Normal tissue complication models for clinically relevant acute esophagitis (>= grade 2) in patients treated with dose differentiated accelerated radiotherapy (DART-bid)

Background: One of the primary dose-limiting toxicities during thoracic irradiation is acute esophagitis (AE). The aim of this study is to investigate dosimetric and clinical predictors for AE grade >= 2 in patients treated with accelerated radiotherapy for locally advanced non-small cell lung cancer (NSCLC). Patients and methods: 66 NSCLC patients were included in the present analysis: 4 stage II, 44 stage IIIA and 18 stage IIIB. All patients received induction chemotherapy followed by dose differentiated accelerated radiotherapy (DART-bid). Depending on size (mean of three perpendicular diameters) tumors were binned in four dose groups: 6 cm 90 Gy. Patients were treated in 3D target splitting technique. In order to estimate the normal tissue complication probability (NTCP),two Lyman models and the cutoff-logistic regression model were fitted to the data with AE >= grade 2 as statistical endpoint. Inter-model comparison was performed with the corrected Akaike information criterion (AIC(c)),which calculates the model's quality of fit (likelihood value) in relation to its complexity (i.e. number of variables in the model) corrected by the number of patients in the dataset. Toxicity was documented prospectively according to RTOG. Results: The median follow up was 686 days (range 84-2921 days), 23/66 patients (35 %) experienced AE >= grade 2. The actuarial local control rates were 72.6 % and 59.4 % at 2 and 3 years, regional control was 91 % at both time points. The Lyman-MED model (D50 = 32.8 Gy, m = 0.48) and the cutoff dose model (D-c = 38 Gy) provide the most efficient fit to the current dataset. On multivariate analysis V38 (volume of the esophagus that receives 38 Gy or above, 95 %-CI 28.2-57.3) was the most significant predictor of AE >= grade 2 (HR = 1.05, CI 1.01-1.09, p = 0.007). Conclusion: Following high-dose accelerated radiotherapy the rate of AE >= grade 2 is slightly lower than reported for concomitant radio-chemotherapy with the additional benefit of markedly increased loco-regional tumor control. In the current patient cohort the most significant predictor of AE was found to be V38. A second clinically useful parameter in treatment planning may be MED (mean esophageal dose)

Identification of the spatio-temporal and fluvial-pluvial sources of flood inundation in the Lower Mekong Basin

Identification of the sources of the spatio-temporal information of flooding is important for flood control and understanding the water dynamic. Flood disasters are generally caused by two main sources: fluvial and pluvial flooding. However, there is a gap in information and challenge of such particular information in the Mekong River Basin (MRB) known as the largest river basin in Southeast Asia. This paper aims to analyze the spatio-temporal hydrograph separations of flooding and to determine the fluvial and pluvial sources of inundation water in the Lower Mekong Basin (LMB) by using a distributed rainfall–runoff–inundation (RRI) model and time–space accounting scheme (T–SAS) method. This study focuses on the two major flood events in 2000 and 2011, whose characteristics were different. The one in 2000 was long in terms of flood duration and it was the historically largest annual total flood water with twice the peak times in July and September. The 2011 flood had the highest flooded water during the peak time; however, its annual total flood water was less than the one in 2000. The results of spatio-temporal sources of flooding indicated that during the flow peak time in 2000 and 2011, the flow at Kratie was mainly contributed by 30-day (67%) and 100-day (98%) precipitation from the upstream. The drainage area of the MRB in China, northern Lao PDR, southern Lao PDR and eastern Thailand, and Cambodia and Vietnam contributed to peak flood at Kratie by 13%, 27%, 33%, and 27% for the 2000 flood and 12%, 33%, 38%, and 16% for the 2011 flood. The source of inundated water in the LMB was derived from upstream flow (fluvial source) of 35–36% and local rainfall (pluvial source) of 64–65%. Even though flood events in 2000 and 2011 had different characteristics, the sources of flood inundation in the LMB for both events were majorly from the local rainfall rather than the upstream flow. The large annual flood volume and long during of flooding in 2000 caused severe total economic damages up to 517 million US$in the LMB countries (Cambodia, Lao PDR, Thailand, and Vietnam), while the high peak inundated water in 2011 with shorter flood duration caused damages of 493 million US$

Attack-Surface Metrics, OSSTMM and Common Criteria Based Approach to “Composable Security” in Complex Systems

In recent studies on Complex Systems and Systems-of-Systems theory, a huge effort has been put to cope with behavioral problems, i.e. the possibility of controlling a desired overall or end-to-end behavior by acting on the individual elements that constitute the system itself. This problem is particularly important in the “SMART” environments, where the huge number of devices, their significant computational capabilities as well as their tight interconnection produce a complex architecture for which it is difficult to predict (and control) a desired behavior; furthermore, if the scenario is allowed to dynamically evolve through the modification of both topology and subsystems composition, then the control problem becomes a real challenge. In this perspective, the purpose of this paper is to cope with a specific class of control problems in complex systems, the “composability of security functionalities”, recently introduced by the European Funded research through the pSHIELD and nSHIELD projects (ARTEMIS-JU programme). In a nutshell, the objective of this research is to define a control framework that, given a target security level for a specific application scenario, is able to i) discover the system elements, ii) quantify the security level of each element as well as its contribution to the security of the overall system, and iii) compute the control action to be applied on such elements to reach the security target. The main innovations proposed by the authors are: i) the definition of a comprehensive methodology to quantify the security of a generic system independently from the technology and the environment and ii) the integration of the derived metrics into a closed-loop scheme that allows real-time control of the system. The solution described in this work moves from the proof-of-concepts performed in the early phase of the pSHIELD research and enrich es it through an innovative metric with a sound foundation, able to potentially cope with any kind of pplication scenarios (railways, automotive, manufacturing, ...)

