Dust environment and dynamical history of a sample of short-period comets: II. 81P/Wild 2 and 103P/Hartley 2

Aims. This paper is a continuation of the first paper in this series, where we presented an extended study of the dust environment of a sample of short-period comets and their dynamical history. On this occasion, we focus on comets 81P/Wild 2 and 103P/Hartley 2, which are of special interest as targets of the spacecraft missions Stardust and EPOXI. Methods. As in the previous study, we used two sets of observational data: a set of images, acquired at Sierra Nevada and Lulin observatories, and the Afρ data as a function of the heliocentric distance provided by the amateur astronomical association Cometas-Obs. The dust environment of comets (dust loss rate, ejection velocities, and size distribution of the particles) was derived from our Monte Carlo dust tail code. To determine their dynamical history we used the numerical integrator Mercury 6.2 to ascertain the time spent by these objects in the Jupiter family Comet region. Results. From the dust analysis, we conclude that both 81P/Wild 2 and 103P/Hartley 2 are dusty comets, with an annual dust production rate of 2.8 × 109 kg yr-1 and (0.4-1.5) × 109 kg yr-1, respectively. From the dynamical analysis, we determined their time spent in the Jupiter family Comet region as ~40 yr in the case of 81P/Wild 2 and ~1000 yr for comet 103P/Hartley 2. These results imply that 81P/Wild 2 is the youngest and the most active comet of the eleven short-period comets studied so far, which tends to favor the correlation between the time spent in JFCs region and the comet activity previously discussed

Antioxidant and antihypertensive properties of liquid and solid state fermented lentils

The effect of liquid (LSF) and solid state fermentation (SSF) of lentils for production of water-soluble fractions with antioxidant and antihypertensive properties was studied. LSF was performed either spontaneously (NF) or by Lactobacillus plantarum (LP) while SSF was performed by Bacillus subtilis (BS). Native lactic flora in NF adapted better than L. plantarum to fermentative broth and BS counts increased 4.0 log CFU/g up to 48 h of SSF. LSF water-soluble fractions had higher (P ≿ 0.05) free amino groups, GABA content, antioxidant and angiotensin I-converting enzyme inhibitory (ACEI) activities than SSF. In addition, GABA and ACEI activity of LSF increased in a time-dependent manner. Proteolysis by BS was limited, with slight changes in free amino groups, while GABA, total phenolic compounds and antioxidant capacity increased throughout fermentation. Higher antihypertensive potential was observed in NF (96 h) characterised by the highest GABA content (10.42 mg/g extract), ACE-inhibitory potency (expressed as IC 50) of 0.18 mg protein/ml and antioxidant capacity of 0.26 mmol Trolox equivalents/g extract. Therefore, water-soluble fermented lentil extracts obtained by LSF are particularly promising as functional ingredients in preventing hypertension. © 2012 Elsevier Ltd. All rights reserved.This work was supported by AGL2010-16310 projects from the Ministerio de Ciencia e Innovación (Spain). M.I.T. is indebted to CONICET (Argentina) for the Foreign Postdoctoral Fellowship under the Scholarship Program for Young Researchers 2010 and R.I.L. to a JAE-pre grant funded by CSIC and FSE-EU.Peer Reviewe

Defective glucose and lipid metabolism in rheumatoid arthritis is determined by chronic inflammation in metabolic tissues.

Rheumatoid arthritis (RA) patients are at increased risk of insulin resistance (IR); however, the specific mechanisms mediating this association are currently unknown. To investigate whether the inflammatory activity associated with RA accounts for the observed defective glucose metabolism and lipid metabolism in these patients. We followed two main strategies: (i) extensive metabolic profiling of a RA cohort of 100 patients and 50 healthy control subjects and (ii) mechanistic studies carried out in both a collagen-induced arthritis mouse model and 3T3-L1 adipocytes treated with conditioned serum from RA patients. Following the exclusion of obese and diabetic subjects, data from RA patients demonstrated a strong link between the degree of systemic inflammation and the development of IR. These results were strengthened by the observation that induction of arthritis in mice resulted in a global inflammatory state characterized by defective carbohydrate and lipid metabolism in different tissues. Adipose tissue was most susceptible to the RA-induced metabolic alterations. These metabolic effects were confirmed in adipocytes treated with serum from RA patients. Our results show that the metabolic disturbances associated with RA depend on the degree of inflammation and identify inflammation of adipose tissue as the initial target leading to IR and the associated molecular disorders of carbohydrate and lipid homeostasis. Thus, we anticipate that therapeutic strategies based on tighter control of inflammation and flares could provide promising approaches to normalize and/or prevent metabolic alterations associated with RA

External validity of docetaxel triplet trials in advanced gastric cancer : are there patients who still benefit?

