Is cannabis a gateway drug? Testing hypotheses about the relationship between cannabis use and the use of other illicit drugs

We outline and evaluate competing explanations of three relationships that have consistently been found between cannabis use and the use of other illicit drugs, namely, ( 1) that cannabis use typically precedes the use of other illicit drugs; and that ( 2) the earlier cannabis is used, and ( 3) the more regularly it is used, the more likely a young person is to use other illicit drugs. We consider three major competing explanations of these patterns: ( 1) that the relationship is due to the fact that there is a shared illicit market for cannabis and other drugs which makes it more likely that other illicit drugs will be used if cannabis is used; ( 2) that they are explained by the characteristics of those who use cannabis; and ( 3) that they reflect a causal relationship in which the pharmacological effects of cannabis on brain function increase the likelihood of using other illicit drugs. These explanations are evaluated in the light of evidence from longitudinal epidemiological studies, simulation studies, discordant twin studies and animal studies. The available evidence indicates that the association reflects in part but is not wholly explained by: ( 1) the selective recruitment to heavy cannabis use of persons with pre-existing traits ( that may be in part genetic) that predispose to the use of a variety of different drugs; ( 2) the affiliation of cannabis users with drug using peers in settings that provide more opportunities to use other illicit drugs at an earlier age; ( 3) supported by socialisation into an illicit drug subculture with favourable attitudes towards the use of other illicit drugs. Animal studies have raised the possibility that regular cannabis use may have pharmacological effects on brain function that increase the likelihood of using other drugs. We conclude with suggestions for the type of research studies that will enable a decision to be made about the relative contributions that social context, individual characteristics, and drug effects make to the relationship between cannabis use and the use of other drugs.

The effects of negative affectivity on self-reported activity limitations in stroke patients:testing the symptom perception, disability and psychosomatic hypotheses

This study investigated whether Negative Affectivity (NA) causes bias in self-report measures of activity limitations or whether NA has a real, non-artifactual association with activity limitations. The Symptom Perception Hypothesis (NA negatively biases self-reporting), Disability Hypothesis (activity limitations cause NA) and Psychosomatic Hypothesis (NA causes activity limitations) were examined longitudinally using both self-report and objective activity limitations measures. Participants were 101 stroke patients and their caregivers interviewed within two weeks of discharge, six weeks later and six months post-discharge. NA and self-report, proxy-report and observed performance activity (walking) limitations were assessed at each interview. NA was associated with activity limitations across measures. Both the Disability and Psychosomatic Hypotheses were supported: initial NA predicted objective activity limitations at six weeks but, additionally, activity limitations at six weeks predicted NA at six months. These results suggest that NA both affects and is affected by activity limitations and does not simply influence reporting.

An autoregressive conditional filtering process to remove intraday seasonal volatility and its application to testing the noisy rational expectations model

We develop a new autoregressive conditional process to capture both the changes and the persistency of the intraday seasonal (U-shape) pattern of volatility in essay 1. Unlike other procedures, this approach allows for the intraday volatility pattern to change over time without the filtering process injecting a spurious pattern of noise into the filtered series. We show that prior deterministic filtering procedures are special cases of the autoregressive conditional filtering process presented here. Lagrange multiplier tests prove that the stochastic seasonal variance component is statistically significant. Specification tests using the correlogram and cross-spectral analyses prove the reliability of the autoregressive conditional filtering process. In essay 2 we develop a new methodology to decompose return variance in order to examine the informativeness embedded in the return series. The variance is decomposed into the information arrival component and the noise factor component. This decomposition methodology differs from previous studies in that both the informational variance and the noise variance are time-varying. Furthermore, the covariance of the informational component and the noisy component is no longer restricted to be zero. The resultant measure of price informativeness is defined as the informational variance divided by the total variance of the returns. The noisy rational expectations model predicts that uninformed traders react to price changes more than informed traders, since uninformed traders cannot distinguish between price changes caused by information arrivals and price changes caused by noise. This hypothesis is tested in essay 3 using intraday data with the intraday seasonal volatility component removed, as based on the procedure in the first essay. The resultant seasonally adjusted variance series is decomposed into components caused by unexpected information arrivals and by noise in order to examine informativeness.

