Estimating Two-Stage Models for Genetic Influences on Alcohol, Tobacco or Drug Use Initiation and Dependence Vulnerability in Twin and Family Data

Genetic research on risk of alcohol, tobacco or drug dependence must make allowance for the partial overlap of risk-factors for initiation of use, and risk-factors for dependence or other outcomes in users. Except in the extreme cases where genetic and environmental risk-factors for initiation and dependence overlap completely or are uncorrelated, there is no consensus about how best to estimate the magnitude of genetic or environmental correlations between Initiation and Dependence in twin and family data. We explore by computer simulation the biases to estimates of genetic and environmental parameters caused by model misspecification when Initiation can only be defined as a binary variable. For plausible simulated parameter values, the two-stage genetic models that we consider yield estimates of genetic and environmental variances for Dependence that, although biased, are not very discrepant from the true values. However, estimates of genetic (or environmental) correlations between Initiation and Dependence may be seriously biased, and may differ markedly under different two-stage models. Such estimates may have little credibility unless external data favor selection of one particular model. These problems can be avoided if Initiation can be assessed as a multiple-category variable (e.g. never versus early-onset versus later onset user), with at least two categories measurable in users at risk for dependence. Under these conditions, under certain distributional assumptions., recovery of simulated genetic and environmental correlations becomes possible, Illustrative application of the model to Australian twin data on smoking confirmed substantial heritability of smoking persistence (42%) with minimal overlap with genetic influences on initiation.

Growth of a Bose-Einstein condensate: a detailed comparison of theory and experiment

We extend the earlier model of condensate growth of Davis et at (Davis M J, Gardiner C W and Ballagh R J 2000 Phys. Rev. A 62 063608) to include the effect of gravity in a magnetic trap. We carry out calculations to model the experiment reported by Kohl et al (Kohl M, Davis M J, Gardiner C W, Hansch T and Esslinger T 2001 Preprint cond-mat/0106642) who study the formation of a rubidium Bose-Einstein condensate for a range of evaporative cooling parameters. We find that, in the regime where our model is valid, the theoretical curves agree with all the experimental data with no fitting parameters. However, for the slowest cooling of the gas the theoretical curve deviates significantly from the experimental curves. It is possible that this discrepancy may be related to the formation of a quasicondensate.

On the importance function in splitting simulation

The splitting method is a simulation technique for the estimation of very small probabilities. In this technique, the sample paths are split into multiple copies, at various stages in the simulation. Of vital importance to the efficiency of the method is the Importance Function (IF). This function governs the placement of the thresholds or surfaces at which the paths are split. We derive a characterisation of the optimal IF and show that for multi-dimensional models the natural choice for the IF is usually not optimal. We also show how nearly optimal splitting surfaces can be derived or simulated using reverse time analysis. Our numerical experiments illustrate that by using the optimal IF, one can obtain a significant improvement in simulation efficiency.

Granulomatous meningoencephalomyelitis in dogs

Granulomatous meningoencephalomyelitis (GME) is a morphological description of an inflammatory disorder of the canine central nervous system (CNS). It has been reported in many areas of the world. including Australia, and is one of the more common nervous disorders of dogs. Most breeds of dogs of both sexes and all ages can be affected but young to middle-aged small and terrier breeds have been stated as being more susceptible. There are variable anatomical forms and distribution of the lesions in the CNS; the presenting clinical signs can reflect singly or collectively cerebellar, cerebral, and brain stem dysfunction. Meningeal and spinal cord involvement are also common. There is no specific diagnostic test but a combination of clinical signs, history and cerebro-spinal fluid cytology are useful indicators. However differential diagnosis from other inflammatory disorders of the brain is difficult. No infectious agent aetiology has been established for GME and therefore no satisfactory therapeutic approach is available. The role of the immune system in terms of either initiating or potentiating the lesions in the CNS appears to be the most likely direction for further investigation into the nature of this disorder.

The first strand transfer reaction of HIV-1 reverse transcription is more efficient in infected cells than in cell-free natural endogenous reverse transcription reactions

Background: In the presence of dNTPs, intact HIV-1 virions are capable of reverse transcribing at least part of their genome, a process known as natural endogenous reverse transcription (NERT). PCR analysis of virion DNA produced by NERT revealed that the first strand transfer reaction (1stST) was inefficient in intact virions, with minus strand (-) strong stop DNA (ssDNA) copy numbers up to 200 times higher than post-1stST products measured using primers in U3 and U5. This was in marked contrast to the efficiency of 1stST observed in single-round cell infection assays, in which (-) ssDNA and U3-U5 copy numbers were indistinguishable. Objectives: To investigate the reasons for the discrepancy in first strand transfer efficiency between intact cell-free virus and the infection process. Study design: Alterations of both NERT reactions and the conditions of cell infection were used to test whether uncoating and/or entry play a role in the discrepancy in first strand transfer efficiency. Results and Conclusions: The difference in 1stST efficiency could not be attributed simply to viral uncoating, since addition of very low concentrations of detergent to NERT reactions removed the viral envelope without disrupting the reverse transcription complex, and these conditions resulted in no improvement in 1stST efficiency. Virus pseudotyped with surface glycoproteins from either vesicular stomatitis virus or amphotrophic murine leukaemia virus also showed low levels of 1stST in low detergent NERT assays and equivalent levels of (-) ssDNA and 1stST in single-round infections of cells, demonstrating that the gp120-mediated infection process did not select for virions capable of carrying out 1stST. These data indicate that a post-entry event or factor may be involved in efficient HIV-1 reverse transcription in vivo. (C) 2002 Elsevier Science B.V. All rights reserved.

