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An approach for minimizing tracking errors in linear time-invariant (LTI) single-input single-output (SISO) discrete-time systems with nonminimum phase (NMP) zeros using filtered basis functions (FBF) is studied. In the FBF method, the control input to the system is expressed as a linear combination of basis functions. The basis functions are forward filtered using the dynamics of the NMP system, and their coefficients are selected to minimize the error in tracking a given desired trajectory. Unlike comparable methods in the literature, the FBF method is shown to be effective in tracking any desired trajectory, irrespective of the location of NMP zeros in the z-plane. The stability of the method and boundedness of the control input and system output are discussed. The control designer is free to choose any suitable set of basis functions that satisfy the criteria discussed in this paper. However, two rudimentary basis functions, one in time domain and the other in frequency domain, are specifically highlighted. The effectiveness of the FBF method is illustrated and analyzed in comparison with the truncated series (TS) approximation method.

This paper presents and compares two methods for trading off energy efficiency and feedforward tracking accuracy using filtered basis functions. In the regular filtered basis function (FBF) approach, the control input to the system is expressed as a linear combination of basis functions. The basis functions are forward filtered using the dynamics of the system and their coefficients selected such that a performance index which penalizes tracking errors is minimized. It is shown that, in the regular FBF approach, varying the number of basis functions can be used to tradeoff energy efficiency (control energy) and tracking accuracy. Another way of achieving the same goal using FBFs is to minimize a weighted sum of tracking and control energy objectives (i.e., linear quadratic tracking) using a fixed number of basis functions. Simulation-based examples are used to compare both approaches with regard to their degree of tradeoff between tracking accuracy and energy efficiency.

Diarrhoea is common in Intensive Care Unit (ICU) patients, with a reported prevalence of 15–38%. Many factors may cause diarrhoea, including Clostridium difficile, drugs (e.g. laxatives, antibiotics) and enteral feeds. Diarrhoea impacts on patient dignity, increases nursing workload and healthcare costs, and exacerbates morbidity through dermal injury, impaired enteral uptake and subsequent fluid imbalance. We analysed a cohort of 9331 consecutive patients admitted to a mixed general intensive care unit to establish the prevalence of diarrhoea in intensive care unit patients, and its relationship with infective aetiology and clinical outcomes. We provide evidence that diarrhoea is common (12.9% (1207/9331) prevalence) in critically ill patients, independently associated with increased intensive care unit length of stay (mean (standard error) 14.8 (0.26) vs 3.2 (0.09) days, p

Two new species of Bactrocera Macquart, namely Bactrocera (Calodacus) harrietensis RamaniDavid, sp. nov. and Bactrocera (Calodacus) chettalli DavidRanganath, sp. nov., are described from the Andaman and Nicobar Islands and Karnataka, India, respectively. Bactrocera (Zeugodacus) semongokensis DrewRomig is recorded for the first time from India.

Ventilator rate, volume, and time parameters are interrelated directly, mechanically, and physiologically, and interactions between intrinsic pulmonary physio-mechanics, pathology and the effects of mechanical ventilation complex. The physiological consequences of mechanical ventilation and risks of ventilator-induced trauma may be exacerbated by lung pathology. Programming of ventilator parameters should be considered within the context of an individualized ventilatory strategy to achieve adequate gas exchange, while minimizing attendant risks of mechanical ventilation. Recommended strategies should be modified within accepted limits to mitigate disease-specific risks. Parameters should subsequently be titrated against blood gas- and ventilator-derived targets, and other clinical variables.

