After surgical excision of early HER2-positive breast cancer and adjuvant chemotherapy, the administration of trastuzumab, a monoclonal antibody against HER2, was associated with longer disease-free ...survival than was observation.
After surgical excision of early HER2-positive breast cancer and adjuvant chemotherapy, the administration of trastuzumab was associated with longer disease-free survival than was observation.
Her2/
neu
(hereafter referred to as HER2) belongs to a family of four transmembrane receptor tyrosine kinases that mediate the growth, differentiation, and survival of cells.
1
,
2
Overexpression of the HER2 protein, amplification of the
HER2
gene, or both occur in approximately 15 to 25 percent of breast cancers, and are associated with aggressive behavior in the tumor.
3
,
4
Trastuzumab (Herceptin, Roche), a humanized monoclonal antibody against the extracellular domain of HER2, has been shown to benefit patients with HER2-positive metastatic breast cancer when administered weekly or every three weeks, alone
5
,
6
or in combination with chemotherapy.
7
,
8
Trastuzumab is . . .
We present the results of the one-year long observational campaign of the type II plateau SN 2005cs, which exploded in the nearby spiral galaxy M51 (the Whirlpool galaxy). This extensive data set ...makes SN 2005cs the best observed low-luminosity, 56Ni-poor type II plateau event so far and one of the best core-collapse supernovae ever. The optical and near-infrared spectra show narrow P-Cygni lines characteristic of this SN family, which are indicative of a very low expansion velocity (about 1000 km s−1) of the ejected material. The optical light curves cover both the plateau phase and the late-time radioactive tail, until about 380 d after core-collapse. Numerous unfiltered observations obtained by amateur astronomers give us the rare opportunity to monitor the fast rise to maximum light, lasting about 2 d. In addition to optical observations, we also present near-infrared light curves that (together with already published ultraviolet observations) allow us to construct for the first time a reliable bolometric light curve for an object of this class. Finally, comparing the observed data with those derived from a semi-analytic model, we infer for SN 2005cs a 56Ni mass of about 3 × 10−3 M⊙, a total ejected mass of 8–13 M⊙ and an explosion energy of about 3 × 1050 erg.
Pre-clinical data suggest p53-dependent anthracycline-induced apoptosis and p53-independent taxane activity. However, dedicated clinical research has not defined a predictive role for TP53 gene ...mutations. The aim of the current study was to retrospectively explore the prognosis and predictive values of TP53 somatic mutations in the BIG 02-98 randomized phase III trial in which women with node-positive breast cancer were treated with adjuvant doxorubicin-based chemotherapy with or without docetaxel.
The prognostic and predictive values of TP53 were analyzed in tumor samples by gene sequencing within exons 5 to 8. Patients were classified according to p53 protein status predicted from TP53 gene sequence, as wild-type (no TP53 variation or TP53 variations which are predicted not to modify p53 protein sequence) or mutant (p53 nonsynonymous mutations). Mutations were subcategorized according to missense or truncating mutations. Survival analyses were performed using the Kaplan-Meier method and log-rank test. Cox-regression analysis was used to identify independent predictors of outcome.
TP53 gene status was determined for 18% (520 of 2887) of the women enrolled in BIG 02-98. TP53 gene variations were found in 17% (90 of 520). Nonsynonymous p53 mutations, found in 16.3% (85 of 520), were associated with older age, ductal morphology, higher grade and hormone-receptor negativity. Of the nonsynonymous mutations, 12.3% (64 of 520) were missense and 3.6% were truncating (19 of 520). Only truncating mutations showed significant independent prognostic value, with an increased recurrence risk compared to patients with non-modified p53 protein (hazard ratio = 3.21, 95% confidence interval = 1.740 to 5.935, P = 0.0002). p53 status had no significant predictive value for response to docetaxel.
p53 truncating mutations were uncommon but associated with poor prognosis. No significant predictive role for p53 status was detected.
ClinicalTrials.gov NCT00174655.
