545 research outputs found
A core outcome set for localised prostate cancer effectiveness trials : protocol for a systematic review of the literature and stakeholder involvement through interviews and a Delphi survey
Acknowledgements We would like to thank Professor Craig Ramsay, Professor Luke Vale, and Professor Vikki Entwistle for their comments on earlier drafts of the protocol. This study is funded by the Cancer Research Aberdeen and North East Scotland (CRANES) charity. Paula Williamson would like to acknowledge funding from the European Union Seventh Framework Programme (FP7/2007-2013, FP7/2007-2011) under grant agreement number 305081 for the COMET initiative, which provided support for this work.Peer reviewedPublisher PD
FoxP3 expression by retinal pigment epithelial cells: transcription factor with potential relevance for the pathology of age-related macular degeneration
Background: Forkhead-Box-Protein P3 (FoxP3) is a transcription factor and marker of regulatory T cells, converting naive T cells into Tregs that can downregulate the effector function of other T cells. We previously detected the expression of FoxP3 in retinal pigment epithelial (RPE) cells, forming the outer blood-retina barrier of the immune privileged eye.
Methods: We investigated the expression, subcellular localization, and phosphorylation of FoxP3 in RPE cells in vivo and in vitro after treatment with various stressors including age, retinal laser burn, autoimmune inflammation, exposure to cigarette smoke, in addition of IL-1 beta and mechanical cell monolayer destruction. Eye tissue from humans, mouse models of retinal degeneration and rats, and ARPE-19, a human RPE cell line for in vitro experiments, underwent immunohistochemical, immunofluorescence staining, and PCR or immunoblot analysis to determine the intracellular localization and phosphorylation of FoxP3. Cytokine expression of stressed cultured RPE cells was investigated by multiplex bead analysis. Depletion of the FoxP3 gene was performed with CRISPR/Cas9 editing.
Results: RPE in vivo displayed increased nuclear FoxP3-expression with increases in age and inflammation, long-term exposure of mice to cigarette smoke, or after laser burn injury. The human RPE cell line ARPE-19 constitutively expressed nuclear FoxP3 under non-confluent culture conditions, representing a regulatory phenotype under chronic stress. Confluently grown cells expressed cytosolic FoxP3 that was translocated to the nucleus after treatment with IL-1 beta to imitate activated macrophages or after mechanical destruction of the monolayer. Moreover, with depletion of FoxP3, but not of a control gene, by CRISPR/Cas9 gene editing decreased stress resistance of RPE cells.
Conclusion: Our data suggest that FoxP3 is upregulated by age and under cellular stress and might be important for RPE function
A core outcome set for localised prostate cancer effectiveness trials
Objective:
To develop a core outcome set (COS) applicable for effectiveness trials of all interventions for localised prostate cancer.
Background:
Many treatments exist for localised prostate cancer, although it is unclear which offers the optimal therapeutic ratio. This is confounded by inconsistencies in the selection, definition, measurement and reporting of outcomes in clinical trials.
Subjects and methods:
A list of 79 outcomes was derived from a systematic review of published localised prostate cancer effectiveness studies and semi-structured interviews with 15 prostate cancer patients. A two-stage consensus process involving 118 patients and 56 international healthcare professionals (HCPs) (cancer specialist nurses, urological surgeons and oncologists) was undertaken, consisting of a three-round Delphi survey followed by a face-to-face consensus panel meeting of 13 HCPs and 8 patients.
Results:
The final COS included 19 outcomes. Twelve apply to all interventions: death from prostate cancer, death from any cause, local disease recurrence, distant disease recurrence/metastases, disease progression, need for salvage therapy, overall quality of life, stress urinary incontinence, urinary function, bowel function, faecal incontinence, sexual function. Seven were intervention-specific: perioperative deaths (surgery), positive surgical margin (surgery), thromboembolic disease (surgery), bothersome or symptomatic urethral or anastomotic stricture (surgery), need for curative treatment (active surveillance), treatment failure (ablative therapy), and side effects of hormonal therapy (hormone therapy). The UK-centric participants may limit the generalisability to other countries, but trialists should reason why the COS would not be applicable. The default position should not be that a COS developed in one country will automatically not be applicable elsewhere.
