Testing hypotheses about the relationship between cannabis use and psychosis

Aim: To model the impact of rising rates of cannabis use on the incidence and prevalence of psychosis under four hypotheses about the relationship between cannabis use and psychosis. Methods: The study modelled the effects on the prevalence of schizophrenia over the lifespan of cannabis in eight birth cohorts: 1940-1944, 1945-1949, 1950-1954, 1955-1959, 1960-1964, 1965-1969, 1970-1974, 1975-1979. It derived predictions as to the number of cases of schizophrenia that would be observed in these birth cohorts, given the following four hypotheses: (1) that there is a causal relationship between cannabis use and schizophrenia; (2) that cannabis use precipitates schizophrenia in vulnerable persons; (3) that cannabis use exacerbates schizophrenia; and (4) that persons with schizophrenia are more liable to become regular cannabis users. Results: There was a steep rise in the prevalence of cannabis use in Australia over the past 30 years and a corresponding decrease in the age of initiation of cannabis use. There was no evidence of a significant increase in the incidence of schizophrenia over the past 30 years. Data on trends the age of onset of schizophrenia did not show a clear pattern. Cannabis use among persons with schizophrenia has consistently been found to be more common than in the general population. Conclusions: Cannabis use does not appear to be causally related to the incidence of schizophrenia, but its use may precipitate disorders in persons who are vulnerable to developing psychosis and worsen the course of the disorder among those who have already developed it. (C) 2003 Elsevier Science Ireland Ltd. All rights reserved.

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.

Life on the ocean wave: Testing some intergroup hypotheses in a naturalistic setting

A survey (N= 352) was conducted among British passengers of a cross-channel ferry. The survey aimed to test hypotheses drawn from Realistic Group Conflict, Social Identity and Contact theories using mainly a correlational design. However, an intervention by members of the outgroup (French fishermen blockading a port) also allowed a quasi-experimental test of the effects of a direct experience of intergroup conflict. Results supported the hypotheses since conflict and national identification were associated with more negative and with less positive attitudes toward the outgroup, while contact had the reverse effects. In addition, the salience of group membership in the contact relationship weakly moderated the effect of contact.

The Swiss heroin trials: testing alternative approaches

Over half a million heroin misusers receive oral methadone maintenance treatment world-wide1 but the maintenance prescription of injectable opioid drugs, like heroin, remains controversial. In 1992 Switzerland began a large scale evaluation of heroin and other injectable opiate prescribing that eventually involved 1035 misusers. 2 3 The results of the evaluation have recently been reported.4 These show that it was feasible to provide heroin by intravenous injection at a clinic, up to three times a day, for seven days a week. This was done while maintaining good drug control, good order, client safety, and staff morale. Patients were stabilised on 500 to 600 mg heroin daily without evidence of increasing tolerance. Retention in treatment was 89% at six months and 69% at 18 months.4 The self reported use of non-prescribed heroin fell signifianctly, but other drug use was minimally affected. The death rate was 1% per year, and there were no deaths from overdose among participants . . . [Full text of this article]

Impact of on-site testing for maternal syphilis on treatment delays, treatment rates, and perinatal mortality in rural South Africa: a randomised controlled trial

Background: Syphilis remains a significant cause of preventable perinatal death in developing countries with many women remaining untested and thus untreated. Syphilis testing in the clinic (on-site testing) may be a useful strategy to overcome this. We studied the impact of on-site syphilis testing on treatment delays and rates, and perinatal mortality. Methods: We conducted a cluster randomised controlled trial among seven pairs of primary healthcare clinics in rural South Africa, comparing on-site testing complemented by laboratory confirmation versus laboratory testing alone. Intervention clinics used the on-site test conducted by primary care nurses, with results and treatment available within an hour. Control clinics sent blood samples to the provincial laboratory, with results returned 2 weeks later. Results: Of 7134 women seeking antenatal care with available test results, 793 (11.1%) tested positive for syphilis. Women at intervention clinics completed treatment 16 days sooner on average (95% confidence interval: 11 to 21), though there was no significant difference in the proportion receiving adequate treatment at intervention (64%) and control (69%) clinics. There was also no significant difference in the proportion experiencing perinatal loss (3.3% v 5.1%; adjusted risk difference: -0.9%; 95% Cl -4.4 to 2.7). Conclusions: Despite reducing treatment delays, the addition of on-site syphilis testing to existing laboratory testing services did not lead to higher treatment rates or reduce perinatal mortality. However on-site testing for syphilis may remain an important option for improving antenatal care in settings where laboratory facilities are not available.

