175 research outputs found
Antimicrobial Susceptibility Trends Observed in Urinary Pathogens Obtained From New York State
International guidelines recommend using local susceptibility data to direct empiric therapy for acute uncomplicated cystitis. We evaluated outpatient urinary isolate susceptibility trends in New York State. Nitrofurantoin had the lowest resistance prevalence whereas trimethoprim-sulfamethoxazole and fluoroquinolones had higher prevalences. This study highlights the need for local outpatient antimicrobial stewardship programs
Enhanced REC collaborative review through video-conferencing
As international collaborative health research activities increase, building research ethics committees (REC) infrastructure and capacity in lowand middle-income countries for efficient and thorough review of research protocols becomes more critical, especially in sub-Saharan Africa. International investigators may face multiple challenges when conducting research in these settings, an important one being the length of time involved in securing REC review and approval. We discuss an approach to the problem that involved organisation of ârapid reviewâ REC sub-committees who met via video-conference for collaborative review of research protocols
Spurious Shear in Weak Lensing with LSST
The complete 10-year survey from the Large Synoptic Survey Telescope (LSST)
will image 20,000 square degrees of sky in six filter bands every few
nights, bringing the final survey depth to , with over 4 billion
well measured galaxies. To take full advantage of this unprecedented
statistical power, the systematic errors associated with weak lensing
measurements need to be controlled to a level similar to the statistical
errors.
This work is the first attempt to quantitatively estimate the absolute level
and statistical properties of the systematic errors on weak lensing shear
measurements due to the most important physical effects in the LSST system via
high fidelity ray-tracing simulations. We identify and isolate the different
sources of algorithm-independent, \textit{additive} systematic errors on shear
measurements for LSST and predict their impact on the final cosmic shear
measurements using conventional weak lensing analysis techniques. We find that
the main source of the errors comes from an inability to adequately
characterise the atmospheric point spread function (PSF) due to its high
frequency spatial variation on angular scales smaller than in the
single short exposures, which propagates into a spurious shear correlation
function at the -- level on these scales. With the large
multi-epoch dataset that will be acquired by LSST, the stochastic errors
average out, bringing the final spurious shear correlation function to a level
very close to the statistical errors. Our results imply that the cosmological
constraints from LSST will not be severely limited by these
algorithm-independent, additive systematic effects.Comment: 22 pages, 12 figures, accepted by MNRA
Heterogeneity in lymphocyte spectrin distribution: ultrastructural identification of a new spectrin-rich cytoplasmic structure.
Preclinical evaluation of cancer immune therapy using patient-derived tumor antigen-specific T cells in a novel xenograft platform.
Objectives: With a rapidly growing list of candidate immune-based cancer therapeutics, there is a critical need to generate highly reliable animal models to preclinically evaluate the efficacy of emerging immune-based therapies, facilitating successful clinical translation. Our aim was to design and validate a novel
Methods: Tumor xenografts are established rapidly in the greater omentum of globally immunodeficient NOD-
Results: The tumors progress rapidly and disseminate in the mice unless patient-derived tumor-specific T cells are introduced. An initial T cell-mediated tumor arrest is later followed by a tumor escape, which correlates with the upregulation of the checkpoint molecules programmed cell death-1 (PD-1) and lymphocyte-activation gene 3 (LAG3) on T cells. Treatment with immune-based therapies that target these checkpoints, such as anti-PD-1 antibody (nivolumab) or interleukin-12 (IL-12), prevented or delayed the tumor escape. Furthermore, IL-12 treatment suppressed PD-1 and LAG3 upregulation on T cells.
Conclusion: Together, these results validate the X-mouse model and establish its potential to preclinically evaluate the therapeutic efficacy of immune-based therapies
Novel phosphatidylserine-binding molecule enhances antitumor T-cell responses by targeting immunosuppressive exosomes in human tumor microenvironments.