Introduction: Emergence of chloroquine (CQ) resistance in Plasmodium falciparum has increased the morbidity and mortality of falciparum malaria worldwide. Artemisinin-based combination therapies are now recommended by the World Health Organization as the first line treatment for falciparum malaria. Numerous molecular markers have been implicated in the CQ and artemisinin resistance. Materials and Methods: A total of 26 confirmed cases of falciparum malaria (by giemsa stained thick and thin smear, quantitative buffy coat, immunochromatographic test, or polymerase chain reaction [PCR]) were included in the study. About 5 ml of ethylenediaminetetraacetic acid blood sample was collected and stored at –20°C till use. Plasmodium DNA was extracted using QIAamp whole blood DNA extraction kit. PCR was done to amplify pfcrt, pfmdr1, pfserca , and pfmrp1 genes and the amplicons obtained were sequenced by Macrogen, Inc., Korea. Single nucleotide polymorphism (SNP) analysis was done using Bio-Edit Sequence Alignment Editor. Results: Out of the four genes targeted, we noted a SNP in the pfcrt gene alone. This SNP (G > T) was noted in the 658 th position of the gene, which was seen in 13 patients. The pfmdr1 and pfserca genes were present in 9 and 14 patients respectively. But we could not find any SNPs in these genes. This SNP in pfcrt gene was not significantly associated with any adverse outcome and neither altered disease progression. Conclusion: Presence of a single SNP may not be associated with any adverse clinical outcome. As the sample size was small, we may have not been able to detect any other known or unknown polymorphisms.

Key Clinical Message We report a case of incidentally diagnosed chronic lymphocytic leukemia (CLL) in a patient with glioblastoma, which responded completely following standard treatment of the glioblastoma with temozolomide and cranial irradiation. The patient remained without an evidence of CLL until his death from recurrent glioblastoma. Further study of temozolomide for the treatment of CLL is indicated.

The Photoconductance Decay (PCD) method in a standard version allows determination of the bulk properties of semiconductors but is not suitable for evaluation of the surface and near-surface region of the wafer during processing. This experiment is concerned with PCD measurements devised specifically for the purpose of electrical probing using temporary contacts of the near-surface (ns-PCD) region of semiconductor substrates, including thin films. The method is tested through the measurements of the single-crystal, indirect bandgap elemental semiconductor wafers (Si and Ge), as well as selected direct bandgap compound semiconductor wafers (GaAs and InP). In the former case, surface properties of the material tested are altered in a controlled fashion and the PCD response to the surface alteration, in terms of the minority carrier lifetime, is measured. In the case of all substrates studied, a direct correlation between carrier lifetime measured using PCD and the condition of the wafer surface was observed. Furthermore, the ns-PCD method was proven very effective in measuring minority carrier lifetime at the semiconductor-dielectric interface without having to form MOS test structures. The results obtained suggest that the modified PCD method employing temporary contacts to the measured surface can be used to monitor the condition of semiconductor surfaces during device processing.

Knowledge transfer is the primary conduit through which management professors communicate what is known about human and organizational dynamics. This process has been conceptualized by the construc...

