Symptom control and quality of life in lux-lung 3 : a phase III study of afatinib or cisplatin/pemetrexed in patients with advanced lung adenocarcinoma with EGFR mutations

Purpose Patient-reported symptoms and health-related quality of life (QoL) benefits were investigated in a randomized, phase III trial of afatinib or cisplatin/pemetrexed. Patients and Methods Three hundred forty-five patients with advanced epidermal growth factor receptor (EGFR) mutation-positive lung adenocarcinoma were randomly assigned 2:1 to afatinib 40 mg per day or up to six cycles of cisplatin/pemetrexed. Lung cancer symptoms and health-related QoL were assessed every 21 days until progression using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 and Lung Cancer-13 questionnaires. Analyses of cough, dyspnea, and pain were preplanned, including percentage of patients who improved on therapy, time to deterioration of symptoms, and change in symptoms over time. Results Questionnaire compliance was high. Compared with chemotherapy, afatinib significantly delayed the time to deterioration for cough (hazard ratio [HR], 0.60; 95% CI, 0.41 to 0.87; P = .007) and dyspnea (HR, 0.68; 95% CI, 0.50 to 0.93; P = .015), but not pain (HR, 0.83; 95% CI, 0.62 to 1.10; P = .19). More patients on afatinib (64%) versus chemotherapy (50%) experienced improvements in dyspnea scores (P lt; .010). Differences in mean scores over time significantly favored afatinib over chemotherapy for cough (P lt; .001) and dyspnea (P = .001). Afatinib showed significantly better mean scores over time in global health status/QoL (P = .015) and physical (P = .001), role (P = .004), and cognitive (P lt; .007) functioning compared with chemotherapy. Fatigue and nausea were worse with chemotherapy, whereas diarrhea, dysphagia, and sore mouth were worse with afatinib (all P = .01). Conclusion In patients with lung adenocarcinoma with EGFR mutations, first-line afatinib was associated with better control of cough and dyspnea compared with chemotherapy, although diarrhea, dysphagia, and sore mouth were worse. Global health status/QoL was also improved over time with afatinib compared with chemotherapy.

Cross-layer design for traffic management in wireless networked control systems

Wireless networked control systems (WNCSs) have been increasingly deployed in industrial applications. As they require timely data packet transmissions, it is difficult to make efficient use of the limited channel resources, particularly in contention based wireless networks in the layered network architecture. Aiming to maintain the WNCSs under critical real-time traffic condition at which the WNCSs marginally meet the real-time requirements, a cross-layer design (CLD) approach is presented in this paper to adaptively adjust the control period to achieve improved channel utilization while still maintaining effective and timely packet transmissions. The effectiveness of the proposed approach is demonstrated through simulation studies.

Recasting the theory of mosquito-borne pathogen transmission dynamics and control

Mosquito-borne diseases pose some of the greatest challenges in public health, especially in tropical and sub-tropical regions of theworld. Efforts to control these diseases have been underpinned by a theoretical framework developed for malaria by Ross and Macdonald, including models, metrics for measuring transmission, and theory of control that identifies key vulnerabilities in the transmission cycle. That framework, especially Macdonald’s formula for R0 and its entomological derivative, vectorial capacity, are nowused to study dynamics and design interventions for many mosquito-borne diseases. A systematic review of 388 models published between 1970 and 2010 found that the vast majority adopted the Ross–Macdonald assumption of homogeneous transmission in a well-mixed population. Studies comparing models and data question these assumptions and point to the capacity to model heterogeneous, focal transmission as the most important but relatively unexplored component in current theory. Fine-scale heterogeneity causes transmission dynamics to be nonlinear, and poses problems for modeling, epidemiology and measurement. Novel mathematical approaches show how heterogeneity arises from the biology and the landscape on which the processes of mosquito biting and pathogen transmission unfold. Emerging theory focuses attention on the ecological and social context formosquito blood feeding, themovement of both hosts and mosquitoes, and the relevant spatial scales for measuring transmission and for modeling dynamics and control.

Integrin αvβ3 upregulates integrin-linked kinase expression in human ovarian cancer cells via enhancement of ILK gene transcription

We previously showed that integrin alphavbeta3 overexpression and engagement by its ligand vitronectin increased adhesion, motility, and proliferation of human ovarian cancer cells. In search of differentially regulated genes involved in these tumor biological events, we previously identified the integrin-linked kinase (ILK) to be under control of alphavbeta3. In the present investigation we demonstrated significantly upregulated ILK protein as a function of alphavbeta3 in two ovarian cancer cell lines, OV-MZ-6 and OVCAR-3, and proved co-localization at the surface of alphavbeta3-overexpressing cells adherent to vitronectin. Increase of ILK protein was reflected by enhanced ILK promoter activity, an effect, which we further characterized with regard to transcriptional response elements involved. Abrogation of NF-kappaB/c-rel or p53 binding augmented ILK promoter activity and preserved induction by alphavbeta3. The AP1-mutant exhibited decreased promoter activity but was also still inducible by alphavbeta3. Disruption of the two DNA consensus motifs for Ets proteins led to divergent observations: mutation of the Ets motif at promoter position -462 bp did not significantly alter promoter activity but still allowed response to alphavbeta3. In contrast, disruption of the second Ets motif at position -85 bp did not only lead to slightly diminished promoter activity but also, in that case, abrogated ILK promoter induction by alphavbeta3. Subsequent co-transfection studies with ets-1 in the presence of the second Ets motif led to additional induction of ILK promoter activity. Taken together, these data suggest that ets-1 binding to the second Ets DNA motif strongly contributes to alphavbeta3-mediated ILK upregulation. By increasing ILK as an important integrin-proximal kinase, alphavbeta3 may promote its intracellular signaling and tumor biological processes arising thereof in favor of ovarian cancer metastasis.

