Mesoionic pyridopyrimidinylium and pyridooxazinylium olates and non-mesoionic pyridopyrimidinones. Structures in the solid state, solution, and matrices

X-Ray crystal structures, C-13 NMR spectra and theoretical calculations (B3LYP/6-31G*) are reported for the mesoionic (zwitterionic) pyridopyrimidinylium- and pyridooxazinyliumolates 2a, 3a and 5a,b as well as the enol ether 11b and the enamine 11c. The 1-NH compounds like 1a, 2a and 3a exist in the mesoionic form in the crystal and in solution, but the OH tautomers such as 1b and 2b dominate in the gas phase as revealed by the Ar matrix IR spectra in conjunction with DFT calculations. All data indicate that the mesoionic compounds can be regarded as intramolecular pyridine-ketene zwitterions (cf. 16 --> 17) with a high degree of positive charge on the pyridinium nitrogen, a long pyridinium N-CO bond (ca. 1.44-1.49 Angstrom), and normal C=O double bonds (ca. 1.22 Angstrom). All mesoionic compounds exhibit a pronounced tilting of the olate C=O groups (the C=O groups formally derived from a ketene) towards the pyridinium nitrogen, giving NCO angles of 110-118 degrees. Calculations reveal a hydrogen bond with 6-CH, analogous to what is found in ketene-pyridine zwitterions and the C3O2-pyridine complex. The 2-OH tautomers of type 1b, 2b, and 11 also show a high degree of zwitterionic character as indicated by the canonical structures 11 12.

Kinematic and non-linear analysis of foldable barrel vaults

Kinematic analysis is conducted to derive the geometric constraints for the geometric design of foldable barrel vaults (FBV) composed of polar or angulated scissor units. Non-linear structural analysis is followed to determine the structural response of FBVs in the fully deployed configuration under static loading. Two load cases are considered: cross wind and longitudinal wind. The effect of varying member sizes, depth-to-span ratio and geometric imperfections is examined. (C) 2000 Elsevier Science Ltd. All rights reserved.

Youth suicide trends in Australian metropolitan and non-metropolitan areas, 1988-1997

Objective: The objective of this study was to examine trends in suicide among 15-34-year-olds living in Australian metropolitan and non-metropolitan areas between 1988 and 1997. Method: Suicide and population data were obtained from the Australian Bureau of Statistics. We calculated overall and method-specific suicide rates for 15-24 and 25-34-year-old males and females separately, according to area of residence defined as non-metropolitan (less than or equal to 20 000 people) or metropolitan. Results: Between 1988 and 1997 suicide rates in 15-24-year-old non-metropolitan males were consistently 50% higher than metropolitan 15-24-year-olds. In 1995-1997, for example, the rates were: 38.2 versus 25.1 per 100 000 respectively (p < 0.0001). The reverse pattern was seen in 25-34-year-old females with higher rates in metropolitan areas (7.5 per 100 000) compared with non-metropolitan areas (6.1 per 100 000, p = 0.21) in 1995-1997. There were no significant differences according to area of residence in 25-34-year-old males or 15-24-year-old females. Over the years studied we found no clear evidence that suicide rates increased to a greater extent in rural than urban areas. Rates of hanging suicide have approximately doubled in both sexes and age groups in both settings over this time. Despite an approximate halving in firearm suicide, rates remain 3-fold higher among non-metropolitan residents. Conclusion: Non-metropolitan males aged 15-24 years have disproportionately higher rates of suicide than their metropolitan counterparts. Reasons for this require further investigation. Hanging is now the most favoured method of non-metropolitan suicide replacing firearms from 10 years ago. Although legislation may reduce method-specific suicide the potential for method-substitution means that overall rates may not fall. More comprehensive interventions are therefore required.

Multiple conformational epitopes are recognized by natural and induced immunity to the E7 protein of human papilloma virus type 16 in man

The reactivity of sera from patients with cervical cancer with the E7 protein of human papilloma virus type 16 (HPV16) was estimated using a novel non-radioactive immunoprecipitation assay and four established protein-and peptide-based immunoassays. Six of 14 sera from patients with cervical cancer and 1 of 10 sera from healthy laboratory staff showed repeated reactivity with E7 in at least one assay. Four of the 7 reactive sera were consistently reactive in more than one assay, but only one was reactive in all four assays. Following immunization with E7, 2 of 5 patients with cervical cancer had increased E7-specific reactivity, measurable in one or more assays. No single assay was particularly sensitive for E7 reactivity, or predictive of cervical cancer. Mapping of E7 reactivity to specific E7 peptides was unsuccessful, suggesting that natural or induced E7 reactivity in human serum is commonly directed to conformational epitopes of E7, These results suggest that each assay employed with is study measures a different aspect of E7 reactivity, and that various reactivities to E7 may manifest following HPV infection or immunization. This finding is of significance for monitoring of E7 immunotherapy and for serological screening for cervical cancer. Copyright (C) 2000 S.Karger, AG. Basel.