Development of a quality use of medicines coding system to rate clinical pharmacists' medication review recommendations

Objective: To develop a 'quality use of medicines' coding system for the assessment of pharmacists' medication reviews and to apply it to an appropriate cohort. Method: A 'quality use of medicines' coding system was developed based on findings in the literature. These codes were then applied to 216 (111 intervention, 105 control) veterans' medication profiles by an independent clinical pharmacist who was supported by a clinical pharmacologist with the aim to assess the appropriateness of pharmacy interventions. The profiles were provided for veterans participating in a randomised, controlled trial in private hospitals evaluating the effect of medication review and discharge counselling. The reliability of the coding was tested by two independent clinical pharmacists in a random sample of 23 veterans from the study population. Main outcome measure: Interrater reliability was assessed by applying Cohen's kappa score on aggregated codes. Results: The coding system based on the literature consisted of 19 codes. The results from the three clinical pharmacists suggested that the original coding system had two major problems: (a) a lack of discrimination for certain recommendations e. g. adverse drug reactions, toxicity and mortality may be seen as variations in degree of a single effect and (b) certain codes e. g. essential therapy were in low prevalence. The interrater reliability for an aggregation of all codes into positive, negative and clinically non-significant codes ranged from 0.49-0.58 (good to fair). The interrater reliability increased to 0.72-0.79 (excellent) when all negative codes were excluded. Analysis of the sample of 216 profiles showed that the most prevalent recommendations from the clinical pharmacists were a positive impact in reducing adverse responses (31.9%), an improvement in good clinical pharmacy practice (25.5%) and a positive impact in reducing drug toxicity (11.1%). Most medications were assigned the clinically non-significant code (96.6%). In fact, the interventions led to a statistically significant difference in pharmacist recommendations in the categories; adverse response, toxicity and good clinical pharmacy practice measured by the quality use of medicine coding system. Conclusion: It was possible to use the quality use of medicine coding system to rate the quality and potential health impact of pharmacists' medication reviews, and the system did pick up differences between intervention and control patients. The interrater reliability for the summarised coding system was fair, but a larger sample of medication regimens is needed to assess the non-summarised quality use of medicines coding system.

The preparation of zinc(II) and cadmium(II) complexes of the pentadentate N3S2 ligand formed from 2,6-diacetylpyridine and S-benzyldithiocarbazate (H2SNNNS) and the X-ray crystal structure of the novel dimeric [Zn2(SNNNS)2] complex

The pentadentate chelating agent, 2,6-diacetylpyridinebis(S-benzyldithiocarbazate) (H2SNNNS) reacts with zinc(II) and cadmium(II) ions forming stable complexes of empirical formula, [M(SNNNS)] (M=Zn2+, Cd2+; SNNNS2 =doubly deprotonated anionic form of the Schiff base). These complexes have been characterized by a variety of physico-chemical techniques. IR and H-1 NMR spectral evidence indicate that the Schiff base coordinates to the zinc(II) and cadmium(II) ions via the pyridine nitrogen atoms, the azomethine nitrogen atoms and the mercaptide sulfur atoms. The crystal and molecular structure of the zinc(II) complex has been determined by X-ray diffraction. The complex is a dimer in which the pyridine nitrogen atom,the azomethine nitrogen atom and the thiolate sulfur atom from one ligand coordinate to one of the zinc(II) ions whereas the azomethine and thiolate sulfur atoms from another ligand complete pentacoordination around the zinc(II) ion, the ligands being coordinated in their deprotonated forms. The coordination geometry about each zinc(II) can be considered as intermediate between a square-pyramid and trigonal-bipyramid. The cadmium(II) complex is also assigned with a dimeric structure. (C) 2003 Elsevier Ltd. All rights reserved.

Indicadores das condições nutricionais na região do Polonoroeste: I. Aspectos metodológicos e características socioeconómicas

O trabalho apresenta os princípios metodológicos que nortearam a organização da Pesquisa Inquérito Nutricional no Polonoroeste. Foram incluídas, também as informações sobre as características sócio-econômicas e sanitárias das famílias estudadas em 1985 na zona urbana de Cáceres-MT. Destas 74% eram radicadas em Cáceres e 13,5% provinham de outros estados ou de outros países, sendo que 76,2% residiam em zona urbana. Quanto a categoria social e renda 52% eram urbanos e 51,0% recebia menos de 2 salários mínimos. O inquérito não atingia os 2 setores mais pobres e populosos da cidade onde as condições são piores e onde vive a maioria da população que migrou mais recentemente para Caceres.

