bluuebunny/crossref_metadata_2025 huggingface dataset:
A TATA binding protein regulatory network that governs transcription complex assembly
Authors: Huisinga Kathryn L , Pugh B Franklin
Published: April 2007

Background

Eukaryotic genes are controlled by proteins that assemble stepwise into a transcription complex. How the individual biochemically defined assembly steps are coordinated and applied throughout a genome is largely unknown. Here, we model and experimentally test a portion of the assembly process involving the regulation of the TATA binding protein (TBP) throughout the yeast genome.

Results

Biochemical knowledge was used to formulate a series of coupled TBP regulatory reactions involving TFIID, SAGA, NC2, Mot1, and promoter DNA. The reactions were then linked to basic segments of the transcription cycle and modeled computationally. A single framework was employed, allowing the contribution of specific steps to vary from gene to gene. Promoter binding and transcriptional output were measured genome-wide using ChIP-chip and expression microarray assays. Mutagenesis was used to test the framework by shutting down specific parts of the network.

Conclusion

The model accounts for the regulation of TBP at most transcriptionally active promoters and provides a conceptual tool for interpreting genome-wide data sets. The findings further demonstrate the interconnections of TBP regulation on a genome-wide scale.
A recessive genetic screen for host factors required for retroviral infection in a library of insertionally mutated Blm-deficient embryonic stem cells
Authors: Wang Wei , Bradley Allan
Published: April 2007

Background

Host factors required for retroviral infection are potential targets for the modulation of diseases caused by retroviruses. During the retroviral life cycle, numerous cellular factors interact with the virus and play an essential role in infection. Cultured embryonic stem (ES) cells are susceptible to retroviral infection, therefore providing access to all of the genes required for this process to take place. In order to identify the host factors involved in retroviral infection, we designed and implemented a scheme for identifying ES cells that are resistant to retroviral infection and subsequent cloning of the mutated gene.

Results

A library of mutant ES cells was established by genome-wide insertional mutagenesis in Blm-deficient ES cells, and a screen was performed by superinfection of the library at high multiplicity with a recombinant retrovirus carrying a positive and negative selection cassette. Stringent negative selection was then used to exclude the infected ES cells. We successfully recovered five independent clones of ES cells that are resistant to retroviral infection. Analysis of the mutations in these clones revealed four different homozygous and one compound heterozygous mutation in the mCat-1 locus, which confirms that mCat-1 is the ecotropic murine leukemia virus receptor in ES cells.

Conclusion

We have demonstrated the feasibility and reliability of this recessive genetic approach to identifying critical genes required for retroviral infection in ES cells; the approach provides a unique opportunity to recover other cellular factors required for retroviral infection. The resulting insertionally mutated Blm-deficient ES cell library might also provide access to essential host cell components that are required for infection and replication for other types of virus.
Evolution of protein complexes by duplication of homomeric interactions
Authors: Pereira-Leal Jose B , Levy Emmanuel D , Kamp Christel , Teichmann Sarah A
Published: April 2007

Background

Cellular functions are accomplished by the concerted actions of functional modules. The mechanisms driving the emergence and evolution of these modules are still unclear. Here we investigate the evolutionary origins of protein complexes, modules in physical protein-protein interaction networks.

Results

We studied protein complexes in Saccharomyces cerevisiae, complexes of known three-dimensional structure in the Protein Data Bank and clusters of pairwise protein interactions in the networks of several organisms. We found that duplication of homomeric interactions, a large class of protein interactions, frequently results in the formation of complexes of paralogous proteins. This route is a common mechanism for the evolution of complexes and clusters of protein interactions. Our conclusions are further confirmed by theoretical modelling of network evolution. We propose reasons for why this is favourable in terms of structure and function of protein complexes.

Conclusion

Our study provides the first insight into the evolution of functional modularity in protein-protein interaction networks, and the origins of a large class of protein complexes.
A major zebrafish polymorphism resource for genetic mapping
Authors: Bradley Kevin M , Elmore J Bradford , Breyer Joan P , Yaspan Brian L , Jessen Jason R , Knapik Ela W , Smith Jeffrey R
Published: April 2007

We have identified 645,088 candidate polymorphisms in zebrafish and observe a single nucleotide polymorphism (SNP) validation rate of 71% to 86%, improving with polymorphism confidence score. Variant sites are non-random, with an excess of specific novel T- and A-rich motifs. We positioned half of the polymorphisms on zebrafish genetic and physical maps as a resource for positional cloning. We further demonstrate bulked segregant analysis using the anchored SNPs as a method for high-throughput genetic mapping in zebrafish.
Global transcriptome analysis of murine embryonic stem cell-derived cardiomyocytes
Authors: Doss Michael Xavier , Winkler Johannes , Chen Shuhua , Hippler-Altenburg Rita , Sotiriadou Isaia , Halbach Marcel , Pfannkuche Kurt , Liang Huamin , Schulz Herbert , Hummel Oliver , Hübner Norbert , Rottscheidt Ruth , Hescheler Jürgen , Sachinidis Agapios
Published: April 2007

Background

Characterization of gene expression signatures for cardiomyocytes derived from embryonic stem cells will help to define their early biologic processes.

