Automated algorithm for CBCT-based dose calculations of prostate radiotherapy with bilateral hip prostheses

ABSTRACTOBJECTIVE:Cone beam CT (CBCT) images contain more scatter than a conventional CT image and therefore provide inaccurate Hounsfield units (HUs). Consequently, CBCT images cannot be used directly for radiotherapy dose calculation. The aim of this study is to enable dose calculations to be performed with the use of CBCT images taken during radiotherapy and evaluate the necessity of replanning.METHODS:A patient with prostate cancer with bilateral metallic prosthetic hip replacements was imaged using both CT and CBCT. The multilevel threshold (MLT) algorithm was used to categorize pixel values in the CBCT images into segments of homogeneous HU. The variation in HU with position in the CBCT images was taken into consideration. This segmentation method relies on the operator dividing the CBCT data into a set of volumes where the variation in the relationship between pixel values and HUs is small. An automated MLT algorithm was developed to reduce the operator time associated with the process. An intensity-modulated radiation therapy plan was generated from CT images of the patient. The plan was then copied to the segmented CBCT (sCBCT) data sets with identical settings, and the doses were recalculated and compared.RESULTS:Gamma evaluation showed that the percentage of points in the rectum with γ < 1 (3%/3 mm) were 98.7% and 97.7% in the sCBCT using MLT and the automated MLT algorithms, respectively. Compared with the planning CT (pCT) plan, the MLT algorithm showed −0.46% dose difference with 8 h operator time while the automated MLT algorithm showed −1.3%, which are both considered to be clinically acceptable, when using collapsed cone algorithm.CONCLUSION:The segmentation of CBCT images using the method in this study can be used for dose calculation. For a patient with prostate cancer with bilateral hip prostheses and the associated issues with CT imaging, the MLT algorithms achieved a sufficient dose calculation accuracy that is clinically acceptable. The automated MLT algorithm reduced the operator time associated with implementing the MLT algorithm to achieve clinically acceptable accuracy. This saved time makes the automated MLT algorithm superior and easier to implement in the clinical setting.ADVANCES IN KNOWLEDGE:The MLT algorithm has been extended to the complex example of a patient with bilateral hip prostheses, which with the introduction of automation is feasible for use in adaptive radiotherapy, as an alternative to obtaining a new pCT and reoutlining the structures

Invasion speeds for structured populations in fluctuating environments

We live in a time where climate models predict future increases in environmental variability and biological invasions are becoming increasingly frequent. A key to developing effective responses to biological invasions in increasingly variable environments will be estimates of their rates of spatial spread and the associated uncertainty of these estimates. Using stochastic, stage-structured, integro-difference equation models, we show analytically that invasion speeds are asymptotically normally distributed with a variance that decreases in time. We apply our methods to a simple juvenile-adult model with stochastic variation in reproduction and an illustrative example with published data for the perennial herb, \emph{Calathea ovandensis}. These examples buttressed by additional analysis reveal that increased variability in vital rates simultaneously slow down invasions yet generate greater uncertainty about rates of spatial spread. Moreover, while temporal autocorrelations in vital rates inflate variability in invasion speeds, the effect of these autocorrelations on the average invasion speed can be positive or negative depending on life history traits and how well vital rates ``remember'' the past

The novel CXCR4 antagonist POL5551 mobilizes hematopoietic stem and progenitor cells with greater efficiency than Plerixafor

Mobilized blood has supplanted bone marrow (BM) as the primary source of hematopoietic stem cells for autologous and allogeneic stem cell transplantation. Pharmacologically enforced egress of hematopoietic stem cells from BM, or mobilization, has been achieved by directly or indirectly targeting the CXCL12/CXCR4 axis. Shortcomings of the standard mobilizing agent, granulocyte colony-stimulating factor (G-CSF), administered alone or in combination with the only approved CXCR4 antagonist, Plerixafor, continue to fuel the quest for new mobilizing agents. Using Protein Epitope Mimetics technology, a novel peptidic CXCR4 antagonist, POL5551, was developed. In vitro data presented herein indicate high affinity to and specificity for CXCR4. POL5551 exhibited rapid mobilization kinetics and unprecedented efficiency in C57BL/6 mice, exceeding that of Plerixafor and at higher doses also of G-CSF. POL5551-mobilized stem cells demonstrated adequate transplantation properties. In contrast to G-CSF, POL5551 did not induce major morphological changes in the BM of mice. Moreover, we provide evidence of direct POL5551 binding to hematopoietic stem and progenitor cells (HSPCs) in vivo, strengthening the hypothesis that CXCR4 antagonists mediate mobilization by direct targeting of HSPCs. In summary, POL5551 is a potent mobilizing agent for HSPCs in mice with promising therapeutic potential if these data can be orroborated in humans

Walk well:a randomised controlled trial of a walking intervention for adults with intellectual disabilities: study protocol