Aim Preoperative radiotherapy has been shown to improve local control in advanced rectal carcinoma compared with surgery alone. Several large randomized trials have confirmed that chemoradiotherapy (CRT) is better than radiotherapy alone. This pilot study was designed to increase the radiation dose using high-dose rate (HDR) brachytherapy boost following preoperative CRT to evaluate whether this strategy improves the outcome of surgery without increase in toxicity. Method Since October 2004, we have used the new rectal HDR applicator for brachytherapy boost in 68 patients following CRT. The patients had CT and MRI Scans as part of staging. All had locally advanced disease either bulky low T2 or T3 with threatened circumferential resection margin and multiple suspicious lymph nodes. They were offered preoperative CRT either by 5-FU infusion 1 g/m2 day 1–4 (week 1 + 5) or by oral capecitabine 825 mg/m2 Monday–Friday for 5 weeks together with CT planned external beam RT 45Gy in 25 fractions over 5 weeks (CRT). Those downstage on repeat MRI scan were offered additional HDR Boost 10Gy directly to the tumour followed by surgery 6–8 weeks later [group A]. Four patients proceeded directly to surgery but because of involved resection margin had a HDR brachytherapy boost as postoperative treatment [group B]. Thirty patients were not planned for immediate surgery after CRT and brachytherapy boost, as they were either elderly or considered high risk for anaesthesia [group C]. Results There were 34 patients (median age 67 (range 39–81) years in group A, including 24 men). The PS was 0–1. The clinical stage at presentation was cT2 in five, cT3 in 23 and T4 in six patients and cN0 in 2, cN1 in 21 and N2 in 11. Thirty-three patients had CRT, and one had radiotherapy alone. All patients completed treatment without interruption. Twenty-nine patients had surgery following CRT and brachytherapy boost including anterior resection in 10 patients, Abdominoperineal excision (APR) in 18 and Hartmann’s resection in one. Five patients did not have the intended surgery. Twenty-four (83%) patients had an RO resection compared with 63% having conventional preoperative CRT using bolus 5FU regimes. Pathological complete remission (pCR) was achieved in 9 (31%) compared with 12% patients having conventional CRT. There was no increase in G 3–4 toxicity from RT and no delay in wound healing or increase in anastomotic leakage. One of the four patients in group B developed local recurrence. The thirty patients in group C who had modified radical CRT followed by brachytherapy boost as a definitive treatment will be reported in a further communication. Conclusion Increasing the dose of radiation by HDR brachytherapy boost appears to improve the RO resection and pCR rates compared with conventional CRT. The follow up is too short to judge its effect on disease-free survival. This study will be extended to compare this strategy in a randomized phase III trial with conventional CRT in patients who are not fit for more intensive CRT (HERCULES).

Introduction Capecitabine provides an attractive alternative to intravenous (IV) 5-flourouracil (5-FU) in chemoradiation regimes for rectal cancer by avoiding the need for intravenous access and inpatient stay. We aimed to compare retrospectively the efficacy of concurrent capecitabine with IV 5-FU in preoperative pelvic chemoradiation schedules for rectal cancer in our centre. Method Patients treated from January 2005 to June 2007 were included. Information was collected on patient characteristics; treatment details; pathological response to treatment; recurrence and survival. All statistical analyses were performed using SPSS V17. Results All patients had pelvic radiation. Ninety-nine patients were treated with capecitabine and 97 with 5FU. The two groups were well matched for age, sex and TNM stage. There were significantly more PS (performance status) 0 patients in the capecitabine group (51% vs 30%) (P = 0.001). Of the 99 patients in the capecitabine group, 91 (92%) were able to undergo surgery with 84 (93%) achieving R0 resection. In the 5-FU group, these proportions were 87 (90%) and 70 (80%). The difference in the rate of R0 resection was statistically significant (P = 0.024). The APR rate was 35% in the capecitabine group compared with 47% in the 5-FU group (P = 0.06). There was no significant difference in pathological complete response (pCR) rates between capecitabine (14%) and 5-FU(12%). A higher pCR rate (30%) was observed in patients who underwent a brachytherapy boost (P = 0.051). There were three local recurrences in the whole patient group, (capecitabine 1; 5-FU 2). Thirty-five patients had distant metastases, 14 in the capecitabine and 21 in the 5-FU group. There was no significant difference in the risk of recurrence between the two groups. Six patients in each group had grade 3 toxicity with diarrhoea being more common with capecitabine. Conclusions Preoperative chemoradiotherapy with capecitabine for rectal cancer is efficacious and comparable to 5-FU (IV). It is more convenient, is well tolerated and avoids the need for inpatient admission.

Insects nurture and protect us, sicken us, kill us. They bring us joy and sorrow. They drive us from fear to hate, then to tolerance. At times they bring us up short to a realisation of the way the world really is, and what we have to do to improve it. Their importance to human welfare transcends the grand battles we fight against them to manage them for our own ends. Most of us hate them, but some of us love them. Indeed at times they even inspire us.

