SNP technologies for drug discovery : a current review

Single nucleotide polymorphisms (SNPs) are unique genetic differences between individuals that contribute in significant ways to the determination of human variation including physical characteristics like height and appearance as well as less obvious traits such as personality, behaviour and disease susceptibility. SNPs can also significantly influence responses to pharmacotherapy and whether drugs will produce adverse reactions. The development of new drugs can be made far cheaper and more rapid by selecting participants in drug trials based on their genetically determined response to drugs. Technology that can rapidly and inexpensively genotype thousands of samples for thousands of SNPs at a time is therefore in high demand. With the completion of the human genome project, about 12 million true SNPs have been identified to date. However, most have not yet been associated with disease susceptibility or drug response. Testing for the appropriate drug response SNPs in a patient requiring treatment would enable individualised therapy with the right drug and dose administered correctly the first time. Many pharmaceutical companies are also interested in identifying SNPs associated with polygenic traits so novel therapeutic targets can be discovered. This review focuses on technologies that can be used for genotyping known SNPs as well as for the discovery of novel SNPs associated with drug response.

What do clients learn from counseling?

Thirty-five clients who received counseling participated in this exploratory study by completing a letter to a friend that described in as much detail as possible what they had learned from counseling. The participants’ written responses were analyzed using a content analysis approach. The analysis indicated that the data were best categorized in terms of three broad areas of learnings (Self, Relations with Others, and the Process of Learning and Change). The Self taxonomy was found to consist of six hierarchical levels. The Relations with Others taxonomy consisted of five hierarchical levels, while the Process of Learning and Change taxonomy consisted of five hierarchical levels. The results suggested that these three taxonomies offer a promising and exciting way to view the impact of counseling within a learning framework. If these taxonomies are found to be stable in future research and clients are easily classified using the taxonomies then this approach may have implications for counseling. It may well be that to maximise the learnings counselors could use specific strategies and techniques to enhance their clients’ learning in the three areas.

Adolescent protective behaviour to reduce drug and alcohol use, alcohol-related harm and interpersonal violence

Typically adolescents' friends are considered a risk factor for adolescent engagement in risk-taking. This study took a more novel approach, by examining adolescent friendship as a protective factor. In particular it investigated friends' potential to intervene to reduce risk-taking. 540 adolescents (mean age 13.47 years) were asked about their intention to intervene to reduce friends' alcohol, drug and alcohol-related harms and about psychosocial factors potentially associated with intervening. More than half indicated that they would intervene in friends' alcohol, drug use, alcohol-related harms and interpersonal violence. Intervening was associated with being female, having friends engage in overall less risk-taking and having greater school connectedness. The findings provide an important understanding of increasing adolescent protective behavior as a potential strategy to reduce alcohol and drug related harms.

Unusual hydrate stabilization in the two-dimensional layered structure of quinacrinium bis(2-carboxy-4,5-dichlorobenzoate) tetrahydrate, a proton-transfer compound of the drug quinacrine

The crystal structure of the hydrated proton-transfer compound of the drug quinacrine [rac-N'-(6-chloro-2-methoxyacridin-9-yl)-N,N-diethylpentane-1,4-diamine] with 4,5-dichlorophthalic acid, C23H32ClN3O2+ . 2(C8H3Cl2O4-).4H2O (I), has been determined at 200 K. The four labile water molecules of solvation form discrete ...O--H...O--H... hydrogen-bonded chains parallel to the quinacrine side chain, the two N--H groups of which act as hydrogen-bond donors for two of the water acceptor molecules. The other water molecules, as well as the acridinium H atom, also form hydrogen bonds with the two anion species and extend the structure into two-dimensional sheets. Between these sheets there are also weak cation--anion and anion--anion pi-pi aromatic ring interactions. This structure represents only the third example of a simple quinacrine derivative for which structural data are available but differs from the other two in that it is unstable in the X-ray beam due to efflorescence, probably associated with the destruction of the unusual four-membered water chain structures.

