Knowledge of immune cell phenotypes in the tumor microenvironment is essential for understanding mechanisms of cancer progression and immunotherapy response. We profiled 45,000 immune cells from ...eight breast carcinomas, as well as matched normal breast tissue, blood, and lymph nodes, using single-cell RNA-seq. We developed a preprocessing pipeline, SEQC, and a Bayesian clustering and normalization method, Biscuit, to address computational challenges inherent to single-cell data. Despite significant similarity between normal and tumor tissue-resident immune cells, we observed continuous phenotypic expansions specific to the tumor microenvironment. Analysis of paired single-cell RNA and T cell receptor (TCR) sequencing data from 27,000 additional T cells revealed the combinatorial impact of TCR utilization on phenotypic diversity. Our results support a model of continuous activation in T cells and do not comport with the macrophage polarization model in cancer. Our results have important implications for characterizing tumor-infiltrating immune cells.
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•Single-cell RNA-seq reveals phenotypic expansion of intratumoral immune cells•Biscuit identifies cell populations that differ in co-expression patterns•T cells reside on continuous activation and differentiation trajectories•Combinatorial environmental inputs and TCR usage shape T cell phenotypes
Single-cell analysis of the breast tumor immune microenvironment, coupled with computational analysis, yields an immune map of breast cancer that points to continuous T cell activation and differentiation states.
VITESS is a software widely used for simulation of neutron scattering experiments. Although originally motivated by instrument design for the European Spallation Source, all major neutron sources are ...available. Existing as well as future instruments on reactor or spallation sources can be designed and optimized, or simulated in a virtual experiment to prepare a measurement, including basic data evaluation. This note gives an overview of the VITESS software concept and usage. New developments are presented, including a 3D visualization of instruments and neutron trajectories, a numerical optimization routine and a parallelization tool allowing to split VITESS simulations on a computer cluster.
A measurement apparatus for observing the foaming of metals is described. It consists of a microfocus X‐ray source, a small heater and a panel detector. The foaming of samples can be recorded in ...real‐time with frequencies up to 9 Hz and resolutions down to 5 μm due to the small spot size. Magnifications up to 10x are obtained by simply changing the distance between source, sample and detector. Foaming of Al alloys and sandwiches was investigated applying different final foaming temperatures, heating rates and blowing agent pre‐treatments. An image analysis program was developed to automatically recognise the foam expansion.
A measurement apparatus for observing the foaming of metals is described. The foaming of samples can be recorded in real‐time with frequencies up to 9 Hz and resolutions down to 5 μm due to the small spot size. Magnifications up to 10× are obtained by simply changing the distance between source, sample and detector. Foaming of Al alloys and sandwiches was investigated and an image analysis program was developed to automatically recognise the foam expansion.
Assays for the analysis of antierythropoietin antibodies (anti-EPO Abs) currently suffer from a high degree of nonspecificity or are cumbersome and time consuming to perform. They are therefore not ...well suited for the analysis of large numbers of human sera samples, a task that has become increasingly important due to an increase in the number of patients developing anti-EPO Abs. The objective of this study was to develop and validate a sensitive and specific ELISA for the determination of anti-EPO Abs that would suit these purposes.
In this new double antigen bridging ELISA, anti-EPO Abs bind via one site to recombinant human erythropoietin (rhEPO)-biotin immobilized to streptavidin-coated microtiter plates (MTPs) and by a second site to rhEPO labelled with digoxigenin (DIG). The amount of bound antibody is determined using an anti-DIG antibody coupled to peroxidase. A rabbit polyclonal anti-EPO Ab purified by immunoadsorption is used as reference antibody preparation.
The dynamic range of this ELISA was 1–75 ng/ml per assay calibrated with the reference antibody preparation. The assay was specific for anti-EPO Abs and did not react with other immunoglobulins (Ig) present in human serum. The lower limit of detection (LLD) of the assay was 0.5 ng/ml, and the lower limit of quantitation (LLQ) was 1.0 ng/ml. Anti-EPO Abs could be detected in the sera of pure red cell aplasia (PRCA) patients. In contrast to previous reports, no anti-EPO Abs could be detected in the sera of patients with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), Sjögren's syndrome (SS), or in the sera of dialysis patients.
A game of cops and robbers Aigner, M.; Fromme, M.
Discrete Applied Mathematics,
01/1984, Letnik:
8, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Let
G be a finite connected graph. Two players, called cop
C and robber
R, play a game on
G according to the following rules. First
C then
R occupy some vertex of
G. After that they move alternately ...along edges of
G. The cop
C wins if he succeeds in putting himself on top of the robber
R, otherwise
R wins. We review an algorithmic characterization and structural description due to Nowakowski and Winkler. Then we consider the general situation where
n cops chase the robber. It is shown that there are graphs on which arbitrarily many cops are needed to catch the robber. In contrast to this result, we prove that for planar graphs 3 cops always suffice to win.
