We present extensive datasets for a class of intermediate-luminosity optical transients known as luminous red novae. They show double-peaked light curves, with an initial rapid luminosity rise to a ...blue peak (at −13 to −15 mag), which is followed by a longer-duration red peak that sometimes is attenuated, resembling a plateau. The progenitors of three of them (NGC 4490−2011OT1, M 101−2015OT1, and SNhunt248), likely relatively massive blue to yellow stars, were also observed in a pre-eruptive stage when their luminosity was slowly increasing. Early spectra obtained during the first peak show a blue continuum with superposed prominent narrow Balmer lines, with P Cygni profiles. Lines of Fe II are also clearly observed, mostly in emission. During the second peak, the spectral continuum becomes much redder, Hα is barely detected, and a forest of narrow metal lines is observed in absorption. Very late-time spectra (∼6 months after blue peak) show an extremely red spectral continuum, peaking in the infrared (IR) domain. Hα is detected in pure emission at such late phases, along with broad absorption bands due to molecular overtones (such as TiO, VO). We discuss a few alternative scenarios for luminous red novae. Although major instabilities of single massive stars cannot be definitely ruled out, we favour a common envelope ejection in a close binary system, with possibly a final coalescence of the two stars. The similarity between luminous red novae and the outburst observed a few months before the explosion of the Type IIn SN 2011ht is also discussed.
Although common among bacteria, lateral gene transfer--the movement of genes between distantly related organisms--is thought to occur only rarely between bacteria and multicellular eukaryotes. ...However, the presence of endosymbionts, such as Wolbachia pipientis, within some eukaryotic germlines may facilitate bacterial gene transfers to eukaryotic host genomes. We therefore examined host genomes for evidence of gene transfer events from Wolbachia bacteria to their hosts. We found and confirmed transfers into the genomes of four insect and four nematode species that range from nearly the entire Wolbachia genome (>1 megabase) to short (<500 base pairs) insertions. Potential Wolbachia-to-host transfers were also detected computationally in three additional sequenced insect genomes. We also show that some of these inserted Wolbachia genes are transcribed within eukaryotic cells lacking endosymbionts. Therefore, heritable lateral gene transfer occurs into eukaryotic hosts from their prokaryote symbionts, potentially providing a mechanism for acquisition of new genes and functions.
Background: In 1995 a meta-analysis of randomised trials investigating the value of adding chemotherapy to primary treatment for non-small cell lung cancer (NSCLC) suggested a small survival benefit ...for cisplatin-based chemotherapy in each of the primary treatment settings. However, the meta-analysis included many small trials and trials with differing eligibility criteria and chemotherapy regimens. Methods: The aim of the Big Lung Trial was to confirm the survival benefits seen in the meta-analysis and to assess quality of life and cost in the supportive care setting. A total of 725 patients were randomised to receive supportive care alone (n = 361) or supportive care plus cisplatin-based chemotherapy (n = 364). Results: 65% of patients allocated chemotherapy (C) received all three cycles of treatment and a further 27% received one or two cycles. 74% of patients allocated no chemotherapy (NoC) received thoracic radiotherapy compared with 47% of the C group. Patients allocated C had a significantly better survival than those allocated NoC: HR 0.77 (95% CI 0.66 to 0.89, p = 0.0006), median survival 8.0 months for the C group v 5.7 months for the NoC group, a difference of 9 weeks. There were 19 (5%) treatment related deaths in the C group. There was no evidence that any subgroup benefited more or less from chemotherapy. No significant differences were observed between the two groups in terms of the pre-defined primary and secondary quality of life end points, although large negative effects of chemotherapy were ruled out. The regimens used proved to be cost effective, the extra cost of chemotherapy being offset by longer survival. Conclusions: The survival benefit seen in this trial was entirely consistent with the NSCLC meta-analysis and subsequent similarly designed large trials. The information on quality of life and cost should enable patients and their clinicians to make more informed treatment choices.
