The anatomy of clinical decision-making in multidisciplinary cancer meetings:A cross-sectional observational study of teams in a natural context

In the UK, treatment recommendations for patients with cancer are routinely made by multidisciplinary teams in weekly meetings. However, their performance is variable.The aim of this study was to explore the underlying structure of multidisciplinary decision-making process, and examine how it relates to team ability to reach a decision.This is a cross-sectional observational study consisting of 1045 patient reviews across 4 multidisciplinary cancer teams from teaching and community hospitals in London, UK, from 2010 to 2014. Meetings were chaired by surgeons.We used a validated observational instrument (Metric for the Observation of Decision-making in Cancer Multidisciplinary Meetings) consisting of 13 items to assess the decision-making process of each patient discussion. Rated on a 5-point scale, the items measured quality of presented patient information, and contributions to review by individual disciplines. A dichotomous outcome (yes/no) measured team ability to reach a decision. Ratings were submitted to Exploratory Factor Analysis and regression analysis.The exploratory factor analysis produced 4 factors, labeled "Holistic and Clinical inputs" (patient views, psychosocial aspects, patient history, comorbidities, oncologists', nurses', and surgeons' inputs), "Radiology" (radiology results, radiologists' inputs), "Pathology" (pathology results, pathologists' inputs), and "Meeting Management" (meeting chairs' and coordinators' inputs). A negative cross-loading was observed from surgeons' input on the fourth factor with a follow-up analysis showing negative correlation (r = -0.19, P &lt; 0.001). In logistic regression, all 4 factors predicted team ability to reach a decision (P &lt; 0.001).Hawthorne effect is the main limitation of the study.The decision-making process in cancer meetings is driven by 4 underlying factors representing the complete patient profile and contributions to case review by all core disciplines. Evidence of dual-task interference was observed in relation to the meeting chairs' input and their corresponding surgical input into case reviews.</p

A Monitor of Beam Polarization Profiles for the TRIUMF Parity Experiment

TRIUMF experiment E497 is a study of parity violation in pp scattering at an energy where the leading term in the analyzing power is expected to vanish, thus measuring a unique combination of weak-interaction flavour conserving terms. It is desired to reach a level of sensitivity of 2x10^-8 in both statistical and systematic errors. The leading systematic errors depend on transverse polarization components and, at least, the first moment of transverse polarization. A novel polarimeter that measures profiles of both transverse components of polarization as a function of position is described.Comment: 19 pages LaTeX, 10 PostScript figures. To appear in Nuclear Instruments and Methods in Physics Research, Section

Interrogation of the Microenvironmental Landscape in Brain Tumors Reveals Disease-Specific Alterations of Immune Cells

Brain malignancies encompass a range of primary and metastatic cancers, including low-grade and high-grade gliomas and brain metastases (BrMs) originating from diverse extracranial tumors. Our understanding of the brain tumor microenvironment (TME) remains limited, and it is unknown whether it is sculpted differentially by primary versus metastatic disease. We therefore comprehensively analyzed the brain TME landscape via flow cytometry, RNA sequencing, protein arrays, culture assays, and spatial tissue characterization. This revealed disease-specific enrichment of immune cells with pronounced differences in proportional abundance of tissue-resident microglia, infiltrating monocyte-derived macrophages, neutrophils, and T cells. These integrated analyses also uncovered multifaceted immune cell activation within brain malignancies entailing converging transcriptional trajectories while maintaining disease- and cell-type-specific programs. Given the interest in developing TME-targeted therapies for brain malignancies, this comprehensive resource of the immune landscape offers insights into possible strategies to overcome tumor-supporting TME properties and instead harness the TME to fight cancer

Parity Violation in Proton-Proton Scattering

Measurements of parity-violating longitudinal analyzing powers (normalized asymmetries) in polarized proton-proton scattering provide a unique window on the interplay between the weak and strong interactions between and within hadrons. Several new proton-proton parity violation experiments are presently either being performed or are being prepared for execution in the near future: at TRIUMF at 221 MeV and 450 MeV and at COSY (Kernforschungsanlage Juelich) at 230 MeV and near 1.3 GeV. These experiments are intended to provide stringent constraints on the set of six effective weak meson-nucleon coupling constants, which characterize the weak interaction between hadrons in the energy domain where meson exchange models provide an appropriate description. The 221 MeV is unique in that it selects a single transition amplitude (3P2-1D2) and consequently constrains the weak meson-nucleon coupling constant h_rho{pp}. The TRIUMF 221 MeV proton-proton parity violation experiment is described in some detail. A preliminary result for the longitudinal analyzing power is Az = (1.1 +/-0.4 +/-0.4) x 10^-7. Further proton-proton parity violation experiments are commented on. The anomaly at 6 GeV/c requires that a new multi-GeV proton-proton parity violation experiment be performed.Comment: 13 Pages LaTeX, 5 PostScript figures, uses espcrc1.sty. Invited talk at QULEN97, International Conference on Quark Lepton Nuclear Physics -- Nonperturbative QCD Hadron Physics & Electroweak Nuclear Processes --, Osaka, Japan May 20--23, 199