Indicadores das condições nutricionais na região do polonoroeste: II. Estudo antropométrico - 1983

Realizou-se o estudo do estado nutricional através da antropometria com o objetivo de descrever a prevalência e a forma da Desnutrição Protéico-Energética em seis cidades da região do Polonoroeste. O exame antropométrico foi aplicado em um grupo de 573 crianças de 3 a 72 meses de idade, de ambos os sexos. Para o tratamento dos dados coletados utilizou-se as classificações propostas por GOMEZ e por WATERLOW, sendo ainda realizada a distribuição do peso e a altura por faixas de percentis. A prevalência de desnutrição encontrada, segundo a classificação de GOMEZ, foi de 51,0%, sendo que o maior percentual foi constatado na cidade de Jauru (79,2%) e o menor na cidade de Araputanga (31,3%). Quanto à forma de desnutrição a de maior prevalência foi a desnutrição pregressa, mostrando com isso um comprometimento acentuado da estatura, confirmado através da distribuição por percentis.

Indicadores das condições nutricionais na região do Polonoroeste: III. Estudo clínico nutricional

O estudo do exame clínico-nutricional é parte do Inquérito Nutricional, realizado no "Diagnóstico em Saúde do Polonoroeste-MT em 1983". No intuito de reconhecer a situação nutricional da população da região em estudo, o grupo do Inquérito Nutricional procedeu ao estudo do Consumo Alimentar das famílias, ao estudo dos dados antropométricos e de sinais clínico-nutricionais de crianças na faixa etária de 3 a 72 meses. Foram examinadas 585 crianças da amostra como proposta por SANCHES & CARVALHEIRO7 adaptado por MEIRELLES e SANCHES. O exame clínico-nutricional foi realizado segundo a metodologia recomendada por JELLIFFE4. Foram encontrados sinais clínicos sugestivos de carência nutricional em 6,6% das crianças; sinais de anemia em 9,7% e de bócio em 2,7%. Não foi possível definir com precisão outros quadros carenciais.

Indicadores das condições nutricionais na região do polonoroeste: IV. Inquérito alimentar em famílias de seis cidades da região do Polonoroeste, Mato Grosso, Brasil, 1983

O trabalho se refere aos dados coletados em inquérito alimentar recordatório de 24h no Inquérito Nutricional da Pesquisa Diagnóstico em Saúde no Polonoroeste em 1983 em 6 cidades da região do Polonoroeste/MT. Como uma primeira aproximação da problemática alimentar da região, o estudo revela os alimentos mais referidos nas entrevistas que são alimentos básicos, fontes de energia, semi-industrializados e de custo mais baixo.

Indicadores das condições nutricionais na região do Polonoroeste: VI. Estudo antropométrico, 1985

A presença da Desnutrição Protéico-Calórica tem sido expressiva no país, retratando diferenças sociais e econômicas das distintas regiões. Como parte da Pesquisa Diagnóstico em Saúde Polonoroeste/1985, realizou-se um estudo antropométrico de peso e altura, em uma amostra de 405 crianças, menores de 6 anos de idade, em Cáceres/MT. Segundo os critérios de GOMEZ, a prevalência da desnutrição foi de 33%, 40% de desnutridos moderados e não sendo registrada a forma grave. A Classificação de WATERLOW indicou a desnutrição pregressa (36%) como a de maior prevalência, sendo os déficits de estatura mais acentuados nas faixas etárias menores de 2 anos, indicando que os programas de saúde à criança, nesta área, devam priorizar os aspectos nutricionais deste grupo etário.

Randomized, double-blind trial comparing indinavir alone, zidovudine alone and indinavir plus zidovudine in antiretroviral therapy-naive hiv-infected individuals with CD4 cell counts between 50 and 250/mm3

Treatment with indinavir has been shown to result in marked decreases in viral load and increases in CD4 cell counts in HIV-infected individuals. A randomized double-blind study to evaluate the efficacy of indinavir alone (800 mg q8h), zidovidine alone (200 mg q8h) or the combination was performed to evaluate progression to AIDS. 996 antiretroviral therapy-naive patients with CD4 cell counts of 50-250/mm3 were allocated to treatment. During the trial the protocol was amended to add lamivudine to the zidovudine-containing arms. The primary endpoint was time to development of an AIDS-defining illness or death. The study was terminated after a protocol-defined interim analysis demonstrated highly significant reductions in progression to a clinical event in the indinavir-containing arms, compared to the zidovudine arm (p<0.0001). Over a median follow-up of 52 weeks (up to 99 weeks), percent reductions in hazards for the indinavir plus zidovudine and indinavir groups compared to the zidovudine group were 70% and 61%, respectively. Significant reductions in HIV RNA and increases in CD4 cell counts were also seen in the indinavir-containing groups compared to the zidovudine group. Improvement in both CD4 cell count and HIV RNA were associated with reduced risk of disease progression. All three regimens were generally well tolerated.

Species, genera et ordines algarum : seu descriptiones succinctae specierum, generum et rodinum, quibus algarum regnum constituitur / auctore Jacobo Georgio Agardh.

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