Collimator design for a clinical brain SPECT/MRI insert

This project's goal is to design a SPECT insert for a clinical MRI system for simultaneous brain SPECT/MR imaging. We assume the stationary SPECT insert will consist of two rings of ∼5x5-cm SiPM-based detectors insensitive to magnetic fields, with 0.8-mm intrinsic resolution. The maximum diameter is 44.5 cm, the minimum diameter is 33 cm to accommodate the patient and MRI receive/transmit coil, and the FOV has a 20 cm diameter. We have compared eight collimator designs: single-, 2x2-, 3x3- and 5+2½- pinhole, and single-, 2-, 3- and 1+2½-slit slit-slat, where ½-pinholes/slits are shared between two detectors. Analytical geometric efficiency was calculated for an activity distribution corresponding to a human brain and a target resolution of 10 mm FWHM at the centre of the FOV. Noise-free data were simulated with and without depth-of-interaction (DOI) information, and reconstructed for uniform, Defrise, Derenzo, and Zubal brain phantoms. For DOI it is assumed that the crystal's first and second half can be differentiated. Comparing the multi-pinhole and multi-slit slit-slat collimators, the former gives better reconstructed uniformity and trans-axial resolution, while the latter gives better axial resolution. Although the 2x2-pinhole and 2-slit designs give the highest sensitivities, they result in a sub-optimal utilization of the detector FOV. The best options are therefore the 5+2½-pinhole and the 1+2½-slit systems, with sensitivities of 4.9*10–4 and 4.0*10–4, respectively. The brain phantom reconstructions with multi-pinhole collimator are superior as compared to slit-slat, especially in terms of symmetry and realistic activity distribution. DOI information reduces artefacts and improves uniformity in geometric phantoms, although the difference is small for the brain phantom. These results favour a multi-pinhole configuration

Moral preferences in helping dilemmas expressed by matching and forced choice

This paper asks whether moral preferences in eight medical dilemmas change as a function of how preferences are expressed, and how people choose when they are faced with two equally attractive help projects. In two large-scale studies, participants first read dilemmas where they “matched” two suggested helping projects (which varied on a single attribute) so that they became equally attractive. They did this by filling in a missing number (e.g., how many male patients must Project M save in order to be equally attractive as Project F which can save 100 female patients). Later, the same participants were asked to choose between the two equally attractive projects. We found robust evidence that people do not choose randomly, but instead tend to choose projects that help female (vs. male), children (vs. adult), innocent (vs. non-innocent), ingroup (vs. outgroup) and existing (vs. future) patients, and imply no (vs. some) risk of a harmful side-effect, even when these projects have been matched as equally attractive as, and save fewer patients than the contrasting project. We also found that some moral preferences are hidden when expressed with matching but apparent when expressed with forced choice. For example, 88–95% of the participants expressed that female and male patients are equally valuable when doing the matching task, but over 80% of them helped female patients in the choice task

PERSiST: a flexible rainfall-runoff modelling toolkit for use with the INCA family of models

Runoff generation processes and pathways vary widely between catchments. Credible simulations of solute and pollutant transport in surface waters are dependent on models which facilitate appropriate, catchment-specific representations of perceptual models of the runoff generation process. Here, we present a flexible, semi-distributed landscape-scale rainfall-runoff modelling toolkit suitable for simulating a broad range of user-specified perceptual models of runoff generation and stream flow occurring in different climatic regions and landscape types. PERSiST (the Precipitation, Evapotranspiration and Runoff Simulator for Solute Transport) is designed for simulating present-day hydrology; projecting possible future effects of climate or land use change on runoff and catchment water storage; and generating hydrologic inputs for the Integrated Catchments (INCA) family of models. PERSiST has limited data requirements and is calibrated using observed time series of precipitation, air temperature and runoff at one or more points in a river network. Here, we apply PERSiST to the river Thames in the UK and describe a Monte Carlo tool for model calibration, sensitivity and uncertainty analysi

P171Elevated free fetal haemoglobin threatens vasculoprotection in the fetal circulation of preeclamptic pregnancy