Early-time optical observations of supernova (SN) 2005cs in the Whirlpool Galaxy (M51) are reported. Photometric data suggest that SN 2005cs is a moderately underluminous Type II plateau SN (SN IIP). ...The SN was unusually blue at early epochs (U−B≈−0.9 about three days after explosion) which indicates very high continuum temperatures. The spectra show relatively narrow P Cygni features, suggesting ejecta velocities lower than observed in more typical SNe IIP. The earliest spectra show weak absorption features in the blue wing of the He i 5876-Å absorption component and, less clearly, of Hβ and Hα. Based on spectral modelling, two different interpretations can be proposed: these features may either be due to high-velocity H and He i components, or (more likely) be produced by different ions (N ii, Si ii). Analogies with the low-luminosity, 56Ni-poor, low-velocity SNe IIP are also discussed. While a more extended spectral coverage is necessary in order to determine accurately the properties of the progenitor star, published estimates of the progenitor mass seem not to be consistent with stellar evolution models.
The
Gaia
Multipeak (GMP) technique can be used to identify large numbers of dual or lensed active galactic nucleus (AGN) candidates at subarcsec separation, allowing us to study both multiple ...supermassive black holes (SMBHs) in the same galaxy and rare, compact lensed systems. The observed samples can be used to test the predictions of the models of SMBH merging when (1) the selection function of the GMP technique is known, and (2) each system has been classified as a dual AGN, a lensed AGN, or an AGN/star alignment. Here we show that the GMP selection is very efficient for separations above 0.15″ when the secondary (fainter) object has a magnitude
G
≲ 20.5. We present the spectroscopic classification of five GMP candidates using VLT/ERIS and Keck/OSIRIS and compare them with the classifications obtained from (a) the near-IR colors of seven systems obtained with LBT/LUCI, and (b) the analysis of the total spatially unresolved spectra. We conclude that colors and integrated spectra can already provide reliable classifications of many systems. Finally, we summarize the confirmed dual AGNs at
z
> 0.5 selected by the GMP technique, and compare this sample with other such systems from the literature, concluding that GMP can provide a large number of confirmed dual AGNs at separations below 7 kpc.
Aims. Since the CGRO operation in 1991–2000, one of the primary unresolved questions about the blazar γ-ray emission has been its possible correlation with the low-energy (in particular optical) ...emission. To help answer this problem, the Whole Earth Blazar Telescope (WEBT) consortium has organized the GLAST-AGILE Support Program (GASP) to provide the optical-to-radio monitoring data to be compared with the γ-ray detections by the AGILE and GLAST satellites. This new WEBT project started in early September 2007, just before a strong γ-ray detection of 0716+714 by AGILE. Methods. We present the GASP-WEBT optical and radio light curves of this blazar obtained in July–November 2007, about various AGILE pointings at the source. We construct NIR-to-UV spectral energy distributions (SEDs), by assembling GASP-WEBT data together with UV data from the Swift ToO observations of late October. Results. We observe a contemporaneous optical-radio outburst, which is a rare and interesting phenomenon in blazars. The shape of the SEDs during the outburst appears peculiarly wavy because of an optical excess and a UV drop-and-rise. The optical light curve is well sampled during the AGILE pointings, showing prominent and sharp flares. A future cross-correlation analysis of the optical and AGILE data will shed light on the expected relationship between these flares and the γ-ray events.
We present new optical and near-infrared (NIR) photometry and spectroscopy of the Type IIP supernova (SN), SN 2004et. In combination with already published data, this provides one of the most ...complete studies of optical and NIR data for any Type IIP SN from just after explosion to +500 d. The contribution of the NIR flux to the bolometric light curve is estimated to increase from 15 per cent at explosion to around 50 per cent at the end of the plateau and then declines to 40 per cent at 300 d. SN 2004et is one of the most luminous IIP SNe which has been well studied and characterized, and with a luminosity of log L= 42.3 erg s−1 and a 56Ni mass of 0.06 ± 0.04 M⊙, it is two times brighter than SN 1999em. We provide parametrized bolometric corrections as a function of time since explosion for SN 2004et and three other IIP SNe that have extensive optical and NIR data. These can be used as templates for future events in optical and NIR surveys without full wavelength coverage. We compare the physical parameters of SN 2004et with those of other well-studied IIP SNe and find that the kinetic energies span a range of 1050–1051 erg. We compare the ejected masses calculated from hydrodynamic models with the progenitor masses and limits derived from pre-discovery images. Some of the ejected mass estimates are significantly higher than the progenitor mass estimates, with SN 2004et showing perhaps the most serious mass discrepancy. With the current models, it appears difficult to reconcile 100 d plateau lengths and high expansion velocities with the low ejected masses of 5–6 M⊙ implied from 7–8 M⊙ progenitors. The nebular phase is studied using very late-time Hubble Space Telescope photometry, along with optical and NIR spectroscopy. The light curve shows a clear flattening at 600 d in the optical and the NIR, which is likely due to the ejecta impacting on circumstellar material. We further show that the O i 6300, 6364 Å line strengths in the nebular spectra of four Type IIP SNe imply ejected oxygen masses of 0.5–1.5 M⊙.