A pilot randomised trial of Medilixir cream shows some promising results, but control treatment may have been inappropriate

Aim To test the efficacy of Medilixir [cream] against the standard treatment of aqueous cream in the provision of relief from the symptoms of postburn itch. Design RCT with two parallel arms. Setting Professor Stuart Pegg Adult Burns Centre, Royal Brisbane and Women's Hospital, Brisbane, Australia. Participants Fifty-two patients aged between 18 and 80 years, admitted directly to the burns centre between 10 March and 22 July 2008, were able to provide informed consent, and had shown no allergic reaction to a patch test with the study medication, were randomised. Patients admitted from intensive care or high dependency were excluded. Main results Effect estimates and confidence intervals were not reported for any of the outcomes; only group means/proportions and P-values from hypothesis testing were provided. More patients in the intervention group reported itch reduction compared to comparison treatment (91 vs. 82%, P=0.001). Itch recurrence after cream application occurred later in the intervention group compared to the control group (P<0.001). Use of antipruritic medication was significantly greater in the control group (P=0.023). There was no difference in sleep disturbance between groups (not quantified). On average, Medilixir took longer to apply than aqueous cream (157s for Medilixir vs. 139s for aqueous cream; mean difference 17s), but authors noted that the groups did not differ significantly (CI for mean difference and P-values were not reported).

Power sharing control with frequency droop in a hybrid microgrid

A microgrid may contain a large number of distributed generators (DGs). These DGs can be either inertial or non-inertial, either dispatchable or non-dispatchable. Moreover, the DGs may operate in plug and play fashion. The combination of these various types of operation makes the microgrid control a challenging task, especially when the microgrid operates in an autonomous mode. In this paper, a new control algorithm for converter interfaced (dispatchable) DG is proposed which facilitates smooth operation in a hybrid microgrid containing inertial and non-inertial DGs. The control algorithm works satisfactorily even when some of the DGs operate in plug and play mode. The proposed strategy is validated through PSCAD simulation studies.

A distributed control based coordination scheme of household PV systems for overvoltage prevention

This paper presents a distributed communication based active power curtailment (APC) control scheme for grid connected photovoltaic (PV) systems to address voltage rise. A simple distribution feeder model is presented and simulated using MATLAB. The resource sharing based control scheme proposed is shown to be effective at reducing voltage rise during times of peak generation and low load. Simulations also show the even distribution of APC using simple communications. Simulations demonstrate the versatility of the proposed control method under major communication failure conditions. Further research may lead to possible applications in coordinated electric vehicle (EV) charging.

Terms of engagement : consensus or control in remote Australian resource management?

Public engagement is a defining feature of collaborative approaches to environmental management (Petts 2006, Whelan and Oliver 2005). Public engagement in this context is focused on incorporating residents and communities of interest in activities like ecological restoration, catchment management, and environmental conservation in a wide range of situations (Nelson and Pettit 2004, Petts 2007). Some authors consider public engagement to be a sign of healthy democratic functioning in society (Skocpol and Fiorina 1999). Others draw attention to overcoming widely noted practical limitations of top-down mechanisms, emphasising that public engagement results in programs being implemented more effectively (Broderick 2005, Leach et al. 1999).

Wide-area control of aggregated power systems

This paper proposes a new method for stabilizing disturbed power systems using wide area measurement and FACTS devices. The approach focuses on both first swing and damping stability of power systems following large disturbances. A two step control algorithm based on Lyapunov Theorem is proposed to be applied on the controllers to improve the power systems stability. The proposed approach is simulated on two test systems and the results show significant improvement in the first swing and damping stability of the test systems.

Control, operation and power sharing among parallel converter-interfaced DERs in a microgrid in the presence of unbalanced and harmonic loads

This paper demonstrates power management and control of DERs in an autonomous MG. The paper focuses on the control and performance of converter-interfaced DERs in voltage controlled mode. Several case studies are considered for a MG based on the different types of loads supplied by the MG (i.e. balanced three-phase, unbalanced, single-phase and harmonic loads). DERs are controlled by adjusting the voltage magnitude and angle in their converter output through droop control, in a decentralized concept. Based on this control method, DERs can successfully share the total demand of the MG in the presence of any type of loads. This includes proper total power sharing, unbalanced power sharing as well as harmonic power sharing, depending on the load types. The efficacy of the proposed power control, sharing and management among DERs in a microgrid is validated through extensive simulation studies using PSCAD/EMTDC.