Background - Walking interventions have been shown to have a positive impact on physical activity (PA) levels, health and wellbeing for adult and older adult populations. There has been very little work carried out to explore the effectiveness of walking interventions for adults with intellectual disabilities. This paper will provide details of the Walk Well intervention, designed for adults with intellectual disabilities, and a randomised controlled trial (RCT) to test its effectiveness. Methods/design - This study will adopt a RCT design, with participants allocated to the walking intervention group or a waiting list control group. The intervention consists of three PA consultations (baseline, six weeks and 12 weeks) and an individualised 12 week walking programme. A range of measures will be completed by participants at baseline, post intervention (three months from baseline) and at follow up (three months post intervention and six months from baseline). All outcome measures will be collected by a researcher who will be blinded to the study groups. The primary outcome will be steps walked per day, measured using accelerometers. Secondary outcome measures will include time spent in PA per day (across various intensity levels), time spent in sedentary behaviour per day, quality of life, self-efficacy and anthropometric measures to monitor weight change. Discussion - Since there are currently no published RCTs of walking interventions for adults with intellectual disabilities, this RCT will examine if a walking intervention can successfully increase PA, health and wellbeing of adults with intellectual disabilities

Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector

The inclusive and dijet production cross-sections have been measured for jets containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The measurements use data corresponding to an integrated luminosity of 34 pb^-1. The b-jets are identified using either a lifetime-based method, where secondary decay vertices of b-hadrons in jets are reconstructed using information from the tracking detectors, or a muon-based method where the presence of a muon is used to identify semileptonic decays of b-hadrons inside jets. The inclusive b-jet cross-section is measured as a function of transverse momentum in the range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet cross-section is measured as a function of the dijet invariant mass in the range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets and the angular variable chi in two dijet mass regions. The results are compared with next-to-leading-order QCD predictions. Good agreement is observed between the measured cross-sections and the predictions obtained using POWHEG + Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet cross-section. However, it does not reproduce the measured inclusive cross-section well, particularly for central b-jets with large transverse momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final version published in European Physical Journal

Performance of the CMS Cathode Strip Chambers with Cosmic Rays

The Cathode Strip Chambers (CSCs) constitute the primary muon tracking device in the CMS endcaps. Their performance has been evaluated using data taken during a cosmic ray run in fall 2008. Measured noise levels are low, with the number of noisy channels well below 1%. Coordinate resolution was measured for all types of chambers, and fall in the range 47 microns to 243 microns. The efficiencies for local charged track triggers, for hit and for segments reconstruction were measured, and are above 99%. The timing resolution per layer is approximately 5 ns

Methods Used in Economic Evaluations of Chronic Kidney Disease Testing — A Systematic Review

Background: The prevalence of chronic kidney disease (CKD) is high in general populations around the world. Targeted testing and screening for CKD are often conducted to help identify individuals that may benefit from treatment to ameliorate or prevent their disease progression. Aims: This systematic review examines the methods used in economic evaluations of testing and screening in CKD, with a particular focus on whether test accuracy has been considered, and how analysis has incorporated issues that may be important to the patient, such as the impact of testing on quality of life and the costs they incur. Methods: Articles that described model-based economic evaluations of patient testing interventions focused on CKD were identified through the searching of electronic databases and the hand searching of the bibliographies of the included studies. Results: The initial electronic searches identified 2,671 papers of which 21 were included in the final review. Eighteen studies focused on proteinuria, three evaluated glomerular filtration rate testing and one included both tests. The full impact of inaccurate test results was frequently not considered in economic evaluations in this setting as a societal perspective was rarely adopted. The impact of false positive tests on patients in terms of the costs incurred in re-attending for repeat testing, and the anxiety associated with a positive test was almost always overlooked. In one study where the impact of a false positive test on patient quality of life was examined in sensitivity analysis, it had a significant impact on the conclusions drawn from the model. Conclusion: Future economic evaluations of kidney function testing should examine testing and monitoring pathways from the perspective of patients, to ensure that issues that are important to patients, such as the possibility of inaccurate test results, are properly considered in the analysis

Expectations and needs of patients with a chronic disease toward self-management and eHealth for self-management purposes

