bluuebunny/crossref_metadata_2025 huggingface dataset:
Collaborative Recovery: An Integrativemodel for Working with Individuals Who Experience Chronic and Recurring Mental Illness
Authors: Oades Lindsay , Deane Frank , Crowe Trevor , Gordon Lambert W , Kavanagh David , Lloyd Chris
Published: December 2009

Objectives: Recovery is an emerging movement in mental health. Evidence for recovery-based approaches is not well developed and approaches to implement recovery-oriented services are not well articulated. The collaborative recovery model (CRM) is presented as a model that assists clinicians to use evidencebased skills with consumers, in a manner consistent with the recovery movement. A current 5 year multisite Australian study to evaluate the effectiveness of CRM is briefly described.

Conclusion: The collaborative recovery model puts into practice several aspects of policy regarding recovery-oriented services, using evidence-based practices to assist individuals who have chronic or recurring mental disorders (CRMD). It is argued that thismodel provides an integrative framework combining (i) evidence-based practice; (ii) manageable and modularized competencies relevant to case management and psychosocial rehabilitation contexts; and (iii) recognition of the subjective experiences of consumers.
Psychiatric Comorbidity: Concepts, Controversies and Alternatives
Authors: Starcevic Vladan
Published: December 2009

Objective: To review various concepts of psychiatric comorbidity, their implications, surrounding controversies and underlying issues. A further aim is to propose an alternative term that might be more clinically useful and meaningful for describing the coexistence of mental disorders.

Conclusions: There is wide dissatisfaction with the concepts of psychiatric comorbidity because ofdifferent meanings, speculations on which they are often based and consequent confusion. Although the coexistence of mental disorders should be studied further so that any patterns in the corresponding relationships can be elucidated, there is a need for conceptual clarity and making the concept more meaningful for clinical practice and treatment. With that in mind, this present paper proposes avoidance of the term comorbidity and introduction of the term ‘co-occurrence’. The latter is defined in this article, and the distinction made between diagnostic co-occurrence and clinically significant co-occurrence.
Consultation–liaison Psychiatry Services to Nursing Homes
Authors: Craig Elizabeth , Pham Hieu
Published: December 2009

Objective: The aim of the present paper is to review current opinion relating to the provision of mental health consultation to nursing homes, and to provide recommendations for future research.

Method: The current literature pertaining to consultation–liaison psychi atry within nursing homes was reviewed.

Results: There is a paucity of well-designed empirical studies of mental health service provision to Australian nursing homes. This is of particular concern given the ageing Australian population and the prevalence of psychiatric symptoms in nursing home residents. Psychiatric consultation and liaison to nursing homes may result in reduced need for crisis inter vention, improved use of behavioural management strategies for the symp toms associated with dementia, and reduced nursing home staff stress and burnout.

Conclusions: Further research is required to evaluate the costs and benefits of providing regular mental health services to nursing homes in Australia, particularly in rural areas. Future service development should be complemented by methodologically sound evaluation.
Restoring Wisdom to the Practice of Psychiatry
Authors: Boyce Philip
Published: December 2009

Objective: While psychiatry is an exciting and rewarding discipline of medicine, the practice of psychiatry has become increasingly simplistic. This address seeks to identify some of the influences that underlie this phenomenon.

Conclusions: The influences include an increased demand for services and pressure on beds, the sway of the pharmaceutical industry with a biological approach being promulgated, excessive managerial constraints with an emphasis on efficiency versus effectiveness, and the acceptance of DSM diagnostic categories of uncertain validity. I argue that we need to rediscover a more wise approach to psychiatric practice. We have to insist upon changes to our training such that trainees are encouraged to get to know their patients and understand them from a biopsychosocial perspective. As a profession, we have to insist on proper care for our patients and work with managers and bureaucrats to ensure that the management of our patients is centred on quality of care and effectiveness over and above efficiency.
Social Engineers and Bystanders: The Limits of ‘Responsibility’ in Indigenous Affairs
Authors: Hunter Ernest
Published: December 2009

Objective: A significant shift is occurring in Australian Indigenous affairs. Contentiously, key Aboriginal and Torres Strait Islander leaders have challenged governments and organizations, both mainstream and Indigenous, to confront ‘passive welfare dependence’. This paper explores some of the social justice implications and considers the roles of non-Indigenous professionals.

Methods: A publication by Pat Dodson and Noel Pearson is used to frame the discussion.

Results: Ambiguity surrounding a number of key concepts and the shifting territory of Indigenous rights has contributed to bureaucratic inertia in Indigenous affairs. A range of ‘new’ concepts is being introduced into the current debate, such as expectancy, reciprocity and mutual obligation, challenging ideas of responsibility, agency and the roles played by non-Indigenous bureaucrats and practitioners.

Conclusions: Regardless of good intentions or social justice motivations, non-Indigenous interventions must be informed by an awareness of the potential to undermine Indigenous agency and, consequently, cause harm.
Developing New Services for Eating Disorders: An Evaluation Study
Authors: Endacott Ruth , Kidd Susan , Deacon-Crouch Melissa , Judd Fiona , Menzel Michelle , Cornett Marian
Published: December 2009

Objective: This paper aims to evaluate the structures and processes of eating disorders services in two regional cities in Australia.