Abstract Context Antibiotic prescription in hospice patients is complicated by the focus on palliative rather than curative care and concerns regarding increasing antibiotic resistance. Objectives To ...estimate the antibiotic use in a national sample of hospice patients and identify facility and patient characteristics associated with antibiotic use in this population. Methods This was an analysis of data from the 2007 National Home and Hospice Care Survey, a nationally representative sample of U.S. hospice agencies. We included data from 3884 patients who died in hospice care. The primary outcome measure was prevalence of antibiotic use in the last seven days of life. Diagnoses, including potential infectious indications for antibiotic use, were defined using International Classification of Diseases, Ninth Revision (ICD-9) codes. Chi-squared tests and t -tests were used to quantify associations of patient and facility characteristics with antibiotic use. Results During the last seven days of life, 27% (95% CI: 24%–30%) of patients received at least one antibiotic and 1.3% (95% CI: 0.7%–2.0%) received three or more antibiotics. Among patients who received at least one antibiotic, 15% (95% CI: 10%–20%) had a documented infectious diagnosis compared with 9% (95% CI: 7%–11%), who had an infectious diagnosis but received no antibiotics. Conclusion In this nationally representative sample, 27% of hospice patients received an antibiotic during the last seven days of life, most without a documented infectious diagnosis. Further research is needed to elucidate the role of antibiotics in this patient population to maintain palliative care goals while reducing unnecessary antibiotic use.
A program package BEAN (BENSC Analysis Program) has been developed to provide a standard for the analysis of one-dimensional neutron spectra gathered at the experiment facilities of BENSC. The main ...purpose was to replace the large number of heterogeneous software packages which has been developed in the past for each neutron spectrometer separately. BEAN runs on a UNIX application server which is embedded in a client/server architecture with NFS filesystem. Data display is performed by means of the PV-WAVE software tools. For easy use the graphical user interface follows the common styling guidelines of Windows programs.
Study objective Resuscitation measures should be guided by previous patient choices about end-of-life care, when they exist; however, documentation of these choices can be unclear or difficult to ...access. We evaluate the concordance of a statewide registry of actionable resuscitation orders unique to Oregon with out-of-hospital and emergency department (ED) care provided for patients found by emergency medical services (EMS) in out-of-hospital cardiac arrest. Methods This was a retrospective cohort study of patients found by EMS providers in out-of-hospital cardiac arrest in 5 counties in 2010. We used probabilistic linkage to match patients found in out-of-hospital cardiac arrest with previously signed documentation of end-of-life decisions in the Oregon Physician Orders for Life-Sustaining Treatment (POLST) registry. We evaluated resuscitation interventions in the field and ED. Results There were 1,577 patients found in out-of-hospital cardiac arrest, of whom 82 had a previously signed POLST form. Patients with POLST do-not-resuscitate orders for whom EMS was called had resuscitation withheld or ceased before hospital admission in 94% of cases (95% confidence interval CI 83% to 99%). Compared with patients with no POLST or known do-not-resuscitate orders, more patients with attempt resuscitation POLST orders had field resuscitation attempted (84% versus 60%; difference 25%; 95% CI 12% to 37%) and were admitted to hospitals (38% versus 17%; difference 20%; 95% CI 3% to 37%), with no documented misinterpretations of the form once CPR was initiated. Conclusion In this sample of patients in out-of-hospital cardiac arrest, out-of-hospital and ED care was generally concordant with previously documented end-of-life orders in the setting of critical illness. Further research is needed to compare the effectiveness of Oregon's POLST system to other methods of end-of-life order documentation.
Timing of POLST Form Completion by Cause of Death Zive, Dana M., MPH; Fromme, Erik K., MD, MCR; Schmidt, Terri A., MD, MS ...
Journal of pain and symptom management,
11/2015, Letnik:
50, Številka:
5
Journal Article
Recenzirano
Odprti dostop
Abstract Context The physician orders for life-sustaining treatment (POLST) paradigm allows health care professionals to document the treatment preferences of patients with advanced illness or ...frailty as portable and actionable medical orders. National standards encourage offering POLST orders to patients for whom clinicians would not be surprised if they died in the next year. Objectives To determine the influence of cause of death on the timing of POLST form completion and on changes to POLST orders as death approaches. Methods This was a cohort study of 18,285 Oregon POLST Registry decedents who died in 2010–2011 matched to Oregon death certificates. Results The median interval between POLST completion and death was 6.4 weeks. Those dying of cancer had forms completed nearer death (median 5.1 weeks) than those with organ failure (10.6 weeks) or dementia (14.5 weeks; P < 0.001). More than 90% of final POLST forms indicated orders for no resuscitation and 65.1% listed orders for comfort measures only. Eleven percent of the sample had multiple registered forms during the two years preceding their death, with the form completed nearest to death more likely than earlier forms to have orders for no resuscitation and comfort measures only, although some later forms did have orders for more treatment. Conclusion More than half of POLST forms were completed in the final two months of life. Cause of death influenced when POLST forms were completed. POLST forms changed in the two years preceding death, more frequently recording fewer life-sustaining treatment orders than the earlier form(s).
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