Symmetric Grothendieck polynomials, skew Cauchy identities, and dual filtered Young graphs

Symmetric Grothendieck polynomials are analogues of Schur polynomials in the K-theory of Grassmannians. We build dual families of symmetric Grothendieck polynomials using Schur operators. With this approach we prove skew Cauchy identity and then derive various applications: skew Pieri rules, dual filtrations of Young's lattice, generating series and enumerative identities. We also give a new explanation of the finite expansion property for products of Grothendieck polynomials

Clusters of Extragalactic Ultra Compact HII Regions

We report on the detection of optically thick free-free radio sources in the galaxies M33, NGC 253, and NGC 6946 using data in the literature. We interpret these sources as being young, embedded star birth regions, which are likely to be clusters of ultracompact HII regions. All 35 of the sources presented in this article have positive radio spectral indices alpha>0 suggesting an optically thick thermal bremsstrahlung emission arising in the HII region surrounding hot stars. Energy requirements indicate a range of a several to >500 O7V star equivalents powering each HII region. Assuming a Salpeter IMF, this corresponds to integrated stellar masses of 0.1--60,000 Msun. For roughly half of the sources in our sample, there is no obvious optical counterpart, giving further support for their deeply embedded nature. Their luminosities and radio spectral energy distributions are consistent with HII regions having electron densities from 1500 cm^-3 to 15000 cm^-3 and radii of 1 - 7 pc. We suggest that the less luminous of these sources are extragalactic ultracompact HII region complexes, those of intermediate luminosity are similar to W49 in the Galaxy, while the brightest will be counterparts to 30 Doradus. These objects constitute the lower mass range of extragalactic ``ultradense HII regions'' which we argue are the youngest stages of massive star cluster formation yet observed. This sample is beginning to fill in the continuum of objects between small associations of ultracompact HII regions and the massive extragalactic clusters that may evolve into globular clusters.Comment: 37 pages, uses AASTeX; scheduled to appear in ApJ v. 559 October 2001. Full postscript version available from http://www.astro.wisc.edu/~chip/Papers/Johnson_Kobulnicky_etal_ApJ559.ps.g

Subpopulation treatment effect pattern plot analysis: a prognostic model for distant recurrence-free survival to estimate delayed adjuvant chemotherapy initiation effect in triple-negative breast cancer

IntroductionTriple-negative breast cancer (TNBC) is a heterogeneous disease associated with a poor prognosis. Delaying in time to start adjuvant chemotherapy (TTC) has been related to an increased risk of distant recurrence-free survival (DRFS). We aimed to develop a prognostic model to estimate the effects of delayed TTC among TNBC risk subgroups.Materials and methodsWe analyzed 687 TNBC patients who received adjuvant chemotherapy at the Instituto Nacional de Enfermedades Neoplasicas (Lima, Peru). Database was randomly divided to create a discovery set (n=344) and a validation set (n=343). Univariate and multivariate Cox regression models were performed to identify prognostic factors for DRFS. Risk stratification was implemented through two models developed based on proportional hazard ratios from significant clinicopathological characteristics. Subpopulation treatment effect pattern plot (STEPP) analysis was performed to determine the best prognostic cut-off points for stratifying TNBC subgroups according to risk scores and estimate Kaplan-Meier differences in 10-year DRFS comparing TTC (≤30 vs.>30 days).ResultsIn univariate analysis, patients aged ≥70 years (HR=4.65; 95% CI: 2.32-9.34; p=<0.001), those at stages pT3-T4 (HR=3.28; 95% CI: 1.57-6.83; p=0.002), and pN2-N3 (HR=3.00; 95% CI: 1.90-4.76; p=<0.001) were notably associated with higher risk. STEPP analysis defined three risk subgroups for each model. Model N°01 categorized patients into low (score: 0–31), intermediate (score:32–64), and high-risk (score: 65–100) cohorts; meanwhile, Model N°02: low (score: 0–26), intermediate (score: 27–55), and high (score: 56–100). Kaplan-Meier plots showed that in the discovery set, patients with TTC>30 days experienced a 17.5% decrease in 10-year DRFS rate (95%CI=6.7-28.3), and the impact was more remarkable in patients who belong to the high-risk subgroup (53.3% decrease in 10 years-DRFS rate). Similar results were found in the validation set.ConclusionsWe developed two prognostic models based on age, pT, and pN to select the best one to classify TNBC. For Model N°02, delayed adjuvant chemotherapy conferred a higher risk of relapse in patients ≥70 years and who were characterized by pT3/T4 and pN2/N3. Thus, more efforts should be considered to avoid delayed TTC in TNBC patients, especially those in high-risk subgroups

A randomized phase II study of lapatinib + pazopanib versus lapatinib in patients with HER2+ inflammatory breast cancer

