Chemotherapy versus supportive care in advanced non-small cell lung cancer: improved survival without detriment to quality of life

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 metaanalysis 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 fromchemotherapy. 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 enablepatients and their clinicians to make more informed treatment choices

Arbitrage and deflators in illiquid markets

This paper presents a stochastic model for discrete-time trading in financial markets where trading costs are given by convex cost functions and portfolios are constrained by convex sets. The model does not assume the existence of a cash account/numeraire. In addition to classical frictionless markets and markets with transaction costs or bid-ask spreads, our framework covers markets with nonlinear illiquidity effects for large instantaneous trades. In the presence of nonlinearities, the classical notion of arbitrage turns out to have two equally meaningful generalizations, a marginal and a scalable one. We study their relations to state price deflators by analyzing two auxiliary market models describing the local and global behavior of the cost functions and constraints

Induction of leaf senescence in Arabidopsis thaliana by long days through a light-dosage effect

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74662/1/j.1399-3054.1996.tb00463.x.pd

An introduction and overview of the Bering Sea Project : volume IV

© The Author(s), 2016. This is the author's version of the work and is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Deep Sea Research Part II: Topical Studies in Oceanography 134 (2016): 3-12, doi:10.1016/j.dsr2.2016.09.002.The seasonal rhythm of sea-ice advance and retreat in the eastern Bering Sea (EBS) moves ice hundreds of kilometers across the broad continental shelf and exerts a powerful influence on the ecology of these waters. In winter, the combination of latitude, geology, winds, and ocean currents produces ice cover extending far into the southern Bering Sea. In the spring and summer, retreating ice, longer daylight hours, and nutrient-rich ocean water result in exceptionally high marine production, vital to both sea life and people. The intense burst of spring production, together with more episodic summer and early fall production, provides the energy that powers the complex food web and ultimately sustains nearly half of the US annual commercial fish landings, as well as providing food and cultural value to thousands of Bering Sea coastal and island residents.Finally, we acknowledge the National Science Foundation (NSF Award No. 1308087) and the North Pacific Research Board (NPRB) for author support during the concluding phase of the Bering Sea Project, and we thank many colleagues at NSF, NPRB, and NOAA for their management partnership and expertise. Funding for the Bering Sea Project was provided by NSF and NPRB, with in-­‐kind contribution from participants.2018-09-1

Column Rank Distances of Rank Metric Convolutional Codes

In this paper, we deal with the so-called multi-shot network coding, meaning that the network is used several times (shots) to propagate the information. The framework we present is slightly more general than the one which can be found in the literature. We study and introduce the notion of column rank distance of rank metric convolutional codes for any given rate and finite field. Within this new framework we generalize previous results on column distances of Hamming and rank metric convolutional codes [3, 8]. This contribution can be considered as a continuation follow-up of the work presented in [10]

Decoding of 2D convolutional codes over an erasure channel

In this paper we address the problem of decoding 2D convolutional codes over an erasure channel. To this end we introduce the notion of neighbors around a set of erasures which can be considered an analogue of the notion of sliding window in the context of 1D convolutional codes. The main idea is to reduce the decoding problem of 2D convolutional codes to a problem of decoding a set of associated 1D convolutional codes. We first show how to recover sets of erasures that are distributed on vertical, horizontal and diagonal lines. Finally we outline some ideas to treat any set of erasures distributed randomly on the 2D plane. © 2016 AIMS

Periodic state-space representations of periodic convolutional codes

In this paper we study the representation of periodically time-varying convolutional codes by means of periodic input-state-output models. In particular, we focus on period two and investigate under which conditions a given two-periodic convolutional code (obtained by alternating two time-invariant encoders) can be represented by a periodic input-state-output system. We first show that one cannot expect, in general, to obtain a periodic input-state-output representation of a periodic convolutional code by means of the individual realizations of each of the associated time-invariant codes. We, however, provide sufficient conditions for this to hold in terms of the column degrees of the associated column reduced generator matrices. Moreover, we derive a sufficient condition to obtain a periodic state-space realization that is minimal. Finally, examples to illustrate the results are presented.publishe

