197 research outputs found

    Design of a very high-resolution small animal PET scanner using a silicon scatter detector insert

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    A small animal positron emission tomography (PET) instrument using a high-resolution solid-state detector insert in a conventional PET system was investigated for its potential to achieve sub-millimeter spatial resolution for mouse imaging. Monte Carlo simulations were used to estimate the effect of detector configurations (thickness, length and radius) on sensitivity. From this initial study, a PET system having an inner cylindrical silicon detector (4 cm ID, 4 cm length and 1.6 cm thickness composed of 16 layers of 300 µm × 300 µm × 1 mm pads), for scattering, surrounded by an outer cylindrical BGO scintillation detector (17.6 cm ID, 16 cm length and 2 cm thickness segmented into 3 mm × 3 mm × 20 mm crystals), for capture was evaluated in detail. In order to evaluate spatial resolution, sensitivity and image quality of the PET system, 2D images of multiple point and cylinder sources were reconstructed with the simulation data including blurring from positron range and annihilation photon acollinearity using filtered backprojection (FBP). Simulation results for 18F demonstrate 340 µm FWHM at the center of the field of view with 1.0% sensitivity from the coincidence of single scattering events in both silicon detectors and 1.0 mm FWHM with 9.0% sensitivity from the coincidence of single scattering in the silicon and full energy absorption of the second photon in the BGO detector.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/58095/2/pmb7_15_019.pd

    Anti-tumour therapeutic efficacy of OX40L in murine tumour model

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    OX40 ligand (OX40L), a member of TNF superfamily, is a co-stimulatory molecule involved in T cell activation. Systemic administration of mOX40L fusion protein significantly inhibited the growth of experimental lung metastasis and subcutaneous (s.c.) established colon (CT26) and breast (4T1) carcinomas. Vaccination with OX40L was significantly enhanced by combination treatment with intra-tumour injection of a disabled infectious single cycle-herpes simplex virus (DISC-HSV) vector encoding murine granulocyte macrophage-colony stimulating factor (mGM-CSF). Tumour rejection in response to OX40L therapy required functional CD4+ and CD8+ T cells and correlated with splenocyte cytotoxic T lymphocytes (CTLs) activity against the AH-1 gp70 peptide of the tumour associated antigen expressed by CT26 cells. These results demonstrate the potential role of the OX40L in cancer immunotherapy

    Performance evaluation of a very high resolution small animal PET imager using silicon scatter detectors

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    A very high resolution positron emission tomography (PET) scanner for small animal imaging based on the idea of inserting a ring of high-granularity solid-state detectors into a conventional PET scanner is under investigation. A particularly interesting configuration of this concept, which takes the form of a degenerate Compton camera, is shown capable of providing sub-millimeter resolution with good sensitivity. We present a Compton PET system and estimate its performance using a proof-of-concept prototype. A prototype single-slice imaging instrument was constructed with two silicon detectors 1 mm thick, each having 512 1.4 mm × 1.4 mm pads arranged in a 32 × 16 array. The silicon detectors were located edgewise on opposite sides and flanked by two non-position sensitive BGO detectors. The scanner performance was measured for its sensitivity, energy, timing, spatial resolution and resolution uniformity. Using the experimental scanner, energy resolution for the silicon detectors is 1%. However, system energy resolution is dominated by the 23% FWHM BGO resolution. Timing resolution for silicon is 82.1 ns FWHM due to time-walk in trigger devices. Using the scattered photons, time resolution between the BGO detectors is 19.4 ns FWHM. Image resolution of 980 µm FWHM at the center of the field-of-view (FOV) is obtained from a 1D profile of a 0.254 mm diameter 18F line source image reconstructed using the conventional 2D filtered back-projection (FBP). The 0.4 mm gap between two line sources is resolved in the image reconstructed with both FBP and the maximum likelihood expectation maximization (ML-EM) algorithm. The experimental instrument demonstrates sub-millimeter resolution. A prototype having sensitivity high enough for initial small animal images can be used for in vivo studies of small animal models of metabolism, molecular mechanism and the development of new radiotracers.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/58094/2/pmb7_10_012.pd

    Interventions to improve continence for children and young people with neurodisability: a national survey of practitioner and family perspectives and experiences.