Knowledge of residence time distribution (RTD), mean residence time (MRT) and degree of axial mixing of solid phase is required for efficient operation of coal gasification process. Radiotracer technique was used to measure the RTD of coal particles in a pilot-scale fluidized bed gasifier (FBG). Two different radiotracers i.e. lanthanum-140 and gold-198 labeled coal particles (100 gm) were independently used as radiotracers. The radiotracer was instantaneously injected into the coal feed line and monitored at the ash extraction line at the bottom and gas outlet at the top of the gasifier using collimated scintillation detectors. The measured RTD data were treated and MRTs of coal/ash particles were determined. The treated data were simulated using tanks-in-series model. The simulation of RTD data indicated good degree of mixing with small fraction of the feed material bypassing/short-circuiting from the bottom of the gasifier. The results of the investigation were found useful for optimizing the design and operation of the FBG, and scale-up of the gasification process.

Radiotracer technique was applied to measure the circulation rates of fine coal particles in standpipe of a pilot-scale bubbling circulating fluidized bed system (CFBS). 198Au adsorbed on coal particles was used as a radiotracer. The radiotracer was injected into the standpipe and monitored at four different downstream locations. The circulation times and circulation rates were determined from the measured tracer concentration curves at different operating conditions. The measured parameters were intended to be used for optimizing the performance of existing CFBSs operating in industry and design of a new CFBS to be used as coal gasifier.

This paper proposes an approach for minimizing tracking errors in systems with non-minimum phase (NMP) zeros by using filtered basis functions. The output of the tracking controller is represented as a linear combination of basis functions having unknown coefficients. The basis functions are forward filtered using the dynamics of the NMP system and their coefficients selected to minimize the errors in tracking a given trajectory. The control designer is free to choose any suitable set of basis functions but, in this paper, a set of basis functions derived from the widely-used non uniform rational B-spline (NURBS) curve is employed. Analyses and illustrative examples are presented to demonstrate the effectiveness of the proposed approach in comparison to popular approximate model inversion methods like zero phase error tracking control.Copyright © 2015 by ASME

A 30-year-old male presented with a 1-day history of left scrotal pain and a tender left testicle and epididymis on physical exam. Scrotal ultrasound showed an avascular, heterogeneous, hypoechoic lesion in the superior left testis suggestive of infarction or neoplasm. The patient was managed conservatively; however, his pain continued and follow-up ultrasound 6 days later showed interval increase in the size of the mass. Left radical orchiectomy was done and pathology result showed segmental infarction of the left testis.

Starting from the power spectral density of Mateacutern stochastic processes, we introduce a new family of splines that is defined in terms of the whitening operator of such processes. We show that these Mateacutern splines admit a stable representation in a B-spline-like basis. We specify the Mateacutern B-splines (causal and symmetric) and identify their key properties; in particular, we prove that these generate a Riesz basis and that they can be written as a product of an exponential with a fractional polynomial B-spline. We also indicate how these new functions bridge the gap between the fractional polynomial splines and the cardinal exponential ones. We then show that these splines provide the optimal reconstruction space for the minimum mean-squared error estimation of Mateacutern signals from their noisy samples. We also propose a digital Wiener-filter-like algorithm for the efficient determination of the optimal B-spline coefficients

This paper describes novel pseudo-online built-in self-test based techniques for detecting and locating multiple faults in lookup tables (LUTs), interconnects and dedicated clock lines of field programmable gate arrays (FPGAs). The techniques use the partial reconfiguration capabilities of modern FPGAs. The methods proposed in this paper find extensive applications in safety critical systems like space probes, which comprises of several subcircuits mapped onto the FPGA and employs online checkers to report misbehaviour of any of these subcircuits. When an online checker reports misbehaviour of one such subcircuit, the methods proposed in this paper attempt to detect and locate the faults, if any, within the faulty subcircuit without shutting down the other subcircuits. The methods presented in the paper preserve the routing structure of the configured application in-place. Experimentally, it is shown that the proposed methods provide good fault-coverage in identifying faults in LUTs, interconnects and dedicated clock lines. ? 2004 Elsevier B.V. All rights reserved.