Voltage regulation, power balancing and battery storage discharge control by smart demand side management and multi-objective decision making

A novel intelligent online demand side management system is proposed for peak load management. The method also regulates the network voltage, balances the power in three phases and coordinates the battery storage discharge within the network. This method uses low cost controllers with low bandwidth two-way communication installed in costumers' premises and at distribution transformers to manage the peak load while maximizing customer satisfaction. A multi-objective decision making process is proposed to select the load(s) to be delayed or controlled. The efficacy of the proposed control system is verified through an event-based developed simulation in Matlab.

Primary control level of parallel distributed energy resources converters in system of multiple interconnected autonomous microgrids within self-healing networks

To minimise the number of load sheddings in a microgrid (MG) during autonomous operation, islanded neighbour MGs can be interconnected if they are on a self-healing network and an extra generation capacity is available in the distributed energy resources (DER) of one of the MGs. In this way, the total load in the system of interconnected MGs can be shared by all the DERs within those MGs. However, for this purpose, carefully designed self-healing and supply restoration control algorithm, protection systems and communication infrastructure are required at the network and MG levels. In this study, first, a hierarchical control structure is discussed for interconnecting the neighbour autonomous MGs where the introduced primary control level is the main focus of this study. Through the developed primary control level, this study demonstrates how the parallel DERs in the system of multiple interconnected autonomous MGs can properly share the load of the system. This controller is designed such that the converter-interfaced DERs operate in a voltage-controlled mode following a decentralised power sharing algorithm based on droop control. DER converters are controlled based on a per-phase technique instead of a conventional direct-quadratic transformation technique. In addition, linear quadratic regulator-based state feedback controllers, which are more stable than conventional proportional integrator controllers, are utilised to prevent instability and weak dynamic performances of the DERs when autonomous MGs are interconnected. The efficacy of the primary control level of the DERs in the system of multiple interconnected autonomous MGs is validated through the PSCAD/EMTDC simulations considering detailed dynamic models of DERs and converters.

An efficient hybrid evolutionary optimization algorithm for daily volt/var control at distribution system including DGs

This paper presents a new hybrid evolutionary algorithm based on Particle Swarm Optimization (PSO) and Ant Colony Optimization (ACO) for daily Volt/Var control in distribution system including Distributed Generators (DGs). Due to the small X/R ratio and radial configuration of distribution systems, DGs have much impact on this problem. Since DGs are independent power producers or private ownership, a price based methodology is proposed as a proper signal to encourage owners of DGs in active power generation. Generally, the daily Volt/Var control is a nonlinear optimization problem. Therefore, an efficient hybrid evolutionary method based on Particle Swarm Optimization and Ant Colony Optimization (ACO), called HPSO, is proposed to determine the active power values of DGs, reactive power values of capacitors and tap positions of transformers for the next day. The feasibility of the proposed algorithm is demonstrated and compared with methods based on the original PSO, ACO and GA algorithms on IEEE 34-bus distribution feeder.

Control strategies to prevent total hip replacement-related infections : a systematic review and mixed treatment comparison

OBJECTIVE: To synthesise the available evidence and estimate the comparative efficacy of control strategies to prevent total hip replacement (THR)-related surgical site infections (SSIs) using a mixed treatment comparison. DESIGN: Systematic review and mixed treatment comparison. SETTING: Hospital and other healthcare settings. PARTICIPANTS: Patients undergoing THR. PRIMARY AND SECONDARY OUTCOME MEASURES: The number of THR-related SSIs occurring following the surgical operation. RESULTS: 12 studies involving 123 788 THRs and 9 infection control strategies were identified. The strategy of 'systemic antibiotics+antibiotic-impregnated cement+conventional ventilation' significantly reduced the risk of THR-related SSI compared with the referent strategy (no systemic antibiotics+plain cement+conventional ventilation), OR 0.13 (95% credible interval (CrI) 0.03-0.35), and had the highest probability (47-64%) and highest median rank of being the most effective strategy. There was some evidence to suggest that 'systemic antibiotics+antibiotic-impregnated cement+laminar airflow' could potentially increase infection risk compared with 'systemic antibiotics+antibiotic-impregnated cement+conventional ventilation', 1.96 (95% CrI 0.52-5.37). There was no high-quality evidence that antibiotic-impregnated cement without systemic antibiotic prophylaxis was effective in reducing infection compared with plain cement with systemic antibiotics, 1.28 (95% CrI 0.38-3.38). CONCLUSIONS: We found no convincing evidence in favour of the use of laminar airflow over conventional ventilation for prevention of THR-related SSIs, yet laminar airflow is costly and widely used. Antibiotic-impregnated cement without systemic antibiotics may not be effective in reducing THR-related SSIs. The combination with the highest confidence for reducing SSIs was 'systemic antibiotics+antibiotic-impregnated cement+conventional ventilation'. Our evidence synthesis underscores the need to review current guidelines based on the available evidence, and to conduct further high-quality double-blind randomised controlled trials to better inform the current clinical guidelines and practice for prevention of THR-related SSIs.