bluuebunny/crossref_metadata_2025 huggingface dataset:
Adverse events in Victorian admissions for elective surgery
Authors: Moje Christine , Jackson Terri J , McNair Peter
Published: February 2010

Objectives: To investigate a method to identify
and understand patterns of adverse events by
utilising secondary data analysis; to identify the
types of complications associated with elective
surgery; to identify any specific ?adverse eventprone?
elective procedures; and to consider the
implications of these patterns for hospital patient
safety programs.
Setting: Public hospitals in Victoria.
Design: Secondary analysis of data on acute
hospital admissions for elective surgery in the
period 1 July 2000 to 30 June 2001, for nonobstetric
patients older than 15 years (n = 177 533).
Main outcome measures: Estimated rates of
adverse events for the most commonly performed
elective surgery procedures; frequency of the
most commonly recorded adverse event types.
Results: Of all admissions, 15.5% had at least
one complication of care. The most frequent firstrecorded
single complication code, in 9.6% of
cases with a complication, was ?Haemorrhage
and haematoma complicating a procedure?. The
most common adverse event categories were
cardiac and circulatory complications (23%),
symptomatic complications (18%), and surgical
and drug-related complications (17%). The procedure
blocks most frequently associated with an
adverse event were coronary artery bypass surgery
(67%), colectomy (52%), hip and knee
arthroplasty (42% and 36%, respectively), and
hysterectomy (20%). The types of complications
associated with the four most adverse eventprone
procedures were cardiac arrhythmias, surgical
adverse events (haemorrhage or laceration),
intestinal obstruction, anaemia, and symptomatic
complications.
Conclusion: Routinely collected data are valuable
in obtaining information on complication types
associated with elective surgery. International
Classification of Diseases codes and surgical
procedure ?blocks? allow very sophisticated investigation
of types of complications and differences
in complication rates for different surgical
approaches. The usefulness of such data relies
on good documentation in the medical record,
thorough coding and periodic data audit. The
limitations of the method described here include
the lack of follow-up after discharge, variable
coding standards between institutions and over
time (potentially distorting information on rates),
lack of information on the causative factors for
some adverse events, and a limited capacity to
support investigation of particular cases. Hospitals
should consider monitoring complication rates
for individual elective procedures or blocks of
similar procedures, and comparing adverse event
rates over time and with peer hospitals as an
integral part of their patient safety programs.
A case study on determining and responding to health managers' priorities for research to assist health service decision making
Authors: Aldrich Rosemary , Bonevski Billie , Wilson Amanda
Published: February 2010

The Newcastle Institute of Public Health (NIPH) is
a collaboration of health service and public health
research groups in the Hunter Region of New
South Wales, Australia which aims to promote the
use of evidence in decision making. However, use
of research evidence in decision making is a
complex process, with many barriers and enablers
described in the literature.
Informed by strategies described in the literature
around developing priority-driven research, NIPH
researchers undertook to determine whether asking
local health decision-makers about their needs
for research information might lead to greater use
of the resulting research evidence to inform health
service management decisions. This paper
describes a process used by NIPH to determine
the research needs of 11 local senior health
managers, our response to specific research
questions, the communication of this research
information, and the outcome.
Introducing nosokinetics: modelling to enhance health system management
Authors: Millard Peter , Mackay Mark
Published: February 2010

THE WORLD POPULATION IS AGEING and there is a
crisis in hospital care. Correlation is not causation;
however, there is an interesting relationship
between the introduction of computer assisted
hospital statistical returns and the crisis in inpatient
care. This issue of Australian Health Review
contains seven papers from the Nosokinetics
Group?s first International Health and Social Care
Modelling Conference held in Adelaide in April
2006. A broad range of practical and theoretical
clinical and managerial topics were discussed at
this conference.
The United Kingdom-based Nosokinetics
Group is a loose worldwide collaboration of
mathematicians, decision scientists, clinicians
and health service personnel developing and
validating models that describe the process of
inpatient care. Literally, nosokinetics brings
together the Greek words for disease (noso) and
movement (kinetics). Hence nosokinetics is the
science of measuring and modelling patient flow
through health and social care systems. The
underlying premise of collaborating members is
that the world will be a better place when the
current tools used to measure the process of care
are replaced by a scientifically validated
approach.
Fast-tracking acute hospital care — from bed crisis to bed crisis
Authors: Rae Brendon , Busby Wendy , Millard Peter H
Published: February 2010

We describe here the results of a continuous
quality improvement (CQI) project, the Delayed
Discharge Project, in a general medicine service
in a New Zealand teaching hospital. Average
length of stay (ALOS) dropped by 2.6 days (6.5 to
3.9), readmission rates did not rise, costs of
service delivery dropped by $2.4 million, patient
numbers increased by 145 (2445 to 2590), while
bed numbers reduced from 56 to 32 and ward
outliers all but disappeared, suggesting success.
However, 2 years after the successful cost-saving
measures were introduced the new system
crashed as a result of additional bed closures and
organisational restructures.
2006 Biennial Health Conference: Exploring and Debating Acute Care Provision
Authors: Flanagan Kerry
Published: February 2010