Placental up-regulation of free fetal haemoglobin (fHbF) occurs in preeclamptic (PE) pregnancy. Heme oxygenase-1 (HO-1) is an important vasculoprotective enzyme in the catabolism of the associated heme porphyrin structure. We have previously shown that fHbF negatively influences the vasculoprotective capacity of the fetal circulation. Here we study fHbF levels in the fetal cord blood of pregnancies complicated by PE; a pathology associated with dysregulated fetoplacental vascular tone. We have previously shown that fHbF binds nitric oxide (NO) to elicit elevated vascular resistance in the fetoplacental circulation, using ex vivo human dual placental perfusion and in vitro placental endothelial cell shear stress studies. Furthermore, fHbF causes morphological changes to the fetoplacental endothelium. Here we hypothesise that elevated levels of fHbF in fetal plasma associated with placental pathology contribute to fetoplacental hypertension. Purpose: To evaluate and derive a robust cord blood collection and processing protocol for the accurate measurement of fetal plasma fHbF levels in normal and PE pregnancies. Methods: Fetal venous cord blood was collected by syringe and needle, or Vacutainer method into either EDTA or citrate tubes, within 10 minutes of partum. Plasma recovery occurred immediately, or after 30 minutes, prior to centrifugation at 2000g x 10 min at room temperature. Following evaluation to reduce mechanical haemolysis, newly collected normal & PE plasma (n=13 & 6, respectively) was subjected to ELISAs for HbF and HO-1. Results: Venipuncture collection of cord venous blood taken from the cord-placenta insertion point by Vacutainer system with a 21G needle, into citrate collection tubes with immediate centrifugation prevented mechanical haemolysis. There was no difference in plasma HO-1 between groups (medians = 5.9 & 5.3 ng/mL; normal & PE, respectively; Mann-Whitney). Whilst there was no difference in fHbF between groups (Mann-Whitney), variability was high in the PE group and there were some very high values for fHbF compared to the normal range, whilst fHbF values in the control group were within a tighter lower range (medians & ranges = 45.9 & 0-206 and 118.8 & 29-640 μg/mL). Conclusion: Fetal plasma HO-1 levels appear stable in preeclamptic fetal plasma, permitting fHbF to remain unchecked in some cases. High pathophysiological levels of fHbF in some cases of PE pregnancies are capable of evoking elevated vascular resistance within the fetoplacental circulation, caused by nitric oxide sequestration and disruption to the endothelium. Further evaluation is require

Exome sequencing of primary breast cancers with paired metastatic lesions reveals metastasis-enriched mutations in the A-kinase anchoring protein family (AKAPs)

Background: Tumor heterogeneity in breast cancer tumors is today widely recognized. Most of the available knowledge in genetic variation however, relates to the primary tumor while metastatic lesions are much less studied. Many studies have revealed marked alterations of standard prognostic and predictive factors during tumor progression. Characterization of paired primary- and metastatic tissues should therefore be fundamental in order to understand mechanisms of tumor progression, clonal relationship to tumor evolution as well as the therapeutic aspects of systemic disease. Methods: We performed full exome sequencing of primary breast cancers and their metastases in a cohort of ten patients and further confirmed our findings in an additional cohort of 20 patients with paired primary and metastatic tumors. Furthermore, we used gene expression from the metastatic lesions and a primary breast cancer data set to study the gene expression of the AKAP gene family. Results: We report that somatic mutations in A-kinase anchoring proteins are enriched in metastatic lesions. The frequency of mutation in the AKAP gene family was 10% in the primary tumors and 40% in metastatic lesions. Several copy number variations, including deletions in regions containing AKAP genes were detected and showed consistent patterns in both investigated cohorts. In a second cohort containing 20 patients with paired primary and metastatic lesions, AKAP mutations showed an increasing variant allele frequency after multiple relapses. Furthermore, gene expression profiles from the metastatic lesions (n = 120) revealed differential expression patterns of AKAPs relative to the tumor PAM50 intrinsic subtype, which were most apparent in the basal-like subtype. This pattern was confirmed in primary tumors from TCGA (n = 522) and in a third independent cohort (n = 182). Conclusion: Several studies from primary cancers have reported individual AKAP genes to be associated with cancer risk and metastatic relapses as well as direct involvement in cellular invasion and migration processes. Our findings reveal an enrichment of mutations in AKAP genes in metastatic breast cancers and suggest the involvement of AKAPs in the metastatic process. In addition, we report an AKAP gene expression pattern that consistently follows the tumor intrinsic subtype, further suggesting AKAP family members as relevant players in breast cancer biology.Peer reviewe