Increasing socio-economic inequalities in drug-induced deaths in Australia : 1981-2002

Introduction and Aims: Since the 1990s illicit drug use death rates in Australia have increased markedly. There is a notable gap in knowledge about changing socio-economic inequalities in drug use death rates. Some limited Australian and overseas data point to higher rates of drug death in the lowest socio-economic groups, but the paucity of available studies and their sometimes conflicting findings need to be addressed. Design and Methods: This paper uses data obtained from the Australian Bureau of Statistics (ABS) to examine changes in age-standardised drug-induced mortality rates for Australian males over the period 1981 – 2002. Socio-economic status was categorised as manual or non-manual work status. Results: With the rapid increase in drug-induced mortality rates in the 1990s, there was a parallel increase in socio-economic inequalities in drug-induced deaths. The decline in drug death rates from 2000 onwards was associated with a decline in socio-economic inequalities. By 2002, manual workers had drug death rates well over twice the rate of non-manual workers. Discussion: Three factors are identified which contribute to these socio-economic inequalities in mortality. First, there has been an age shift in deaths evident only for manual workers. Secondly, there has been an increase in availability until 1999 and a relative decline in the cost of the drug, which most often leads to drug death (heroin). Thirdly, there has been a shift to amphetamine use which may lead to significant levels of morbidity, but few deaths. [Najman JM, Toloo G, Williams GM. Increasing socio-economic inequalities in drug-induced deaths in Australia: 1981–2002.

Learning journals as a counseling strategy

The effects of counseling have been subject to extensive examination including the meta-analyses of Lipsey and Wilson (1993) and Matt and Navarro (1997). The results of these analyses demonstrated the positive effects of counseling interventions but do not indicate how, when, and why these benefits eventuated (Paul, 1967; Shadish & Sweeney, 1991), nor do they consider mediating variables. Much of the research in this area has involved the measurement of quantitative behavioral outcomes and short-term behavioral change (Steenbarger & Smith, 1996). However, there has been a recent move toward more qualitative, process-orientated research (Polkingthorne, 1994). This move addresses the previous methodological myopia but neglects the place of learning in the counseling process. It is suggested that if learning is viewed as underpinning all counseling, then clients should be able to transfer what they have learned from the counseling experience to problematical situations without the need for further counseling.

Differences between journalistic and academic accounts of child sexual abuse in Australia

The paper uses qualitative textual analysis to compare journalistic and academic accounts of child sexual abuse. There are seven main differences. Academic accounts suggest higher levels of neglect, emotional abuse, and physical abuse than sexual abuse in Australia, by contrast, journalistic accounts highlight sexual abuse. Academic accounts suggest that child sexual abuse in Australia is decreasing; journalistic accounts suggest that it is increasing. Academic accounts suggest that the majority of cases of child sexual abuse are perpetrated by family members; journalistic accounts focus on abuse by institutional figures (teachers, priests) or by strangers. Academic accounts have shown that innocent sexual play is a normal part of childhood development; journalistic accounts suggest that any sexual play is either a sign of abuse, or in itself constitutes sexual abuse. Academic accounts suggest that one of the best ways to prevent sexual abuse is for children to receive sex education; journalistic accounts suggest that children finding out about sex leads to sexual abuse. Academic accounts can gather data from the victims; journalistic accounts are excluded from doing so. Academic researchers talk to abusers in order to understand how child sexual abuse can be prevented; journalistic accounts exclude the voices of child sexual abusers.

Mailed treatment to augment primary care for alcohol disorders : a randomised controlled trial

Introduction and Aims: Remote delivery of interventions is needed to address large numbers of people with alcohol use disorders who are spread over large areas. Previous correspondence trials typically examined its effects as stand-alone treatment. This study aimed to test whether adding postal treatment to general practitioner (GP) support would lower alcohol use more than GP intervention alone. Design and Methods: A single-blind, randomised controlled trial with a crossover design was conducted over 12 months on 204 people with alcohol use disorders. Participants in an immediate correspondence condition received treatment over the first 3 months; those receiving delayed treatment received it in months 3–6. Results: Few participants were referred from GPs, and little intervention was offered by them. At 3 months, 78% of participants remained in the study. Those in immediate treatment showed greater reductions in alcohol per week, drinking days, anxiety, depression and distress than those in the delayed condition. However, post-treatment and follow-up outcomes still showed elevated alcohol use, depression, anxiety and distress. Greater baseline anxiety predicted better alcohol outcomes, although more mental distress at baseline predicted dropout. Discussion and Conclusions: The study gave consistent results with those from previous research on correspondence treatments, and showed that high levels of participant engagement over 3 months can be obtained. Substantial reductions in alcohol use are seen, with indications that they are well maintained. However, many participants continue to show high-risk alcohol use and psychological distress.

