er estimation in the longitudinal study.Particle radiography (pRad) has been proposed and investigated as a promising tool for particle therapy as it provides a water equivalent thickness (WET) image of the patient. In single-event particle imaging, for each measured particle, the related most likely path (MLP) through the object is estimated to account for multiple Coulomb scattering (MCS). In previous studies, the accuracy limit of the MLP has been used to determine the spatial resolution limit. In this work, we investigate the limit of the spatial resolution achievable with different pRad algorithms based on a theoretical model of the particle scattering for an ideal beam and detector. First, we investigate binning the particles in a plane seated at the depth of the object of interest (plane-of-interest binning; PIB) and extend existing theoretical considerations also to objects not located in the binning plane. We use this to model the spatial resolution in case of binning the particles directly at the front or rear tracker (FTB and RTB, respectively). Further, we investigate evenly distributing the particles' WET along their trajectory into pixel channels and creating the pRad image as channel mean (along-path-binning; APB). Monte Carlo simulations are used to qualitatively investigate the different algorithms and to validate the theoretical predictions. We show that projecting the scattered particle paths onto a single image will inevitably result in a limited spatial resolution lower than expected from only the MLP uncertainty. Only in the case where the depth of a feature is known and used as binning depth for PIB, the spatial resolution of that feature is equal to the path estimation accuracy. check details For the APB algorithm the spatial resolution decreases with increasing depth in the object, especially if the true particle path through the object would be known. The derived theoretical models will be useful for future development of improved pRad reconstruction algorithms.
To identify the relative positions of the ultimate RBE, at a LET value of LET
(where the LET-RBE turnover point occurs independently of dose), and of the maximum LET (LET
) for a range of ions from protons to Iron ions.
For a range of relativistic velocities (β), the kinetic energies, LET values and ranges for each ion are obtained using SRIM software. For protons and helium ions, the LET changes with β are plotted and LET
is compared with LET
For all the ions studied the residual ranges of particles at LET
and LET
are subtracted to provide the physical separation (S) between LET
and LET
.
Graphical methods are used to show the above parameters for protons and helium ions. For all the ions studied, LET
occurs at kinetic energies which are higher than those at LET
, so the ultimate maximal RBE occurs proximal to the Bragg peak for individual particles and not beyond it, as is commonly supposed. The distance S, between LET
and LET
, appears to increase linearly with the atomic charge vtraversed by a single particle.
The association between dysregulated thyroid hormone function and cancer risk is inconclusive, especially among different age groups and uncommon malignancies. We sought to determine the relation of TSH and free T4 levels with overall cancer risk as well as risk of specific cancer types.
Data on thyroid hormone profile was collected from 375 635 Israeli patients with no prior history of cancer. Cancer cases were identified via the Israel National Cancer Registry. Cox proportional hazards model was used to assess hazard ratios for overall cancer as well as 20 cancer subgroups.
In this study, 23 808 cases of cancer were detected over median follow up of 10.9 years. Among patients younger than 50 at inclusion, TSH in the hyperthyroid range, elevated free T4 and subclinical hyperthyroidism were associated with increased cancer risk (HR 1.3, 1.28 and 1.31, respectively). In contrast, patients 50 or older with clinical hyperthyroidism were at lower cancer risk (HR 0.64). Elevated TSH was associated with decreased risk of prostate cancer (HR 0.67). Log-TSH elevation was associated with decreased risk of thyroid cancer (HR 0.82) and increased risk of melanoma (HR 1.11) and uterine cancer (HR 1.27). Elevated free T4 was associated with increased lung cancer risk (HR 1.54), while free T4 levels above the normal range and clinical hyperthyroidism were related to lower colorectal cancer risk (HR 0.59 and 0.08, respectively).
Thyroid hormones display opposing effects on cancer risk, based on patient age and cancer type.
Thyroid hormones display opposing effects on cancer risk, based on patient age and cancer type.
Androgens are important modulators of immune cell function. The local generation of active androgens from circulating precursors is an important mediator of androgen action in peripheral target cells or tissues. We aimed to characterize the activation of classic and 11-oxygenated androgens in human peripheral blood mononuclear cells (PBMCs).
PBMCs were isolated from healthy male donors and incubated ex vivo with precursors and active androgens of the classic and 11-oxygenated androgen pathways. Steroids were quantified by liquid chromatography-tandem mass spectrometry. The expression of genes encoding steroid-metabolizing enzymes was assessed by quantitative PCR.
PBMCs generated eight-fold higher amounts of the active 11-oxygenated androgen 11-ketotestosterone than the classic androgen testosterone from their respective precursors. We identified the enzyme AKR1C3 as the major reductive 17β-hydroxysteroid dehydrogenase in PBMCs responsible for both conversions and found that within the PBMC compartment nrs to the anti-viral immune defense. This potentially links intracrine 11-oxygenated androgen generation to the previously observed decreased NK cell cytotoxicity and increased infection risk in primary adrenal insufficiency. In addition, we show that PBMCs continue to generate 11-ketotestosterone if the cellular component of whole blood samples is not removed in a timely fashion, which could affect measurements of this active androgen in routine clinical biochemistry.check details
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