Tests of the Intersensory Redundancy Hypothesis across early postnatal development

The Intersensory Redundancy Hypothesis (IRH; Bahrick & Lickliter, 2000, 2002, 2012) predicts that early in development information presented to a single sense modality will selectively recruit attention to modality-specific properties of stimulation and facilitate learning of those properties at the expense of amodal properties (unimodal facilitation). Vaillant (2010) demonstrated that bobwhite quail chicks prenatally exposed to a maternal call alone (unimodal stimulation) are able to detect a pitch change, a modality-specific property, in subsequent postnatal testing between the familiarized call and the same call with altered pitch. In contrast, chicks prenatally exposed to a maternal call paired with a temporally synchronous light (redundant audiovisual stimulation) were unable to detect a pitch change. According to the IRH (Bahrick & Lickliter, 2012), as development proceeds and the individual's perceptual abilities increase, the individual should detect modality-specific properties in both nonredundant, unimodal and redundant, bimodal conditions. However, when the perceiver is presented with a difficult task, relative to their level of expertise, unimodal facilitation should become evident. The first experiment of the present study exposed bobwhite quail chicks 24 hr after hatching to unimodal auditory, nonredundant audiovisual, or redundant audiovisual presentations of a maternal call for 10min/hr for 24 hours. All chicks were subsequently tested 24 hr after the completion of the stimulation (72 hr following hatching) between the familiarized maternal call and the same call with altered pitch. Chicks from all experimental groups (unimodal, nonredundant audiovisual, and redundant audiovisual exposure) significantly preferred the familiarized call over the pitch-modified call. The second experiment exposed chicks to the same exposure conditions, but created a more difficult task by narrowing the pitch range between the two maternal calls with which they were tested. Chicks in the unimodal and nonredundant audiovisual conditions demonstrated detection of the pitch change, whereas the redundant audiovisual exposure group did not show detection of the pitch change, providing evidence of unimodal facilitation. These results are consistent with predictions of the IRH and provide further support for the effects of unimodal facilitation and the role of task difficulty across early development.

An Autoregressive Conditional Filtering Process to remove Intraday Seasonal Volatility and its Application to Testing the Noisy Rational Expectations Model

We develop a new autoregressive conditional process to capture both the changes and the persistency of the intraday seasonal (U-shape) pattern of volatility in essay 1. Unlike other procedures, this approach allows for the intraday volatility pattern to change over time without the filtering process injecting a spurious pattern of noise into the filtered series. We show that prior deterministic filtering procedures are special cases of the autoregressive conditional filtering process presented here. Lagrange multiplier tests prove that the stochastic seasonal variance component is statistically significant. Specification tests using the correlogram and cross-spectral analyses prove the reliability of the autoregressive conditional filtering process. In essay 2 we develop a new methodology to decompose return variance in order to examine the informativeness embedded in the return series. The variance is decomposed into the information arrival component and the noise factor component. This decomposition methodology differs from previous studies in that both the informational variance and the noise variance are time-varying. Furthermore, the covariance of the informational component and the noisy component is no longer restricted to be zero. The resultant measure of price informativeness is defined as the informational variance divided by the total variance of the returns. The noisy rational expectations model predicts that uninformed traders react to price changes more than informed traders, since uninformed traders cannot distinguish between price changes caused by information arrivals and price changes caused by noise. This hypothesis is tested in essay 3 using intraday data with the intraday seasonal volatility component removed, as based on the procedure in the first essay. The resultant seasonally adjusted variance series is decomposed into components caused by unexpected information arrivals and by noise in order to examine informativeness.