Outcomes of transient evoked otoacoustic emission testing in 6-year-old school children: A comparison with pure tone screening and tympanometry

Objectives: (1) To establish test performance measures for Transient Evoked Otoacoustic Emission testing of 6-year-old children in a school setting; (2) To investigate whether Transient Evoked Otoacoustic Emission testing provides a more accurate and effective alternative to a pure tone screening plus tympanometry protocol. Methods: Pure tone screening, tympanometry and transient evoked otoacoustic emission data were collected from 940 subjects (1880 ears), with a mean age of 6.2 years. Subjects were tested in non-sound-treated rooms within 22 schools. Receiver operating characteristics curves along with specificity, sensitivity, accuracy and efficiency values were determined for a variety of transient evoked otoacoustic emission/pure tone screening/tympanometry comparisons. Results: The Transient Evoked Otoacoustic Emission failure rate for the group was 20.3%. The failure rate for pure tone screening was found to be 8.9%, whilst 18.6% of subjects failed a protocol consisting of combined pure tone screening and tympanometry results. In essence, findings from the comparison of overall Transient Evoked Otoacoustic Emission pass/fail with overall pure tone screening pass/fail suggested that use of a modified Rhode Island Hearing Assessment Project criterion would result in a very high probability that a child with a pass result has normal hearing (true negative). However, the hit rate was only moderate. Selection of a signal-to-noise ratio (SNR) criterion set at greater than or equal to 1 dB appeared to provide the best test performance measures for the range of SNR values investigated. Test performance measures generally declined when tympanometry results were included, with the exception of lower false alarm rates and higher positive predictive values. The exclusion of low frequency data from the Transient Evoked Otoacoustic Emission SNR versus pure tone screening analysis resulted in improved performance measures. Conclusions: The present study poses several implications for the clinical implementation of Transient Evoked Otoacoustic Emission screening for entry level school children. Transient Evoked Otoacoustic Emission pass/fail criteria will require revision. The findings of the current investigation offer support to the possible replacement of pure tone screening with Transient Evoked Otoacoustic Emission testing for 6-year-old children. However, they do not suggest the replacement of the pure tone screening plus tympanometry battery. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.

Power of the joint segregation analysis method for testing mixed major-gene and polygene inheritance models of quantitative traits

Understanding the genetic architecture of quantitative traits can greatly assist the design of strategies for their manipulation in plant-breeding programs. For a number of traits, genetic variation can be the result of segregation of a few major genes and many polygenes (minor genes). The joint segregation analysis (JSA) is a maximum-likelihood approach for fitting segregation models through the simultaneous use of phenotypic information from multiple generations. Our objective in this paper was to use computer simulation to quantify the power of the JSA method for testing the mixed-inheritance model for quantitative traits when it was applied to the six basic generations: both parents (P-1 and P-2), F-1, F-2, and both backcross generations (B-1 and B-2) derived from crossing the F-1 to each parent. A total of 1968 genetic model-experiment scenarios were considered in the simulation study to quantify the power of the method. Factors that interacted to influence the power of the JSA method to correctly detect genetic models were: (1) whether there were one or two major genes in combination with polygenes, (2) the heritability of the major genes and polygenes, (3) the level of dispersion of the major genes and polygenes between the two parents, and (4) the number of individuals examined in each generation (population size). The greatest levels of power were observed for the genetic models defined with simple inheritance; e.g., the power was greater than 90% for the one major gene model, regardless of the population size and major-gene heritability. Lower levels of power were observed for the genetic models with complex inheritance (major genes and polygenes), low heritability, small population sizes and a large dispersion of favourable genes among the two parents; e.g., the power was less than 5% for the two major-gene model with a heritability value of 0.3 and population sizes of 100 individuals. The JSA methodology was then applied to a previously studied sorghum data-set to investigate the genetic control of the putative drought resistance-trait osmotic adjustment in three crosses. The previous study concluded that there were two major genes segregating for osmotic adjustment in the three crosses. Application of the JSA method resulted in a change in the proposed genetic model. The presence of the two major genes was confirmed with the addition of an unspecified number of polygenes.