Real-time systems are an important class of process control systems that need to respond to events under time constraints, or deadlines. Such systems may also be required to deliver service in spite of hardware or software faults in their components. This fault-tolerant characteristic is especially critical in systems whose failure can cause economic disaster and/or loss of lives. This paper reports recent research in the area of analytical modeling of the three major characteristics of real-time systems: timeliness, dependability, and external environmental dependencies. The paper starts with a brief introduction to analytical modeling frameworks such as Markov models and stochastic petri nets. This is followed by an examination of advances in modeling response-time distributions, reliability, distributed messaging services, and software fault-tolerance in real-time systems.

IntroductionThe admission of high-risk patients to critical care after surgery is a recommended standard of care. Nevertheless, poor compliance against this recommendation has been repeatedly demonstrated in large epidemiological studies. It is unclear whether this is due to reasons of capacity, equipoise, poor quality clinical care or because hospitals are working creatively to create capacity for augmented care on normal surgical wards. The EPIdemiology of Critical Care after Surgery study aims to address these uncertainties.Methods and analysisOne-week observational cohort study in the UK and Australasia. All patients undergoing inpatient (overnight stay) surgery will be included. All will have prospective data collection on risk factors, surgical procedure and postoperative outcomes including the primary outcome of morbidity (measured using the Postoperative Morbidity Survey on day 7 after surgery) and secondary outcomes including length of stay and mortality. Data will also be collected on critical care referral and admission, surgical cancellations and critical care occupancy. The epidemiology of patient characteristics, processes and outcomes will be described. Inferential techniques (multilevel multivariable regression, propensity score matching and instrumental variable analysis) will be used to evaluate the relationship between critical care admission and postoperative outcome.Ethics and disseminationThe study has received ethical approval from the National Research Ethics Service in the UK and equivalent in Australasia. The collection of patient identifiable data without prior consent has been approved by the Confidentiality Advisory Group (England and Wales) and the Public Privacy and Patient Benefit Panel (Scotland). In these countries, patient identifiable data will be used to link prospectively collected data with national registers of death and inpatient administrative data. The study findings will be disseminated using a multimedia approach with the support of our lay collaborators, to patients, public, policy-makers, clinical and academic audiences.

We present a qualitative review of the state of the field of entrepreneurship education in North America, in which we examine such topics such as the growth of field, its attempts to differentiate ...

We review the literature on evidence-based best practices regarding how to enhance methodological transparency when conducting empirical research. We focus on transparency because it is a precondit...

Two new species of genus Bactrocera Macquart, namely B. ( Sinodacus ) brevipunctata David and Hancock , sp. nov. and B. ( Bactrocera ) furcata David and Hancock, sp. nov., are described from India. B . ( B .) aethriobasis Hardy, B. ( B. ) rubigina Wang & Zhao, B. ( B. ) syzygii Tsuruta & White and B. ( B .) tuberculata (Bezzi) are recorded for the first time from India. Updated keys to twelve subgenera of Bactrocera and Indian species of Bactrocera ( Bactrocera ) are also provided.

Monitoring mouse behavior is a critical step in the development of modern pharmacotherapies.Here we describe the application of a novel method that utilizes a touch display computer (tablet) and software to detect, record, and report fine motor behaviors. A consumer-grade tablet device is placed in the bottom of a specially made acrylic cage allowing the animal to walk on the device (MouseTrapp). We describe its application in open field (for general locomotor studies) which measures step lengths and velocity. The device can perform light-dark (anxiety) tests by illuminating half of the screen and keeping the other half darkened. A divider is built into the lid of the device allowing the animal free access to either side.Treating mice with amphetamine and the delta opioid peptide receptor agonist SNC80 stimulated locomotor activity on the device. Amphetamine increased step velocity but not step length during its peak effect (40-70min after treatment), thus indicating detection of subtle amphetamine-induced effects. Animals showed a preference (74% of time spent) for the darkened half compared to the illuminated side.Animals were videotaped within the chamber to compare quadrant crosses to detect motion on the device. The slope, duration and magnitude of quadrant crosses tightly correlated with overall locomotor activity as detected by MouseTrapp.We suggest that modern touch display devices such as MouseTrapp will be an important step toward automation of behavioral analyses for characterizing phenotypes and drug effects.