An R-package for the Estimation and Testing of Multiple Covariates and Biomarker Interactions for Survival Data Based on Local Partial Likelihood

When we study the variables that a ffect survival time, we usually estimate their eff ects by the Cox regression model. In biomedical research, e ffects of the covariates are often modi ed by a biomarker variable. This leads to covariates-biomarker interactions. Here biomarker is an objective measurement of the patient characteristics at baseline. Liu et al. (2015) has built up a local partial likelihood bootstrap model to estimate and test this interaction e ffect of covariates and biomarker, but the R code developed by Liu et al. (2015) can only handle one variable and one interaction term and can not t the model with adjustment to nuisance variables. In this project, we expand the model to allow adjustment to nuisance variables, expand the R code to take any chosen interaction terms, and we set up many parameters for users to customize their research. We also build up an R package called "lplb" to integrate the complex computations into a simple interface. We conduct numerical simulation to show that the new method has excellent fi nite sample properties under both the null and alternative hypothesis. We also applied the method to analyze data from a prostate cancer clinical trial with acid phosphatase (AP) biomarker.

Defensive role of allelopathic secondary compounds in plants I: testing two independent general hypotheses

This study tests two general and independent hypotheses with the basic assumption that phytoactive secondary compounds produced by plants evolved primarily as plant defences against competitor plant species. The first hypothesis is that the production and main way of release of phytoactive compounds reflect an adaptive response to climatic conditions. Thus, higher phytoactivity by volatile compounds prevails in plants of hot, dry environments, whereas higher phytoactivity by water-soluble compounds is preponderant in plants from wetter environments. The second hypothesis is that synergy between plant phytoactive compounds is widespread, due to the resulting higher energy efficiency and economy of resources. The first hypothesis was tested on germination and early growth of cucumber treated with either water extracts or volatiles from leaves or vegetative shoot tops of four Mediterranean-type shrubs. The second hypothesis was tested on germination of subterranean clover treated with either water extracts of leaves or vegetative shoot tops of one tree and of three Mediterranean-type shrubs or with each of the three fractions obtained from water extracts. Our data do not support either hypotheses. We found no evidence for higher phytoactivity in volatile compounds released by plants that thrive in hot, dry Mediterranean-type environments. We also found no evidence for the predominance of synergy among the constituents of fractions. To the contrary, we found either antagonism or no interaction of effects among allelopathic compounds.

Micromorphological and hardness analyses of human and bovine sclerotic dentin: a comparative study

The purpose of this study was to test the hypothesis that both human and bovine sclerotic dentin have similar hardness properties, in addition to similar micromorphological characteristics. Sixteen teeth (8 human and 8 bovine) exhibiting exposed dentin in the incisal edge and showing characteristics typical of sclerosis were used. Vickers surface microhardness testing was conducted. Three areas of the dentin surface of each specimen were selected. All teeth were processed for scanning electron microscopy in order to estimate the amount (in percentage) of solid dentin on the sclerotic dentin surface. The data were compared by Student's t test (α = 0.05). The micromorphological and microhardness data were compared by Pearson's linear correlation test (α = 0.05). The mean percentages of solid dentin of human and bovine sclerotic dentin were similar (human 90.71 ± 0.83 and bovine 89.08 ± 0.81, p = 0.18). The mean microhardness value (VHN) of human sclerotic dentin was significantly higher than that of bovine sclerotic dentin (human 45.26 ± 2.92 and bovine 29.93 ± 3.83, p = 0.006). No correlation was found between the microhardness values and the amount of solid dentin in the sclerotic dentin, irrespective of the species considered (human R² = 0.0240, p = 0.714; bovine R² = 0.0017, p = 0.923; and combined R² = 0.038, p = 0.46). We concluded that although both bovine and human sclerotic dentin present a similar amount of solid tissue, human sclerotic dentin presents higher microhardness than bovine sclerotic dentin.