NO ABSTRACT
Chronic illness and consumer inequality: the impact of health costs on people with chronic illnesses in rural and regional Australia
Authors: Walker Christine
Published: February 2010

This paper presents the results of a survey undertaken
in rural and regional Victoria in 2003 on the
total costs faced by households caring for people
with chronic illnesses. The impact of these costs
for the households is discussed in the context of
neo-liberal policy development by Australian governments
and the effects of those policies on such
households.
Editorial
Authors: Yarmo-Roberts Deborah
Published: February 2010

INDIVIDUALS ARE LIVING longer than ever before,
with a propensity to acquire debilitating conditions,
often with comorbidities. This necessitates
care delivered from many sectors of the
service system. This issue?s featured Models of
Care article, ?Integrated care facilitation for
older patients with complex health care needs
reduces hospital demand? on page 451
describes a model of care which aimed to
coordinate health care services for older adults.
One of the successes of this model was the
employment of personal care facilitators, who
assisted the patients in understanding their
health condition, which promoted self-management
in accessing required services.
Information management: the limitations of ROI
Authors: Leggat Sandra G
Published: February 2010

THE REVIEW OF the 60-year history of the Australian
Healthcare and Hospitals Association highlights
the important role of information and
information management in enhancing the Australian
health care system. In 1990 Peter Read, the
National Director of the (then) Australian Hospital
Association, suggested that the health system
would soon have
hospitals where there are proper information
systems which allow managers to identify
problem areas by intra and inter hospital comparisons;
hospitals where managers know how
much treatment does cost and more importantly
how much it should cost; and hospitals
where the incentives encourage efficient high
quality care and where payment received has
some relevance to the cost of treatment given.1
But 2007 is almost over and, as outlined by Jared
Dart our n=1 author (page 510), we are still waiting!
Government funders and health service organisations
typically view information as a cost to be
managed and not as an asset in which to invest.
While investment in health care information management
and technology cannot often be justified
on economic or financial terms (that is, the financial
return on investment [ROI]), a broader perspective
that included the positive impact on the
quality of care, the improvement in patient safety
and patient satisfaction, and the reduction in social
costs would favourably tip the investment scale. A
paradigm shift is required to balance an overriding
concern with return on investment with return to
care.
This issue focuses on work that is being completed
on information foundations (pages 523, 531,
540 and 546), exploitation of technology (page 527)
and the use of information to improve care. I would
like to draw your attention to the paper by Watson,
Rayner, and Lumley from Mother and Child Health
Research that outlines their experience in obtaining
ethics approval for a study of preterm birth
(page 514). This paper provides an example of the
information inefficiencies that we have created and
perpetuate in our health care system.
Don?t miss this issue?s Models of Care paper by
Francis and colleagues (page 499) and the concept
of health in older age (page 642).
Mature use of casemix — are we there yet?
Authors: Balnave Lai-Mun , Reid Beth A
Published: February 2010

In this paper we consider the progress made in
using casemix in Australia. We argue that while
the casemix infrastructure has been highly developed
and the casemix-based funding systems of
some states are mature, there is still more development
needed to use the data for clinical questions
such as quality improvement activities.
Further research is needed to establish what is
needed to describe the impact of casemix on
clinicians and hospitals in a context of increasing
accountability and transparency and where questions of efficiency cannot be ignored.
Supporting work practices, improving patient flow and monitoring performance using a clinical information management system
Authors: Poulos Christopher J , Gazibarich Boris M , Eagar Kathy
Published: February 2010

Providing information technology solutions to clinicians
to support their work practices benefits
clinicians, administrators and patients. We present
our 8-year experience with an inexpensive information
management system which provides clinical
and business process support for clinicians
and bed managers. The system has been used by
an area rehabilitation and aged care service to
manage inpatient consultations and patient flow
across nine hospitals. Performance monitoring of
the time from referral to consultation, the number,
type and outcome of consultations, and the time
taken to access a rehabilitation or subacute bed is
also provided. Read-only access to the system for
clinicians and bed managers outside the rehabilitation
and aged care service allows greater transparency.
The AROC Annual Report: the state of rehabilitation in Australia 2006
Authors: Simmonds Frances , Stevermuer Tara
Published: February 2010

This is the second comprehensive annual report
that describes patients discharged from subacute
inpatient rehabilitation programs provided by facilities
that are members of the Australasian Rehabilitation
Outcomes Centre (AROC).
The inaugural annual report was published in April
2007 and described the 2005 data. (Aust Health
Rev 2007: 31 Suppl 1: s31-s53.)
The real business of health care
Authors: Leggat Sandra G
Published: February 2010

THIS ISSUE CONTAINS papers that consider some
of the complex issues within human resource
management (HRM) in health care. In health
systems the care provided has tended to be craftbased
production ? a trained health professional
provides his or her craft for individual patients,
with little need for management. Influencing the
relationship between practitioner and patient has
been limited by professional autonomy and the
different cultures that exist among the specialised
health professional groups. These differences are
illustrated by Perkins et al by the results of a
survey of starting and finishing undergraduate
medical, nursing and pharmacy students
(page 252).
People with an intellectual disability in the discourse of chronic and complex conditions: an invisible group?
Authors: Goddard Linda , Davidson Patricia M , Daly John , Mackey Sandra
Published: February 2010