Drug susceptibility testing of anaerobic protozoa

A simple technique for routine, reproducible global surveillance of the drug susceptibility status of the anaerobic protozoa Trichomonas, Entamoeba, and Giardia is described, Data collected using this technique can be readily compared among different laboratories and with previously reported data. The technique employs a commercially available sachet and bag system to generate a low-oxygen environment and log, drug dilutions in microtiter plates, which can be monitored without aerobic exposure, to assay drug-resistant laboratory lines and clinically resistant isolates. MICs (after 2 days) of 3.2 and 25 muM indicated metronidazole-sensitive and highly clinically resistant isolates of T. vaginalis in anaerobic assays, respectively. The aerobic MICs were 25 and > 200 muM. MICs (1 day) of 12.5 to 25 muM were found for axenic lines of E. histolytica, and MICs for G. duodenalis (3 days) ranged from 6.3 muM for metronidazole-sensitive isolates to 50 muM for laboratory metronidazole-resistant lines. This technique should encourage more extensive monitoring of drug resistance in these organisms.

Immunohistochemistry versus microsatellite instability testing in phenotyping colorectal tumors

Purpose: To compare microsatellite instability (MSI) testing with immunohistochemical (IHC) detection of hMLH1 and hMSH2 in colorectal cancer. Patients and Methods: Colorectal cancers from 1, 144 patients were assessed for DNA mismatch repair deficiency by two methods: MSI testing and IHC detection of hMLH1 and hMSH2 gene products. High-frequency MSI (MSI-H) was defined as more than 30% instability of at least five markers; low-level MSI (MSI-L) was defined as 1% to 29% of loci unstable. Results: Of 1, 144 tumors tested, 818 showed intact expression of hMLH1 and hMSH2. Of these, 680 were microsatellite stable (MSS), 27 were MSI-H, and 111 were MSI-L. In all, 228 tumors showed absence of hMLH1 expression and 98 showed absence of hMSH2 expression: all were MSI-H. Conclusion: IHC in colorectal tumors for protein products hMLH1 and hMSH2 provides a rapid, cost-effective, sensitive (92.3%), and extremely specific (100%) method for screening for DNA mismatch repair defects. The predictive value of normal IHC for an MSS/MSI-L phenotype was 96.7%, and the predictive value of abnormal IHC was 100% for an MSI-H phenotype. Testing strategies must take into account acceptability of missing some cases of MSI-H tumors if only IHC is performed. (C) 2002 by American Society of Clinical Oncology.

Testing insect movement theory: empirical analysis of pest data routinely collected from agricultural crops

Observations of an insect's movement lead to theory on the insect's flight behaviour and the role of movement in the species' population dynamics. This theory leads to predictions of the way the population changes in time under different conditions. If a hypothesis on movement predicts a specific change in the population, then the hypothesis can be tested against observations of population change. Routine pest monitoring of agricultural crops provides a convenient source of data for studying movement into a region and among fields within a region. Examples of the use of statistical and computational methods for testing hypotheses with such data are presented. The types of questions that can be addressed with these methods and the limitations of pest monitoring data when used for this purpose are discussed. (C) 2002 Elsevier Science B.V. All rights reserved.