With the growing research, the Network on chip (NoC) architecture provides an opportunity for high scalability and freedom from the limitations of complex wiring. In this paper, a survey of five differential routing architecture comparisons and its results are analyzed. The five different architectures namely, low latency router by Look ahead adaptivity, NoC router with look ahead Bypass. Look ahead routing algorithm for 3D-NOC architecture, Wormhole switching architecture and Connection-oriented service in MANGO clockless NOC are the mentioned architectures. In accordance with the comparison results, the different types of Best effort routing and Guaranteed Services (GS) arbitrations are easily plugged into the router, which indicates a significant improvement in jitter which can be easily achieved.

Recent research in automobile exhaust catalysts has addressed the substitution of platinum-group metals Pt, Pd and Rh by metals such as Cu, Co, Ag, Zn, Mn and Sr exchanged or impregnated on zeolites, TiO2 or Zro2 carriers. These catalysts have the potential of becoming good alternatives to the commercial three-way catalysts to convert pollutant hydrocarbons (HC), carbon monoxide (CO) and nitrogen oxides (NOx). This paper describes a technique based on neural networks, to correlate the catalyst synthesis variables and resulting exhaust conversion. The optimum catalyst composition and operating conditions for a specified exhaust conversion are determined A back-propagation algorithm was used to train the feed-forward neural network consisting of two hidden layers with 45 and 60 neurons in the first and second hidden layers respectively, with optimum values of the learning factor and momentum gain coefficient. The effects of the operating and compositional parameters on NOx conversion by Cu-ZSM-5 we...

Factors influencing the solid acidity in molybdenum oxides supported on silica-alumina were studied theoretically by means of self-consistent Hartree-Fock (HF), electron-correlated Moller-Plesset (MP2) and local density functional (LDF) quantum mechanical calculations of acid site models. This work was aimed at elucidating relationships between the chemical composition, surface geometry and the electronic properties of the solid acid catalysts. Local structures of unsupported and supported molybdenum oxide inferred from earlier experimental results were studied using cluster models. Relationships between the structural transformations in the molybdenum oxide tetrahedra and the changes in Bronsted-Lewis acidity were identified. The experimentally observed effect of the catalyst support composition on the acid strength of the supported molybdenum oxide catalyst was interpreted in terms of the calculated charge redistribution and molecular orbital energies. An acid site structure is proposed to explain the effect of Mo loading on the Bronsted acidity. The calculated changes in infrared vibration frequencies agree with the measured ones and support the mechanism proposed for the acidity changes on Mo loading.

Veda is a generative testing system that supports the design and administration of tests, on-line and off-line. Veda provides tools for test designers to create question generators. Veda authenticates the candidate‘s identity, administers a test, evaluates the candidate‘s answers and keeps a record of the candidate‘s scores. The system also provides facilities for item analysis. There are provisions for computing statistical indices for individual questions, based on data from tests administered. These indices can be used for item evaluation and improvement. An interesting feature of Veda‘s design is the security features built into it. Cryptographic techniques have been used to create a system offering a high degree of protection against leakage, theft or unauthorized modification. Veda was developed using the programming language C, under the UNIX operating system, and is in heavy use

Two new species of Bactrocera Macquart, namely Bactrocera (Calodacus) harrietensis Ramani & David, sp. nov. and Bactrocera (Calodacus) chettalli David & Ranganath, sp. nov., are described from the Andaman and Nicobar Islands and Karnataka, India, respectively. Bactrocera (Zeugodacus) semongokensis Drew & Romig is recorded for the first time from India.