This multi-center Phase II study evaluated lapatinib, pazopanib, and the combination in patients with relapsed HER2+ inflammatory breast cancer. In Cohort 1, 76 patients were randomized 1:1 to receive lapatinib 1,500 mg + placebo or lapatinib 1,500 mg + pazopanib 800 mg (double-blind) once daily until disease progression, unacceptable toxicity, or death. Due to high-grade diarrhea observed with this dose combination in another study (VEG20007), Cohort 1 was closed. The protocol was amended such that an additional 88 patients (Cohort 2) were randomized in a 5:5:2 ratio to receive daily monotherapy lapatinib 1,500 mg, lapatinib 1,000 mg + pazopanib 400 mg, or monotherapy pazopanib 800 mg, respectively. The primary endpoint was overall response rate (ORR). Secondary endpoints included duration of response, progression-free survival (PFS), overall survival, and safety. In Cohort 1, ORR for the lapatinib (n = 38) and combination (n = 38) arms was 29 and 45 %, respectively; median PFS was 16.1 and 14.3 weeks, respectively. Grade ≥3 adverse events (AEs) were more frequent in the combination arm (71 %) than in the lapatinib arm (24 %). Dose reductions and interruptions due to AEs were also more frequent in the combination arm (45 and 53 %, respectively) than in the lapatinib monotherapy arm (0 and 11 %, respectively). In Cohort 2, ORR for patients treated with lapatinib (n = 36), lapatinib + pazopanib (n = 38), and pazopanib (n = 13) was 47, 58, and 31 %, respectively; median PFS was 16.0, 16.0, and 11.4 weeks, respectively. In the lapatinib, combination, and pazopanib therapy arms, grade ≥3 AEs were reported for 17, 50, and 46 % of patients, respectively, and the incidence of discontinuations due to AEs was 0, 24, and 23 %, respectively. The lapatinib–pazopanib combination was associated with a numerically higher ORR but no increase in PFS compared to lapatinib alone. The combination also had increased toxicity resulting in more dose reductions, modifications, and treatment delays. Activity with single-agent lapatinib was confirmed in this population

Silent progression in disease activity-free relapsing multiple sclerosis.

ObjectiveRates of worsening and evolution to secondary progressive multiple sclerosis (MS) may be substantially lower in actively treated patients compared to natural history studies from the pretreatment era. Nonetheless, in our recently reported prospective cohort, more than half of patients with relapsing MS accumulated significant new disability by the 10th year of follow-up. Notably, "no evidence of disease activity" at 2 years did not predict long-term stability. Here, we determined to what extent clinical relapses and radiographic evidence of disease activity contribute to long-term disability accumulation.MethodsDisability progression was defined as an increase in Expanded Disability Status Scale (EDSS) of 1.5, 1.0, or 0.5 (or greater) from baseline EDSS = 0, 1.0-5.0, and 5.5 or higher, respectively, assessed from baseline to year 5 (±1 year) and sustained to year 10 (±1 year). Longitudinal analysis of relative brain volume loss used a linear mixed model with sex, age, disease duration, and HLA-DRB1*15:01 as covariates.ResultsRelapses were associated with a transient increase in disability over 1-year intervals (p = 0.012) but not with confirmed disability progression (p = 0.551). Relative brain volume declined at a greater rate among individuals with disability progression compared to those who remained stable (p < 0.05).InterpretationLong-term worsening is common in relapsing MS patients, is largely independent of relapse activity, and is associated with accelerated brain atrophy. We propose the term silent progression to describe the insidious disability that accrues in many patients who satisfy traditional criteria for relapsing-remitting MS. Ann Neurol 2019;85:653-666

Consideraciones éticas relacionadas al manejo de muestras de investigación en cáncer

Molecular analysis of human biological material allows the identification of future biomarkers to improve the management of patients with cancer. However, the handling of these samples requires particular ethical considerations. Different organizations such as the European Council and government agencies of the United States have generated different documents with definitions, mechanisms, and regulations to avoid putting at risk of harm or violating the rights of donors of biological samples. Finally, all these documents have evolved over time and have allowed research institutions to have standard committees and regulations in ethics. Thus, legal institutions can create precedents and generate coherent sentences.El análisis molecular de material biológico humano permite la identificación de futuros biomarcadores para mejorar el manejo de pacientes con cáncer. Sin embargo, el manejo de estas muestras requiere consideraciones éticas particulares. Distintas organizaciones como el Consejo Europeo y agencias de gobierno de Estados Unidos han generado distintos documentos con definiciones, mecanismos y reglamentos para evitar poner en riesgo de daño o vulnerar los derechos de los donantes de muestras biológicas. Finalmente, todos estos documentos han evolucionado en el tiempo y han permitido que las instituciones de investigación cuenten con comités y regulaciones en ética estándares. Así, las instituciones legales puedan crear precedentes y generar sentencias coherentes

The coronal line regions of planetary nebulae NGC6302 and NGC6537: 3-13um grating and echelle spectroscopy

We report on advances in the study of the cores of NGC6302 and NGC6537 using infrared grating and echelle spectroscopy. In NGC6302, emission lines from species spanning a large range of ionization potential, and in particular [SiIX]3.934um, are interpreted using photoionization models (including CLOUDY), which allow us to reestimate the central star's temperature to be about 250000K. All of the detected lines are consistent with this value, except for [AlV] and [AlVI]. Aluminium is found to be depleted to one hundredth of the solar abundance, which provides further evidence for some dust being mixed with the highly ionized gas (with photons harder than 154eV). A similar depletion pattern is observed in NGC6537. Echelle spectroscopy of IR coronal ions in NGC6302 reveals a stratified structure in ionization potential, which confirms photoionization to be the dominant ionization mechanism. The lines are narrow (< 22km/s FWHM), with no evidence of the broad wings found in optical lines from species with similar ionization potentials, such as [NeV]3426A. We note the absence of a hot bubble, or a wind blown bipolar cavity filled with a hot plasma, at least on 1'' and 10km/s scales. We also provide accurate new wavelengths for several of the infrared coronal lines observed with the echelle.Comment: Accepted for publication in MNRA

Lung Cancer in Peru

Peru is a South American nation with a growing and aging population of 31 million people with a life expectancy at birth of 76.7 years. The country is divided into 25 regions, 79% of the population is urban, and Lima, the capital, concentrates more than a third of the population.1 Although Peru is an upper-middle-income country, health expenditure represents only 5.1% of the gross domestic product, which is lower than the average of Latin America and the Caribbean (LATAM) (8.56%).2 Out-of-pocket health expenditure is 30.9%.3 Peru has a comprehensive National Cancer Plan and two population-based cancer registries in Lima and Arequipa.Revisión por pare