Results

A transgenic α-myosin heavy chain (MHC) embryonic stem cell lineage was generated, exhibiting puromycin resistance and expressing enhanced green fluorescent protein (EGFP) under the control of the α-MHC promoter. A puromycin-resistant, EGFP-positive, α-MHC-positive cardiomyocyte population was isolated with over 92% purity. RNA was isolated after electrophysiological characterization of the cardiomyocytes. Comprehensive transcriptome analysis of α-MHC-positive cardiomyocytes in comparison with undifferentiated α-MHC embryonic stem cells and the control population from 15-day-old embryoid bodies led to identification of 884 upregulated probe sets and 951 downregulated probe sets in α-MHC-positive cardiomyocytes. A subset of upregulated genes encodes cytoskeletal and voltage-dependent channel proteins, and proteins that participate in aerobic energy metabolism. Interestingly, mitosis, apoptosis, and Wnt signaling-associated genes were downregulated in the cardiomyocytes. In contrast, annotations for genes upregulated in the α-MHC-positive cardiomyocytes are enriched for the following Gene Ontology (GO) categories: enzyme-linked receptor protein signaling pathway (GO:0007167), protein kinase activity (GO:0004672), negative regulation of Wnt receptor signaling pathway (GO:0030178), and regulation of cell size (O:0008361). They were also enriched for the Biocarta p38 mitogen-activated protein kinase signaling pathway and Kyoto Encyclopedia of Genes and Genomes (KEGG) calcium signaling pathway.

Conclusion

The specific pattern of gene expression in the cardiomyocytes derived from embryonic stem cells reflects the biologic, physiologic, and functional processes that take place in mature cardiomyocytes. Identification of cardiomyocyte-specific gene expression patterns and signaling pathways will contribute toward elucidating their roles in intact cardiac function.
Adenovirus type 5 exerts genome-wide control over cellular programs governing proliferation, quiescence, and survival
Authors: Miller Daniel L , Myers Chad L , Rickards Brenden , Coller Hilary A , Flint S Jane
Published: April 2007

Background

Human adenoviruses, such as serotype 5 (Ad5), encode several proteins that can perturb cellular mechanisms that regulate cell cycle progression and apoptosis, as well as those that mediate mRNA production and translation. However, a global view of the effects of Ad5 infection on such programs in normal human cells is not available, despite widespread efforts to develop adenoviruses for therapeutic applications.

Results

We used two-color hybridization and oligonucleotide microarrays to monitor changes in cellular RNA concentrations as a function of time after Ad5 infection of quiescent, normal human fibroblasts. We observed that the expression of some 2,000 genes, about 10% of those examined, increased or decreased by a factor of two or greater following Ad5 infection, but were not altered in mock-infected cells. Consensus k-means clustering established that the temporal patterns of these changes were unexpectedly complex. Gene Ontology terms associated with cell proliferation were significantly over-represented in several clusters. The results of comparative analyses demonstrate that Ad5 infection induces reversal of the quiescence program and recapitulation of the core serum response, and that only a small subset of the observed changes in cellular gene expression can be ascribed to well characterized functions of the viral E1A and E1B proteins.

Conclusion

These findings establish that the impact of adenovirus infection on host cell programs is far greater than appreciated hitherto. Furthermore, they provide a new framework for investigating the molecular functions of viral early proteins and information relevant to the design of conditionally replicating adenoviral vectors.
Deciphering the molecular machinery of stem cells: a look at the neoblast gene expression profile
Authors: Rossi Leonardo , Salvetti Alessandra , Marincola Francesco M , Lena Annalisa , Deri Paolo , Mannini Linda , Batistoni Renata , Wang Ena , Gremigni Vittorio
Published: April 2007

Background

Mammalian stem cells are difficult to access experimentally; model systems that can regenerate offer an alternative way to characterize stem cell related genes. Planarian regeneration depends on adult pluripotent stem cells - the neoblasts. These cells can be selectively destroyed using X-rays, enabling comparison of organisms lacking stem cells with wild-type worms.

Results

Using a genomic approach we produced an oligonucleotide microarray chip (the Dj600 chip), which was designed using selected planarian gene sequences. Using this chip, we compared planarians treated with high doses of X-rays (which eliminates all neoblasts) with wild-type worms, which led to identification of a set of putatively neoblast-restricted genes. Most of these genes are involved in chromatin modeling and RNA metabolism, suggesting that epigenetic modifications and post-transcriptional regulation are pivotal in neoblast regulation. Comparing planarians treated with low doses of X-rays (after which some radiotolerant neoblasts re-populate the planarian body) with specimens irradiated with high doses and unirradiated control worms, we identified a group of genes that were upregulated as a consequence of low-dose X-ray treatment. Most of these genes encode proteins that are known to regulate the balance between death and survival of the cell; our results thus suggest that genetic programs that control neoblast cytoprotection, proliferation, and migration are activated by low-dose X-rays.

Conclusion

The broad differentiation potential of planarian neoblasts is unparalleled by any adult stem cells in the animal kingdom. In addition to our validation of the Dj600 chip as a valuable platform, our work contributes to elucidating the molecular mechanisms that regulate the self-renewal and differentiation of neoblasts.
Gene expression patterns during adaptation of a helminth parasite to different environmental niches
Authors: Jolly Emmitt R , Chin Chen-Shan , Miller Steve , Bahgat Mahmoud M , Lim KC , DeRisi Joseph , McKerrow James H
Published: April 2007

Background

Schistosome bloodflukes are complex trematodes responsible for 200 million cases of schistosomiasis worldwide. Their life cycle is characterized by a series of remarkable morphological and biochemical transitions between an invertebrate host, an aquatic environment, and a mammalian host. We report a global transcriptional analysis of how this parasite alters gene regulation to adapt to three distinct environments.