Background: Self-management is considered as an essential component of chronic care by primary care professionals. eHealth is expected to play an important role in supporting patients in their self-management. For effective implementation of eHealth it is important to investigate patients’ expectations and needs regarding self-management and eHealth. The objectives of this study are to investigate expectations and needs of people with a chronic condition regarding self-management and eHealth for self-management purposes, their willingness to use eHealth, and possible differences between patient groups regarding these topics. Methods: Five focus groups with people with diabetes (n = 14), COPD (n = 9), and a cardiovascular condition (n = 7) were conducted in this qualitative research. Separate focus groups were organized based on patients’ chronic condition. The following themes were discussed: 1) the impact of the chronic disease on patients’ daily life; 2) their opinions and needs regarding self-management; and 3) their expectations and needs regarding, and willingness to use, eHealth for self-management purposes. A conventional content analysis approach was used for coding. Results: Patient groups seem to differ in expectations and needs regarding self-management and eHealth for self-management purposes. People with diabetes reported most needs and benefits regarding self-management and were most willing to use eHealth, followed by the COPD group. People with a cardiovascular condition mentioned having fewer needs for self-management support, because their disease had little impact on their life. In all patient groups it was reported that the patient, not the care professional, should choose whether or not to use eHealth. Moreover, participants reported that eHealth should not replace, but complement personal care. Many participants reported expecting feelings of anxiety by doing measurement themselves and uncertainty about follow-up of deviant data of measurements. In addition, many participants worried about the implementation of eHealth being a consequence of budget cuts in care. Conclusion: This study suggests that aspects of eHealth, and the way in which it should be implemented, should be tailored to the patient. Patients’ expected benefits of using eHealth to support self-management and their perceived controllability over their disease seem to play an important role in patients’ willingness to use eHealth for self-management purposes

Soluble CD14 in cerebrospinal fluid is associated with markers of inflammation and axonal damage in untreated HIV-infected patients: a retrospective cross-sectional study

Background: HIV-associated cognitive impairment has declined since the introduction of combination antiretroviral treatment (cART). However, milder forms of cognitive impairment persist. Inflammation in the cerebrospinal fluid (CSF) has been associated with cognitive impairment, and CSF neurofilament light chain protein (NFL) and CSF neopterin concentrations are increased in those patients. Microbial translocation in HIV infection has been suggested to contribute to chronic inflammation, and lipopolysaccharide (LPS) and soluble CD14 (sCD14) are markers of microbial translocation and the resulting monocyte activation, respectively. We hypothesised that microbial translocation contributes to inflammation and axonal damage in the central nervous system (CNS) in untreated HIV infection. / Methods: We analyzed paired samples of plasma and CSF from 62 HIV-infected, untreated patients without cognitive symptoms from Sahlgrenska University Hospital, Gothenburg, Sweden. Measurements of neopterin and NFL in CSF were available from previous studies. Plasma and CSF sCD14 was measured using ELISA (R&D, Minneapolis, MN), and plasma and CSF LPS was measured using LAL colorimetric assay (Lonza, Walkersville, MD, USA). Univariate and multivariate regression analyses were performed. / Results: LPS in plasma was associated with plasma sCD14 (r = 0.31, P = 0.015), and plasma sCD14 was associated with CSF sCD14 (r = 0.32, P = 0.012). Furthermore, CSF sCD14 was associated with NFL (r = 0.32, P = 0.031) and neopterin (r = 0.32, P = 0.012) in CSF. LPS was not detectable in CSF. In a multivariate regression model CSF sCD14 remained associated with NFL and neopterin after adjusting for age, CD4+ cell count, and HIV RNA in CSF. / Conclusions: In a group of untreated, HIV-infected patients LPS was associated with sCD14 in plasma, and plasma sCD14 was associated CSF sCD14. CSF sCD14 were associated with markers of CNS inflammation and axonal damage. This suggest that microbial translocation might be a driver of systemic and CNS inflammation. However, LPS was not detectable in the CSF, and since sCD14 is a marker of monocyte activation sCD14 may be increased due to other causes than microbial translocation. Further studies regarding cognitive impairment and biomarkers are warranted to fully understand causality

The Environment of the Binary Neutron Star Merger GW170817

We present Hubble Space Telescope (HST) and Chandra imaging, combined with Very Large Telescope MUSE integral field spectroscopy of the counterpart and host galaxy of the first binary neutron star merger detected via gravitational-wave emission by LIGO and Virgo, GW170817. The host galaxy, NGC 4993, is an S0 galaxy at z = 0.009783. There is evidence for large, face-on spiral shells in continuum imaging, and edge-on spiral features visible in nebular emission lines. This suggests that NGC 4993 has undergone a relatively recent ($\lesssim 1$ Gyr) "dry" merger. This merger may provide the fuel for a weak active nucleus seen in Chandra imaging. At the location of the counterpart, HST imaging implies there is no globular or young stellar cluster, with a limit of a few thousand solar masses for any young system. The population in the vicinity is predominantly old with lesssim1% of any light arising from a population with ages $\lt 500\,\mathrm{Myr}$. Both the host galaxy properties and those of the transient location are consistent with the distributions seen for short-duration gamma-ray bursts, although the source position lies well within the effective radius (${r}_{e}\sim 3$ kpc), providing an r e -normalized offset that is closer than $\sim 90 \%$ of short GRBs. For the long delay time implied by the stellar population, this suggests that the kick velocity was significantly less than the galaxy escape velocity. We do not see any narrow host galaxy interstellar medium features within the counterpart spectrum, implying low extinction, and that the binary may lie in front of the bulk of the host galaxy