Book Review of: Supervising postgraduates from non-English speaking backgrounds

No abstract

A randomized trial of a problem-based learning approach for teaching epidemiology

Purpose. To conduct a controlled trial of traditional and problem-based learning (PBL) methods of teaching epidemiology. Method. All second-year medical students (n = 136) at The University of Western Australia Medical School were offered the chance to participate in a randomized controlled trial of teaching methods fur an epidemiology course. Students who consented to participate (n = 80) were randomly assigned to either a PBL or a traditional course. Students who did not consent or did not return the consent form (n = 56) were assigned to the traditional course, Students in both streams took identical quizzes and exams. These scores, a collection of semi-quantitative feedback from all students, and a qualitative analysis of interviews with a convenience sample of six students from each stream were compared. Results. There was no significant difference in performances on quizzes or exams between PBL and traditional students. Students using PBL reported a stronger grasp of epidemiologic principles, enjoyed working with a group, and, at the end of the course, were more enthusiastic about epidemiology and its professional relevance to them than were students in the traditional course. PBL students worked more steadily during the semester but spent only marginally more time on the epidemiology course overall. Interviews corroborated these findings. Non-consenting students were older (p < 0.02) and more likely to come from non-English-speaking backgrounds (p < 0.005). Conclusions. PBL provides an academically equivalent but personally far richer learning experience. The adoption of PBL approaches to medical education makes it important to study whether PBL presents particular challenges for students whose first language is not the language of instruction.

Reducing the harms caused by cannabis use: the policy debate in Australia

The debate about cannabis policy in Australia has revolved around the harms that cannabis causes to users and the community, on the one hand, and the harms that are caused by the prohibition of its use, on the other. This paper assesses evidence on: (1) the harms caused to users and the community by cannabis use (derived from the international scientific literature) and (2) the harms that arise from prohibition (as reflected in Australian research). The most probable harms caused by cannabis use include: an increased risk of motor vehicle accidents; respiratory disease; dependence; adverse effects on adolescent development; and the exacerbation of psychosis. The harms of the current prohibition on cannabis use policy are less tangible but probably include: the creation of a large blackmarket; disrespect for a widely broken law; harms to the reputation of the unlucky few cannabis users who are caught and prosecuted; lack of access to cannabis for medical uses; and an inefficient use of law enforcement resources. Cannabis policy unavoidably involves trade offs between competing values that should be made by the political process. Australian cannabis policy has converged on a solution which continues to prohibit cannabis but reduces the severity of penalties for cannabis use by either removing criminal penalties or diverting first time cannabis offenders into treatment and education. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.

Allowing the medical use of cannabis

Cannabis has been advocated as a treatment for nausea, vomiting, wasting, pain and muscle spasm in cancer, HIV/AIDS, and neurological disorders. Such uses are prohibited by law; cannabinoid drugs are not registered for medical use in Australia and a smoked plant product is unlikely to be registered. A New South Wales Working Party has recommended granting exemption from prosecution to patients who are medically certified to have specified medical conditions. This proposal deserves to be considered by other State and Territory governments.

Passive smoking and lung cancer: a cumulative meta-analysis

Objective: To review the epidemiological evidence for the association between passive smoking and lung cancer. Method: Primary studies and meta-analyses examining the relationship between passive smoking and lung cancer were identified through a computerised literature search of Medline and Embase, secondary references, and experts in the field of passive smoking. Primary studies meeting the inclusion criteria were meta-analysed. Results From 1981 to the end of 1999 there have been 76 primary epidemiological studies of passive smoking and lung cancer, and 20 meta-analyses. There were 43 primary studies that met the inclusion criteria for this meta-analysis; more studies than previous assessments. The pooled relative risk (RR) for never-smoking women exposed to environmental tobacco smoke (ETS) from spouses, compared with unexposed never-smoking women was 1.29 (95% CI 1.17-1.43). Sequential cumulative meta-analysed results for each year from 1981 were calculated: since 1992 the RR has been greater than 1.25. For Western industrialised countries the RR for never-smoking women exposed to ETS compared with unexposed never-smoking women, was 1.21 (95% CI 1.10-1.33). Previously published international spousal meta-analyses have all produced statistically significant RRs greater than 1.17. Conclusions The abundance of evidence in this paper, and the consistency of findings across domestic and workplace primary studies, dosimetric extrapolations and meta-analyses, clearly indicates that non-smokers exposed to ETS are at increased risk of lung cancer. Implications: The recommended public health policy is for a total ban on smoking in enclosed public places and work sites.

Challenges and approaches to estimating mortality attributable to the use of selected illicit drugs

A number of unique challenges are faced when attempting to estimate mortality attributable to illicit drugs. The hidden nature of illicit drug use creates difficulties in quantifying the prevalence of such use; identifying adverse health effects associated with exposure, and calculating the risk of these effects. The use of cohort studies of drug users allows the identification of causes of mortality associated with drug use and the determination of the risk of these causes. This risk estimate can then be used in conjunction with estimates of the prevalence of drug use to, extrapolate the burden of mortality. We identify a number of such studies and present some solutions to the major challenges faced when attempting to estimate the global burden of mortality attributable to illicit drug use. Copyright (C) 2001 S. Karger AG, Basel.

Labelled tableaux for non-normal modal logics

In this paper we show how to extend KEM, a tableau-like proof system for normal modal logic, in order to deal with classes of non-normal modal logics, such as monotonic and regular, in a uniform and modular way.