People with an intellectual disability and their
families experience poorer health care compared
with the general population. Living with an intellectual
disability is often challenged by coexisting
complex and chronic conditions, such as gastrointestinal
and respiratory conditions. A literature
review was undertaken to document the needs of
this vulnerable population, and consultation was
undertaken with mothers of children with disabilities
and with professionals working within disability
services for people with an intellectual disability
and their families. Based on this review, there is a
need to increase the profile of people with an
intellectual disability in the discourse surrounding
chronic and complex conditions. Strategies such
as guideline and competency development may
better prepare health professions to care for people
with disabilities and chronic and complex care
needs and their families.
Enhancing psychosocial care for people with cancer in rural communities: what can remote counselling offer?
Authors: Shepherd Louise , Goldstein David , Olver Ian , Parle Michael
Published: February 2010

Rural cancer patients are often disadvantaged in
access to psychological services. We reviewed
remote counselling research for psychological
support using telephone, videoconferencing, and
the Internet as a potential solution. Telephone
counselling is the most extensively researched,
while there are encouraging findings in emerging
research about videoconferencing and Internetbased
psychological care. Where no face-to-face
psychological service exists, these technologies
are promising, yet unproven. Less variable methods
are needed to better assess the technology
and therapeutic approach for stronger evidence.
A health impact assessment on the construction phase of a major hospital redevelopment
Authors: Maxwell Michelle , Harris Patrick , Peters Sharon , Thornell Mark , D'Souza Leah
Published: February 2010

A prospective health impact assessment (HIA)
was conducted to identify potential health impacts
arising from the planned redevelopment of Liverpool
Hospital, a major teaching hospital in New
South Wales, Australia. A multidisciplinary team of
health professionals oversaw the HIA and a core
project team led by population health practitioners
conducted the HIA using a structured, stepwise
process. Methods used to gather data for the
identification of impacts were a literature review,
development of a population profile and consultation
with stakeholders. A range of positive and
negative health impacts were identified and an
assessment matrix was used to prioritise the
health impacts and develop recommendations for
the proponents of the redevelopment plan.The
HIA added value to the planning process for the
hospital redevelopment, increasing capacity to
conduct future HIAs.
The negative impact on nurses of lack of alignment of information systems with public hospital strategic goals
Authors: Firth Lucy A , Mellor David J , Francis Peter S
Published: February 2010

The objectives of this study were to investigate the
degree to which hospital information systems are
aligned with hospital strategies and how they
impact on nurses. Semi-structured interviews
were conducted with nine hospital staff from a
range of disciplines in a large public hospital in
Australia. The interviews revealed that the focus of
hospital information systems on administration
has meant that applications to support the
patient?s clinical journey have been deemed unaffordable.
A consequence is that the historic use of
the nurses? station as a source of verbal information
about patients has continued, with negative
impacts on nurses? perceived role and status, and
the possible exacerbation of the clash between
administrative and clinical cultures. We conclude
that hospitals need clear strategies, with alignment
of information systems. To do otherwise can
undermine culture and morale, while disrupting
workflows and patients? clinical journeys.
Divisions of general practice:a status review
Authors: Pegram Robert , Sprogis Arn , Buckpitt Jeff
Published: February 2010

This paper looks at the emergence of divisions of general practice in Australia.Divisions are local groups of general practitioners working to integrate general practiceinto the wider health system and to explore opportunities for improving servicedelivery, teaching and research. There are now 116 divisions of general practice,covering over 95- per cent of the Australian population. Projects and infrastructurefunding was approximately $35 million in 1994?95.Divisions have enabled general practitioners to retain their autonomy whileresponding to a government health reform process which depends on theirparticipation. They are a uniquely Australian solution to the problems confrontinggeneral practice in the 1990s, bridging the gap that previously existed betweenindividual general practitioners and the health system as a whole.The Divisions and Projects program is being evaluated using a variety ofmethods which allow feedback into the program in a timely way. The program thusremains sensitive to new strategies and directions, either from the general practitionersthemselves or from other stakeholders.
An overview of the role of government in the organisation and provision of health services in Japan
Authors: Walker Christopher
Published: February 2010

This article is illustrated with reference to health services in the Tokyo Prefecture.It seeks to describe the role of government in the organisation and provision of healthservices in Japan. It is based on experiences gained from a three-month placementat the Tokyo Metropolitan Government Bureau of Public Health in late 1994.Wherever possible the article identifies similarities and differences between theJapanese and Australian health care systems. Part of the analysis has been to identifyareas where opportunities exist for Australian health service providers to developfurther cooperation with particular sectors of the Japanese health system and alsowhere the potential for the export of health services may exist.The health systems of Australia and Japan have points of similarity anddifference. Essentially both systems operate within the context of a compulsoryuniversal health insurance system. However, unlike Australia, the bulk of serviceprovision in Japan is left to the private sector, while government retains the primaryrole of regulator. It is interesting to observe that while the Australian health caresystem is currently exploring options to expand the service range and level ofparticipation of private sector services in health care delivery (within the context ofuniversal health insurance), the Japanese health care system appears to be examiningoptions through which further government intervention can improve service accessand service efficiency. Japan presents opportunities to observe the benefits anddisadvantages of predominantly private sector provision within the context ofuniversal health insurance coverage.
Casemix funding in psychiatry:Some problems and common pitfalls
Authors: Hay Phillipa J , Pearce Trevor
Published: February 2010