Method: Stakeholder evaluation undertaken between 2002 and 2005 uses interviews, questionnaires and service delivery data to examine: structure and patient profile of the two services, barriers and success factors and local factors influencing development of the services.

Results: The Bendigo service provided secondary consultation and specialist management with upskilling of primary care workers as a key goal. Patients were referred to the service via mental health triage. The Geelong service initially offered assessment only, with direct access for the general public. Treatment was offered from early 2004. The Bendigo service assessed 41 patients, 63% were diagnosed with anorexia nervosa or bulimia nervosa. Most patients had a moderate or severe eating disorder. The Geelong service assessed 186 patients, 55% were diagnosed with anorexia nervosa or bulimia nervosa and 80% of this subset had not previously been treated for an eating disorder. General practitioners identified barriers to development of the services as: problems with capacity building and unrealistic expectations. The success factors were providing a locally based service with credible clinicians and effective communication.

Conclusions: Activity analysis demonstrates that the goals for both services were met. There is a need to measure both short- and long-term patient outcomes in order to fully assess effectiveness and applicability to other settings. Local factors, such as availability of specialist providers, would need to be taken into account.
Extended Matching Questions and the Royal Australian and New Zealand College of Psychiatrists Written Examination: An Overview
Authors: Samuels Anthony
Published: December 2009

Objective: To provide an overview, for trainees and fellows, of the Extended Matching Question, a new question type recently introduced in the Royal Australian and New Zealand College of Psychiatrists written examination. The characteristics, technical aspects and construction of these question types are discussed. Some pointers for candidates and those setting questions are outlined.

Conclusions: Extended Matching Questions are now commonly used to test medical knowledge in many areas of medicine, including psychiatry. They represent a transparent, evidence-based approach to the assessment of medical knowledge, which lends itself to electronic marking and statistical analysis. These questions facilitate the development of question banks and provide an easily accessible oversight of what areas of the curriculum have been examined.
From Golden Beaches to the Heartland: Reflections of NSW Rural Trainees
Authors: De Moore Gregory , Smith Kathleen , Earle Maree
Published: December 2009

Objective: To describe the training experiences of rural-based psychiatry trainees in New South Wales.

Method: Semistructured interviews were conducted with psychiatry trainees, rural psychiatrists and rural mental health administrators. The interviews were, for the most part, conducted face to face.

Results: Three factors that make this programme work are the opportunity to start training in a rural centre, a local psychiatrist who can act as guide and mentor and the initiative of this group of registrars. Three obstacles are a perceived lack of flexibility in College guidelines, isolation from peers and insufficient support when relocating to the city for specialty terms.

Conclusions: The NSW rural psychiatry training project is an exciting development. Three years on, it represents the best avenue for creating a locally based rural psychiatrist network. It stands as a model for the rest of the country.
Drug-Induced Psychosis Associated with Crystalline Methamphetamine
Authors: Dore Glenys , Sweeting Melinda
Published: December 2009

Objective: A case of drug-induced psychosis related to crystalline meth amphetamine is described, highlighting the phenomenology and relevant treatment.

Results: A 44-year-old woman with borderline personality traits and severe drug dependence developed a protracted drug-induced psychosis related to chronic high-dose crystalline methamphetamine use. Complete resolution of symptoms occurred with antipsychotic medication and abstinence from methamphetamine. Rapid recurrence of symptoms occurred at a time of high stress associated with minimal methamphetamine use and cessation of low-dose quetiapine. Symptoms rapidly resolved with abstinence, quetiapine and reduction of stressors.

Conclusions: A drug-induced psychosis resembling paranoid schizophrenia can occur with repeated or high-dose use of methamphetamine. While this generally resolves rapidly with cessation of stimulant use, some cases of protracted drug-induced psychosis in vulnerable individuals have been documented. Behavioural sensitization can also occur, and neuroleptics may prevent the recurrence of further psychosis triggered by ongoing low-dose methamphetamine use.
The ‘Mentally Disordered’ Provisions of the New South Wales Mental Health Act 1990: Their Ethical Standing and Effect on Services
Authors: Patfield Martyn
Published: December 2009

Objective: To consider whether the mentally disordered provisions of the NSW Mental Health Act 1990 can be ethically justified and whether any departure from the usual justification for compulsory care comes at a cost.

Conclusions: The shaky ethical standing of these provisions has encouraged mental health services in NSW to play a role in controlling unacceptable behaviour, even in the absence of mental illness. This places the Act in an exceptional position in comparison to other Western Mental Health Acts. It is causing increasing strain on services as well as having unforseen consequences on those detained.
Chronic Mental Illness and Community Treatment Resistance
Authors: Holmes Alex , Hodge Mark , Lenten Simon , Fielding John , Castle David , Velakoulis Dennis , Bradley Gail
Published: December 2009

Objectives: The movement from institutional to community care has been a key component of national mental health reform in Australia. In Victoria, where a model of community care has been fully implemented, a specialized forensic hospital is the sole remaining stand-alone psychiatric inpatient facility and access to long-term inpatient beds is severely limited. Clinical experience suggests that some high-needs patients are not well serviced by this structure. These patients are placing an increasing burden on a wide range of community services outside mental health. This paper aims to define more clearly this patient group, explore the limitations of their management and outline potential pathways for service development.