Results

Utilizing a genomic microarray made of 12,000 45-50-mer oligonucleotides based on expressed sequence tags, three different developmental stages of the schistosome parasite were analyzed by pair-wise comparisons of transcript hybridization signals. This analysis resulted in the identification of 1,154 developmentally enriched transcripts.

Conclusion

This study expands the repertoire of schistosome genes analyzed for stage-specific expression to over 70% of the predicted genome. Among the new associations identified are the roles of robust protein synthesis and programmed cell death in development of cercariae in the sporocyst stages, the relative paucity of cercarial gene expression outside of energy production, and the remarkable diversity of adult gene expression programs that reflect adaptation to the host bloodstream and an average lifespan that may approach 10 years.
Effective psychotherapy in a racially and culturally diverse society
Authors: Bhui Kamaldeep , Morgan Neil
Published: April 2007

This article is aimed at psychotherapists and health practitioners who have not reflected on the role of race, culture and ethnicity in the provision of psychological treatments. We highlight the key issues of importance in engagement, assessment and ongoing therapy, supporting practitioners to reach a stage of pre-competency. Competency will be achieved with additional training, supervision and innovation.
Cardiovascular monitoring with acetylcholinesterase inhibitors: a clinical protocol
Authors: Rowland Jeremy P. , Rigby John , Harper Adam C. , Rowland Rosalind
Published: April 2007

There has been significant anxiety among prescribers regarding the potential for cardiac adverse effects associated with acetylcholinesterase (AChE) inhibitors in Alzheimer's disease. There is no consensus on how to manage this cardiovascular risk, and memory clinics vary widely in their practice. Review of published evidence reveals that the incidence of cardiovascular side-effects is low, and that serious adverse events are rare. Intensive cardiovascular screening such as pre-treatment electrocardiograms or 24 h cardiac monitoring is not justified. Furthermore, there are no high-risk groups to target. This article suggests pragmatic guidelines for managing cardiovascular risk in patients receiving AChE inhibitors. The guidelines are intended to be easy to incorporate into routine clinical practice in a memory clinic.
Improving the health of psychiatrists
Authors: Firth-Cozens Jenny
Published: April 2007

Although the physical health of doctors is largely better than that of the general population, they continue to have high levels of stress, depression and substance misuse. These aspects of mental ill health are particularly elevated in psychiatrists, and in a number of studies psychiatrists have also been found to be those doctors most likely to face disciplinary proceedings. This article explores the individual and organisational causes of these problems and the ways they may interact within the psychiatrist's work role, and suggests a variety of possible interventions to improve the mental health of doctors in psychiatry.
CPD and the portfolio psychiatrist
Authors: Gunn John
Published: April 2007

As the age at which psychiatrists leave the National Health Service falls, and as the importance of CPD grows, there is an increasing urgency to assist the professional development and the licensing of portfolio practitioners. A survey undertaken to gain an impression of the experiences of this group of members of the Royal College of Psychiatrists highlighted considerable difficulties for some. Recommendations are made here both for individual members and for the CPD structures within the College. In particular, it is suggested that the College help with the appraisal of members who are outside managed organisations and that enhanced responsibilities be given to regional CPD coordinators. Individual members should see the peer group as the centre of their CPD activities, take a flexible approach to their own CPD, and advise other members of their peer group accordingly.
Value of standard personality assessments in informing clinical decision-making in a medium secure unit
Authors: Duggan Conor , Mason Lauren , Banerjee Penny , Milton John
Published: April 2007

Background

Assessing those with personality disorder for treatment in secure settings is known to be unsatisfactory.

Aim

To examine the utility of a standardised assessment of offenders with personality disorder referred for treatment in secure care in a naturalistic study.

Method

A consecutive series of 89 men were assessed with a battery of four recommended instruments measuring personality and risk. Decisions on whether or not to admit were based on a multidisciplinary discussion informed by these assessments.

Results

Of the 89 comprehensively assessed referrals, 60 (67%) were offered admission. High scores on the Psychopathy Checklist–Revised (especially on Factor 1) was the only measure that was associated with rejection. Of 44 patients discharged, 29 (66%) failed to complete treatment; none of the pre-admission assessments distinguished ‘completers' from ‘non-completers'. Although skills were acquired on the unit, follow-up of 24 men in the community showed that this had only a marginal effect on re-offending rate (58%).

Conclusions

Current recommended assessment methods appear unsatisfactory in identifying those who either (a) complete treatment or (b) benefit from treatment. Our results throw doubt on their value.
Altered memory and affective instability in prisoners assessed for dangerous and severe personality disorder
Authors: Kirkpatrick Tim , Joyce Eileen , Milton John , Duggan Conor , Tyrer Peter , Rogers Robert D.
Published: April 2007

Background

Previous studies of borderline personality disorder report neuropsychological impairments in several domains, including memory. No studies have compared memory functioning in high-risk prisoners with borderline personality disorder with similar prisoners with other personality disorders.