The aims of this study were to evaluate the accuracy of AN-DRG version 2.0 codings.Ninety-two separations, covering three of the most commonly occurring AN-DRGsin psychiatry, were reviewed by a psychiatrist. The AN-DRG diagnosis was thencompared to that given by morbidity coders. There was agreement for 69 (79- per cent)separations and disagreement for 18 (21- per cent) separations. Recoding of the 18separations altered average length of stay data and the funding received. The high errorrate of coding stimulated changes to the training of morbidity coders and registrars.
Protecting patient confidentiality in hospitals
Authors: Mulligan E.A
Published: February 2010

As new methods of electronic data storage and distribution appear in hospitals, newchallenges in protecting confidentiality have emerged. At the same time, demands for?seamless? care and the desire to share information between clinicians are motivatinghospitals to relax barriers to the transfer of patient information.Increasing numbers of users at multiple sites compound the difficulty of ensuringinformation systems security. Hospital policy may demand that requests by patientsto restrict the distribution of personal information be respected, while existingelectronic systems are not able to deliver on this promise.Compliance with the Information Privacy Principles of the Commonwealth PrivacyAct 1988 and the Australian Standard 4400?1995 ?Personal privacy protection inhealth care information systems? will provide a useful framework for managing these challenges. However, their implementation will require some forethought.
Outcome evaluation in nursing in Australia, 1960-1980
Authors: Middleton Sandy , Lumby Judy
Published: February 2010

While empirical evaluation of the outcome of patient care has come to the fore inrecent years due to political initiatives, there has always been a professional interestby nurses in the end result of their care. A review of the literature shows that outcomeevaluation was advocated for nursing as early as the 1860s by Florence Nightingale.This article explores the evolvement of outcome evaluation within nursing inAustralia, discussing its origins during the 1960s and 1970s. The measurement ofpatient outcomes is more relevant than ever before, with the recent drive for anevidence-based approach to nursing care.
Mental health and general practice:Improving linkages using a total quality management approach
Authors: Tobin Margaret , Norris Gus
Published: February 2010

This paper reports on a project to implement total quality management strategies toimprove the linkages between general practitioners and specialist mental healthservices. The project implemented a process of change and objectively assessed thesuccess of the process. The project involved all mental health staff (n = 100) in theSt George Division of Psychiatry and Mental Health. General practitioners registeredwith the St George Division of General Practice were invited to participate in thechange process. The project showed that the attempts to engage general practitionersin the ongoing care of patients with chronic mental illness is unlikely to be successfuluntil mental health services promote general practitioner linkages as an ongoing servicegoal, relevant at all levels of delivery.
Relocation for treatment for leukaemia: A description of need
Authors: McGrath Pam
Published: February 2010

As rural Queenslanders are isolated geographically due to dispersed populationpatterns, they are often required to travel long distances to access services, especiallyservices of a specialist nature. The distress of this relocation for treatment is particularlyintensified for patients with leukaemia and associated haematological disorders andtheir carers, as they must often relocate for long periods of time and face invasive anddemanding treatments away from the comfort of their own homes. Because suchtreatments are now highly technical and specialised, even patients from moreurbanised areas are also required to relocate for prolonged specialist treatment notavailable locally. Consequently, for many rural and urban patients with leukaemia,relocation for specialist treatment is a major concern.This discussion presents findings from recent research on a Queensland Governmentinitiative, the Patient Transit Assistance Scheme, designed to address this concern.These findings indicate a high level of hardship for these patients and their familieswho must travel long distances, often relocate for long periods, and endure additionalfinancial burdens at a time when a majority are dependent on government assistance.
The Allied Health BONE Team:An interdisciplinary approach to orthopaedic early discharge and admission prevention
Authors: Bandis Susan , Murtagh Shelley , Solia Robyn
Published: February 2010

This paper presents the conceptual framework, activities and outcomes of the AlliedHealth BONE (Best Orthopaedic New Enterprise) Team, an early discharge incentiveat the Gold Coast Hospital. The clinical team of a physiotherapist, occupationaltherapist and social worker provided services within an interdisciplinary model of carewith the aim of reducing the length of stay of acute adult orthopaedic patients. Theteam provided intervention in the community, the accident and emergencydepartment, pre-admission clinic and orthopaedic wards to patients with hip andknee replacements, back pain and upper femoral fractures. This paper reports datafrom the first six months of the project, demonstrating success in improving thecontinuity of care provided to orthopaedic patients and reducing the length of stayin target groups by 24%.
A comparison of the impact of hospital reform on medical subcultures in some Australian and New Zealand hospitals
Authors: Degeling Pieter , Sage David , Kennedy John , Perkins Rod , Zhang Kai
Published: February 2010