Background: The purpose of our study was to develop an online calculator to estimate the effect of docetaxel triplets (DPF) in first line of advanced gastric cancer (AGC), and to assess the external validity of docetaxel trials in individual patients. Methods: The study includes patients with HER2(-) AGC treated with platin and fluoropyrimidine (PF) or with DPF in first line. Treatment effect and interactions were assessed using Bayesian accelerated failure time models. Result: The series comprises 1376 patients; 238 treated with DPF and 1138 with PF between 2008 and 2019. DPF was associated with increased progression-free survival (PFS) and overall survival (OS) with time ratio (TR) 1.27 (95% credible interval [CrI], 1.15-1.40), and TR 1.19 (95% CrI, 1.09-1.27), respectively. Serious adverse events were more common with DPF, particularly hematological effects (32% vs 22%). Younger participants received greater DPF dose density without achieving greater disease control, while severe toxicity was likewise higher. DPF yielded superior OS in Lauren intestinal (TR 1.27, 95% CrI, 1.08-1.11) vs diffuse subtype (TR 1.17, 95% CrI, 1.09-1.24) and the probability of increasing OS > 15% was 90% vs 67% in each subtype, respectively. The effect dwindles over time, which can be attributed to pathological changes and clinical practice changes. Conclusion: Our study confirms the effect of DPF is highly dependent on several clinical-pathological variables, with discreet and gradually declining benefit over platinum doublets in later years, at the expense of increased toxicity. These results may help to underpin the idea that external validity of AGC trials should be revised regularly

Autistic Perspectives on the Future of Clinical Autism Research

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Second-line treatment in advanced gastric cancer: Data from the Spanish AGAMENON registry

Background: Second-line treatments boost overall survival in advanced gastric cancer (AGC). However, there is a paucity of information as to patterns of use and the results achieved in actual clinical practice. Materials and methods: The study population comprised patients with AGC in the AGAMENON registry who had received second-line. The objective was to describe the pattern of second-line therapies administered, progression-free survival following second-line (PFS-2), and post-progression survival since first-line (PPS). Results: 2311 cases with 2066 progression events since first-line (89.3%) were recorded; 245 (10.6%) patients died during first-line treatment and 1326/2066 (64.1%) received a second-line. Median PFS-2 and PPS were 3.1 (95% CI, 2.9-3.3) and 5.8 months (5.5-6.3), respectively. The most widely used strategies were monoCT (56.9%), polyCT (15.0%), ramucirumab+CT (12.6%), platinum-reintroduction (8.3%), trastuzumab+CT (6.1%), and ramucirumab (1.1%). PFS-2/PPS medians gradually increased in monoCT, 2.6/5.1 months; polyCT 3.4/6.3 months; ramucirumab+CT, 4.1/6.5 months; platinum-reintroduction, 4.2/6.7 months, and for the HER2+ subgroup in particular, trastuzumab+CT, 5.2/11.7 months. Correlation between PFS since first-line and OS was moderate in the series as a whole (Kendall's τ = 0.613), lower in those subjects who received second-line (Kendall's τ = 0.539), especially with ramucirumab+CT (Kendall's τ = 0.413). Conclusion: This analysis reveals the diversity in second-line treatment for AGC, highlighting the effectiveness of paclitaxel-ramucirumab and, for a selected subgroup of patients, platinum reintroduction; both strategies endorsed by recent clinical guidelines

On the dust environment of comet C/2012 S1 (ISON) from 12 AU pre-perihelion to the end of its activity around perihelion

A Monte Carlo dust tail model has been applied to extract the dust environment parameters of the comet C/2012 S1 (ISON) from both Earth-based and SOHO LASCO C3 observations, performed from about six astronomical units (AU) inbound, to just after perihelion passage, when only a small portion of the original comet nucleus has survived in the form of a cloud of tiny particles. The early Afρ and image data are consistent with particle ejection from an extended active area located at latitudes 35°N to 90°N (for a prograde rotating nucleus), with the spin axis having a large obliquity (I 70°). This configuration nicely fits the early images and Afρ data until 3.9 AU inbound, when the emission should become isotropic in order to fit the data. The analysis of LASCO images reveals that, assuming an original nucleus of R N = 500 m with ρ = 1000 kg m-3, at least half of its mass was vaporized when the comet was at about 17 R ⊙ inbound. We conclude that at that time the nucleus suffered a cataclysmic fragmentation releasing a huge amount of material of 2.3 ×1011 kg, equivalent to a sphere of 380 m in radius with density 1000 kg m-3. The surviving material after perihelion passage consists of very small dust particles of 0.1-50 μm in radius with a total mass of just 6.7×10 8 kg. © 2014. The American Astronomical Society. All rights reserved