Monoterpene indole alkaloids from Vinca minor L. (Apocynaceae): Identification of new structural scaffold for treatment of Alzheimer's disease

One undescribed indole alkaloid together with twenty-two known compounds have been isolated from aerial parts of Vinca minor L. (Apocynaceae). The chemical structures of the isolated alkaloids were determined by a combination of MS, HRMS, 1D, and 2D NMR techniques, and by comparison with literature data. The NMR data of several alkaloids have been revised, corrected, and missing data have been supplemented. Alkaloids isolated in sufficient quantity were screened for their in vitro acetylcholinesterase (AChE; E.C. 3.1.1.7) and butyrylcholinesterase (BuChE; E.C. 3.1.1.8) inhibitory activity. Selected compounds were also evaluated for prolyl oligopeptidase (POP; E.C. 3.4.21.26), and glycogen synthase 3β-kinase (GSK-3β; E.C. 2.7.11.26) inhibition potential. Significant hBuChE inhibition activity has been shown by (−)-2-ethyl-3[2-(3-ethylpiperidinyl)-ethyl]-1H-indole with an IC50 value of 0.65 ± 0.16 μM. This compound was further studied by enzyme kinetics, along with in silico techniques, to reveal the mode of inhibition. This compound is also predicted to cross the blood-brain barrier (BBB) through passive diffusion

Parity Violation in Proton-Proton Scattering at 221 MeV

The parity-violating longitudinal analyzing power, Az, has been measured in pp elastic scattering at an incident proton energy of 221 MeV. The result obtained is Az =(0.84 +/- 0.29 (stat.) +/- 0.17 (syst.)) x 10^{-7}. This experiment is unique in that it selects a single parity violating transition amplitude, 3P2-1D2, and consequently directly constrains the weak meson-nucleon coupling constant h^pp_rho When this result is taken together with the existing pp parity violation data, the weak meson-nucleon coupling constants h^pp_rho and h^pp_omega can, for the first time, both be determined.Comment: 8 pages RevTeX4, 3 PostScript figures. Conclusion revised. New information about weak coupling constants adde

The First HET Planet: A Companion to HD 37605

We report the first detection of a planetary-mass companion to a star using the High Resolution Spectrograph (HRS) of the Hobby-Eberly Telescope (HET). The HET-HRS now gives routine radial velocity precision of 2-3 m/s for high SNR observations of quiescent stars. The planetary-mass companion to the metal-rich K0V star HD37605 has an orbital period of 54.23 days, an orbital eccentricity of 0.737, and a minimum mass of 2.84 Jupiter masses. The queue-scheduled operation of the Hobby-Eberly Telescope enabled us to discovery of this relatively short-period planet with a total observation time span of just two orbital periods. The ability of queue-scheduled large-aperture telescopes to respond quickly to interesting and important results demonstrates the power of this new approach in searching for extra-solar planets as well as in other ares of research requiring rapid response time critical observations.Comment: 4 Pages, 2 figures. Accepted in Astrophysical Journal Letters, http://austral.as.utexas.edu/planets/hd37605/hd37605.htm

Phenotypic diversity of T cells in human primary and metastatic brain tumors revealed by multiomic interrogation.

The immune-specialized environment of the healthy brain is tightly regulated to prevent excessive neuroinflammation. However, after cancer development, a tissue-specific conflict between brain-preserving immune suppression and tumor-directed immune activation may ensue. To interrogate potential roles of T cells in this process, we profiled these cells from individuals with primary or metastatic brain cancers via integrated analyses on the single-cell and bulk population levels. Our analysis revealed similarities and differences in T cell biology between individuals, with the most pronounced differences observed in a subgroup of individuals with brain metastasis, characterized by accumulation of CXCL13-expressing CD39 &lt;sup&gt;+&lt;/sup&gt; potentially tumor-reactive T (pTRT) cells. In this subgroup, high pTRT cell abundance was comparable to that in primary lung cancer, whereas all other brain tumors had low levels, similar to primary breast cancer. These findings indicate that T cell-mediated tumor reactivity can occur in certain brain metastases and may inform stratification for treatment with immunotherapy

Parity Violation in Proton-Proton Scattering at 221 MeV

TRIUMF experiment 497 has measured the parity violating longitudinal analyzing power, A_z, in pp elastic scattering at 221.3 MeV incident proton energy. This paper includes details of the corrections, some of magnitude comparable to A_z itself, required to arrive at the final result. The largest correction was for the effects of first moments of transverse polarization. The addition of the result, A_z=(0.84 \pm 0.29 (stat.) \pm 0.17 (syst.)) \times 10^{-7}, to the pp parity violation experimental data base greatly improves the experimental constraints on the weak meson-nucleon coupling constants h^{pp}_\rho and h^{pp}_\omega, and has implications for the interpretation of electron parity violation experiments.Comment: 17 pages RevTeX, 14 PostScript figures. Revised version with additions suggested by Phys. Rev.