Phase Diagram Of The Biham-Middleton-Levine Traffic Model In Three Dimensions

We study numerically the behavior of the Biham-Middleton-Levine traffic model in three dimensions. Our extensive numerical simulations show that the phase diagram for this model in three dimensions is markedly different from that in one and two dimensions. In addition to the full speed moving as well as the completely jamming phases, whose respective average asymptotic car speeds $$ equal one and zero, we observe an extensive region of car densities $\rho$ with a low but non-zero average asymptotic car speed. The transition from this extensive low average asymptotic car speed region to the completely jamming region is at least second order. We argue that this low speed region is a result of the formation of a spatially-limited-extended percolating cluster. Thus, this low speed phase is present in $n > 3$ dimensional Biham-Middleton-Levine model as well.Comment: Minor clarifications, 1 figure adde

HER2 Inhibition in Gastric Cancer-Novel Therapeutic Approaches for an Established Target.

Gastric cancer is a leading cause of cancer-related deaths globally. Human epidermal growth receptor 2 (HER2) overexpression of HER2 gene amplification is present in 20% of gastric cancers and defines a subset amenable to HER2-directed therapeutics. The seminal ToGA study led to routine use of the monoclonal antibody trastuzumab in conjunction to platinum-fluoropyridimine first-line chemotherapy for HER2-positive gastric cancers as standard-of-care. Although limited progress was made in the decade following ToGA, there is now an abundance of novel therapeutic approaches undergoing investigation in parallel. Additionally, new data from randomised trials have indicated efficacy of the antibody-drug conjugate trastuzumab deruxtecan in chemorefractory patients and increased responses with the addition of first-line immune checkpoint blockade to trastuzumab and chemotherapy. This review will outline the data supporting HER2 targeting in gastric cancers, discuss mechanisms of response and resistance to HER2-directed therapies and summarise the emerging therapies under clinical evaluation that may evolve the way we manage this subset of gastric cancers in the future

A VELOUR post hoc subset analysis: prognostic groups and treatment outcomes in patients with metastatic colorectal cancer treated with aflibercept and FOLFIRI

The VELOUR study demonstrated a survival benefit for FOLFIRI + aflibercept versus FOLFIRI + placebo in metastatic colorectal cancer (mCRC) patients who progressed on oxaliplatin-based chemotherapy. Continued divergence of overall survival (OS) curves in the intension to treat (ITT) population, with the survival advantage persisting beyond median survival time, suggested subpopulations might have different magnitudes of survival gain. Additionally, 10% of patients within VELOUR had recurrence during or within 6 months of completing oxaliplatin-based adjuvant therapy (adjuvant fast relapsers) - previously identified as having poorer survival outcomes

Clinical Development of PD-1/PD-L1 Immunotherapy for Gastrointestinal Cancers: Facts and Hopes.

Gastrointestinal (GI) cancers are among the most deadly malignancies. Although serial incremental survival benefits have been made with cytotoxic chemotherapy with metastatic disease, a plateau of achievement has been reached. Applying modern integrative genomic technology, distinct molecular subgroups have been identified in GI cancers. This not only highlighted the heterogeneity in tumors of each primary anatomical site but also identified novel therapeutic targets in distinct molecular subgroups and might improve the yield of clinical success. Molecular characteristics of tumors and their interaction with the tumor microenvironment would further affect development of combination therapy, including immunotherapy. Currently, immune checkpoint blockade attracts the most intense research, and the successful integration of these novel agents in GI cancers in the treatment paradigm requires an in-depth understanding of the diverse immune environment of these cancers. Clin Cancer Res; 23(20); 6002-11. ©2017 AACR

Mesospheric anomalous diffusion during noctilucent clouds

The Andenes specular meteor radar shows meteor-trail diffusion rates increasing on average by ~ 20% at times and locations where a lidar observes noctilucent clouds (NLCs). This high-latitude effect has been attributed to the presence of charged NLC but this study shows that such behaviors result predominantly from thermal tides. To make this claim, the current study evaluates data from three stations, at high-, mid-, and low-latitudes, for the years 2012 to 2016, comparing diffusion to show that thermal tides correlate strongly with the presence of NLCs. This data also shows that the connection between meteor-trail diffusion and thermal tide occurs at all altitudes in the mesosphere, while the NLC influence exists only at high-latitudes and at around peak of NLC layer. This paper discusses a number of possible explanations for changes in the regions with NLCs and leans towards the hypothesis that relative abundance of background electron density plays the leading role. A more accurate model of the meteor trail diffusion around NLC particles would help researchers determine mesospheric temperature and neutral density profiles from meteor radars.Public versio

CP violation and CKM phases from angular distributions for BsB_s decays into admixtures of CP eigenstates

We investigate the time-evolutions of angular distributions for $B_s$ decays into final states that are admixtures of CP-even and CP-odd configurations. A sizable lifetime difference between the $B_s$ mass eigenstates allows a probe of CP violation in time-dependent untagged angular distributions. Interference effects between different final state configurations of $B_s\to D^{*+}_s D^{*-}_s$, $J/\psi \phi$ determine the Wolfenstein parameter $\eta$ from untagged data samples, or -- if one uses $|V_{ub}|/|V_{cb}|$ as an additional input -- the notoriously difficult to measure CKM angle $\gamma$. Another determination of $\gamma$ is possible by using isospin symmetry of strong interactions to relate untagged data samples of $B_s\to K^{\ast+} K^{\ast-}$ and $B_s\to K^{\ast0} \overline{K^{\ast0}}$. We note that the untagged angular distribution for $B_s\to\rho^0 \phi$ provides interesting information about electroweak penguins.Comment: 19 pages, LaTeX, no figure

Incorporating development of a patient-reported outcome instrument in a clinical drug development program: examples from a heart failure program.

BackgroundPatient-reported outcome (PRO) measures can be used to support label claims if they adhere to US Food & Drug Administration guidance. The process of developing a new PRO measure is expensive and time-consuming. We report the results of qualitative studies to develop new PRO measures for use in clinical trials of omecamtiv mecarbil (a selective, small molecule activator of cardiac myosin) for patients with heart failure (HF), as well as the lessons learned from the development process.MethodsConcept elicitation focus groups and individual interviews were conducted with patients with HF to identify concepts for the instrument. Cognitive interviews with HF patients were used to confirm that no essential concepts were missing and to assess patient comprehension of the instrument and items.ResultsDuring concept elicitation, the most frequently reported HF symptoms were shortness of breath, tiredness, fluid retention, fatigue, dizziness/light-headedness, swelling, weight fluctuation, and trouble sleeping. Two measures were developed based on the concepts: the Heart Failure Symptom Diary (HF-SD) and the Heart Failure Impact Scale (HFIS). Findings from cognitive interviews suggested that the items in the HF-SD and HFIS were relevant and well understood by patients. Multiple iterations of concept elicitation and cognitive interviews were needed based on FDA request for a broader patient population in the qualitative study. Lessons learned from the omecamtiv mecarbil PRO/clinical development program are discussed, including challenges of qualitative studies, patient recruitment, expected and actual timelines, cost, and engagement with various stakeholders.ConclusionDevelopment of a new PRO measure to support a label claim requires significant investment and early planning, as demonstrated by the omecamtiv mecarbil program