Objectives: The non-small cell lung cancer (NSCLC) meta-analysis suggested a survival benefit for cisplatin-based chemotherapy when given in addition to surgery, radical radiotherapy or ‘best ...supportive care’. However, it included many small trials and trials with differing eligibility criteria and chemotherapy regimens. The aim of the Big Lung Trial was therefore to run a large pragmatic trial to confirm the survival benefits seen in the meta-analysis. Methods: In the surgery setting, a total of 381 patients were randomised to chemotherapy (C, 192 patients) or no chemotherapy (NoC, 189 patients). C was three 3-weekly cycles of cisplatin/vindesine, mitomycin/ifosfamide/cisplatin, mitomycin/vinblastine/cisplatin or vinorelbine/cisplatin. Results: Chemotherapy was given before surgery in 3% of patients whilst 97% received adjuvant chemotherapy. Baseline characteristics were: median age 61 years, 69% male, 48% squamous cell, 93% WHO PS 0-1, 27% stage I, 38% stage II, and 34% stage III. Complete resection was achieved in approximately 95% of patients. In the C group, 13% received no chemotherapy, 21% one or two cycles, and 64% all three cycles of their prescribed chemotherapy (60% of the latter with no delays or modification). 30% had grade 3/4 toxicity, mainly haematological, nausea/vomiting and neutropenic fever, and six patients were reported as having a treatment-related death. 198 (52%) of patients have died, but there is currently no evidence of a benefit in overall survival to the C group: HR 1.02 (95% CI 0.77–1.35), P=0.90). Conclusions: This trial has failed to observe a survival benefit with adjuvant chemotherapy following complete resection of stage I–III NSCLC. However, the hazard ratio and 95% confidence intervals are consistent with the previously reported meta-analysis and two large recently reported trials, which suggest a small survival benefit with cisplatin-based chemotherapy.
This phase III randomized trial compared two chemotherapy regimens, gemcitabine plus carboplatin and mitomycin, ifosfamide, and cisplatin, in chemotherapy-naive patients with advanced non-small-cell ...lung cancer (NSCLC). The regimens were compared with regard to effects on survival, response rates, toxicity, and quality of life.
Eligible patients had previously untreated stage IIIB or IV NSCLC suitable for cisplatin-based chemotherapy. Randomly assigned patients were to receive four cycles, each at 3-week intervals, of carboplatin area under the curve of 5 on day 1 plus gemcitabine 1,200 mg/m(2) on days 1 and 8 (GCa) or mitomycin 6 mg/m(2), ifosfamide 3g/m(2), and cisplatin 50 mg/m(2) on day 1 (MIC).
Between February 1999 and August 2001, 422 patients (GCa, n = 212; MIC, n = 210) were randomly assigned in the United Kingdom. The majority of patients received the intended four cycles (GCa, 64%; MIC, 61%). There was a significant survival advantage for GCa compared with MIC (hazard ratio, 0.76; 95% CI, 0.61 to 0. 93; P = .008). Median survival was 10 months with GCa and 7.6 months with MIC (difference, 2.4 months; 95% CI, 1.0 to 4.0), and 1-year survival was 40% with GCa and 30% with MIC (difference, 10%; 95% CI, 3% to 18%). Overall response rates were similar (42% for GCa v 41% for MIC; P = .84). More thrombocytopenia occurred with GCa (P = .03), but this was not associated with increased hospital admission or fatality. GCa caused less nausea, vomiting, constipation, and alopecia and was associated with fewer admissions for administration and better quality of life.
In patients with advanced NSCLC, GCa chemotherapy was shown to be a better-tolerated treatment that conferred a survival advantage over MIC.
Chemotherapy for non-small-cell lung cancer (NSCLC) remains controversial. We describe the two largest reported, randomized, parallel trials designed to determine whether the addition of chemotherapy ...influences duration and quality of life in localized, unresectable (mitomycin, ifosfamide, cisplatin MIC1 trial) and extensive (MIC2 trial) disease.
Ambulatory patients with NSCLC, aged 75 years or younger, with localized disease, were randomized in MIC1 to receive up to four cycles of chemotherapy (CT: mitomycin 6 mg/m(2), ifosfamide 3 g/m(2), and cisplatin 50 mg/m(2)) every 21 days, followed by radical radiotherapy (CT + RT) or radiotherapy (RT) alone. Extensive-stage patients were randomized in MIC2 to identical chemotherapy plus palliative care (CT + PC) or palliative care (PC) alone. Short-term change in quality of life (QOL) was assessed in a subgroup of patients. Data from the two trials were combined to allow multivariate and stratified survival analyses.
