446 research outputs found
Managing the delivery of iconic football stadiums in England
The English football premier league has become the most
popular sports league in the world; with ardent fans and
audiences all over the world. The potential business
opportunities that this growth holds have therefore
attracted investors who are keen to buy shares in the
clubs and sign up the best footballers that money can buy.
Underpinning the growth in all of the premier league clubs
is a desire to make a distinct statement of identity as part
of a competitive strategy. One way to achieve this is
through the design and construction of iconic football
stadiums. This paper explores the specific project
management challenges associated with delivery of iconic
football stadiums in England and draws lessons for the
management of similar iconic infrastructure projects. A
study of project management best practice and some case
studies shows that key issues which are common to these
projects are centred on design management; choice of
procurement route; client management; and stakeholder
expectation management. These issues are not necessarily
unique to the project management of iconic football
stadiums but are amplified by the context of these
projects. The emphasis on iconic status in a competitive
market also means that stadium projects should be
conceived and delivered in the context of other strategic
projects which should be clearly understood by the project
management team
Multiple sclerosis and psychiatric disorders : comorbidity and sibling risk in a nationwide Swedish cohort
Background: Psychiatric disorders are known to be prevalent in Multiple Sclerosis (MS).
Objective: To study comorbidity between MS and bipolar disorder, schizophrenia and depression in a nation-wide cohort and to determine whether shared genetic liability underlies the putative association.
Methods: We identified ICD-diagnosed patients with MS (n=16,467), bipolar disorder (n=30,761), schizophrenia (n= 22,781) and depression (n=172,479) in the Swedish National Patient Register and identified their siblings in the Multi-Generation Register. The risk of MS was compared in psychiatric patients and in matched unexposed individuals. Shared familial risk between MS and psychiatric disorders was estimated by sibling comparison.
Results: The risk of MS was increased in patients with bipolar disorder (hazard ratio [HR] 1.8, 95% confidence interval [CI] 1.6-2.2, p<0.0001) and depression (HR 1.9, 95% CI 1.7-2.0, p<0.0001). MS risk in schizophrenia was decreased (HR 0.6, 95% CI 0.4-0.9, p=0.005). The association between having a sibling with a psychiatric disorder and developing MS was not significant.
Conclusion: We found a strong positive association between MS and bipolar disorder and depression that could not be explained by genetic liability. The unexpected negative association between MS and schizophrenia might be spurious or indicate possible protective mechanisms that warrant further exploration.Stockholm County CouncilThe Swedish Research CouncilKarolinska InstitutetAccepte
odor discrimination abilities in hygienic honey bees (Apis mellifera L.) using proboscis extension reflex conditioning
To understand the effect of abnormal brood odors on the initiation or control of hygienic behavior in honey bee
An exploratory study looking at the relationship marketing techniques used in the music festival industry
There are current issues and trends in the music festival
market, which may affect the success of an event, and market saturation
is at the forefront of these issues. Previous literature, maintaining
the need for a marketing approach to festivals, identifi es the need
for maintaining strong stakeholder relationships in order to succeed
in a business environment; attention has been focused to the theory
of relationship marketing (RM) because of the recognition that this
practice is complementary to the marketing of festivals. The very nature
of the music festival as an annual, usually, 4-day event means that
effective marketing is needed to keep connections with the consumer
throughout the year. This article focuses on the RM techniques
utilised within the music festival industry from the viewpoint of the
festival organiser in an attempt to establish how festival organisations
value and monitor organisational relationships. This article explores
the extent to which these relationships are valued and managed;
furthermore, the variations between these intricate relationships
are considered by focusing on those held with the organisation ’ s
consumers and sponsors, the results of which have provided the
ability to establish the importance and relevance of RM to the industry
and further identify the marketing communication methods employed
to establish and maintain such relationships. In-depth, convergent
interviews have been conducted with a segment of music festival
organisers from a range of events. The results have been integrated
with the study of current literature to best exemplify these issues. It
has been established that RM has a strong role in today ’ s commercial
and independent music festival industry; technological advances are
enabling the organiser to support online relationships further and
increase consumer loyalty. There is a need to expand the research
further because of the complexity of organisational relationships and
the varying categories of festivals
Design management: changing roles of the professions
This paper sets out to explore how recent changes in
procurement in construction have affected the roles that
professions play in the design process. It discusses how
professions that traditionally took the role of design
manager now find themselves participating within
previously unforeseen contexts, working in multidisciplinary
teams led by contractors and with changed
responsibilities at the design stage. Supply chain members
who were not previously involved during the early project
phases are being engaged at the earliest phases of the
project life cycle and even taking leadership roles while
designers sometimes work as supply chain partners.
A study of design in construction and other sectors shows
that in dealing with design management issues it is critical
to deepen appreciation for the unique characteristics of
design and the design process. The paper argues that
contractors and designers taking on design management
roles in a dynamic industry seeking to explore best
practice and innovative approaches to procurement and in
the delivery of projects need to acquire new skills,
management education and develop the necessary
qualities
Analysis of tumor template from multiple compartments in a blood sample provides complementary access to peripheral tumor biomarkers.