Start Over and Survive : A Brief Intervention For Substance Abuse in Early Psychosis

Over the last decade, brief intervention for alcohol problems has become a well-validated and accepted treatment, with bried interventions frequently showing equivalence in terms of outcome to more extended treatments (Bien et al, 1993). A recent review of this studies found that heavy drinkers who received interventions of less than 1 h were almost twice as likely to moderate their drinking over the following 6-12 months as did those not receiving intervention (Wilk etal, 1997).Some studies have used motivational interviewing (MI) strategies (Monti et al, 1999); others have simply given information ajnd advice to reduce drinking (Fleming et al, 1997). Leaflets or information on strategies to assist in the attempt or follow-up sessions are sometimes provided (Fleming et al, 1997). In general practice research, provision of one or more follow-up sessions increases the reliability of intake reductions across studies (Poikolainen, 1999).

Teachers reporting suspected child sexual abuse : results of a three-state study

Over 3000 cases of child sexual abuse are identified every year in Australia, but the real incidence is higher still. As a strategy to identify child sexual abuse, Australian States and Territories have enacted legislation requiring members of selected professions, including teachers, to report suspected cases. In addition, policy-based reporting obligations have been developed by professions, including the teaching profession. These legislative and industry-based developments have occurred in a context of growing awareness of the incidence and consequences of child sexual abuse. Teachers have frequent contact and close relationships with children, and possess expertise in monitoring changes in children’s behaviour. Accordingly, teachers are seen as being well-placed to detect and report suspected child sexual abuse. To date, however, there has been little empirical research into the operation of these reporting duties. The extent of teachers’ awareness of their duties to report child sexual abuse is unknown. Further, there is little evidence about teachers’ past reporting practice. Teachers’ duties to report sexual abuse, especially those in legislation, differ between States, and it is not known whether or how these differences affect reporting practice. This article presents results from the first large-scale Australian survey of teachers in three States with different reporting laws: New South Wales, Queensland, and Western Australia. The results indicate levels of teacher knowledge of reporting duties, reveal evidence about past reporting practice, and provide insights into anticipated future reporting practice and legal compliance. The findings have implications for reform of legislation and policy, training of teachers about the reporting of child sexual abuse, and enhancement of child protection.

Applying Stafford and Warr’s Reconceptualization of Deterrence Theory to drug driving : can it predict those likely to offend?

In December 2007, random roadside drug testing commenced in Queensland, Australia. Subsequently, the aim of this study was to explore the preliminary impact of Queensland’s drug driving legislation and enforcement techniques by applying Stafford and Warr’s [Stafford, M. C., & Warr, M. (1993). A reconceptualization of general and specific deterrence. Journal of Research in Crime and Delinquency, 30, 123-135] reconceptualization of deterrence theory. Completing a comprehensive drug driving questionnaire were 899 members of the public, university students, and individuals referred to a drug diversion program. Of note was that approximately a fifth of participants reported drug driving in the past six months. Additionally, the analysis indicated that punishment avoidance and vicarious punishment avoidance were predictors of the propensity to drug drive in the future. In contrast, there were indications that knowing of others apprehended for drug driving was not a sufficient deterrent. Sustained testing and publicity of the legislation and countermeasure appears needed to increase the deterrent impact for drug driving.

An intervention for substance abuse in schizophrenia

Describes a cognitive-behavioral intervention for alcohol and cannabis abuse with schizophrenic patients. The intervention integrates substance abuse treatment with other aspects of psychosis management, including assessment, use of anti-psychotic medication, and training in coping skills.