Pathway Profiling and Rational Trial Design for Studies in Advanced Stage Cervical Carcinoma: A Review and a Perspective

Multiple genetic abnormalities will have occurred in advanced cervical cancer and multiple targeting is likely to be needed to control tumor growth. To date, dominant therapeutic targets under scrutiny for cervical cancer treatment have been EGFR pathway and angiogenesis inhibition as well as anti-HPV vaccines. The potentially most effective targets to be blocked may be downstream from the membrane receptor or at the level of the nucleus. Alterations of the pathways involved in DNA repair and in checkpoint activations, as well as the specific site of HPV genome integration, appear worth assessing. For genetic mutational analysis, complete exon sequencing may become the norm in the future but at this stage frequent mutations (that matter) can be verified by PCR analysis. A precise documentation of relevant alterations of a large spectrum of protein biomarkers can be carried out by reverse phase protein array (RPPA) or by multiplex analysis. Clinical decision-making on the drug(s) of choice as a function of the biological alteration will need input from bio-informatics platforms as well as novel statistical designs. Endpoints are yet to be defined such as the loss (or reappearance) of a predictive biomarker. Single or dual targeting needs to be explored first in relevant preclinical animal and in xenograft models prior to clinical deployment

The Cooperative Participatory Evaluation of Renewable Technologies on Ecosystem Services (CORPORATES)

Publisher PD

AEGIS-X: The Chandra Deep Survey of the Extended Groth Strip

We present the AEGIS-X survey, a series of deep Chandra ACIS-I observations of the Extended Groth Strip. The survey comprises pointings at 8 separate positions, each with nominal exposure 200ks, covering a total area of approximately 0.67 deg2 in a strip of length 2 degrees. We describe in detail an updated version of our data reduction and point source detection algorithms used to analyze these data. A total of 1325 band-merged sources have been found to a Poisson probability limit of 4e-6, with limiting fluxes of 5.3e-17 erg/cm2/s in the soft (0.5-2 keV) band and 3.8e-16 erg/cm2/s in the hard (2-10 keV) band. We present simulations verifying the validity of our source detection procedure and showing a very small, <1.5%, contamination rate from spurious sources. Optical/NIR counterparts have been identified from the DEEP2, CFHTLS, and Spitzer/IRAC surveys of the same region. Using a likelihood ratio method, we find optical counterparts for 76% of our sources, complete to R(AB)=24.1, and, of the 66% of the sources that have IRAC coverage, 94% have a counterpart to a limit of 0.9 microJy at 3.6 microns (m(AB)=23.8). After accounting for (small) positional offsets in the 8 Chandra fields, the astrometric accuracy of the Chandra positions is found to be 0.8 arcsec RMS, however this number depends both on the off-axis angle and the number of detected counts for a given source. All the data products described in this paper are made available via a public website.Comment: 17 pages, 9 figures. Accepted for publication in ApJS. Data products are available at http://astro.imperial.ac.uk/research/aegis

Participatory scenario development for environmental management:A methodological framework illustrated with experience from the UK uplands

A methodological framework is proposed for participatory scenario development on the basis of evidence from the literature, and is tested and refined through the development of scenarios for the future of UK uplands. The paper uses a review of previous work to justify a framework based around the following steps: i) define context and establish whether there is a basis for stakeholder engagement in scenario development; ii) systematically identify and represent relevant stakeholders in the process; iii) define clear objectives for scenario development with stakeholders including spatial and temporal boundaries; iv) select relevant participatory methods for scenario development, during initial scenario construction, evaluation and to support decision-making based on scenarios; and v) integrate local and scientific knowledge throughout the process. The application of this framework in case study research suggests that participatory scenario development has the potential to: i) make scenarios more relevant to stakeholder needs and priorities; ii) extend the range of scenarios developed; iii) develop more detailed and precise scenarios through the integration of local and scientific knowledge; and iv) move beyond scenario development to facilitate adaptation to future change. It is argued that participatory scenario development can empower stakeholders and lead to more consistent and robust scenarios that can help people prepare more effectively for future change

The Mid-IR and X-ray Selected QSO Luminosity Function

We present the J-band luminosity function of 1838 mid-infrared and X-ray selected AGNs in the redshift range 0<z<5.85. These luminosity functions are constructed by combining the deep multi-wavelength broad-band observations from the UV to the mid-IR of the NDWFS Bootes field with the X-ray observations of the XBootes survey and the spectroscopic observations of the same field by AGES. Our sample is primarily composed of IRAC-selected AGNs, targeted using modifications of the Stern et al.(2005) criteria, complemented by MIPS 24 microns and X-ray selected AGNs to alleviate the biases of IRAC mid-IR selection against z~4.5 quasars and AGNs faint with respect to their hosts. This sample provides an accurate link between low and high redshift AGN luminosity functions and does not suffer from the usual incompleteness of optical samples at z~3. We find that the space density of the brightest quasars strongly decreases from z=3 to z=0, while the space density of faint quasars is at least flat, and possibly increasing, over the same redshift range. At z>3 we observe a decrease in the space density of quasars of all brightnesses. We model the luminosity function by a double power-law and find that its evolution cannot be described by either pure luminosity or pure density evolution, but must be a combination of both. Our best-fit model has bright and faint power-law indices consistent with the low redshift measurements based on the 2QZ and 2SLAQ surveys and it generally agrees with the number of bright quasars predicted by other LFs at all redshifts. If we construct the QSO luminosity function using only the IRAC-selected AGNs, we find that the biases inherent to this selection method significantly modify the behavior of phi*(z) only for z<1 and have no significant impact upon the characteristic magnitude M*_J(z).Comment: Corrected minor typo in equations (4) and (6). Accepted for publication in The Astrophysical Journal. 56 pages + 6 tables + 16 figure

Integrating stakeholder knowledge through modular cooperative participatory processes for marine spatial planning outcomes (CORPORATES)

This research was funded by the UK Natural Environment Research Council NERC (Knowledge Exchange Award 2014-2016) RC Grant reference: NE/M000184/1Peer reviewedPostprin

New directions in cellular therapy of cancer: a summary of the summit on cellular therapy for cancer

A summit on cellular therapy for cancer discussed and presented advances related to the use of adoptive cellular therapy for melanoma and other cancers. The summit revealed that this field is advancing rapidly. Conventional cellular therapies, such as tumor infiltrating lymphocytes (TIL), are becoming more effective and more available. Gene therapy is becoming an important tool in adoptive cell therapy. Lymphocytes are being engineered to express high affinity T cell receptors (TCRs), chimeric antibody-T cell receptors (CARs) and cytokines. T cell subsets with more naïve and stem cell-like characteristics have been shown in pre-clinical models to be more effective than unselected populations and it is now possible to reprogram T cells and to produce T cells with stem cell characteristics. In the future, combinations of adoptive transfer of T cells and specific vaccination against the cognate antigen can be envisaged to further enhance the effectiveness of these therapies