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    Objective Describe families’ experiences of interventions to improve continence in children and young people with neurodisability, and health professionals’ and school and social care staff’s perspectives regarding factors affecting intervention use. Design Four online surveys were developed and advertised to parent carers, young people with neurodisability, health professionals and school and social care staff, via societies, charities, professional contacts, schools, local authorities, and national parent carer and family forums, who shared invitations with their networks. Survey questions explored: difficulties helping children and young people use interventions; acceptability of interventions and waiting times; ease of use and availability of interventions, and facilitators and barriers to improving continence. Results 1028 parent carers, 26 young people, 352 health professionals and 202 school and social care staff registered to participate. Completed surveys were received from 579 (56.3%) parent carers, 20 (77%) young people, 193 (54.8%) health professionals, and 119 (58.9%) school and social care staff. Common parent carer-reported difficulties in using interventions to help their children and young people to learn to use the toilet included their child’s lack of understanding about what was required (reported by 337 of 556 (60.6%) parent carers who completed question) and their child’s lack of willingness (343 of 556, 61.7%). Almost all (142 of 156, 91%) health professionals reported lack of funding and resources as barriers to provision of continence services. Many young people (14 of 19, 74%) were unhappy using toilet facilities while out and about. Conclusions Perceptions that children lack understanding and willingness, and inadequate facilities impact the implementation of toileting interventions for children and young people with neurodisability. Greater understanding is needed for children to learn developmentally appropriate toileting skills. Further research is recommended around availability and acceptability of interventions to ensure quality of life is unaffected

    Polypoid Endobronchial Lung Cyst with Bronchoscopic Removal : A Case Report

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    Pulmonary bronchogenic cyst in adults is rare and the typical appearance is a sharply circumscribed, round or oval nodule or mass, usually in the medial third of the lungs. Bronchial polyps are rare histopathologically distinct nonneoplastic endobronchial lesions and are classified as multiple papillomas, solitary papillomas, and inflammatory polyps. We herein report a patient with polypoid endobronchial lung cyst. A 68-yr-old woman presented with a discomfort and pain in the right upper chest of four weeks??duration. Chest radiography revealed a cystic lesion in the right upper lung. Computed tomography revealed a 4×5 cm sized large cyst. Neither enlarged mediastinal lymph nodes nor extrabronchial involvements were observed. Flexible bronchoscopy revealed a peduncular polyp about 2 cm in length originating from the anterior segment of right upper lung. After bronchoscopic removal of polyp, cystic lesion of the right upper lung disappeared

    CAR-T cell. the long and winding road to solid tumors

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    Adoptive cell therapy of solid tumors with reprogrammed T cells can be considered the "next generation" of cancer hallmarks. CAR-T cells fail to be as effective as in liquid tumors for the inability to reach and survive in the microenvironment surrounding the neoplastic foci. The intricate net of cross-interactions occurring between tumor components, stromal and immune cells leads to an ineffective anergic status favoring the evasion from the host's defenses. Our goal is hereby to trace the road imposed by solid tumors to CAR-T cells, highlighting pitfalls and strategies to be developed and refined to possibly overcome these hurdles

    Period and Cohort Changes in Americans’ Support for Marijuana Legalization: Convergence and Divergence across Social Groups

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    We cast fresh light on how and why Americans’ views on marijuana legalization shifted between 1973 and 2014. Results from age-period-cohort models show a strong negative effect of age and relatively high levels of support for legalization among baby boom cohorts. Despite the baby boom effect, the large increase in support for marijuana legalization is predominantly a broad, period-based change in the population. Additional analyses demonstrate that differences in support for legalization by education, region, and religion decline, that differences by political party increase, and that differences between whites and African Americans reverse direction. We conclude by discussing the implications of these findings and by identifying promising directions for future research on this topic

    Inflammasome-independent role of AIM2 in suppressing colon tumorigenesis via DNA-PK and Akt

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    The inflammasome activates caspase-1 and the release of interleukin-1β (IL-1β) and IL-18, and several inflammasomes protect against intestinal inflammation and colitis-associated colon cancer (CAC) in animal models. The absent in melanoma 2 (AIM2) inflammasome is activated by double-stranded DNA, and AIM2 expression is reduced in several types of cancer, but the mechanism by which AIM2 restricts tumor growth remains unclear. We found that Aim2-deficient mice had greater tumor load than Asc-deficient mice in the azoxymethane/dextran sodium sulfate (AOM/DSS) model of colorectal cancer. Tumor burden was also higher in Aim2−/−/ApcMin/+ than in APCMin/+ mice. The effects of AIM2 on CAC were independent of inflammasome activation and IL-1β and were primarily mediated by a non–bone marrow source of AIM2. In resting cells, AIM2 physically interacted with and limited activation of DNA-dependent protein kinase (DNA-PK), a PI3K-related family member that promotes Akt phosphorylation, whereas loss of AIM2 promoted DNA-PK–mediated Akt activation. AIM2 reduced Akt activation and tumor burden in colorectal cancer models, while an Akt inhibitor reduced tumor load in Aim2−/− mice. These findings suggest that Akt inhibitors could be used to treat AIM2-deficient human cancers
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