Conclusion:
We have established a COS for trials of effectiveness in localised prostate cancer, applicable across all interventions which should be measured in all localised prostate cancer effectiveness trials
A comparison of the measurement properties of the Juvenile Arthritis Functional Assessment Scale with the childhood health assessment questionnaire in daily practice
We compared the measurement properties of a performance test (Juvenile Arthritis Functional Assessment Scale; JAFAS) with a questionnaire-based instrument (Childhood Health Assessment Questionnaire; CHAQ) to measure functional ability in patients with juvenile idiopathic arthritis on the level of individual items. In 28 consecutive children visiting an outpatient paediatrics clinic, the JAFAS (range 0â20) and CHAQ (range 0â3) were applied, and measures of disease activity and joint range of motion (ROM) were determined. Twenty-eight children with a median age of 10Â years and median disease duration of 3.2Â years were included. The median JAFAS score was 0, and the median CHAQ score was 0.125. Cronbachâs alpha was 0.92 for the JAFAS and 0.96 for the CHAQ. The Spearman correlation coefficient between the JAFAS and the CHAQ was 0.55 (Pâ<â0.01). With six out of ten items, the JAFAS classified the child as less disabled than with corresponding CHAQ activities. Overall, associations with measures of disease activity and ROM were higher for the CHAQ than for the JAFAS. A performance test (JAFAS) does not appear to have an added benefit over the questionnaire-based assessment (CHAQ) of physical function in a cross-sectional study
Role of Engrailed-2 (EN2) as a prostate cancer detection biomarker in genetically high risk men
Controversy surrounds the use of PSA as a biomarker for prostate cancer detection, leaving an unmet need for a novel biomarker in this setting; urinary EN2 may identify individuals with clinically relevant prostate cancer. Male BRCA1 and BRCA2 mutation carriers are at increased risk of clinically significant prostate cancer and may benefit from screening. Urine samples from 413 BRCA1 and BRCA2 mutation carriers and controls were evaluated. Subjects underwent annual PSA screening with diagnostic biopsy triggered by PSA > 3.0â
ng/ml; 21 men were diagnosed with prostate cancer. Urinary EN2 levels were measured by ELISA and had a sensitivity of 66.7% and specificity of 89.3% for cancer detection. There was no statistically significant difference in EN2 levels according to genetic status or Gleason score. Urinary EN2 may be useful as a non-invasive early biomarker for prostate cancer detection in genetically high-risk individuals
Technical Aspects of Flow Cytometry-based Measurable Residual Disease Quantification in Acute Myeloid Leukemia: Experience of the European LeukemiaNet MRD Working Party
Measurable residual disease (MRD) quantified by multiparameter flow cytometry (MFC) is a strong and independent prognostic
factor in acute myeloid leukemia (AML). However, several technical factors may affect the final read-out of the assay. Experts from
the MRD Working Party of the European LeukemiaNet evaluated which aspects are crucial for accurate MFC-MRD measurement.
Here, we report on the agreement, obtained via a combination of a cross-sectional questionnaire, live discussions, and a Delphi poll.
The recommendations consist of several key issues from bone marrow sampling to final laboratory reporting to ensure quality and
reproducibility of results. Furthermore, the experiences were tested by comparing two 8-color MRD panels in multiple laboratories.
The results presented here underscore the feasibility and the utility of a harmonized theoretical and practical MFC-MRD assessment
and are a next step toward further harmonization
Astrophysically Triggered Searches for Gravitational Waves: Status and Prospects
In gravitational-wave detection, special emphasis is put onto searches that
focus on cosmic events detected by other types of astrophysical observatories.