Impacts of chronic stress on urinary bladder function & recovery through modification of PACAP signaling

Stress can cause or contribute to bladder dysfunction though specific effects remain unclear. Individuals with interstitial cystitis (IC)/bladder pain syndrome (BPS) experience increased symptom severity with stress, including pain and increased urgency and frequency of voiding. Further research can identify stress-related changes to urinary mechanisms, such as changes in sensory neurotransmitters and subsequent receptor expression. These factors could then become targets for future therapies providing bladder dysfunction relief. Alterations in PACAP and TRPV channel expression have been shown in sensory pathways in response to disease. My research studied the effects of chronic stress on bladder function and the potential for PACAP(6-38), a PACAP antagonist, to recover normal function. Mice went through a repeated variate stress regime followed by bladder tube implant and cystometrogram recording. Bladder, dorsal root ganglia (DRG), and spinal cord tissues were collected and immunostained for the presence of TRPV1, TRPV4, and PACAP expression. Chronic stress decreased inter-contraction interval (ICI) and bladder capacity while increasing bladder pressures. Both control and stressed male and female mice showed improvement following a 30-minute intravesical infusion of PACAP(6-38), with ICI and bladder capacity measures having the most consistent improvement across groups. PACAP and TRPV1 expression was upregulated in the bladder afferent pathway. These findings suggest that chronic stress can contribute to bladder dysfunction, and it seems to be mediated in part by upregulation of PACAP and TRPV channel activity. With further research, these factors may be valid molecular targets for therapy. As chronic stress may present alone or in combination with other conditions (IC/BPS, injury, etc.), it is critical to understand stress-related changes in order to reduce or eliminate their impact

Control, Process Facilitation, and Requirements Change in Offshore Requirements Analysis: The Provider Perspective

Process, technology, and project factors have been increasingly driving organizations to offshore early software development phases, such as requirements analysis. This emerging trend necessitates greater control and process facilitation between client and vendor sites. The effectiveness of control and facilitation has, however, not been examined within the context of requirements analysis and change. In this study, we examine the role of control and facilitation in managing changing requirements and on success of requirements gathering in the Indian offshore software development environment. Firms found that control by client-site coordinators had a positive impact on requirements analysis success while vender site-coordinators did not have similar influence. Process facilitation by client site-coordinators affected requirements phase success indirectly through control. The study concludes with recommendations for research and practice

Omnidirectional Sensory and Motor Volumes in Electric Fish

Active sensing organisms, such as bats, dolphins, and weakly electric fish, generate a 3-D space for active sensation by emitting self-generated energy into the environment. For a weakly electric fish, we demonstrate that the electrosensory space for prey detection has an unusual, omnidirectional shape. We compare this sensory volume with the animal's motor volume—the volume swept out by the body over selected time intervals and over the time it takes to come to a stop from typical hunting velocities. We find that the motor volume has a similar omnidirectional shape, which can be attributed to the fish's backward-swimming capabilities and body dynamics. We assessed the electrosensory space for prey detection by analyzing simulated changes in spiking activity of primary electrosensory afferents during empirically measured and synthetic prey capture trials. The animal's motor volume was reconstructed from video recordings of body motion during prey capture behavior. Our results suggest that in weakly electric fish, there is a close connection between the shape of the sensory and motor volumes. We consider three general spatial relationships between 3-D sensory and motor volumes in active and passive-sensing animals, and we examine hypotheses about these relationships in the context of the volumes we quantify for weakly electric fish. We propose that the ratio of the sensory volume to the motor volume provides insight into behavioral control strategies across all animals

Fuzzy-logic-based control, filtering, and fault detection for networked systems: A Survey

This paper is concerned with the overview of the recent progress in fuzzy-logic-based filtering, control, and fault detection problems. First, the network technologies are introduced, the networked control systems are categorized from the aspects of fieldbuses and industrial Ethernets, the necessity of utilizing the fuzzy logic is justified, and the network-induced phenomena are discussed. Then, the fuzzy logic control strategies are reviewed in great detail. Special attention is given to the thorough examination on the latest results for fuzzy PID control, fuzzy adaptive control, and fuzzy tracking control problems. Furthermore, recent advances on the fuzzy-logic-based filtering and fault detection problems are reviewed. Finally, conclusions are given and some possible future research directions are pointed out, for example, topics on two-dimensional networked systems, wireless networked control systems, Quality-of-Service (QoS) of networked systems, and fuzzy access control in open networked systems.This work was supported in part by the National Natural Science Foundation of China under Grants 61329301, 61374039, 61473163, and 61374127, the Hujiang Foundation of China under Grants C14002 andD15009, the Engineering and Physical Sciences Research Council (EPSRC) of the UK, the Royal Society of the UK, and the Alexander von Humboldt Foundation of Germany