Purpose
The optimal macronutrient composition of the diet for the management of type 2 diabetes is debated, particularly with regard to the ideal proportion of fat and carbohydrates. The aim of the ...study was to explore the association of different proportions of fat and carbohydrates of the diet—within the ranges recommended by different guidelines—with metabolic risk factors.
Methods
We studied 1785 people with type 2 diabetes, aged 50–75, enrolled in the TOSCA.IT Study. Dietary habits were assessed using a validated food-frequency questionnaire (EPIC). Anthropometry, fasting lipids, HbA1c and C-reactive protein (CRP) were measured.
Results
Increasing fat intake from <25 to ≥35 % is associated with a significant increase in LDL-cholesterol, triglycerides, HbA1c and CRP (
p
< 0.05). Increasing carbohydrates intake from <45 to ≥60 % is associated with significantly lower triglycerides, HbA1c and CRP (
p
< 0.05). A fiber intake ≥15 g/1000 kcal is associated with a better plasma lipids profile and lower HbA1c and CRP than lower fiber consumption. A consumption of added sugars of ≥10 % of the energy intake is associated with a more adverse plasma lipids profile and higher CRP than lower intake.
Conclusions
In people with type 2 diabetes, variations in the proportion of fat and carbohydrates of the diet, within the relatively narrow ranges recommended by different nutritional guidelines, significantly impact on the metabolic profile and markers of low-grade inflammation. The data support the potential for reducing the intake of fat and added sugars, preferring complex, slowly absorbable, carbohydrates.
To report a descriptive analysis of the virological results of Influenza-like illness (ILI) surveillance, comparing the frequency of detection of respiratory viruses during the pre-pandemic ...(2018-2019) and SARS-CoV-2 pandemic (2020-2021) winter seasons in Lombardy (Northern Italy).
From week 46 to week 17 of the following year, nasal-pharyngeal swabs (NPS) collected from ILIs were tested for influenza viruses (IV), RSV, rhinovirus and enterovirus with specific real-time RT-PCR assays. In 2020-2021, SARS-CoV-2 molecular detection was also included.
464 and 446 NPS were collected in 2018-2019 and 2020-2021, respectively. Sex distribution was similar between these two seasons (males: 51.5% vs 47%, P=0.165), while mean age was statistically higher in 2020-2021 (28.2 years IQR: 40.5 vs. 43.6 years IQR: 32.6, P<0.0001). ILI incidence was significantly higher in 2018/19 compared with 2020/21 season season (5.4/1,000 inhabitants vs. 1.9/1,000 inhabitants, P< 0.0001.ILI cases <15 years were less reported in 2020-2021 than in 2018-2019 season (P<0.0001). Contrary, those >15 years were more reported in 2020-2021 than in 2018-2019 (15-44 years, P=0.008; 45-64 years, P=0.002; ≥65 years, P<0.0001). In 2018-2019, IV and RSV accounted for 55% and 10% of ILIs, whereas in 2020-2021 no circulation of these viruses was observed. Enterovirus detections decreased from 3.4% in 2018-2019 to 0.4% in 2020-2021 (P=0.01), while rhinoviruses were detected at higher frequency in the latter season (8.6% vs. 11.9%, P=0.07). SARS-CoV-2 was detected in 25.3% of NPS in 2020-2021.
Since the beginning of the pandemic, non-pharmaceutical measures, including use of face-masks, was massively applied to contrast SARS-CoV-2 spread. This dramatically reduced the incidence of ILI, the circulation of SARS-CoV-2 and other respiratory viruses (such as IV and RSV) transmitted by droplets, but did not reduce rhinovirus detection, which continued to circulate in 2020-2021 season. ILIs surveillance has demonstrated to be able to capture changes in the epidemiology of respiratory viruses and it should be sustained and improved to increase the capture of ILI remained with unknown etiology.
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