The astrophysical triggers, e.g. from gamma-ray and X-ray satellites, optical
telescopes and neutrino observatories, provide a trigger time for analyzing
gravitational wave data coincident with the event. In certain cases the
expected frequency range, source energetics, directional and progenitor
information is also available. Beyond allowing the recognition of gravitational
waveforms with amplitudes closer to the noise floor of the detector, these
triggered searches should also lead to rich science results even before the
onset of Advanced LIGO. In this paper we provide a broad review of LIGO's
astrophysically triggered searches and the sources they target
Search for gravitational waves associated with the InterPlanetary Network short gamma ray bursts
We outline the scientific motivation behind a search for gravitational waves
associated with short gamma ray bursts detected by the InterPlanetary Network
(IPN) during LIGO's fifth science run and Virgo's first science run. The IPN
localisation of short gamma ray bursts is limited to extended error boxes of
different shapes and sizes and a search on these error boxes poses a series of
challenges for data analysis. We will discuss these challenges and outline the
methods to optimise the search over these error boxes.Comment: Methods paper; Proceedings for Eduardo Amaldi 9 Conference on
Gravitational Waves, July 2011, Cardiff, U
Swift follow-up observations of candidate gravitational-wave transient events
We present the first multi-wavelength follow-up observations of two candidate
gravitational-wave (GW) transient events recorded by LIGO and Virgo in their
2009-2010 science run. The events were selected with low latency by the network
of GW detectors and their candidate sky locations were observed by the Swift
observatory. Image transient detection was used to analyze the collected
electromagnetic data, which were found to be consistent with background.
Off-line analysis of the GW data alone has also established that the selected
GW events show no evidence of an astrophysical origin; one of them is
consistent with background and the other one was a test, part of a "blind
injection challenge". With this work we demonstrate the feasibility of rapid
follow-ups of GW transients and establish the sensitivity improvement joint
electromagnetic and GW observations could bring. This is a first step toward an
electromagnetic follow-up program in the regime of routine detections with the
advanced GW instruments expected within this decade. In that regime
multi-wavelength observations will play a significant role in completing the
astrophysical identification of GW sources. We present the methods and results
from this first combined analysis and discuss its implications in terms of
sensitivity for the present and future instruments.Comment: Submitted for publication 2012 May 25, accepted 2012 October 25,
published 2012 November 21, in ApJS, 203, 28 (
http://stacks.iop.org/0067-0049/203/28 ); 14 pages, 3 figures, 6 tables;
LIGO-P1100038; Science summary at
http://www.ligo.org/science/Publication-S6LVSwift/index.php ; Public access
area to figures, tables at
https://dcc.ligo.org/cgi-bin/DocDB/ShowDocument?docid=p110003
Search for Gravitational Waves from Low Mass Compact Binary Coalescence in LIGO's Sixth Science Run and Virgo's Science Runs 2 and 3
We report on a search for gravitational waves from coalescing compact
binaries using LIGO and Virgo observations between July 7, 2009 and October 20,
2010. We searched for signals from binaries with total mass between 2 and 25
solar masses; this includes binary neutron stars, binary black holes, and
binaries consisting of a black hole and neutron star. The detectors were
sensitive to systems up to 40 Mpc distant for binary neutron stars, and further
for higher mass systems. No gravitational-wave signals were detected. We report
upper limits on the rate of compact binary coalescence as a function of total
mass, including the results from previous LIGO and Virgo observations. The
cumulative 90%-confidence rate upper limits of the binary coalescence of binary
neutron star, neutron star- black hole and binary black hole systems are 1.3 x
10^{-4}, 3.1 x 10^{-5} and 6.4 x 10^{-6} Mpc^{-3}yr^{-1}, respectively. These
upper limits are up to a factor 1.4 lower than previously derived limits. We
also report on results from a blind injection challenge.Comment: 11 pages, 5 figures. For a repository of data used in the
publication, go to:
. Also see the
announcement for this paper on ligo.org at:
<http://www.ligo.org/science/Publication-S6CBCLowMass/index.php
- âŠ