Seven hundred ninety-seven eligible patients were randomized, 446 in MIC1 and 351 in MIC2. MIC CT improved survival in both trials (significantly in MIC2). The median survival time in MIC1 was 11.7 months (CT + RT) versus 9.7 months (RT alone) (P =.14); whereas in MIC2, median survival time was 6.7 months (CT + PC) compared with 4. 8 months (PC alone) (P =.03). QOL, assessed in 134 patients from start of trial to week 6, showed improvement with chemotherapy and deterioration with standard treatment. In the combined analysis of 797 randomized patients, the positive effect of MIC on survival was significant overall (P =.01) and after adjusting for prognostic factors (P =.01).
MIC chemotherapy prolongs survival in unresectable NSCLC without compromising QOL.
The Big Lung Trial (BLT) was a large, pragmatic trial to evaluate the addition of chemotherapy to primary treatment (ie, surgery, radical radiotherapy, or supportive care) in non-small-cell lung ...cancer (NSCLC). In the supportive care group, there was a small but significant survival benefit in patients treated with chemotherapy compared with supportive care alone (no chemotherapy). A substudy was undertaken to evaluate the quality of life (QoL) implications of the treatment options. QoL was assessed using European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaires C30 (QLQ-C30) and LC17, and daily diary cards.
EORTC QLQ-C30 and LC17 were collected at 0, 6 to 8, 12, 18, and 24 weeks. Diary cards were completed during the first 12 weeks of the study. The primary end point was global QoL at 12 weeks.
A total of 273 patients were randomly assigned: 138 to no chemotherapy and 135 to chemotherapy. There was no evidence of a large detrimental effect on QoL of chemotherapy. No statistically significant differences in global QoL or physical/emotional functioning, fatigue and dyspnea, and pain were detected at 12 weeks. Higher rates of palliative radiotherapy in the no chemotherapy arm may have lessened differences in QoL. Global QoL, role functioning, fatigue, appetite loss, and constipation were prognostic indicators of survival at 12 weeks.
There were no important adverse effects of chemotherapy on QoL.
Copper and Zn isotope ratios of well-characterized samples from three ore facies in the Devonian Alexandrinka volcanic-hosted massive sulphide (VHMS) deposit, southern Urals, were measured using ...multi collector ICP-MS (MC-ICP-MS) and show variations linked to depositional environment and mineralogy. The samples analysed derived from: a) hydrothermal–metasomatic vein stockwork, b) a hydrothermal vent chimney, and c) reworked clastic sulphides. As the deposit has not been significantly deformed or metamorphosed after its formation, it represents a pristine example of ancient seafloor mineralization. Variations in δ
65Cu (where δ
65Cu
=
(
65Cu
/
63Cu)
sample
/
(
65Cu
/
63Cu)
standard
−
1
*
1000) and δ
66Zn (where δ
66Zn
=
(
66Zn
/
64Zn)
sample
/
(
66Zn
/
64Zn)
standard
−
1
*
1000) of 0.63 and 0.66‰, respectively, are significantly greater than analytical uncertainty for both isotope ratios (±
0.07‰, 2
σ). Very limited isotopic fractionation is observed in primary Cu minerals from the stockwork and chimney, whereas the Zn isotopic composition of the stockwork varies significantly with the mineralogy. Chalcopyrite-bearing samples from the stockwork have lighter δ
66Zn by ∼
0.4‰ relative to sphalerite dominated samples, which may be due to equilibrium partitioning of isotopically light Zn into chalcopyrite during its precipitation. δ
66Zn also showed significant variation in the chimney, with an enrichment in heavy isotopes toward the chimney rim of ∼
0.26‰, which may be caused by changing temperature (hence fractionation factor), or Raleigh distillation. Post-depositional seafloor oxidative dissolution and re-precipitation in the clastic sediments, possibly coupled with leaching, led to systematic negative shifts in Cu and Zn isotope compositions relative to the primary sulphides. Copper shows the most pronounced fractionation, consistent with the reduction of Cu(II) to Cu(I) during supergene mineralization. However, the restricted range in δ
65Cu is unlike modern sulphides at mid oceanic ridges where a large range of Cu isotope, of up to 3‰ has been observed
Rouxel, O., Fouquet, Y., Ludden, J.N., 2004. Copper isotope systematics of the Lucky Strike, Rainbow, and Logatchev sea-floor hydrothermal fields on the Mid-Atlantic Ridge. Econ. Geol. 99, 585–600; Zhu, X.K., O'Nions, R.K., Guo, Y., Belshaw, N.S., Rickard, D., 2000. Determination of natural Cu-isotope variation by plasma source mass spectrometry: implications for use as geochemical tracers. Chem. Geol. 163, 139–149.