Conclusions: A population of complex patients with chronic mental illness are not effectively contained within a ‘good enough’ communitybased mental health system. Active debate is required regarding the com-munity's willingness to tolerate the risks and challenges that arise from the current approach. A collaborative care model involving case-based and incentive funding in combination with community-integrated complex care units may improve the care of these patients.
Australasian Dialectical Behaviour Therapy Pilot Outcome Study: Effectiveness, Utility and Feasibility
Authors: Brassington Jan , Krawitz Roy
Published: December 2009

Objectives: This paper aims to describe the outcome of 10 patients treated in a New Zealand pilot study of dialectical behaviour therapy (DBT) for people with borderline personality disorder (BPD), and to ascertain the clinical utility and feasibility of implementing DBT into a standard New Zealand public mental health service.

Method: Patients had a clinical and an International Personality Disorder Examination diagnosis of BPD and received 6 months of standard DBT treatment. Rating scales used were the Millon Clinical Muliaxial Inventory, 3rd edition (MCMI-III) and the Symptom Checklist 90-Revised (SCL-90-R), which were completed pre treatment and post treatment. Pre–post treatment data were completed on inpatient resource usage. Qualitative patient interviews were conducted post treatment.

Results: There were statistically significant improvements in functioning on 10 of the 24 MCMI-III subscales (p < 0.03 to p < 0.0008), including notably the borderline personality subscale (p < 0.01) and the anxiety (p < 0.05) and depression (p < 0.001) subscales. There was a statistically significant improvement on the Global Severity Index of the SCL-90-R (p < 0.001) and on 10 of the 12 SCL-90-R scales (p < 0.05 to p < 0.001). The hospital bed days used decreased from 0.57 days per patient per month to 0.2 days per patient per month.

Conclusions: These preliminary results document the clinical effectiveness of DBT. Dialectical behaviour therapy has practical and clinical utility of relevance to Australasian public mental health services. A DBT service can be successfully implemented within existing public mental health services.
The Quest to Fund Research: Playing Research Lotto
Authors: Cleary Michelle , Walter Garry , Hunt Glenn
Published: December 2009

Objective: To provide some direction for those interested in obtaining funding with the purpose of highlighting opportunities for beginner researchers in the health-care field.

Method: Features of a good grant application are described and an audit of seven mental health professional journals was undertaken, the latter to determine, inter alia, whether the paper reported research findings and whether the authors received formal research funding.

Result: The audit revealed that many types of papers that are published do not receive formal research funding and describe, for example, services, training issues, clinical practice and education programmes.

Conclusion: Innovative and enterprising efforts are required to secure clinical research funding. Submissions must be detailed, comprehensive and relevant, but the onus is also on the researcher to ensure a feasible study, where funding obligations can be fulfilled and findings readily disseminated. Many research studies are conducted without achieving competitive funding, and getting published –and getting started in writing –does not hinge on conducting formal research or receiving research funding.
A Framework for Mental Health Consumers to Evaluate Service Provision
Authors: Malins Gillian , Morland Kim , Strang Jon , Dowson Trevor , Hunt Sandra , Williamson David , Mason Michael , Eman Yvonne , Oades Lindsay
Published: December 2009

Objectives: This paper outlines a proposed framework including values, principles and steps, developed by consumers, to evaluate mental health services from a consumer's perspective.

Method: A research team consisting of consumer researchers, established academics and students developed the framework. The team had already conducted qualitative research with consumers of mental health services. Using these experiences and the evaluation literature, the proposed framework was developed over a series of 13 meetings.

Results: An evaluation framework, which describes the values underpinning consumer-directed evaluation of mental health services and the principles and steps to follow in conducting this type of evaluation, is presented.

Conclusions: The evaluation framework will guide consumers and services in conducting consumer-directed evaluation of mental health services, and assist in developing more genuine consumer participation in services.
Assessment of Distress and Burden in Australian Private Psychiatric Inpatients
Authors: Page Andrew , Hooke Geoff , O'brien Natalie , Defelice Nick
Published: December 2009

Objectives: The study aimed to examine (i) the extent of the objective and subjective burden of care experienced by carers of individuals attending Australian private psychiatric hospitals, (ii) the degree to which a carer's distress was influenced by the patient's symptoms and the burden of care experienced.

Methods: A group of 135 inpatient-carer dyads, for inpatients who attended three Australian private psychiatric clinics, completed measures of distress (Depression Anxiety Stress Scales) and caregiver burden (Burden Assessment Scale; BAS) during an inpatient admission to a private psychiatric hospital.

Results: The level of burden reported by carers was comparable with overseas data. Factor analysis was used to identify the key dimensions of the BAS. The chief concerns of carers related to worries about the patient and disruption to activities.