Flexural and diametral tensile strength of composite resins

This study evaluated the flexural strength (sf) and the diametral tensile strength (st) of light-cured composite resins, testing the hypothesis that there is a positive relation between these properties. Twenty specimens were fabricated for each material (Filtek Z250- 3M-Espe; AM- Amelogen, Ultradent; VE- Vit-l-escence, Ultradent; EX- Esthet-X, Dentsply/Caulk), following ISO 4049 and ANSI/ADA 27 specifications and the manufacturers’ instructions. For the st test, cylindrical shaped (4 mm x 6 mm) specimens (n = 10) were placed with their long axes perpendicular to the applied compressive load at a crosshead speed of 1.0 mm/min. The sf was measured using the 3-point bending test, in which bar shaped specimens (n = 10) were tested at a crosshead speed of 0.5 mm/min. Both tests were performed in a universal testing machine (EMIC 2000) recording the fracture load (N). Strength values (MPa) were calculated and statistically analyzed by ANOVA and Tukey (a = 0.05). The mean and standard deviation values (MPa) were Z250-45.06 ± 5.7; AM-35.61 ± 5.4; VE-34.45 ± 7.8; and EX-42.87 ± 6.6 for st; and Z250-126.52 ± 3.3; AM-87.75 ± 3.8; VE-104.66 ± 4.4; and EX-119.48 ± 2.1 for sf. EX and Z250 showed higher st and sf values than the other materials evaluated (p < 0.05), which followed a decreasing trend of mean values. The results confirmed the study hypothesis, showing a positive relation between the material properties examined.

Array-CGH testing in spontaneous abortions with normal karyotypes

In about 50% of first trimester spontaneous abortion the cause remains undetermined after standard cytogenetic investigation. We evaluated the usefulness of array-CGH in diagnosing chromosome abnormalities in products of conception from first trimester spontaneous abortions. Cell culture was carried out in short- and long-term cultures of 54 specimens and cytogenetic analysis was successful in 49 of them. Cytogenetic abnormalities (numerical and structural) were detected in 22 (44.89%) specimens. Subsequent, array-CGH based on large insert clones spaced at ~1 Mb intervals over the whole genome was used in 17 cases with normal G-banding karyotype. This revealed chromosome aneuplodies in three additional cases, giving a final total of 51% cases in which an abnormal karyotype was detected. In keeping with other recently published works, this study shows that array-CGH detects abnormalities in a further ~10% of spontaneous abortion specimens considered to be normal using standard cytogenetic methods. As such, array-CGH technique may present a suitable complementary test to cytogenetic analysis in cases with a normal karyotype.

A new genus and two new species of Stevardiinae (Characiformes: Characidae) with a hypothesis on their relationships based on morphological and histological data

Lepidocharax, new genus, and Lepidocharax diamantina and L. burnsi new species from eastern Brazil are described herein. Lepidocharax is considered a monophyletic genus of the Stevardiinae and can be distinguished from the other members of this subfamily except Planaltina, Pseudocorynopoma, and Xenurobrycon by having the dorsal-fin origin vertically aligned with the anal-fin origin, vs. dorsal fin origin anterior or posterior to anal-fin origin. Additionally the new genus can be distinguished from those three genera by not having the scales extending over the ventral caudal-fin lobe modified to form the dorsal border of the pheromone pouch organ or to represent a pouch scale in sexually mature males. In this paper, we describe these two recently discovered species and the ultrastructure of their spermatozoa.

Estimating HIV-1 incidence using the serologic testing algorithm for recent HIV infections at HIV counseling and testing centers in the city of São Paulo, Brazil

The network of HIV counseling and testing centers in São Paulo, Brazil is a major source of data used to build epidemiological profiles of the client population. We examined HIV-1 incidence from November 2000 to April 2001, comparing epidemiological and socio-behavioral data of recently-infected individuals with those with long-standing infection. A less sensitive ELISA was employed to identify recent infection. The overall incidence of HIV-1 infection was 0.53/100/year (95% CI: 0.31-0.85/100/year): 0.77/100/year for males (95% CI: 0.42-1.27/100/year) and 0.22/100/ year (95% CI: 0.05-0.59/100/year) for females. Overall HIV-1 prevalence was 3.2% (95% CI: 2.8-3.7%), being 4.0% among males (95% CI: 3.3-4.7%) and 2.1% among females (95% CI: 1.6-2.8%). Recent infections accounted for 15% of the total (95% CI: 10.2-20.8%). Recent infection correlated with being younger and male (p = 0.019). Therefore, recent infection was more common among younger males and older females.