BACKGROUND: The human tumor microenvironment (TME) is a complex and dynamic milieu of diverse acellular and cellular components, creating an immunosuppressive environment, which contributes to tumor progression. We have previously shown that phosphatidylserine (PS) expressed on the surface of exosomes isolated from human TMEs is causally linked to T-cell immunosuppression, representing a potential immunotherapeutic target. In this study, we investigated the effect of ExoBlock, a novel PS-binding molecule, on T-cell responses in the TME.
METHODS: We designed and synthesized a new compound, (ZnDPA)
RESULTS: ExoBlock was able to bind PS with high avidity and was found to consistently and significantly block the immunosuppressive activity of human ovarian tumor and melanoma-associated exosomes in vitro. ExoBlock was also able to significantly enhance T cell-mediated tumor suppression in vivo in both the X-mouse and the OTX model. In the X-mouse model, ExoBlock suppressed tumor recurrence in a T cell-dependent manner. In the OTX model, ExoBlock treatment resulted in an increase in the number as well as function of CD4 and CD8 T cells in the TME, which was associated with a reduction in tumor burden and metastasis, as well as in the number of circulating PS+ exosomes in tumor-bearing mice.
CONCLUSION: Our results establish that targeting exosomal PS in TMEs with ExoBlock represents a promising strategy to enhance antitumor T-cell responses
Humanized Mouse Model of Ovarian Cancer Recapitulates Patient Solid Tumor Progression, Ascites Formation, and Metastasis
Ovarian cancer is the most common cause of death from gynecological cancer. Understanding the biology of this disease, particularly how tumor-associated lymphocytes and fibroblasts contribute to the progression and metastasis of the tumor, has been impeded by the lack of a suitable tumor xenograft model. We report a simple and reproducible system in which the tumor and tumor stroma are successfully engrafted into NOD-scid IL2RÎłnull (NSG) mice. This is achieved by injecting tumor cell aggregates derived from fresh ovarian tumor biopsy tissues (including tumor cells, and tumor-associated lymphocytes and fibroblasts) i.p. into NSG mice. Tumor progression in these mice closely parallels many of the events that are observed in ovarian cancer patients. Tumors establish in the omentum, ovaries, liver, spleen, uterus, and pancreas. Tumor growth is initially very slow and progressive within the peritoneal cavity with an ultimate development of tumor ascites, spontaneous metastasis to the lung, increasing serum and ascites levels of CA125, and the retention of tumor-associated human fibroblasts and lymphocytes that remain functional and responsive to cytokines for prolonged periods. With this model one will be able to determine how fibroblasts and lymphocytes within the tumor microenvironment may contribute to tumor growth and metastasis, and will make it possible to evaluate the efficacy of therapies that are designed to target these cells in the tumor stroma
LSST Science Book, Version 2.0
A survey that can cover the sky in optical bands over wide fields to faint
magnitudes with a fast cadence will enable many of the exciting science
opportunities of the next decade. The Large Synoptic Survey Telescope (LSST)
will have an effective aperture of 6.7 meters and an imaging camera with field
of view of 9.6 deg^2, and will be devoted to a ten-year imaging survey over
20,000 deg^2 south of +15 deg. Each pointing will be imaged 2000 times with
fifteen second exposures in six broad bands from 0.35 to 1.1 microns, to a
total point-source depth of r~27.5. The LSST Science Book describes the basic
parameters of the LSST hardware, software, and observing plans. The book
discusses educational and outreach opportunities, then goes on to describe a
broad range of science that LSST will revolutionize: mapping the inner and
outer Solar System, stellar populations in the Milky Way and nearby galaxies,
the structure of the Milky Way disk and halo and other objects in the Local
Volume, transient and variable objects both at low and high redshift, and the
properties of normal and active galaxies at low and high redshift. It then
turns to far-field cosmological topics, exploring properties of supernovae to
z~1, strong and weak lensing, the large-scale distribution of galaxies and
baryon oscillations, and how these different probes may be combined to
constrain cosmological models and the physics of dark energy.Comment: 596 pages. Also available at full resolution at
http://www.lsst.org/lsst/sciboo
Fundamental limitations of LIGA x-ray lithography: sidewall offset, slope and minimum feature size
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