Improved sensitivity at synchrotrons using edge illumination X-ray phase-contrast imaging

The application of the X-ray phase-contrast ‘edge illumination’ principle to the highly coherent beams available at synchrotron radiation facilities is presented here. We show that, in this configuration, the technique allows achieving unprecedented angular sensitivity, of the order of few nanoradians. The results are obtained at beamlines of two different synchrotron radiation facilities, using various experimental conditions. In particular, different detectors and X-ray energies (12 keV and 85 keV) were employed, proving the flexibility of the method and the broad range of conditions over which it can be applied. Furthermore, the quantitative separation of absorption and refraction information, and the application of the edge illumination principle in combination with computed tomography, are also demonstrated. Thanks to its extremely high phase sensitivity and its flexible applicability, this technique will both improve the image quality achievable with X-ray phase contrast imaging and allow tackling areas of application which remain unexplored until now

X-Ray Phase-Contrast Imaging with Nanoradian Angular Resolution

We present a new quantitative x-ray phase-contrast imaging method based on the edge illumination principle, which allows achieving unprecedented nanoradian sensitivity. The extremely high angular resolution is demonstrated theoretically and through experimental images obtained at two different synchrotron radiation facilities. The results, achieved at both very high and very low x-ray energies, show that this highly sensitive technique can be efficiently exploited over a very broad range of experimental conditions. This method can open the way to new, previously inaccessible scientific applications in various fields including biology, medicine and materials science

Applications of a non-interferometric x-ray phase contrast imaging method with both synchrotron and conventional sources

We have developed a totally incoherent, non-interferometric x-ray phase contrast imaging (XPCI) method. This is based on the edge illumination (EI) concept developed at the ELETTRA synchrotron in Italy in the late ‘90s. The method was subsequently adapted to the divergent beam generated by a conventional source, by replicating it for every detector line through suitable masks. The method was modelled both with the simplified ray-tracing and with the more rigorous wave-optics approach, and in both cases excellent agreement with the experimental results was found. The wave-optics model enabled assessing the methods’ coherence requirements, showing that they are at least an order of magnitude more relaxed than in other methods, without this having negative consequences on the phase sensitivity. Our masks have large pitches (up to 50 times larger than in grating interferometry, for example), which allows for manufacturing through standard lithography, scalability, cost-effectiveness and easiness to align. When applied to a polychromatic and divergent beam generated by a conventional source, the method enables the detection of strong phase effects also with uncollimated, unapertured sources with focal spots of up to 100 mm, compatible with the state-of-the-art in mammography. When used at synchrotrons, it enables a contrast increase of orders of magnitude over other methods. Robust phase retrieval was proven for both coherent and incoherent sources, and additional advantages are compatibility with high x-ray energies and easy implementation of phase sensitivity in two directions simultaneously. This paper briefly summarizes these achievements and reviews some of the key results

Edge illumination and coded-aperture X-ray phase-contrast imaging: Increased sensitivity at synchrotrons and lab-based translations into medicine, biology and materials science

The edge illumination principle was first proposed at Elettra (Italy) in the late nineties, as an alternative method for achieving high phase sensitivity with a very simple and flexible set-up, and has since been under continuous development in the radiation physics group at UCL. Edge illumination allows overcoming most of the limitations of other phase-contrast techniques, enabling their translation into a laboratory environment. It is relatively insensitive to mechanical and thermal instabilities and it can be adapted to the divergent and polychromatic beams provided by X-ray tubes. This method has been demonstrated to work efficiently with source sizes up to 100m, compatible with state-of-the-art mammography sources. Two full prototypes have been built and are operational at UCL. Recent activity focused on applications such as breast and cartilage imaging, homeland security and detection of defects in composite materials. New methods such as phase retrieval, tomosynthesis and computed tomography algorithms are currently being theoretically and experimentally investigated. These results strongly indicate the technique as an extremely powerful and versatile tool for X-ray imaging in a wide range of applications

Medicine, material science and security: the versatility of the coded-aperture approach

The principal limitation to the widespread deployment of X-ray phase imaging in a variety of applications is probably versatility. A versatile X-ray phase imaging system must be able to work with polychromatic and non-microfocus sources (for example, those currently used in medical and industrial applications), have physical dimensions sufficiently large to accommodate samples of interest, be insensitive to environmental disturbances (such as vibrations and temperature variations), require only simple system set-up and maintenance, and be able to perform quantitative imaging. The coded-aperture technique, based upon the edge illumination principle, satisfies each of these criteria. To date, we have applied the technique to mammography, materials science, small-animal imaging, non-destructive testing and security. In this paper, we outline the theory of coded-aperture phase imaging and show an example of how the technique may be applied to imaging samples with a practically important scale

Mouse mammary tumor virus-like gene sequences are present in lung patient specimens

<p>Abstract</p> <p>Background</p> <p>Previous studies have reported on the presence of Murine Mammary Tumor Virus (MMTV)-like gene sequences in human cancer tissue specimens. Here, we search for MMTV-like gene sequences in lung diseases including carcinomas specimens from a Mexican population. This study was based on our previous study reporting that the INER51 lung cancer cell line, from a pleural effusion of a Mexican patient, contains MMTV-like <it>env </it>gene sequences.</p> <p>Results</p> <p>The MMTV-like <it>env </it>gene sequences have been detected in three out of 18 specimens studied, by PCR using a specific set of MMTV-like primers. The three identified MMTV-like gene sequences, which were assigned as INER6, HZ101, and HZ14, were 99%, 98%, and 97% homologous, respectively, as compared to GenBank sequence accession number <ext-link ext-link-id="AY161347" ext-link-type="gen">AY161347</ext-link>. The INER6 and HZ-101 samples were isolated from lung cancer specimens, and the HZ-14 was isolated from an acute inflammatory lung infiltrate sample. Two of the <it>env </it>sequences exhibited disruption of the reading frame due to mutations.</p> <p>Conclusion</p> <p>In summary, we identified the presence of MMTV-like gene sequences in 2 out of 11 (18%) of the lung carcinomas and 1 out of 7 (14%) of acute inflamatory lung infiltrate specimens studied of a Mexican Population.</p