Conclusion: The burden experienced by carers needs to be recognized and addressed to ensure that they are able to continue to provide the care and support required by psychiatric inpatients. Present data are discussed in terms of the best way to support the carers of psychiatric inpatients.
Aboriginal Mental Health Workers and the Improving Indigenous Mental Health Service Delivery Model in the ‘Top End’
Authors: Nagel Tricia , Thompson Carolyn
Published: December 2009

Objectives: This article reviews the changing Aboriginal mental health service delivery model of Top End Mental Health Services, and highlights the importance of Aboriginal mental health workers in improving communication with Aboriginal patients. The Australian Integrated Mental Health Initiative Northern Territory Indigenous stream (AIMHI NT) is introduced.

Method: Baseline measures of AIMHI NT in 2003, and findings from two clinical file audits (1996 and 2001) at Royal Darwin Hospital inpatient unit are presented. The files were audited for a range of assessment and treatment interventions.

Results: The audits reveal significant improvements in Aboriginal inpatient care between 1995 and 2001.

Conclusion: Aboriginal mental health workers provide essential services as cross-cultural brokers in the setting of Aboriginal mental illness. The improvements in care found in this file audit coincide with the commencement of employment of Aboriginal mental health workers in the inpatient unit. The AIMHI consultation reveals broad support for employment of more Aboriginal mental health workers in the Top End.
Borderline Personality Disorder: A Pilot Survey about Clinician Views on Defensive Practice
Authors: Krawitz Roy , Batcheler Mike
Published: December 2009

Objective: To conduct a pilot survey about clinician views on defensive practice when working with adults with borderline personality disorder.

Method: All mental health clinicians from adult community, crisis and inpatient services of a district public mental health service who attended a routine team meeting completed a survey questionnaire (n = 29).

Results: Defensive practice was common, with 85% of clinicians having practised in the previous year in a manner that they believed was not in the best interests of their patients.

Conclusions: The findings support clinical impressions of a significant gap between clinician views on best practice and actual practice. The potential importance of the findings warrants a comprehensive multicentred study.
A Case of Schizophrenia with Complete Agenesis of the Corpus Callosum
Authors: Chinnasamy Dhamodharan , Rudd Rebecca , Velakoulis Dennis
Published: December 2009

Objective: To describe the case of a person with schizophrenia and agenesis of the corpus callosum.

Conclusion: A 24-year-old Caucasian woman with schizophrenia was incidentally found to have complete agenesis of the corpus callosum. A comprehensive neuropsychiatric assessment allowed management to be specifically tailored to the patient's unique clinical profile.
The Role of Child and Adolescent Mental Health Services in Suicide Prevention in New Zealand
Authors: Fortune Sarah , Clarkson Hugh
Published: December 2009

Objective: We consider the role of child and adolescent mental health services (CAMHS) in the prevention of suicide by young people in New Zealand by examining the conflicting demands placed on CAMHS as a result of public expectation, health-care policy and structures, the current focus in the health sector on risk assessment and the inability of CAMHS to see all the young people who may consider suicide in any given year.

Conclusions: We suggest that CAMHS are currently under significant pressures which are inadvertently leading to distortions of clinical practice away from the clinical needs of suicidal children, adolescents and their families towards risk assessment and risk management strategies. The inability of CAMHS to offer comprehensive services to all young people considering suicide may be addressed by greater provision of consult–liaison activities, better understanding between clinicians and health managers, and improvements in clinical skills.
Prevalence of Psychotropic Use in a South Australian Population
Authors: Goldney Robert , Bain Marcus
Published: December 2009

Objective: To determine the prevalence of psychotropic medication use in a South Australian population.

Methods: Face-to-face interviews with a random and representative sample of the South Australian population (at least 15 years of age) living in metropolitan and rural areas between March and June 2004.

Results: From 4700 households selected, 3015 participants were interviewed (65.9% response rate). Of the respondents, 10.6% were taking psychotropic medications; psychotropic drug use was higher in females (14.4%) than in males (6.8%), and increased with age. Antidepressants were the most common category of psychotropics reported by respondents (6.8%), followed by anxiolytics (1.8%), hypnotics and sedatives (1.5%) and antipsychotics (0.6%). The majority (64.8%) of those respondents who were taking a tricyclic antidepressant were on a dose of 50 mg or less. Only 0.07% of respondents were taking lithium.

Conclusions: The use of psychotropic medications was higher than recently reported studies conducted in the UK, the USA, Europe and Canada. More detailed enquiry about the indication for such use appears desirable in order to ascertain whether higher use in this Australian population is clinically appropriate.
Grief and Courage in a River Town: A Pilot Project in the Aboriginal Community of Kempsey, New South Wales
Authors: Cleworth Sally , Smith Wayne , Sealey Robyn
Published: December 2009

Objective: To describe a pilot project implemented in Kempsey, NSW, whereby a psychiatry registrar worked in a community-controlled Aboriginal medical service, Durri Aboriginal Corporation Medical Service, which provides mental health services for Aboriginal people.