One Hundred Years of Lung Cancer Spiro, Stephen G; Silvestri, Gerard A
American journal of respiratory and critical care medicine,
09/2005, Letnik:
172, Številka:
5
Journal Article
Recenzirano
A hundred years ago, lung cancer was a reportable disease, and it is now the commonest cause of death from cancer in both men and women in the developed world, and before long, will reach that level ...in the developing world as well. The disease has no particular symptoms or signs for its detection at an early stage. Most patients therefore present with advanced stage IIIB or IV disease. Screening tests began in the 1950s with annual chest x-ray films and sputum cytology but they resulted in no improvement in overall mortality compared with control subjects. The same question is now being asked of spiral low-dose computed tomographic scanning. There have been big refinements in the staging classification of lung cancer and advances in stage identification using minimally invasive technology. Postsurgical mortality has declined from the early days of the 1950s but 5-year cure rates have only barely improved. The addition of chemotherapy to radical radiotherapy, together with novel radiotherapy techniques, is gradually improving the outcome for locally advanced, inoperable non-small cell lung cancer. Chemotherapy offers modest survival improvement for patients with non-small cell lung cancer, the modern agents being better tolerated resulting in an improved quality of life. The management of small cell lung cancer, which appeared so promising at the beginning of the 1970s, has hit a plateau with very little advance in outcome over the last 15 years. The most important and cost-effective management for lung cancer is smoking cessation, but for those with the disease, novel agents and treatment approaches are urgently needed.
Oral etoposide is an active single agent in small-cell lung cancer (SCLC) and is widely prescribed as first-line treatment as an alternative to intravenous combination chemotherapy in patients with ...extensive disease.
The intention of this study was to determine if the effects of oral etoposide therapy on survival and quality of life are equivalent to those of intravenous chemotherapy.
In a randomized trial of palliative treatment in advanced SCLC, oral etoposide (100 mg given twice daily for 5 days) was compared with intravenous chemotherapy consisting of alternating cycles of cisplatin and etoposide (PE) and cyclophosphamide, doxorubicin, and vincristine (CAV). Six cycles of chemotherapy were administered every 21 days in both regimens. Symptom control and quality of life were measured with the Rotterdam Symptom Checklist and a daily diary card. In January 1996, after 155 patients had been randomly assigned from a projected intake of 365 patients, an independent Data Monitoring Committee examined the interim results. Survival was determined by the Kaplan-Meier method, and the logrank test was used to compare treatments. For quality-of-life comparisons, average scores were calculated for each time point. The Mann-Whitney U test was used to determine any significant overall differences between treatments. For the Rotterdam Symptom Checklist, separate analyses were done for each subset (psychological well-being, physical symptoms, lung cancer symptoms, treatment symptoms, activity, and quality of life). Response rates and toxicity scores were compared by using chi2. All statistical tests were two-sided.
Survival was inferior at 1 year in the oral etoposide group compared with intravenous therapy (9.8% for oral versus 19.3% for intravenous; difference = 9.5%; 95% confidence interval of difference = 0.3%-18.7%; P<.05), and there was a trend toward inferior overall survival. Median survival was 4.8 months for oral treatment and 5.9 months for intravenous therapy. Progression-free survival was worse in the oral etoposide arm (median = 3.6 months versus 5.6 months; P<.001), as well as overall response rate (32.9% versus 46.3%; P<.01). With the exception of acute nausea and vomiting associated with intravenous chemotherapy, all aspects of symptom control and quality of life were either the same or worse in the oral etoposide group. Study closure was recommended.
These interim results show that this schedule of oral etoposide is inferior to intravenous chemotherapy in the treatment of advanced SCLC and should not be used as first-line treatment of this disease.
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