Targeted cancer therapeutics are promised to have a major impact on cancer treatment and survival. Successful application of these novel treatments requires a molecular definition of a patient\u27s disease typically achieved through the use of tissue biopsies. Alternatively, allowing longitudinal monitoring, biomarkers derived from blood, isolated either from circulating tumor cell derived DNA (ctcDNA) or circulating cell-free tumor DNA (ccfDNA) may be evaluated. In order to use blood derived templates for mutational profiling in clinical decisions, it is essential to understand the different template qualities and how they compare to biopsy derived template DNA as both blood-based templates are rare and distinct from the gold-standard. Using a next generation re-sequencing strategy, concordance of the mutational spectrum was evaluated in 32 patient-matched ctcDNA and ccfDNA templates with comparison to tissue biopsy derived DNA template. Different CTC antibody capture systems for DNA isolation from patient blood samples were also compared. Significant overlap was observed between ctcDNA, ccfDNA and tissue derived templates. Interestingly, if the results of ctcDNA and ccfDNA template sequencing were combined, productive samples showed similar detection frequency (56% vs 58%), were temporally flexible, and were complementary both to each other and the gold standard. These observations justify the use of a multiple template approach to the liquid biopsy, where germline, ctcDNA, and ccfDNA templates are employed for clinical diagnostic purposes and open a path to comprehensive blood derived biomarker access
Human CLEC9A antibodies deliver Wilms' tumor 1 (WT1) antigen to CD141+ dendritic cells to activate naïve and memory WT1‐specific CD8+ T cells
Objectives
Vaccines that prime Wilms' tumor 1 (WT1)‐specific CD8+ T cells are attractive cancer immunotherapies. However, immunogenicity and clinical response rates may be enhanced by delivering WT1 to CD141+ dendritic cells (DCs). The C‐type lectin‐like receptor CLEC9A is expressed exclusively by CD141+ DCs and regulates CD8+ T‐cell responses. We developed a new vaccine comprising a human anti‐CLEC9A antibody fused to WT1 and investigated its capacity to target human CD141+ DCs and activate naïve and memory WT1‐specific CD8+ T cells.
Methods
WT1 was genetically fused to antibodies specific for human CLEC9A, DEC‐205 or β‐galactosidase (untargeted control). Activation of WT1‐specific CD8+ T‐cell lines following cross‐presentation by CD141+ DCs was quantified by IFNγ ELISPOT. Humanised mice reconstituted with human immune cell subsets, including a repertoire of naïve WT1‐specific CD8+ T cells, were used to investigate naïve WT1‐specific CD8+ T‐cell priming.
Results
The CLEC9A‐WT1 vaccine promoted cross‐presentation of WT1 epitopes to CD8+ T cells and mediated priming of naïve CD8+ T cells more effectively than the DEC‐205‐WT1 and untargeted control‐WT1 vaccines.
Conclusions
Delivery of WT1 to CD141+ DCs via CLEC9A stimulates CD8+ T cells more potently than either untargeted delivery or widespread delivery to all Ag‐presenting cells via DEC‐205, suggesting that cross‐presentation by CD141+ DCs is sufficient for effective CD8+ T‐cell priming in humans. The CLEC9A‐WT1 vaccine is a promising candidate immunotherapy for malignancies that express WT1
Oral curcumin for Alzheimer's disease: tolerability and efficacy in a 24-week randomized, double blind, placebo-controlled study
Introduction: Curcumin is a polyphenolic compound derived from the plant Curcuma Long Lin that has been demonstrated to have antioxidant and anti-inflammatory effects as well as effects on reducing beta-amyloid aggregation. It reduces pathology in transgenic models of Alzheimer's disease (AD) and is a promising candidate for treating human AD. The purpose of the current study is to generate tolerability and preliminary clinical and biomarker efficacy data on curcumin in persons with AD. Methods: We performed a 24-week randomized, double blind, placebo-controlled study of Curcumin C3 Complex® with an open-label extension to 48 weeks. Thirty-six persons with mild-to-moderate AD were randomized to receive placebo, 2 grams/day, or 4 grams/day of oral curcumin for 24 weeks. For weeks 24 through 48, subjects that were receiving curcumin continued with the same dose, while subjects previously receiving placebo were randomized in a 1:1 ratio to 2 grams/day or 4 grams/day. The primary outcome measures were incidence of adverse events, changes in clinical laboratory tests and the Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) at 24 weeks in those completing the study. Secondary outcome measures included the Neuropsychiatric Inventory (NPI), the Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL) scale, levels of Aβ1-40 and Aβ1-42 in plasma and levels of Aβ1-42, t-tau, p-tau181 and F2-isoprostanes in cerebrospinal fluid. Plasma levels of curcumin and its metabolites up to four hours after drug administration were also measured. Results: Mean age of completers (n = 30) was 73.5 years and mean Mini-Mental Status Examination (MMSE) score was 22.5. One subject withdrew in the placebo (8%, worsened memory) and 5/24 subjects withdrew in the curcumin group (21%, 3 due to gastrointestinal symptoms). Curcumin C3 Complex® was associated with lowered hematocrit and increased glucose levels that were clinically insignificant. There were no differences between treatment groups in clinical or biomarker efficacy measures. The levels of native curcumin measured in plasma were low (7.32 ng/mL). Conclusions: Curcumin was generally well-tolerated although three subjects on curcumin withdrew due to gastrointestinal symptoms. We were unable to demonstrate clinical or biochemical evidence of efficacy of Curcumin C3 Complex® in AD in this 24-week placebo-controlled trial although preliminary data suggest limited bioavailability of this compound. Trial registration ClinicalTrials.gov Identifier: NCT00099710
Skills in the green economy: recycling promises in the UK e-waste management sector
In advanced economies the ‘greening’ of the economy is widely seen as promising extensive job creation and upskilling, alongside its other benefits. In popular and policy rhetoric, the growing importance of ‘green skills’ is asserted frequently. This paper critically examines these claims within the context of the electronic waste management sector in the UK. Drawing on the cases of a non profit organisation and a small private enterprise in North West England, we observe that despite government support for developing skills in e-waste, both the development and utilisation of skills remain minimal. Critically, the relatively more skill-intensive process of reuse is substantially less profitable than recycling and resource capture. The paper concludes by noting that the expectations from the green economy for high quality jobs need to be assessed within the context of similar, misplaced celebrations of previous transformations of work in order to avoid recycling the same promises
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