Conclusions: The Aboriginal Mental Health Workers and psychiatry registrar jointly managed a significant number of Aboriginal people, often with assistance from the local mental health service at Kempsey. The registrar gained insight into the local Aboriginal community and more culturally appropriate clinical methods, as well as some cultural factors that can influence the presentation and management of mental illnesses. The Aboriginal Mental Health Workers increased their clinical knowledge and confidence through working with the registrar.
Do Clinical Pathways Really Improve Clinical Performance in Mental Health Settings?
Authors: Brett Emmerson , Aaron Frost , Lisa Fawcett , Emma Ballantyne , Warren Ward , Stan Catts
Published: December 2009

Objective: Royal Brisbane and Women's Hospital (RBWH) Mental Health developed and trialled two clinical pathways on psychosis and depression between 2001 and 2003 with the aim of improving a range of clinical and financial parameters. There was a strong commitment from senior management, appropriate resources were allocated and there was adequate staff support. Following a 6-month trial, the pathways were reworked extensively and combined into an acute inpatient pathway. From October 2003 to 2004, we trialled the acute inpatient clinical pathway, and monitored clinical and financial parameters.

Conclusion: Over this 12-month period, the acute inpatient clinical pathway failed to demonstrate improvement on a range of clinical and financial parameters and its use was ceased. This trial lends support to the view that the complexity, individuality and variability of mental disorders means that clinical pathways are not beneficial in mental health settings.
Parenting and Mental Illness: A Pilot Group Programme for Parents
Authors: Ruth Phelan , Lana Lee , Deb Howe , Garry Walter
Published: December 2009

Objective: To describe a pilot group programme for parents with a mental illness that was developed and implemented on the NSW Central Coast.

Conclusions: The Parenting and Mental Illness Group Program is a 6week group programme that is followed by four weekly, individual home visits. Data from the Eyberg Child Behaviour Inventory and Parenting Scale suggest the programme produced positive outcomes in children's behaviour and parenting practices; the programme was also viewed favourably by participants. While encouraging, these findings require replication, using larger numbers and evaluation of the programme in other sites. Supported by an evidence base, programmes such as this will be important to implement if mental health services are to improve outcomes for parents with mental health problems and their children.
Using the Internet to Enhance the Treatment of Depression
Authors: Robertson Lucy , Smith Michael , Castle David , Tannenbaum Dennis
Published: December 2009

Objective: Deficiencies in Australia's mental health systems persist despite over a decade of mental health reform. Recent developments in ehealth provide the opportunity to facilitate health reform and improve services. This paper presents preliminary findings from the implementation of a comprehensive e-health system, called RecoveryRoad, which was designed to augment the routine clinical treatment of depression.

Methods: Depressed patients (n = 144) were referred to RecoveryRoad from a public hospital and public and private clinics in Perth, Western Australia. Online features included secure e-consultations, progress monitoring questionnaires, psychoeducation and evidence-based therapy. Treating clinicians had online access to patients’ progress monitoring outcomes and e-consultations. There were two types of adherence reminders: automated email reminders and personalized case management delivered by email and telephone.

Results: Adherence to the system was high (from 53% to 84%, depending on the modality of reminder), and self-reported medication adherence was over 90%. Average depression severity declined from severe to mild by the eighth session, a large effect (d = 1.0). Both clinicians and patients were generally satisfied with the programme and reported that it improved clini-cian–patient relationships. Clinicians also reported that it helped patients to better manage depression.

Conclusions: Preliminary findings support the feasibility of comprehensive e-health systems in enhancing the delivery of mental health care.
Malingered Psychosis Leading to Involuntary Psychiatric Hospitalization
Authors: Waite Susan , Geddes Andy
Published: December 2009

Objective: To describe a patient with feigned psychosis who was admitted to an acute psychiatric unit under the Mental Health Act, and to discuss the clinical features of malingering in this treatment setting.

Method: Case report.

Results: A 40-year-old man with no known past psychiatric history was brought by police to the Emergency Department. He gave a history of paranoia, hallucinations and bizarre behaviour and was admitted to a secure ward. Treatment with parenteral medication was required due to hostile and aggressive behaviour. Collateral history was inconsistent with his reported symptoms and, when confronted with this information, he acknowledged fabricating his symptoms in order to obtain a disability pension.

Conclusions: It is important to consider malingering as a differential diagnosis in patients who present with atypical features and have clear external incentives for their behaviour. With improved health literacy and access to health information, individuals who are marginalized in society and have limited social and occupational opportunities may malinger symptoms for obvious personal gain. Inconsistency between reported symptoms and clinical observations, as well as contradictory collateral information from multiple sources, are helpful tools in diagnosing malingering. It is important for clinicians to identify malingerers early and limit unnecessary admissions.
Visualizing histone modifications in living cells: spatiotemporal dynamics of H3 phosphorylation during interphase
Authors: Hayashi-Takanaka Yoko , Yamagata Kazuo , Nozaki Naohito , Kimura Hiroshi
Published: December 2009