Aims

To explore mnemonic impairments in prisoners undergoing personality assessment as part of the dangerous and severe personality disorder initiative or detained in a medium secure facility.

Method

We investigated memory function in 18 prisoners with borderline personality disorder and 18 prisoners with other personality disorders.

Results

Prisoners with borderline personality disorder exhibited a pattern of multi-modal impairments in the immediate and delayed recall of verbal and visual information, with some association with affective instability. These deficits were not associated with the severity of personality disturbance.

Conclusions

These data suggest that memory deficits have some specificity in relation to the constituent traits of borderline personality disorder and indicate that neuropsychological assessment may be a source of useful adjunctive information for distinguishing between the cognitive and psychological difficulties of individual prisoners.
Developmental trajectories associated with juvenile sexually abusive behaviour and emerging severe personality disorder in childhood: 3-year study
Authors: Vizard Eileen , Hickey Nicole , McCrory Eamon
Published: April 2007

Background

Little is known about the developmental trajectories of juveniles presenting with sexually abusive behaviour or emerging severe personality disorder traits.

Aims

To investigate whether ‘age at onset’ of sexually abusive behaviour and whether emerging severe personality disorder traits are associated with specific developmental profiles.

Method

A retrospective file review of 280 juveniles presenting with sexually abusive behaviour was conducted and follow-up Offenders Index data were analysed.

Results

Juveniles with early onset (<11 years) of sexually abusive behaviour had higher levels of psychosocial adversity and early childhood antisocial behaviour compared with those with late onset. Emerging severe personality disorder traits were associated with higher levels of psychosocial adversity, antisocial behaviour, convictions and predatory sexually abusive behaviour.

Conclusions

Preliminary evidence supports the existence of distinct developmental trajectories within this population and points to a key role for traits of emerging severe personality disorder.
Aetiology of the relationship between callous-unemotional traits and conduct problems in childhood
Authors: Viding Essi , Frick Paul J. , Plomin Robert
Published: April 2007

Background

A callous and unemotional disposition is an indicator of early-onset antisocial behaviour.

Aims

To investigate the extent to which genetic influences contribute to the overlap between callous–unemotional traits and conduct problems in a large population sample of 7-year-old twins.

Method

Teachers provided ratings of callous-unemotional traits and conduct problems for 3434 twin pairs from the Twins Early Development Study. Model-fitting analyses were performed across the continuum of scores and at the extremes.

Results

The phenotypic relationship was primarily genetically mediated, both across the continuum and at the extremes and was substantial.

Conclusions

At 7 years of age, genetic influences on callous–unemotional traits overlap substantially with genetic influences on conduct problems. This combination should guide selection criteria in future molecular genetic studies.
Understanding the structure of the Psychopathy Checklist – Revised
Authors: Cooke David J. , Michie Christine , Skeem Jennifer
Published: April 2007

Psychopathy is the key construct in the Dangerous and Severe Personality Disorder (DSPD) Programme. The Psychopathy Checklist – Revised is used as a primary means of selection for the programme. The Checklist confounds two distinct constructs – personality disorder and criminal behaviour. This confound is important both practically and theoretically. For example, under the criteria for DSPD it is necessary to demonstrate that personality disorder has afunctional link with future risk of criminal behaviour. The confound has been exacerbated recently by claims that criminal behaviour is a core feature of psychopathic disorder. This contention is based on inappropriate analytical methods. In this paper we examine the source of this confound and illustrate how inappropriate methods can mislead.
Critical developments in the assessment of personality disorder
Authors: Tyrer Peter , Coombs Natalie , Ibrahimi Fatema , Mathilakath Anand , Bajaj Priya , Ranger Maja , Rao Bharti , Din Raana
Published: April 2007

Background

The assessment of personality disorder is currently inaccurate, largely unreliable, frequently wrong and in need of improvement.

Aims

To describe the errors inherent in the current systems and to indicate recent ways of improving personality assessment.

Method

Historical review, description of recent developments, including temporal stability, and of studies using document-derived assessment.

Results

Studies of interrater agreement and accuracy of diagnosis in complex patients with independently established personality status using document-derived assessment (PAS–DOC) with a four personality cluster classification, showed very good agreement between raters for the flamboyant cluster B group of personalities, generally good agreement for the anxious/dependent cluster C group and inhibited (obsessional) cluster D group, but only fair agreement for the withdrawn cluster A group. Overall diagnostic accuracy was 71%.

Conclusions

Personality function or diathesis, a fluctuating state, is a better description than personality disorder. The best form of assessment is one that uses longitudinal repeated measures using a four-dimensional system.
Assessment and treatment of violence-prone forensic clients: an integrated approach
Authors: Wong Stephen C. P. , Gordon Audrey , Gu Deqiang
Published: April 2007

Background

A risk-reduction treatment programme complemented by a focused assessment, both guided by the risk–need–responsivity principles, is suggested as the preferred treatment for violence-prone individuals with personality disorder.

Aims

Violence Reduction Programme (VRP) and Violence Risk Scale (VRS) were used to illustrate the design and implementation of such an approach. Participants from a similarly designed Aggressive Behaviour Control Programme were used to illustrate the principles discussed and to test programme efficacy.