Localization and Characterization of STRO-1+ Cells in the Deer Pedicle and Regenerating Antler

The annual regeneration of deer antlers is a unique developmental event in mammals, which as a rule possess only a very limited capacity to regenerate lost appendages. Studying antler regeneration can therefore provide a deeper insight into the mechanisms that prevent limb regeneration in humans and other mammals, and, with regard to medical treatments, may possibly even show ways how to overcome these limitations. Traditionally, antler regeneration has been characterized as a process involving the formation of a blastema from de-differentiated cells. More recently it has, however, been hypothesized that antler regeneration is a stem cell-based process. Thus far, direct evidence for the presence of stem cells in primary or regenerating antlers was lacking. Here we demonstrate the presence of cells positive for the mesenchymal stem cell marker STRO-1 in the chondrogenic growth zone and the perivascular tissue of the cartilaginous zone in primary and regenerating antlers as well as in the pedicle of fallow deer (Dama dama). In addition, cells positive for the stem cell/progenitor cell markers STRO-1, CD133 and CD271 (LNGFR) were isolated from the growth zones of regenerating fallow deer antlers as well as the pedicle periosteum and cultivated for extended periods of time. We found evidence that STRO-1+ cells isolated from the different locations are able to differentiate in vitro along the osteogenic and adipogenic lineages. Our results support the view that the annual process of antler regeneration might depend on the periodic activation of mesenchymal progenitor cells located in the pedicle periosteum. The findings of the present study indicate that not only limited tissue regeneration, but also extensive appendage regeneration in a postnatal mammal can occur as a stem cell-based process

A state space approach to periodic convolutional codes

In this paper we study periodically time-varying convolutional codes by means of input-state-output representations. Using these representations we investigate under which conditions a given time-invariant convolutional code can be transformed into an equivalent periodic time-varying one. The relation between these two classes of convolutional codes is studied for period 2. We illustrate the ideas presented in this paper by constructing a periodic time-varying convolutional code from a time-invariant one. The resulting periodic code has larger free distance than any time-invariant convolutional code with equivalent parameters

Transcriptional and Post-Transcriptional Mechanisms for Oncogenic Overexpression of Ether À Go-Go K+ Channel

The human ether-à-go-go-1 (h-eag1) K+ channel is expressed in a variety of cell lines derived from human malignant tumors and in clinical samples of several different cancers, but is otherwise absent in normal tissues. It was found to be necessary for cell cycle progression and tumorigenesis. Specific inhibition of h-eag1 expression leads to inhibition of tumor cell proliferation. We report here that h-eag1 expression is controlled by the p53−miR-34−E2F1 pathway through a negative feed-forward mechanism. We first established E2F1 as a transactivator of h-eag1 gene through characterizing its promoter region. We then revealed that miR-34, a known transcriptional target of p53, is an important negative regulator of h-eag1 through dual mechanisms by directly repressing h-eag1 at the post-transcriptional level and indirectly silencing h-eag1 at the transcriptional level via repressing E2F1. There is a strong inverse relationship between the expression levels of miR-34 and h-eag1 protein. H-eag1antisense antagonized the growth-stimulating effects and the upregulation of h-eag1 expression in SHSY5Y cells, induced by knockdown of miR-34, E2F1 overexpression, or inhibition of p53 activity. Therefore, p53 negatively regulates h-eag1 expression by a negative feed-forward mechanism through the p53−miR-34−E2F1 pathway. Inactivation of p53 activity, as is the case in many cancers, can thus cause oncogenic overexpression of h-eag1 by relieving the negative feed-forward regulation. These findings not only help us understand the molecular mechanisms for oncogenic overexpression of h-eag1 in tumorigenesis but also uncover the cell-cycle regulation through the p53−miR-34−E2F1−h-eag1 pathway. Moreover, these findings place h-eag1 in the p53−miR-34−E2F1−h-eag1 pathway with h-eag as a terminal effecter component and with miR-34 (and E2F1) as a linker between p53 and h-eag1. Our study therefore fills the gap between p53 pathway and its cellular function mediated by h-eag1