Posttranslational histone modifications regulate both gene expression and genome integrity. Despite the dynamic nature of these modifications, appropriate real-time monitoring systems are lacking. In this study, we developed a method to visualize histone modifications in living somatic cells and preimplantation embryos by loading fluorescently labeled specific Fab antibody fragments. The technique was used to study histone H3 Ser10 (H3S10) phosphorylation, which occurs during chromosome condensation in mitosis mediated by the aurora B kinase. In aneuploid cancer cells that frequently missegregate chromosomes, H3S10 is phosphorylated just before the chromosomes condense, whereas aurora B already accumulates in nuclei during S phase. In contrast, in nontransformed cells, phosphorylated H3S10 foci appear for a few hours during interphase, and transient exposure to an aurora B–selective inhibitor during this period induces chromosome missegregation. These results suggest that, during interphase, moderate aurora B activity or H3S10 phosphorylation is required for accurate chromosome segregation. Visualizing histone modifications in living cells will facilitate future epigenetic and cell regulation studies.
The Cul3–KLHL21 E3 ubiquitin ligase targets Aurora B to midzone microtubules in anaphase and is required for cytokinesis
Authors: Maerki Sarah , Olma Michael H. , Staubli Titu , Steigemann Patrick , Gerlich Daniel W. , Quadroni Manfredo , Sumara Izabela , Peter Matthias
Published: December 2009

Cul3 (Cullin3)-based E3 ubiquitin ligases recently emerged as critical regulators of mitosis. In this study, we identify two mammalian BTB (Bric-a-brac–Tramtrack–Broad complex)-Kelch proteins, KLHL21 and KLHL22, that interact with Cul3 and are required for efficient chromosome alignment. Interestingly, KLHL21 but not KLHL22 is necessary for cytokinesis and regulates translocation of the chromosomal passenger complex (CPC) from chromosomes to the spindle midzone in anaphase, similar to the previously described BTB-Kelch proteins KLHL9 and KLHL13. KLHL21 directly binds to Aurora B and mediates ubiquitination of Aurora B in vitro. In contrast to KLHL9 and KLHL13, KLHL21 localizes to midzone microtubules in anaphase and recruits Aurora B and Cul3 to this region. Together, our results suggest that different Cul3 adaptors nonredundantly regulate Aurora B during mitosis, possibly by ubiquitinating different pools of Aurora B at distinct subcellular localizations.
Disease-specific gene repositioning in breast cancer
Authors: Meaburn Karen J. , Gudla Prabhakar R. , Khan Sameena , Lockett Stephen J. , Misteli Tom
Published: December 2009

Genomes are nonrandomly organized within the three-dimensional space of the cell nucleus. Here, we have identified several genes whose nuclear positions are altered in human invasive breast cancer compared with normal breast tissue. The changes in positioning are gene specific and are not a reflection of genomic instability within the cancer tissue. Repositioning events are specific to cancer and do not generally occur in noncancerous breast disease. Moreover, we show that the spatial positions of genes are highly consistent between individuals. Our data indicate that cancer cells have disease-specific gene distributions. These interphase gene positioning patterns may be used to identify cancer tissues.
MGL1 promotes adipose tissue inflammation and insulin resistance by regulating 7/4hi monocytes in obesity
Authors: Westcott Daniel J. , DelProposto Jennifer B. , Geletka Lynn M. , Wang Tianyi , Singer Kanakadurga , Saltiel Alan R. , Lumeng Carey N.
Published: December 2009

Adipose tissue macrophages (ATMs) play a critical role in obesity-induced inflammation and insulin resistance. Distinct subtypes of ATMs have been identified that differentially express macrophage galactose-type C-type lectin 1 (MGL1/CD301), a marker of alternatively activated macrophages. To evaluate if MGL1 is required for the anti-inflammatory function of resident (type 2) MGL1+ ATMs, we examined the effects of diet-induced obesity (DIO) on inflammation and metabolism in Mgl1−/− mice. We found that Mgl1 is not required for the trafficking of type 2 ATMs to adipose tissue. Surprisingly, obese Mgl1−/− mice were protected from glucose intolerance, insulin resistance, and steatosis despite having more visceral fat. This protection was caused by a significant decrease in inflammatory (type 1) CD11c+ ATMs in the visceral adipose tissue of Mgl1−/− mice. MGL1 was expressed specifically in 7/4hi inflammatory monocytes in the blood and obese Mgl1−/− mice had lower levels of 7/4hi monocytes. Mgl1−/− monocytes had decreased half-life after adoptive transfer and demonstrated decreased adhesion to adipocytes indicating a role for MGL1 in the regulation of monocyte function. This study identifies MGL1 as a novel regulator of inflammatory monocyte trafficking to adipose tissue in response to DIO.
Preformed portals facilitate dendritic cell entry into afferent lymphatic vessels
Authors: Pflicke Holger , Sixt Michael
Published: December 2009

Although both processes occur at similar rates, leukocyte extravasation from the blood circulation is well investigated, whereas intravasation into lymphatic vessels has hardly been studied. In contrast to a common assumption—that intra- and extravasation follow similar molecular principles—we previously showed that lymphatic entry of dendritic cells (DCs) does not require integrin-mediated adhesive interactions. In this study, we demonstrate that DC-entry is also independent of pericellular proteolysis, raising the question of whether lymphatic vessels offer preexisting entry routes. We find that the perilymphatic basement membrane of initial lymphatic vessels is discontinuous and therefore leaves gaps for entering cells. Using a newly developed in situ live cell imaging approach that allows us to dynamically visualize the cells and their extracellular environment, we demonstrate that DCs enter through these discontinuities, which are transiently mechanically dilated by the passaging cells. We further show that penetration of the underlying lymphatic endothelial layer occurs through flap valves lacking continuous intercellular junctions. Together, we demonstrate free cellular communication between interstitium and lymphatic lumen.
Estimation of the centre of a diffraction peak by triggering the goniometer-angle readingsviaphoton detection
Authors: Mana Giovanni , Krempel Jochen , Ferroglio Luca
Published: December 2009