Method

The VRS was used to assess risk/need and treatment readiness, and DSM–III/IV psychiatric diagnoses of 203 federal offenders.

Results

Participants had a high probability of violent recidivism and many violence-linked criminogenic needs, similar to offenders with high PCL–R scores. Most had antisocial personality disorder and substance use disorders; in terms of treatment-readiness, most were in the contemplation stage of change. Outcome evaluation results support the objectives of the VRP.

Conclusions

Integrating risk–need–responsivity principles in assessment and treatment can provide useful guidelines for intervention with violence-prone forensic clients with personality disorder.
Mental health of US Gulf War veterans 10 years after the war
Authors: Toomey Rosemary , Kang Han K. , Karlinsky Joel , Baker Dewleen G. , Vasterling Jennifer J. , Alpern Renee , Reda Domenic J. , Henderson William G. , Murphy Frances M. , Eisen Seth A.
Published: April 2007

Background

Gulf War veterans reported multiple psychological symptoms immediately after the war; the temporal course of these symptoms remains unclear.

Aims

To assess the prevalence of war-era onset mental disorders in US veterans deployed to the Gulf War and in non-deployed veterans 10 years after the war.

Method

Mental disorders were diagnosed using structured clinical interviews. Standard questionnaires assessed symptoms and quality of life.

Results

Gulf War-era onset mental disorders were more prevalent in deployed veterans (18.1%, n=1061) compared with non-deployed veterans (8.9%, n=1128). The prevalence of depression and anxiety declined 10 years later in both groups, but remained higher in the deployed group, who also reported more symptoms and a lower quality of life than the non-deployed group. Remission of depression may be related to the presence of comorbid psychiatric disorders and level of education. Remission of anxiety was related to treatment with medication.

Conclusions

Gulf War deployment was associated with an increased prevalence of mental disorders, psychological symptoms and a lower quality of life beginning during the war and persisting at a lower rate 10 years later.
Dementia Screening Questionnaire for Individuals with Intellectual Disabilities
Authors: Deb Shoumitro , Hare Monika , Prior Lindsay , Bhaumik Sabyasachi
Published: April 2007

Background

Many adults with Down's syndrome develop Alzheimer's dementia relatively early in their lives, but accurate clinical diagnosis remains difficult.

Aims

To develop a user-friendly observer-rated dementia screening questionnaire with strong psychometric properties for adults with intellectual disabilities.

Method

We used qualitative methods to gather information from carers of people with Down's syndrome about the symptoms of dementia. This provided the items for the Dementia Screening Questionnaire for Individuals with Intellectual Disabilities (DSQIID), which we then tested for its psychometric properties.

Results

The DSQIID was administered to carers of 193 adults with Down's syndrome, 117 of whom were examined by clinicians who confirmed a diagnosis of dementia for 49 according to modified ICD–10 criteria. We established that a total score of 20 provides maximum sensitivity (0.92) and optimum specificity (0.97) for screening. The DSQIID has sound internal consistency (α = 0.91) for all its 53 items, and good test–retest and interrater reliability. We established a good construct validity by dividing the items into four factors.

Conclusions

The DSQIID is a valid, reliable and user-friendly observer-rated questionnaire for screening for dementia among adults with Down's syndrome.
Possibilities for the prevention and treatment of cognitive impairment and dementia
Authors: Burke David , Hickie Ian , Breakspear Michael , Götz Jürgen
Published: April 2007

The human brain has a remarkable capacity for plasticity, but does it have the capacity for repair and/or regeneration? On the basis of controversial new evidence we speculate that the answer may be ‘yes', and suggest that clinicians should therefore approach cognitive impairment and dementia with a new, cautious optimism.
Antipsychotic prescribing for behavioural and psychological symptoms of dementia
Authors: Soyinka Ayodeji , Lawley David
Published: April 2007

Aims and Method

To review the quality of information and advice contained in correspondence from old age psychiatrists to general practitioners (GPs) regarding the prescription of antipsychotic drugs for the management of behavioural and psychological symptoms of dementia. Discharge summaries (n=22) and subsequent out-patient review letters were examined and compared with evidence-based guidelines in two phases of an audit cycle; first in 2002 and latterly in 2005.

Results

Practice was below acceptable standards during both phases of the audit cycle, with an actual drop in the quality of explicit advice given to GPs in 2005, despite national publicity about the issues and guidance from the Royal College of Psychiatrists.

Clinical Implications

The prescription of antipsychotic drugs is associated with an adverse prognosis for people with dementia. As such, it is imperative that such treatment is regularly reviewed and time limited. Old age psychiatrists need to ensure that this message is communicated to their primary care colleagues.
The Risk Management Authority in Scotland and the forensic psychiatrist as risk assessor
Authors: Tuddenham Laurence , Baird John
Published: April 2007

The Risk Management Authority (RMA), Scotland's new body which oversees the conduct of assessments of convicted offenders placed on risk assessment orders, recently held its first annual lecture. This was given by Scotland's new Solicitor General, who observed that risk assessment orders are likely to be reserved for ‘extraordinary crimes committed by extraordinary people’. The first risk assessment orders have been made by Scottish courts and the risk assessors' reports are awaited with interest, not least in England, which has taken a different approach to dangerous offenders (Darjee & Crichton, 2002). It seems timely to review the more novel aspects of the Scottish system and the issues they raise for forensic psychiatry.
Biology of Influenza A Virus
Authors: CHEUNG TIMOTHY K. W. , POON LEO L. M.
Published: April 2007