Development and mechanical testing of a short intramedullary nail for fixation of femoral rotational osteotomy in cerebral palsy patients

Background: Rotational osteotomy is frequently indicated to correct excessive femoral anteversion in cerebral palsy patients. Angled blade plate is the standard fixation device used when performed in the proximal femur, but extensile exposure is required for plate accommodation. The authors developed a short locked intramedullary nail to be applied percutaneously in the fixation of femoral rotational osteotomies in children with cerebral palsy and evaluated its mechanical properties. Methods: The study was divided into three stages. In the first part, a prototype was designed and made based on radiographic measurements of the femoral medullary canal of ten-year-old patients. In the second, synthetic femoral models based on rapid-prototyping of 3D reconstructed images of patients with cerebral palsy were obtained and were employed to adjust the nail prototype to the morphological changes observed in this disease. In the third, rotational osteotomies were simulated using synthetic femoral models stabilized by the nail and by the AO-ASIF fixed-angle blade plate. Mechanical testing was done comparing both devices in bending-compression and torsion. Results: The authors observed proper adaptation of the nail to normal and morphologically altered femoral models, and during the simulated osteotomies. Stiffness in bending-compression was significantly higher in the group fixed by the plate (388.97 +/- 57.25 N/mm) than in that fixed by the nail (268.26 +/- 38.51 N/mm) as torsional relative stiffness was significantly higher in the group fixed by the plate (1.07 +/- 0.36 Nm/degrees) than by the nail (0.35 +/- 0.13 Nm/degrees). Conclusions: Although the device presented adequate design and dimension to fit into the pediatric femur, mechanical tests indicated that the nail was less stable than the blade plate in bending-compression and torsion. This may be a beneficial property, and it can be attributed to the more flexible fixation found in intramedullary devices.

TESTING THE DISTANCE-DUALITY RELATION WITH GALAXY CLUSTERS AND TYPE Ia SUPERNOVAE

In this Letter, we propose a new and model-independent cosmological test for the distance-duality (DD) relation, eta = D(L)(z)(1 + z)(-2)/D(A)(z) = 1, where D(L) and D(A) are, respectively, the luminosity and angular diameter distances. For D(L) we consider two sub-samples of Type Ia supernovae (SNe Ia) taken from Constitution data whereas D(A) distances are provided by two samples of galaxy clusters compiled by De Filippis et al. and Bonamente et al. by combining Sunyaev-Zeldovich effect and X-ray surface brightness. The SNe Ia redshifts of each sub-sample were carefully chosen to coincide with the ones of the associated galaxy cluster sample (Delta z < 0.005), thereby allowing a direct test of the DD relation. Since for very low redshifts, D(A)(z) approximate to D(L)(z), we have tested the DD relation by assuming that. is a function of the redshift parameterized by two different expressions: eta(z) = 1 + eta(0)z and eta(z) = 1 +eta(0)z/(1 + z), where eta(0) is a constant parameter quantifying a possible departure from the strict validity of the reciprocity relation (eta(0) = 0). In the best scenario (linear parameterization), we obtain eta(0) = -0.28(-0.44)(+0.44) (2 sigma, statistical + systematic errors) for the De Filippis et al. sample (elliptical geometry), a result only marginally compatible with the DD relation. However, for the Bonamente et al. sample (spherical geometry) the constraint is eta(0) = -0.42(-0.34)(+0.34) (3 sigma, statistical + systematic errors), which is clearly incompatible with the duality-distance relation.

The B0.5IVe CoRoT target HD 49330 I. Photometric analysis from CoRoT data

Context. Be stars undergo outbursts producing a circumstellar disk from the ejected material. The beating of non-radial pulsations has been put forward as a possible mechanism of ejection. Aims. We analyze the pulsational behavior of the early B0.5IVe star HD 49330 observed during the first CoRoT long run towards the Galactical anticenter (LRA1). This Be star is located close to the lower edge of the beta Cephei instability strip in the HR diagram and showed a 0.03 mag outburst during the CoRoT observations. It is thus an ideal case for testing the aforementioned hypothesis. Methods. We analyze the CoRoT light curve of HD 49330 using Fourier methods and non-linear least square fitting. Results. In this star, we find pulsation modes typical of beta Cep stars (p modes) and SPB stars (g modes) with amplitude variations along the run directly correlated with the outburst. These results provide new clues about the origin of the Be phenomenon as well as strong constraints on the seismic modelling of Be stars.