In nuclear spectroscopy by crystal diffraction, peak sharpness and low count rate make the jitter of the goniometer angle a limit to resolution. A device that uses the photon detection to trigger the reading of the angle allows information to be preserved, notwithstanding noise. A Bayesian analysis is applied to estimate the centre of the diffraction peak, without binning the recorded angles.
Theoretical analysis of apical bonding in copper(II) chelates withN-substituted amino acids
Authors: Miličević Ante , Raos Nenad
Published: December 2009

The interdependence between the side of apical coordination of H2O and steric crowding at the apical positions was investigated on a set of 34 copper(II) bis-complexes withN- andN,N-substituted amino acids. As a measure of steric crowding, overlapping volumesV* were used, calculated using a modified overlapping spheres method. Steric crowding around the apically bonded ligand was the same for this set of complexes as for the copper(II) bis-complexes with naturally occurring amino acids, with the optimal occupied volume values between 1 and 1.5 Å3. The interdependence between the length of the apical bond and distortion of the coordination polyhedron was also studied. The apical bond length showed sigmoidal dependence on the magnitude of distortion.
MLDB: macromolecule ligand database
Authors: Saravanan S. E. , Karthi R. , Sathish K. , Kokila K. , Sabarinathan R. , Sekar K.
Published: December 2009

MLDB (macromolecule ligand database) is a knowledgebase containing ligands co-crystallized with the three-dimensional structures available in the Protein Data Bank. The proposed knowledgebase serves as an open resource for the analysis and visualization of all ligands and their interactions with macromolecular structures. MLDB can be used to search ligands, and their interactions can be visualized both in text and graphical formats. MLDB will be updated at regular intervals (weekly) with automated Perl scripts. The knowledgebase is intended to serve the scientific community working in the areas of molecular and structural biology. It is available free to users around the clock and can be accessed at http://dicsoft2.physics.iisc.ernet.in/mldb/.
Increased levels of the inflammatory biomarker C‐reactive protein at baseline are associated with childhood sickle cell vasocclusive crises
Authors: Krishnan Suba , Setty Yamaja , Betal Suhita G. , Vijender Vaidyula , Rao Koneti , Dampier Carlton , Stuart Marie
Published: December 2009

Several lines of evidence suggest that sickle cell disease (SCD) is associated with a chronic inflammatory state. In this study of 70 children with SCD at steady state evaluated by a broad panel of biomarkers representing previously examined mechanisms of pathogenicity in SCD, high sensitivity C‐reactive protein (hs‐CRP), a marker of low‐grade, systemic inflammation, emerged as the most significant laboratory correlate of hospitalizations for pain or vaso‐occlusive (VOC) events. While markers of increased haemolytic status, endothelial activation and coagulation activation all correlated positively with VOC events by univariate analysis, baseline hs‐CRP levels provided the most significant contribution to the association in multiple regression models (22%), and, hs‐CRP, along with age, provided the best fit in negative binomial models. These data highlight the clinical relevance of the role of inflammation in paediatric VOC, providing both a rationale for future therapeutic strategies targeting inflammation in microvessel occlusive complications of SCD, and the potential clinical use of hs‐CRP as a biomarker in childhood SCD.
188Re anti‐CD66 radioimmunotherapy combined with reduced‐intensity conditioning and in‐vivo T cell depletion in elderly patients undergoing allogeneic haematopoietic cell transplantation
Authors: Lauter Anett , Strumpf Annette , Platzbecker Uwe , Schetelig Johannes , Wermke Martin , Radke Jörgen , Kiani Alexander , Wunderlich Gerd , Thiede Christian , Ehninger Gerhard , Kotzerke Jorg , Bornhäuser Martin
Published: December 2009

The addition of radioimmunotherapy to conventional and reduced‐intensity conditioning has been shown to be feasible and effective. Within an ongoing prospective phase II trial, 22 patients with advanced myeloid malignancies and a median age of 65 years (range 54–76) received anti‐CD66 Rhenium radioimmunotherapy followed by fludarabine (150 mg/m2), busulfan (8 mg/kg) and alemtuzumab (75 mg) before allogeneic haematopoietic stem cell transplantation from matched sibling (n = 7) and unrelated donors (n = 15). The extramedullary toxicity in the first 100 d post‐transplantation was limited and all patients engrafted with complete donor chimaerism. The incidence of non‐relapse mortality at day 100 and after 2 years was 4·5% and 23%, respectively. The probability of overall survival at 2 years was 40%. A comparison with a younger historical cohort (median age 57 years) having received the same dose of fludarabine and busulfan but neither radioimmunotherapy nor alemtuzumab showed no difference in outcome. Although the use of alemtuzumab reduced the incidence of acute graft‐versus‐host‐disease, it was associated with a relapse incidence of 40% despite the incorporation of radioimmmunotherapy. In summary, we confirmed the feasibility of combined radioimmunotherapy and reduced‐intensity conditioning in elderly patients. Further optimisation, probably involving less T cell depletion, is necessary before a randomized comparison with standard conditioning can be planned.
Alemtuzumab is safe and effective as immunosuppressive treatment for aplastic anaemia and single‐lineage marrow failure: a pilot study and a survey from the EBMT WPSAA
Authors: Risitano Antonio Maria , Selleri Carmine , Serio Bianca , Torelli Giovanni Fernando , Kulagin Alexander , Maury Sébastien , Halter Jörg , Gupta Vikas , Bacigalupo Andrea , Sociè Gerard , Tichelli André , Schrezenmeier Hubert , Marsh Judith , Passweg Jakob , Rotoli Bruno ,   on behalf of the Working Party Severe Aplastic Anaemia (WPSAA) of the European Group for Blood and Marrow Transplantation (EBMT)
Published: December 2009