Abstract:  The outbreaks of avian influenza A virus in poultry and humans over the last decade posed a pandemic threat to human. Here, we discuss the basic classification and the structure of influenza A virus. The viral genome contains eight RNA viral segments and the functions of viral proteins encoded by this genome are described. In addition, the RNA transcription and replication of this virus are reviewed.
Molecular Characteristics of the Nipah Virus Glycoproteins
Authors: DIEDERICH SANDRA , MAISNER ANDREA
Published: April 2007

Abstract:  Nipah virus (NiV) is a highly pathogenic paramyxovirus, which emerged in 1998 from fruit bats in Malaysia and caused an outbreak of severe respiratory disease in pigs and fatal encephalitis in humans with high mortality rates. In contrast to most paramyxoviruses, NiV can infect a large variety of mammalian species. Due to this broad host range, its zoonotic potential, its high pathogenicity for humans, and the lack of effective vaccines or therapeutics, NiV was classified as a biosafety level 4 pathogen. This article provides an overview of the molecular characteristics of NiV focusing on the structure, functions, and unique biological properties of the two NiV surface glycoproteins, the receptor‐binding G protein, and the fusion protein F. Since viral glycoproteins are major determinants for cell tropism and virus spread, a detailed knowledge of these proteins can help to understand the molecular basis of viral pathogenicity.
West Nile Virus
Authors: YIANNAKOULIAS NIKOLAOS W. , SVENSON LAWRENCE W.
Published: April 2007

Abstract:  The appearance and spread of West Nile virus (WNv) in North America represent a recent example of how mosquito‐borne diseases can develop in new settings. Understanding the epidemiological, biological, and geographical aspects of WNv is critical to developing a greater understanding of how newly emerging, migrating, or evolving vector‐borne infectious disease can develop globally. To aid in the allocation of resources that mitigate future outbreaks and to better understand the geographic nature of WNv in the North American prairies, we employ spatial and nonspatial modeling methods to predict municipal‐level risk of human WNv infection rates. We use data based on a combination of routinely collected electronic data sources. Our findings suggest general agreement between spatial and nonspatial approaches, and results are consistent with seroprevalence‐based estimates. We suggest that spatial models based on administrative data can offer estimates of relative risk in human populations at less cost, and in a timelier manner than estimates based on serology specimens.
Phase II Trial of Infusional Fluorouracil, Leucovorin, Mitomycin, and Dipyridamole in Locally Advanced Unresectable Pancreatic Adenocarcinoma: SWOG S9700
Authors: Isacoff William H. , Bendetti Jacqueline K. , Barstis John J. , Jazieh Abdul-Rahman , Macdonald John S. , Philip Philip A.
Published: April 2007

Purpose

To test the hypothesis that dual biochemical modulation of fluorouracil (FU) in combination with mitomycin improves the survival of patients with pancreas cancer.

Patients and Methods

Eligibility included stage II or III unresectable adenocarcinoma of the pancreas, performance status of 0 to 2, and adequate organ function. Treatment included FU 200 mg/m2/d via continuous intravenous infusion for 4 weeks followed by 1 week of rest; leucovorin 30 mg/m2 administered via intravenous bolus infusion on days 1, 8, 15, and 22, followed by 1 week rest; mitomycin 10 mg/m2 intravenous bolus infusion every 6 weeks for a total of four doses. Dipyridamole 75 mg was administered orally three times daily during the FU administration.

Results

Fifty patients (median age, 61 years; 23 males, 27 females) with localized unresectable pancreatic cancer were eligible for this trial. Twenty-seven patients survived past 1 year for a 1-year survival probability of 54% (95% CI, 40% to 68%). Overall, the objective response rate was 26% (confirmed and unconfirmed) in the 47 patients with measurable disease, with two complete responders. Six of the responding patients underwent curative successful resection of the tumor. The most common toxicity to treatment was stomatitis. Three patients had reversible hemolytic uremic syndrome. Five patients experienced grade 4 toxicity. There were no treatment-related deaths.

Conclusion

Potential improvement in survival and resectability of localized unresectable pancreatic cancer may be attained without radiation. The strategy of dual biochemical modulation of FU warrants additional investigation in a randomized fashion.
We Should Desist Using RECIST, at Least in GIST
Authors: Benjamin Robert S. , Choi Haesun , Macapinlac Homer A. , Burgess Michael A. , Patel Shreyaskumar R. , Chen Lei L. , Podoloff Donald A. , Charnsangavej Chuslip
Published: April 2007

Purpose

Response Evaluation Criteria in Solid Tumors (RECIST) are insensitive in evaluating imatinib-treated gastrointestinal stromal tumors (GISTs). Response by Choi criteria, a 10% decrease in size or a 15% decrease in density on contrast-enhanced CT, correlated well in a small training set of patients who showed response as measured by positron emission tomography, and was more predictive of time to tumor progression (TTP) than response by RECIST. This study was designed to validate these observations in an independent data set.

Patients and Methods

Fifty-eight patients with imatinib-treated GISTs were evaluated by RECIST and Choi criteria. TTP was compared with TTP in the training set. Patients were analyzed initially with follow-up to 28 months, extended to 60 months for survival analysis.