This article examines similarities and differences in the way that hospital staff in Australia and New Zealand are evaluating efforts to improve quality, clinical effectiveness and service integration, and to strengthen clinical accountability. We draw on data from a cross-national study of hospital staff in Australia and New Zealand. The results highlight the way in which respondents' views about reform are influenced by the interplay of two factors: the impact of respondents' occupational backgrounds (our findings point to differences in the profession-based subcultures of medicine, nursing and general management and the way that these are reflected in respondents' assessments of particular aspects of reform); and the way that the impact of professional subcultures may be mitigated by differences between the systems in which respondents were located, including differences between the programs of reform that have been pursued in each country. The implications of these findings are discussed.
N-cadherin ligation, but not Sonic hedgehog binding, initiates Cdo-dependent p38α/β MAPK signaling in skeletal myoblasts
Authors: Lu Min , Krauss Robert S.
Published: February 2010

The p38α/β mitogen-activated protein kinase (MAPK) pathway promotes muscle-specific gene expression and myoblast differentiation but how pathway activity is initiated during these processes is poorly understood. During myoblast differentiation, the intracellular region of the promyogenic cell surface protein Cdo (also known as Cdon) binds to Bnip-2 and JLP, scaffold proteins for Cdc42 and p38α/β MAPK, respectively. The Bnip-2/Cdc42 and JLP/p38α/β complexes associate in a Cdo-dependent manner, resulting in Bnip-2/Cdc42-dependent p38α/β activation and stimulation of cell differentiation. Although the Cdo ectodomain binds to several different proteins, it is unclear how Cdo-dependent p38α/β activation is initiated. In myoblasts, Cdo interacts with the cell–cell adhesion molecule N-cadherin. Cdo also binds directly to the secreted morphogen Sonic hedgehog (Shh) to promote Shh pathway signaling. We report here that N-cadherin ligation activates p38α/β in myoblasts in a Cdo-, Bnip-2-, and JLP-dependent manner. Furthermore, these proteins and activated Cdc42 cluster at sites of N-cadherin ligation. In contrast, neither JLP nor Bnip-2 is associated with Cdo bound to Shh, and Shh does not activate p38α/β in myoblasts. Taken together, these results link cadherin-based cell–cell adhesion to a defined signaling pathway (Cdo → p38α/β) that directly regulates a cell-type-specific differentiation program. Furthermore, they are consistent with a model whereby Cdo serves as a multifunctional coreceptor with mechanistically distinct roles in multiple signaling pathways.
Islet amyloid deposition limits the viability of human islet grafts but not porcine islet grafts
Authors: Potter K. J. , Abedini A. , Marek P. , Klimek A. M. , Butterworth S. , Driscoll M. , Baker R. , Nilsson M. R. , Warnock G. L. , Oberholzer J. , Bertera S. , Trucco M. , Korbutt G. S. , Fraser P. E. , Raleigh D. P. , Verchere C. B.
Published: February 2010

Islet transplantation is a promising treatment for diabetes but long-term success is limited by progressive graft loss. Aggregates of the beta cell peptide islet amyloid polypeptide (IAPP) promote beta cell apoptosis and rapid amyloid formation occurs in transplanted islets. Porcine islets are an attractive alternative islet source as they demonstrate long-term graft survival. We compared the capacity of transplanted human and porcine islets to form amyloid as an explanation for differences in graft survival. Human islets were transplanted into streptozotocin-diabetic immune-deficient mice. Amyloid deposition was detectable at 4 weeks posttransplantation and was associated with islet graft failure. More extensive amyloid deposition was observed after 8 weeks. By contrast, no amyloid was detected in transplanted neonatal or adult porcine islets that had maintained normoglycemia for up to 195 days. To determine whether differences in IAPP sequence between humans and pigs could explain differences in amyloid formation and transplant viability, we sequenced porcine IAPP. Porcine IAPP differs from the human sequence at 10 positions and includes substitutions predicted to reduce its amyloidogenicity. Synthetic porcine IAPP was considerably less amyloidogenic than human IAPP as determined by transmission electron microscopy, circular dichroism, and thioflavin T binding. Viability assays indicated that porcine IAPP is significantly less toxic to INS-1 beta cells than human IAPP. Our findings demonstrate that species differences in IAPP sequence can explain the lack of amyloid formation and improved survival of transplanted porcine islets. These data highlight the potential of porcine islet transplantation as a therapeutic approach for human diabetes.
Activatable cell penetrating peptides linked to nanoparticles as dual probes for in vivo fluorescence and MR imaging of proteases
Authors: Olson Emilia S. , Jiang Tao , Aguilera Todd A. , Nguyen Quyen T. , Ellies Lesley G. , Scadeng Miriam , Tsien Roger Y.
Published: February 2010