Bone Marrow-Derived Cells from Male Donors Do Not Contribute to the Endometrial Side Population of the Recipient

Accumulated evidence demonstrates the existence of bone marrow-derived cells origin in the endometria of women undergoing bone marrow transplantation (BMT). In these reports, cells of a bone marrow (BM) origin are able to differentiate into endometrial cells, although their contribution to endometrial regeneration is not yet clear. We have previously demonstrated the functional relevance of side population (SP) cells as the endogenous source of somatic stem cells (SSC) in the human endometrium. The present work aims to understand the presence and contribution of bone marrow-derived cells to the endometrium and the endometrial SP population of women who received BMT from male donors. Five female recipients with spontaneous or induced menstruations were selected and their endometrium was examined for the contribution of XY donor-derived cells using fluorescent in situ hybridization (FISH), telomapping and SP method investigation. We confirm the presence of XY donor-derived cells in the recipient endometrium ranging from 1.7% to 2.62%. We also identify 0.45–0.85% of the donor-derived cells in the epithelial compartment displaying CD9 marker, and 1.0–1.83% of the Vimentin-positive XY donor-derived cells in the stromal compartment. Although the percentage of endometrial SP cells decreased, possibly being due to chemotherapy applied to these patients, they were not formed by XY donor-derived cells, donor BM cells were not associated with the stem cell (SC) niches assessed by telomapping technique, and engraftment percentages were very low with no correlation between time from transplant and engraftment efficiency, suggesting random terminal differentiation. In conclusion, XY donor-derived cells of a BM origin may be considered a limited exogenous source of transdifferentiated endometrial cells rather than a cyclic source of BM donor-derived stem cells

How useful are systematic reviews for informing palliative care practice? Survey of 25 Cochrane systematic reviews

<p>Abstract</p> <p>Background</p> <p>In contemporary medical research, randomised controlled trials are seen as the gold standard for establishing treatment effects where it is ethical and practical to conduct them. In palliative care such trials are often impractical, unethical, or extremely difficult, with multiple methodological problems. We review the utility of Cochrane reviews in informing palliative care practice.</p> <p>Methods</p> <p>Published reviews in palliative care registered with the Cochrane Pain, Palliative and Supportive Care Group as of December 2007 were obtained from the Cochrane Database of Systematic Reviews, issue 1, 2008. We reviewed the quality and quantity of primary studies available for each review, assessed the quality of the review process, and judged the strength of the evidence presented. There was no prior intention to perform any statistical analyses.</p> <p>Results</p> <p>25 published systematic reviews were identified. Numbers of included trials ranged from none to 54. Within each review, included trials were heterogeneous with respect to patients, interventions, and outcomes, and the number of patients contributing to any single analysis was generally much lower than the total included in the review. A variety of tools were used to assess trial quality; seven reviews did not use this information to exclude low quality studies, weight analyses, or perform sensitivity analysis for effect of low quality. Authors indicated that there were frequently major problems with the primary studies, individually or in aggregate. Our judgment was that the reviewing process was generally good in these reviews, and that conclusions were limited by the number, size, quality and validity of the primary studies.</p> <p>We judged the evidence about 23 of the 25 interventions to be weak. Two reviews had stronger evidence, but with limitations due to methodological heterogeneity or definition of outcomes. No review provided strong evidence of no effect.</p> <p>Conclusion</p> <p>Cochrane reviews in palliative care are well performed, but fail to provide good evidence for clinical practice because the primary studies are few in number, small, clinically heterogeneous, and of poor quality and external validity. They are useful in highlighting the weakness of the evidence base and problems in performing trials in palliative care.</p

TCR signal strength controls thymic differentiation of discrete proinflammatory gamma delta T cell subsets

The mouse thymus produces discrete gd T cell subsets that make either interferon-g (IFN-g) or interleukin 17 (IL-17), but the role of the T cell antigen receptor (TCR) in this developmental process remains controversial. Here we show that Cd3g+/− Cd3d+/− (CD3 double-haploinsufficient (CD3DH)) mice have reduced TCR expression and signaling strength on gd T cells. CD3DH mice had normal numbers and phenotypes of ab thymocyte subsets, but impaired differentiation of fetal Vg6+ (but not Vg4+) IL-17- producing gd T cells and a marked depletion of IFN-g-producing CD122+ NK1.1+ gd T cells throughout ontogeny. Adult CD3DH mice showed reduced peripheral IFN-g+ gd T cells and were resistant to experimental cerebral malaria. Thus, TCR signal strength within specific thymic developmental windows is a major determinant of the generation of proinflammatory gd T cell subsets and their impact on pathophysiology

Interactions between lymphocytes and myeloid cells regulate pro- versus anti-tumor immunity

Tumor-associated myeloid cells have been implicated in regulating many of the “hallmarks of cancer” and thus fostering solid tumor development and metastasis. However, the same innate leukocytes also participate in anti-tumor immunity and restraint of malignant disease. While many factors regulate the propensity of myeloid cells to promote or repress cancerous growths, polarized adaptive immune responses by B and T lymphocytes have been identified as regulators of many aspects of myeloid cell biology by specifically regulating their functional capabilities. Here, we detail the diversity of heterogeneous B and T lymphocyte populations and their impacts on solid tumor development through their abilities to regulate myeloid cell function in solid tumors