amount of solar energy received by various body locations is computed for direct, diffuse and reflected radiation separately. Dosimetric measurements obtained in field conditions were used to assess the model performance. The model predicted exposure to solar UV adequately with a symmetric mean absolute percentage error of 13% and half of the predictions within 17% range of the measurements. Using this tool, solar UV exposure patterns were investigated with respect to the relative contribution of the direct, diffuse and reflected radiation. Exposure doses for various body parts and exposure scenarios of a standing individual were assessed using erythemally-weighted UV ground irradiance data measured in 2009 at Payerne, Switzerland as input. For most anatomical sites, mean daily doses were high (typically 6.2-14.6 Standard Erythemal Dose, SED) and exceeded recommended exposure values. Direct exposure was important during specific periods (e. g. midday during summer), but contributed moderately to the annual dose, ranging from 15 to 24% for vertical and horizontal body parts, respectively. Diffuse irradiation explained about 80% of the cumulative annual exposure dose.

A new technique to measure micromotion distribution around a cementless femoral stem.

The interfacial micromotion is closely associated to the long-term success of cementless hip prostheses. Various techniques have been proposed to measure them, but only a few number of points over the stem surface can be measured simultaneously. In this paper, we propose a new technique based on micro-Computer Tomography (μCT) to measure locally the relative interfacial micromotions between the metallic stem and the surrounding femoral bone. Tantalum beads were stuck at the stem surface and spread at the endosteal surface. Relative micromotions between the stem and the endosteal bone surfaces were measured at different loading amplitudes. The estimated error was 10μm and the maximal micromotion was 60μm, in the loading direction, at 1400N. This pilot study provided a local measurement of the micromotions in the 3 direction and at 8 locations on the stem surface simultaneously. This technique could be easily extended to higher loads and a much larger number of points, covering the entire stem surface and providing a quasi-continuous distribution of the 3D interfacial micromotions around the stem. The new measurement method would be very useful to compare the induced micromotions of different stem designs and to optimize the primary stability of cementless total hip arthroplasty.

Methods for integration site distribution analyses in animal cell genomes.

The question of where retroviral DNA becomes integrated in chromosomes is important for understanding (i) the mechanisms of viral growth, (ii) devising new anti-retroviral therapy, (iii) understanding how genomes evolve, and (iv) developing safer methods for gene therapy. With the completion of genome sequences for many organisms, it has become possible to study integration targeting by cloning and sequencing large numbers of host-virus DNA junctions, then mapping the host DNA segments back onto the genomic sequence. This allows statistical analysis of the distribution of integration sites relative to the myriad types of genomic features that are also being mapped onto the sequence scaffold. Here we present methods for recovering and analyzing integration site sequences.

High-intensity running and plantar-flexor fatigability and plantar-pressure distribution in adolescent runners.

CONTEXT: Fatigue-induced alterations in foot mechanics may lead to structural overload and injury. OBJECTIVES: To investigate how a high-intensity running exercise to exhaustion modifies ankle plantar-flexor and dorsiflexor strength and fatigability, as well as plantar-pressure distribution in adolescent runners. DESIGN: Controlled laboratory study. SETTING: Academy research laboratory. PATIENTS OR OTHER PARTICIPANTS: Eleven male adolescent distance runners (age = 16.9 ± 2.0 years, height = 170.6 ± 10.9 cm, mass = 54.6 ± 8.6 kg) were tested. INTERVENTION(S): All participants performed an exhausting run on a treadmill. An isokinetic plantar-flexor and dorsiflexor maximal-strength test and a fatigue test were performed before and after the exhausting run. Plantar-pressure distribution was assessed at the beginning and end of the exhausting run. MAIN OUTCOME MEASURE(S): We recorded plantar-flexor and dorsiflexor peak torques and calculated the fatigue index. Plantar-pressure measurements were recorded 1 minute after the start of the run and before exhaustion. Plantar variables (ie, mean area, contact time, mean pressure, relative load) were determined for 9 selected regions. RESULTS: Isokinetic peak torques were similar before and after the run in both muscle groups, whereas the fatigue index increased in plantar flexion (28.1%; P = .01) but not in dorsiflexion. For the whole foot, mean pressure decreased from 1 minute to the end (-3.4%; P = .003); however, mean area (9.5%; P = .005) and relative load (7.2%; P = .009) increased under the medial midfoot, and contact time increased under the central forefoot (8.3%; P = .01) and the lesser toes (8.9%; P = .008). CONCLUSIONS: Fatigue resistance in the plantar flexors declined after a high-intensity running bout performed by adolescent male distance runners. This phenomenon was associated with increased loading under the medial arch in the fatigued state but without any excessive pronation.