High-resolution imaging of molecules intrinsically involved in malignancy and metastasis would be of great value for clinical detection and staging of tumors. We now report in vivo visualization of matrix metalloproteinase activities by MRI and fluorescence of dendrimeric nanoparticles coated with activatable cell penetrating peptides (ACPPs), labeled with Cy5, gadolinium, or both. Uptake of such nanoparticles in tumors is 4- to 15-fold higher than for unconjugated ACPPs. With fluorescent molecules, we are able to detect residual tumor and metastases as small as 200 μm, which can be resected under fluorescence guidance and analyzed histopathologically with fluorescence microscopy. We show that uptake via this mechanism is comparable to that of other near infrared protease sensors, with the added advantage that the approach is translatable to MRI. Once activated, the Gd-labeled nanoparticles deposit high levels (30–50 μM) of Gd in tumor parenchyma with even higher amounts deposited in regions of infiltrative tumor, resulting in useful T
1
contrast lasting several days after injection. These results should improve MRI-guided clinical staging, presurgical planning, and intraoperative fluorescence-guided surgery. The approach may be generalizable to deliver radiation-sensitizing and chemotherapeutic agents.
Scaling and shear transformations capture beak shape variation in Darwin’s finches
Authors: Campàs O. , Mallarino R. , Herrel A. , Abzhanov A. , Brenner M. P.
Published: February 2010

Evolution by natural selection has resulted in a remarkable diversity of organism morphologies that has long fascinated scientists and served to establish the first relations among species. Despite the essential role of morphology as a phenotype of species, there is not yet a formal, mathematical scheme to quantify morphological phenotype and relate it to both the genotype and the underlying developmental genetics. Herein we demonstrate that the morphological diversity in the beaks of Darwin’s Finches is quantitatively accounted for by the mathematical group of affine transformations. Specifically, we show that all beak shapes of Ground Finches (genus
Geospiza
) are related by scaling transformations (a subgroup of the affine group), and the same relationship holds true for all the beak shapes of Tree, Cocos, and Warbler Finches (three distinct genera). This analysis shows that the beak shapes within each of these groups differ only by their scales, such as length and depth, which are genetically controlled by
Bmp4
and
Calmodulin
. By measuring
Bmp4
expression in the beak primordia of the species in the genus
Geospiza
, we provide a quantitative map between beak morphology and the expression levels of
Bmp4
. The complete morphological variation within the beaks of Darwin’s finches can be explained by extending the scaling transformations to the entire affine group, by including shear transformations. Altogether our results suggest that the mathematical theory of groups can help decode morphological variation, and points to a potentially hierarchical structure of morphological diversity and the underlying developmental processes.
Transcriptional corepressor TLE1 functions with Runx2 in epigenetic repression of ribosomal RNA genes
Authors: Ali Syed A. , Zaidi Sayyed K. , Dobson Jason R. , Shakoori Abdul R. , Lian Jane B. , Stein Janet L. , van Wijnen Andre J. , Stein Gary S.
Published: February 2010

Epigenetic control of ribosomal RNA (rRNA) gene transcription by cell type-specific regulators, such as the osteogenic transcription factor Runx2, conveys cellular memory of growth and differentiation to progeny cells during mitosis. Here, we examined whether coregulatory proteins contribute to epigenetic functions that are mitotically transmitted by Runx2 in osteoblastic cells. We show that the transcriptional corepressor Transducin Like Enhancer-1 (TLE1) associates with rRNA genes during mitosis and interphase through interaction with Runx2. Mechanistically, depletion of TLE1 relieves Runx2-mediated repression of rRNA genes transcription and selectively increases histone modifications linked to active transcription. Biologically, loss of TLE-dependent rRNA gene repression coincides with increased global protein synthesis and enhanced cell proliferation. Our findings reinforce the epigenetic marking target genes by phenotypic transcription factors in mitosis and demonstrate a requirement for retention of coregulatory factors to sustain physiological control of gene expression during proliferation of lineage committed cells.
Endocytosis and clathrin-uncoating defects at synapses of auxilin knockout mice
Authors: Yim Yang-In , Sun Tao , Wu Ling-Gang , Raimondi Andrea , De Camilli Pietro , Eisenberg Evan , Greene Lois E.
Published: February 2010

Neuronally expressed auxilin and ubiquitously expressed cyclin-G-dependent kinase (GAK) are homologous proteins that act as cochaperones to support the Hsc70-dependent clathrin uncoating of clathrin-coated vesicles. GAK was previously shown to be essential in mouse during embryonic development and in the adult. We have now engineered an auxilin knockout mouse. Mutant mice had a high rate of early postnatal mortality and surviving pups generally had a lower body weight than wild-type pups, although they had a normal life span. GAK was up-regulated as much as 3-fold in the brains of both surviving neonates and adult mutant mice. An increased number of clathrin-coated vesicles and empty cages were present at knockout synapses both in situ and in primary neuronal cultures. Additionally, clathrin-mediated endocytosis of synaptic vesicles in knockout hippocampal neurons was impaired, most likely due to sequestration of coat components in assembled coats and cages. Collectively, our results demonstrate the specialized role of auxilin in the recycling of synaptic vesicles at synapses, but also show that its function can be partially compensated for by up-regulation of GAK.
Tight Junction–associated MARVEL Proteins MarvelD3, Tricellulin, and Occludin Have Distinct but Overlapping Functions
Authors: Raleigh David R. , Marchiando Amanda M. , Zhang Yong , Shen Le , Sasaki Hiroyuki , Wang Yingmin , Long Manyuan , Turner Jerrold R.
Published: February 2010