Powder forging of a sintered Al-3.8Cu-1Mg-0.8Si-O.1Sn alloy

The forging characteristics of an Al-Cu-Mg-Si-Sn alloy are examined using it new testing strategy which incorporates a double truncated cone specimen and finite element modelling. This sample geometry produces controlled strain distributions within a single specimen and can readily identify the specific strain required to achieve a specific microstructural event by matching the metallographic data with the strain profiles calculated from finite element software, The friction conditions were determined using the conventional friction ring test, which was evaluated using finite element software. The rheological properties of the alloy, evaluated from compression testing of right cylinders, are similar to the properties of conventional aluminium forgings. A hoop strain develops at the outer diameter of the truncated cones and this leads to pore opening at the outer few millimetres. The porosity is effectively removed when the total strain equals the net compressive strain. The strain profiles that develop in the truncated cones are largely independent of the processing temperature and the strain rate although the strain required for pore closure increases as the forging temperature is reduced. This suggests that the microstructure and the strain rate sensitivity may also be important factors controlling pore behaviour. (C) 2002 Elsevier Science B.V. All rights reserved.

Testing the applicability of molecular genetic markers to population analyses of scleratinian corals

The abundance of coral reefs worldwide is in decline, and despite the ecological importance of reefs, only a limited number of DNA markers have been identified for scleractinian coral genetic studies. This paper addresses the search for new coral molecular markers and investigates the applicability of the cytochrome c oxidase subunit I (COI), the internal transcribed spacer region 1 (ITS1), and the pocilloporin gene to the question of intraspecific variation in the scleractinian coral Pocillopora verrucosa along the southeast African coastline. The COI fragment was 710 bp long and was identical for P. verrucosa (n = 10) and P. damicornis (n = 3). Only two different ITS1 sequences were found (differing by 13 bp insertion), but more importantly, 24% of the sequences were heterogenous indicating that different multiple copies of the sequence exist. Pocilloporin is an intronless gene that was absolutely conserved throughout all P. verrucosa populations (n = 50). Thus, the three DNA regions studied appear unsuitable for the population genetic analyses of P. verrucosa.

Testing the link between the latitudinal gradient in species richness and rates of molecular evolution

Numerous hypotheses have been proposed to explain latitudinal gradients in species richness, but all are subject to ongoing debate. Here we examine Rohde's (1978, 1992) hypothesis, which proposes that climatic conditions at low latitudes lead to elevated rates of speciation. This hypothesis predicts that rates of molecular evolution should increase towards lower latitudes, but this prediction has never been tested. We discuss potential links between rates of molecular evolution and latitudinal diversity gradients, and present the first test of latitudinal variation in rates of molecular evolution. Using 45 phylogenetically independent, latitudinally separated pairs of bird species and higher taxa, we compare rates of evolution of two mitochondrial genes and DNA-DNA hybridization distances. We find no support for an effect of latitude on rate of molecular evolution. This result casts doubt on the generality of a key component of Rohde's hypothesis linking climate and speciation.

A mechanistic model for carbon dioxide corrosion of mild steel in the presence of protective iron carbonate films - Part 3: Film growth model

A model of iron carbonate (FeCO3) film growth is proposed, which is an extension of the recent mechanistic model of carbon dioxide (CO2) corrosion by Nesic, et al. In the present model, the film growth occurs by precipitation of iron carbonate once saturation is exceeded. The kinetics of precipitation is dependent on temperature and local species concentrations that are calculated by solving the coupled species transport equations. Precipitation tends to build up a layer of FeCO3 on the surface of the steel and reduce the corrosion rate. On the other hand, the corrosion process induces voids under the precipitated film, thus increasing the porosity and leading to a higher corrosion rate. Depending on the environmental parameters such as temperature, pH, CO2 partial pressure, velocity, etc., the balance of the two processes can lead to a variety of outcomes. Very protective films and low corrosion rates are predicted at high pH, temperature, CO2 partial pressure, and Fe2+ ion concentration due to formation of dense protective films as expected. The model has been successfully calibrated against limited experimental data. Parametric testing of the model has been done to gain insight into the effect of various environmental parameters on iron carbonate film formation. The trends shown in the predictions agreed well with the general understanding of the CO2 corrosion process in the presence of iron carbonate films. The present model confirms that the concept of scaling tendency is a good tool for predicting the likelihood of protective iron carbonate film formation.