Results

Patients who met Choi response criteria on CT at 2 months had significantly better TTP than those who did not (P = .0002), whereas response group by RECIST was not significantly correlated with TTP. Even when the 98 patients from both sets were analyzed together, the response group by RECIST did not correlate significantly with TTP, whereas response group by Choi criteria did correlate significantly with TTP. Disease-specific survival (DSS) was also significantly correlated with response group by Choi criteria (P = .04), but not with response group by RECIST.

Conclusion

Choi response criteria are reproducible, more sensitive, and more precise than RECIST in assessing the response of GISTs to imatinib mesylate. Response by Choi criteria, unlike response by RECIST, correlates significantly with TTP and DSS. Response by Choi criteria should be incorporated routinely into future studies of GIST therapy. We should desist using RECIST, at least in GIST.
Pain Management in Hospitalized Cancer Patients: A Systematic Review
Authors: Goldberg Gabrielle R. , Morrison R. Sean
Published: April 2007

Purpose

To assist cancer centers in improving pain management, we conducted a systematic review of institutional interventions designed to improve the assessment and treatment of pain in hospitalized cancer patients.

Methods

We performed a MEDLINE search for all English-language articles published from January 1966 through February 2006 using the medical subject headings terms of pain or pain measurement and outcome assessment (health care) or quality assurance (health care). Selected bibliographies were also searched. Studies were reviewed if they included clinical interventions directed at improving the treatment of cancer pain across an institution or nursing unit. Meta-analyses and randomized controlled trials or other controlled studies were included where possible. If no such trials were identified, then the best evidence available from studies with other designs was included.

Results

Five interventions were identified. These interventions included professional and patient education, instituting regular pain assessment (pain as a vital sign), audit of pain results and feedback to clinical staff, computerized decisional support systems, and specialist-level pain consultation services. Most studies were small in size and used quasiexperimental pre-post test designs. Successes were reported in increasing patient satisfaction, increasing documentation of pain intensity, and improving nurses’ knowledge and attitudes. No study reported successful interventions that consistently improved patients’ pain severity.

Conclusion

Although professional knowledge and attitudes about pain and nursing pain assessment rates have been shown to be improvable, no systematic, hospital-wide intervention has yet to be associated with improvement in pain severity. Future research on the development of new interventions, perhaps targeted specifically at physicians, is urgently needed.
Open-Label Phase III Trial of Panitumumab Plus Best Supportive Care Compared With Best Supportive Care Alone in Patients With Chemotherapy-Refractory Metastatic Colorectal Cancer
Authors: Van Cutsem Eric , Peeters Marc , Siena Salvatore , Humblet Yves , Hendlisz Alain , Neyns Bart , Canon Jean-Luc , Van Laethem Jean-Luc , Maurel Joan , Richardson Gary , Wolf Michael , Amado Rafael G.
Published: April 2007

Purpose

Panitumumab is a fully human monoclonal antibody directed against the epidermal growth factor receptor (EGFR). We compared the activity of panitumumab plus best supportive care (BSC) to that of BSC alone in patients with metastatic colorectal cancer who had progressed after standard chemotherapy.

Patients and Methods

We randomly assigned 463 patients with 1% or more EGFR tumor cell membrane staining, measurable disease, and radiologic documentation of disease progression during or within 6 months of most recent chemotherapy to panitumumab 6 mg/kg every 2 weeks plus BSC (n = 231) or BSC alone (n = 232). Tumor assessments by blinded central review were scheduled from week 8 until disease progression. The primary end point was progression-free survival (PFS). Secondary end points included objective response, overall survival (OS), and safety. BSC patients who progressed could receive panitumumab in a cross-over study.

Results

Panitumumab significantly prolonged PFS (hazard ratio [HR], 0.54; 95% CI, 0.44 to 0.66, [P < .0001]). Median PFS time was 8 weeks (95% CI, 7.9 to 8.4) for panitumumab and 7.3 weeks (95% CI, 7.1 to 7.7) for BSC. Mean (standard error) PFS time was 13.8 (0.8) weeks for panitumumab and 8.5 (0.5) weeks for BSC. Objective response rates also favored panitumumab over BSC; after a 12-month minimum follow-up, response rates were 10% for panitumumab and 0% for BSC (P < .0001). No difference was observed in OS (HR, 1.00; 95% CI, 0.82 to 1.22), which was confounded by similar activity of panitumumab after 76% of BSC patients entered the cross-over study. Panitumumab was well tolerated. Skin toxicities, hypomagnesaemia, and diarrhea were the most common toxicities observed. No patients had grade 3/4 infusion reactions.

Conclusion

Panitumumab significantly improved PFS with manageable toxicity in patients with chemorefractory colorectal cancer.
Cytotoxicity of Dimethylacetamide and Pharmacokinetics in Children Receiving Intravenous Busulfan
Authors: Hempel Georg , Oechtering Doris , Lanvers-Kaminsky Claudia , Klingebiel Thomas , Vormoor Josef , Gruhn Bernd , Boos Joachim
Published: April 2007

Purpose

To assess the cytotoxicity and the exposure of N,N-dimethylacetamide (DMA) in children during high-dose therapy with an intravenous (IV) formulation of busulfan containing the potentially hepatotoxic and neurotoxic DMA as a solvent.