In vitro studies have demonstrated that occludin and tricellulin are important for tight junction barrier function, but in vivo data suggest that loss of these proteins can be overcome. The presence of a heretofore unknown, yet related, protein could explain these observations. Here, we report marvelD3, a novel tight junction protein that, like occludin and tricellulin, contains a conserved four-transmembrane MARVEL (MAL and related proteins for vesicle trafficking and membrane link) domain. Phylogenetic tree reconstruction; analysis of RNA and protein tissue distribution; immunofluorescent and electron microscopic examination of subcellular localization; characterization of intracellular trafficking, protein interactions, dynamic behavior, and siRNA knockdown effects; and description of remodeling after in vivo immune activation show that marvelD3, occludin, and tricellulin have distinct but overlapping functions at the tight junction. Although marvelD3 is able to partially compensate for occludin or tricellulin loss, it cannot fully restore function. We conclude that marvelD3, occludin, and tricellulin define the tight junction–associated MARVEL protein family. The data further suggest that these proteins are best considered as a group with both redundant and unique contributions to epithelial function and tight junction regulation.
How significant is a protein structure similarity with TM-score = 0.5?
Authors: Xu Jinrui , Zhang Yang
Published: February 2010

Motivation: Protein structure similarity is often measured by root mean squared deviation, global distance test score and template modeling score (TM-score). However, the scores themselves cannot provide information on how significant the structural similarity is. Also, it lacks a quantitative relation between the scores and conventional fold classifications. This article aims to answer two questions: (i) what is the statistical significance of TM-score? (ii) What is the probability of two proteins having the same fold given a specific TM-score?

Results: We first made an all-to-all gapless structural match on 6684 non-homologous single-domain proteins in the PDB and found that the TM-scores follow an extreme value distribution. The data allow us to assign each TM-score a P-value that measures the chance of two randomly selected proteins obtaining an equal or higher TM-score. With a TM-score at 0.5, for instance, its P-value is 5.5 × 10−7, which means we need to consider at least 1.8 million random protein pairs to acquire a TM-score of no less than 0.5. Second, we examine the posterior probability of the same fold proteins from three datasets SCOP, CATH and the consensus of SCOP and CATH. It is found that the posterior probability from different datasets has a similar rapid phase transition around TM-score=0.5. This finding indicates that TM-score can be used as an approximate but quantitative criterion for protein topology classification, i.e. protein pairs with a TM-score >0.5 are mostly in the same fold while those with a TM-score <0.5 are mainly not in the same fold.

Contact:  zhng@umich.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
Spinal 5-HT7 Receptors Play an Important Role in the Antinociceptive and Antihyperalgesic Effects of Tramadol and Its Metabolite, O-Desmethyltramadol, via Activation of Descending Serotonergic Pathways
Authors: Yanarates Omer , Dogrul Ahmet , Yildirim Vedat , Sahin Altan , Sizlan Ali , Seyrek Melik , Akgül Özgür , Kozak Orhan , Kurt Ercan , Aypar Ulku
Published: February 2010

Background

Tramadol is an analgesic drug, and its mechanism of action is believed to be mediated by the mu-opioid receptor. A further action of tramadol has been identified as blocking the reuptake of serotonin (5-HT). One of the most recently identified subtypes of 5-HT receptor is the 5-HT7 receptor. Thus, the authors aimed to examine the potential role of serotonergic descending bulbospinal pathways and spinal 5-HT7 receptors compared with that of the 5-HT2A and 5-HT3 receptors in the antinociceptive and antihyperalgesic effects of tramadol and its major active metabolite O-desmethyltramadol (M1) on phasic and postoperative pain models.

Methods

Nociception was assessed by the radiant heat tail-flick and plantar incision test in male Balb-C mice (25-30 g). The serotonergic pathways were lesioned with an intrathecal injection of 5,7-dihydroxytryptamine. The selective 5-HT7, 5-HT2, and 5-HT3 antagonists; SB-269970 and SB-258719; ketanserin and ondansetron were given intrathecally.

Results

Systemically administered tramadol and M1 produced antinociceptive and antihyperalgesic effects. The antinociceptive effects of both tramadol and M1 were significantly diminished in 5-HT-lesioned mice. Intrathecal injection of SB-269970 (10 microg) and SB-258719 (20 microg) blocked both tramadol- and M1-induced antinociceptive and antihyperalgesic effects. Ketanserin (20 mumicrog) and ondansetron (20 microg) were unable to reverse the antinociceptive and antihyperalgesic effects of tramadol and M1.