An alemtuzumab‐based experimental immunosuppressive treatment (IST) regimen was investigated in 35 patients with severe aplastic anaemia (SAA), pure red cell (PRCA) or pure white cell aplasia (PWCA). Alemtuzumab total dose was 73–103 mg s.c., followed by cyclosporine. No serious toxicity due to the regimen was observed. Adverse events were clinically irrelevant; infectious events were rare. The total response rate was 58%, 84% and 100% in SAA, PRCA and PWCA, respectively, with corresponding 6 months cumulative response probabilities of 84%, 84% and 100%. Subcutaneous alemtuzumab is a feasible and sufficiently safe IST regimen for patients suffering from immune‐mediated marrow failures.
Connectivity of lobster (Homarus americanus) populations in the coastal Gulf of Maine: part II. Coupled biophysical dynamics
Authors: INCZE LEWIS , XUE HUIJIE , WOLFF NICHOLAS , XU DANYA , WILSON CARL , STENECK ROBERT , WAHLE RICHARD , LAWTON PETER , PETTIGREW NEAL , CHEN YONG
Published: December 2009

We used a coupled biophysical model to investigate larval transport and connectivity patterns in the Gulf of Maine lobster (Homarus americanus) population. Biological ‘particles’ were released at over 21 000 locations every 10 days over a 4‐month hatching period, and were followed from hatching through late postlarval stage. In addition to circulation and dispersion, model calculations included spatial patterns of egg production, temporal patterns of hatching, temperature‐dependent development, vertical distribution and mortality. We ran the model for three larval production seasons using the same hatching patterns and individual‐based modeling parameters but different flow patterns in the coastal current system. Model results gave distribution and abundance patterns of competent postlarvae that closely resembled observed, alongshore patterns of lobster settlement density. We evaluated the relative contribution of all source regions to the total number of competent postlarvae in a series of medium‐size zones along the coastal shelf, many of which are used in lobster management. Connectivity depended on many factors, including patterns of egg production and transport, and the location and size of the receiving zones. Self recruitment ranged from a few percent to >90% of competent postlarvae. Although it was common for postlarvae to come from many, often distant, sources, most of the competent postlarvae in a zone originated within one to two zones in the prevailing ‘up‐stream’ direction, forming shorter connections along the coast than the energetic currents might otherwise suggest. Inshore migrations during summer hatching may contribute to these shorter patterns of connectivity. Transport in the prevailing ‘upstream’ direction was also indicated.
Demersal fish and invertebrate biomass in relation to an offshore hypoxic zone along the US West Coast
Authors: KELLER AIMEE A. , SIMON VICTOR , CHAN FRANCIS , WAKEFIELD W. W. , CLARKE M. E. , BARTH JOHN A. , KAMIKAWA DAN , FRUH ERICA L.
Published: December 2009

In August 2007, as part of the NOAA National Marine Fisheries Service (NMFS) West Coast Groundfish Bottom Trawl Survey, we examined the biomass of demersal organisms in a known hypoxic area off the Oregon coast. Although observed each summer, the intensity of hypoxia has varied annually (2002–2007) with the greatest temporal and spatial extent noted in 2006. In 2007 we identified the geographic extent of the hypoxic zone and sampled 17 stations along two depth contours (50 and 70 m) within the area. A Sea‐Bird SBE 19plus equipped with a dissolved oxygen (DO) sensor was attached to the bottom trawl to monitor oxygen concentration during each tow. Bottom DO concentrations at all stations were hypoxic with means along the tow tracts ranging from 0.43 to 1.27 mL L−1. Total catch per unit effort (ln CPUE, kg hectare−1) and species diversity (number of species, N) were significantly and positively related to oxygen concentration along the hypoxic gradient. In addition, CPUE (natural log‐transformed) for eight fish species and five benthic invertebrate species were significantly and positively related to bottom oxygen concentration within the hypoxic region. Condition factors for five fish species, as well as Dungeness crab (Cancer magister) increased with increased bottom oxygen levels along the hypoxic gradient. Historical catch (2003–2006) within the hypoxic zone indicates that biomass was significantly lower in 2006, the year with the lowest bottom DO levels, relative to other years.