Patients and Methods

Eighteen children aged 0.9 to 17.3 years (median age, 4.0 years) received IV busulfan in 15 doses of 0.7 to 1.0 mg/kg busulfan containing overall DMA amounts of between 5 mmol (437 mg) and 70.5 mmol (6,142 mg) per dose. Plasma concentrations of DMA and busulfan were quantified and analyzed using nonlinear mixed-effects modeling. Four different leukemic cell lines were incubated with DMA, and cytotoxicity was assessed in comparison with busulfan as well as in a combination reflecting the ratio in the formulation.

Results

Maximal plasma concentrations of DMA up to 3.09 mmol/L were observed. No accumulation of the solvent occurred. Instead, the trough levels decreased over the 4 treatment days. The population pharmacokinetic analysis revealed a clearance of 86.9 mL h−1 kg−1 ± 27% that increased to 298 mL h−1 kg−1 on the fourth day and a volume of distribution of 469 mL kg ± 22% (population mean ± interindividual variability). DMA volume of distribution correlated with the volume of distribution of busulfan. The cytotoxicity of DMA in vitro was 3 orders of magnitude lower than that of busulfan. No synergism was observed.

Conclusion

The lack of accumulation of DMA confirms that there is no safety concern related to the DMA content in this IV busulfan formulation. The contribution of DMA to the antileukemic effect of the formulation seems to be limited.
Tabu Search and Simulated Annealing Algorithms for Scheduling in Flow Shops with Lot Streaming
Authors: Marimuthu S , Ponnambalam S G , Jawahar N
Published: April 2007

This paper addresses the problem of making sequencing and scheduling decisions for n Jobs in m-machine flow shops with a lot sizing constraint. Lot streaming (lot sizing) is the process of creating sublots to move the completed portion of a production sublot to downstream machines. The planning decisions become more complex when lot streaming is allowed. There is scope for efficient metaheuristics for scheduling problems in an m machine flow shop with lot streaming. In recent years, much attention has been given to heuristics and search techniques. This paper proposes two metaheuristics, namely a simulated annealing algorithm (SA) and a tabu search algorithm (TABU), to evolve the optimal sequence for makespan and total flow time criteria in an m-machine flow shop with lot streaming. The algorithms are evaluated by means of comparison with Baker's algorithm for 2 m/c cases and the makespan criterion, which proves the capability of both of them.
Surface Modification for Orthopaedic Titanium Alloy by Wide-Area Electron Beam
Authors: Okada A , Uno Y , Uemura K , Raharjo P , McGeough J A
Published: April 2007

Wide-area electron beam (WAEB) irradiation was proposed as a new surface-finishing process for orthopaedic titanium alloy products. The surface roughness could be reduced from Rz = 10 μm to Rz = 0.7 μm all over the wide circular surface within a diameter of 60 mm in just a few minutes under optimum electron beam conditions. In this paper, the surface structure and the surface characteristics of WAEB-irradiated surface are discussed. The crystal grain size becomes small and the microstructure in the surface vicinity changes under WAEB irradiation. The corrosion resistance and the repellency can be improved simultaneously with the surface smoothing. Therefore, the WAEB irradiation method enables highly efficient surface smoothing and surface modification of orthopaedic titanium alloy.
Post-Consumer Waste Management Issues in the Footwear Industry
Authors: Staikos T , Rahimifard S
Published: April 2007

Currently, 17 billion pairs of shoes are produced worldwide every year, and this figure continues to rise. This creates an enormous amount of post-consumer (end-of-life) shoe waste that is currently being disposed of in landfill sites around the world. The research reported in this paper is an initial investigation into realization of a holistic approach to application of recovery and recycling in the footwear industry. The paper provides a brief review of the trends in the footwear sector regarding the amount of end-of-life waste produced, together with existing reuse and recycling activities. It also presents an integrated waste management framework by combining a mix of design and material improvements, as well as reuse, recycling, and energy recovery activities, and concludes by examining the challenges in establishing end-of-life product recovery procedures for post-consumer shoes.
Numerical and Experimental Investigation of Cylinder Cavity Flows
Authors: Bazyma L , Kuleshov V
Published: April 2007

It is well known that supersonic flow around bodies with cavities located on the nose is accompanied by pulsation. A forward-facing cavity may be regarded as a resonance tube. The flow in forward-facing cavities have been the subject for many experimental and numerical investigations. However, the majority models used in their experiments were blunt, hemispherical nose pieces with an axial cylindrical cavity of variable depth. In general, the cavity resonated at the primary-mode frequency, and the bow shock oscillated in a stable, symmetric manner about the nose. However, for intermediate cavity lengths, 0.4 ≤ L/D ≤ 0.7, the pressure signal switched randomly between the two modes of oscillation. The numerical and the experimental research of a supersonic flow past the cylinder with a cavity is carried out in the given work. Relative depth of a cavity ( L/D, D-cylinder diameter) varied in a range from 0.3 up to 1.6. Experiments for Mach number M = 3, Reynolds number Re > 106 and two-, three-dimensional numerical modelling were carried out. Shock wave bimodal pulsations have been experimentally found for depth of a cavity L/D = 0.4. Comparison of the experimental and numerical data has shown their good conformity.