Conclusions

These findings suggest that the descending serotonergic pathways and spinal 5-HT7 receptors play a crucial role in the antinociceptive and antihyperalgesic effects of tramadol and M1.
Diabetes-associated Alterations in Volatile Anesthetic Actions on Contractile Response to Norepinephrine in Isolated Mesenteric Resistance Arteries
Authors: Yoshino Jun , Akata Takashi , Shirozu Kazuhiro , Izumi Kaoru , Hoka Sumio
Published: February 2010

Background

Clinical concentrations of volatile anesthetics significantly influence contractile response to the sympathetic neurotransmitter norepinephrine although its precise mechanisms remain unclarified. In this study, we investigated its possible alterations in diabetes, as well as its underlying mechanisms.

Methods

Isometric force was recorded in small mesenteric arteries from streptozotocin-induced diabetic and age-matched control rats.

Results

The concentration-response curve for acetylcholine-induced endothelium-dependent relaxation was shifted to the right in diabetic arteries compared with controls. The concentration-response curve for norepinephrine-induced contraction was shifted to the left and upward by both endothelial denudation and diabetic induction. In the presence of endothelium, isoflurane or sevoflurane enhanced norepinephrine-induced contraction in control arteries but not in diabetic arteries; however, in its absence, both anesthetics identically inhibited norepinephrine-induced contraction in both groups. In control arteries, the isoflurane- or sevoflurane-induced enhancement was not affected by adrenomedullin22-52, calcitonin gene-related peptide8-37, 18beta-glycyrrhetinic acid, N-nitro l-arginine, ouabain, Ba, indomethacin, losartan, ketanserin, BQ-123, and BQ-788.

Conclusions

In diabetes, vascular responses to acetylcholine, norepinephrine, and volatile anesthetics are altered in mesenteric resistance arteries, presumably reflecting endothelial dysfunction and possibly underlying circulatory instability during administration of either anesthetic. Some endothelial mechanisms that are impaired in diabetes would be involved in the anesthetic-induced enhancement of norepinephrine-induced contraction. However, the vasoregulatory mechanism mediated by adrenomedullin, calcitonin gene-related peptide, myoendothelial gap junction, nitric oxide, endothelium-derived hyperpolarizing factor, cyclooxygenase products, angiotensin II, serotonin, or endothelin-1, all of which have been suggested to be impaired in diabetes, would not be involved in the enhancement.
Neurally Adjusted Ventilatory Assist Increases Respiratory Variability and Complexity in Acute Respiratory Failure
Authors: Schmidt Matthieu , Demoule Alexandre , Cracco Christophe , Gharbi Alexandre , Fiamma Marie-Noëlle , Straus Christian , Duguet Alexandre , Gottfried Stewart B. , Similowski Thomas
Published: February 2010

Background

Neurally adjusted ventilatory assist (NAVA) is a partial ventilatory support mode where positive pressure is provided in relation to diaphragmatic electrical activity (EAdi). Central inspiratory activity is normally not monotonous, but it demonstrates short-term variability and complexity. The authors reasoned that NAVA should produce a more "natural" or variable breathing pattern than other modes. This study compared respiratory variability and complexity during pressure support ventilation (PSV) and NAVA.

Methods

Flow and EAdi were recorded during routine PSV (tidal volume approximately 6-8 ml/kg) and four NAVA levels (1-4 cm H2O/microVEAdi) in 12 intubated patients. Breath-by-breath variability of flow and EAdi-related variables was quantified by the coefficient of variation (CV) and autocorrelation analysis. Complexity of flow and EAdi was described using noise titration, largest Lyapunov exponent, Kolmogorov-Sinai entropy, and three-dimensional phase portraits.

Results

Switching from PSV to NAVA increased the CV and decreased the autocorrelation for most flow-related variables in a dose-dependent manner (P < 0.05, partial eta for the CV of mean inspiratory flow 0.642). The changes were less marked for EAdi. A positive noise limit was consistently found for flow and EAdi. Largest Lyapunov exponent and Kolmogorov-Sinai entropy for flow were greater during NAVA than PSV and increased with NAVA level (P < 0.05, partial eta 0.334 and 0.312, respectively). Largest Lyapunov exponent and Kolmogorov-Sinai entropy for EAdi were not influenced by ventilator mode.

Conclusions

Compared with PSV, NAVA increases the breathing pattern variability and complexity of flow, whereas the complexity of EAdi is unchanged. Whether this improves clinical outcomes remains to be determined.
Body fat influences departure from stopover sites in migratory birds: evidence from whole-island telemetry
Authors: Goymann Wolfgang , Spina Fernando , Ferri Andrea , Fusani Leonida
Published: February 2010

Migration remains one of the great mysteries of animal life. Small migratory birds rely on refuelling stopovers after crossing ecological barriers such as deserts or seas. Previous studies have suggested that fuel reserves may determine stopover duration but this hypothesis could not be tested because of methodological limitations. Here, we provide evidence that subcutaneous fat stores determine stopover duration by measuring the permanence of migratory garden warblers (
Sylvia borin
) on a small Mediterranean island during spring migration with telemetry methods. Garden warblers with large amounts of fat stores departed the island significantly sooner than lean birds. All except one fat bird left the island on the same evening after capture, with a mean total stopover estimate of 8.8 hours. In contrast, the mean estimated total stopover duration of lean birds was 41.3 hours. To our knowledge, this is the first study that measures the true minimum stopover duration of a songbird during migration.