Suppressed Charge Dispersion via Resonant Tunneling in a Single-Channel Transmon

We demonstrate strong suppression of charge dispersion in a semiconductor-based transmon qubit across Josephson resonances associated with a quantum dot in the junction. On resonance, dispersion is drastically reduced compared to conventional transmons with corresponding Josephson and charging energies. We develop a model of qubit dispersion for a single-channel resonance, which is in quantitative agreement with experimental data

Optical Properties of Deep Ice at the South Pole - Absorption

We discuss recent measurements of the wavelength-dependent absorption coefficients in deep South Pole ice. The method uses transit time distributions of pulses from a variable-frequency laser sent between emitters and receivers embedded in the ice. At depths of 800 to 1000 m scattering is dominated by residual air bubbles, whereas absorption occurs both in ice itself and in insoluble impurities. The absorption coefficient increases approximately exponentially with wavelength in the measured interval 410 to 610 nm. At the shortest wavelength our value is about a factor 20 below previous values obtained for laboratory ice and lake ice; with increasing wavelength the discrepancy with previous measurements decreases. At around 415 to 500 nm the experimental uncertainties are small enough for us to resolve an extrinsic contribution to absorption in ice: submicron dust particles contribute by an amount that increases with depth and corresponds well with the expected increase seen near the Last Glacial Maximum in Vostok and Dome C ice cores. The laser pulse method allows remote mapping of gross structure in dust concentration as a function of depth in glacial ice.Comment: 26 pages, LaTex, Accepted for publication in Applied Optics. 9 figures, not included, available on request from [email protected]

Exome sequencing of primary breast cancers with paired metastatic lesions reveals metastasis-enriched mutations in the A-kinase anchoring protein family (AKAPs)

Abstract Background Tumor heterogeneity in breast cancer tumors is today widely recognized. Most of the available knowledge in genetic variation however, relates to the primary tumor while metastatic lesions are much less studied. Many studies have revealed marked alterations of standard prognostic and predictive factors during tumor progression. Characterization of paired primary- and metastatic tissues should therefore be fundamental in order to understand mechanisms of tumor progression, clonal relationship to tumor evolution as well as the therapeutic aspects of systemic disease. Methods We performed full exome sequencing of primary breast cancers and their metastases in a cohort of ten patients and further confirmed our findings in an additional cohort of 20 patients with paired primary and metastatic tumors. Furthermore, we used gene expression from the metastatic lesions and a primary breast cancer data set to study the gene expression of the AKAP gene family. Results We report that somatic mutations in A-kinase anchoring proteins are enriched in metastatic lesions. The frequency of mutation in the AKAP gene family was 10% in the primary tumors and 40% in metastatic lesions. Several copy number variations, including deletions in regions containing AKAP genes were detected and showed consistent patterns in both investigated cohorts. In a second cohort containing 20 patients with paired primary and metastatic lesions, AKAP mutations showed an increasing variant allele frequency after multiple relapses. Furthermore, gene expression profiles from the metastatic lesions (n = 120) revealed differential expression patterns of AKAPs relative to the tumor PAM50 intrinsic subtype, which were most apparent in the basal-like subtype. This pattern was confirmed in primary tumors from TCGA (n = 522) and in a third independent cohort (n = 182). Conclusion Several studies from primary cancers have reported individual AKAP genes to be associated with cancer risk and metastatic relapses as well as direct involvement in cellular invasion and migration processes. Our findings reveal an enrichment of mutations in AKAP genes in metastatic breast cancers and suggest the involvement of AKAPs in the metastatic process. In addition, we report an AKAP gene expression pattern that consistently follows the tumor intrinsic subtype, further suggesting AKAP family members as relevant players in breast cancer biology