We conducted a review and analysis of the journey of Organizational Research Methods (ORM) during the first 18 years of its existence (i.e., 1998-2015). First, we offer an analysis of the compositi...

NoC designs can be accepted to provision general communications between multiple IPs above multi-processor schemes on chip. In this effort we demonstrate the forming and imitation based exploration of some current architectures intended for Network on Chip (NoC). Specifically in this paper focus on the time synchronization based network, it hasthe Routing Integrated Time Synchronization protocol (RITS) that integrates post-facto time sync into a routing service also its achieved high result for QoS improvement in network. RITS, as well as reactive techniques in general, is superior to many proactive time sync protocols with respect to communication overhead. The best effort (BF) analysis of a representative reactive technique, the Routing Integrated Time Synchronization protocol (RITS) shows that in the general case, the presence of slack time cause RITS to Guaranteed throughput with the size of the network. We have using a shortest path based Traffic aware algorithm to time based data transmission quickly and efficiently on their network. It has more secure and easy to transfer data from one mobile node to another mobile node on the network.

Entreprenurial passion has been of great interest to scholars due to its impact on several key outcomes for entreprenurs, despite the mixed findings. We evaluate the role of emotional labor in infl...

Accurate delineation, diagnosis, and treatment planning of skull base lesions require knowledge of the complex anatomy of the skull base. Because the skull base cannot be directly evaluated, imaging is critical for the diagnosis and management of skull base diseases. Although computed tomography (CT) is excellent for outlining the bony detail, magnetic resonance (MR) imaging provides better soft tissue detail and is helpful for evaluating the adjacent meninges, brain parenchyma, and bone marrow of the skull base. Thus, CT and MR imaging are often used together for evaluating skull base lesions. This article focuses on the radiologic anatomy of the skull base pertinent to MR imaging evaluation.

This case report describes the immediate effects of a new rehabilitation tool on gait in a chronic stroke patient. Specifically, we measured step length symmetry and gait velocity in a 47 year-old male stroke patient who was currently receiving outpatient physical therapy. Objective gait measurements were taken using the GAITRite before, during, and after a 5 minute training session. Step length symmetry improved 26% during the first minute of training, 71% by the fifth minute of training, and 72% after a 5 minute rest period post-training. Gait velocity increased by 5.5% after 5 minutes of training. Clinical research is warranted to validate this new training tool as a useful adjunctive rehabilitation activity for improving spatial and temporal aspects of gait after stroke.

This paper presents a summary of the evidence review group (ERG) report into the clinical effectiveness and cost-effectiveness of gefitinib for the first-line treatment of locally advanced or metastatic non-small cell lung cancer, in accordance with the licensed indication, based upon the manufacturer's submission to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal process. The submitted clinical evidence consisted of the IRESSA Pan-ASian Study (IPASS); a phase III open-label randomised controlled trial conducted in 87 centres in East Asia which compared the use of gefitinib with paclitaxel/carboplatin in 1217 chemotherapy (CTX)-naive patients with stage IIIB/IV pulmonary adenocarcinoma. The manufacturer's submission focused on a subgroup of patients in IPASS who were epidermal growth factor receptor (EGFR) gene mutation-positive (M+) (n = 261; 21% of the total IPASS population). The primary clinical outcome was progression-free survival (PFS). Secondary outcomes included overall survival, clinically relevant improvement in quality of life and adverse events (AEs). Cost-effectiveness was measured in terms of incremental cost per quality-adjusted life-year (QALY). In the overall population, PFS was significantly longer in patients treated with gefitinib than in those treated with paclitaxel/carboplatin (hazard ratio 0.74, 95% confidence interval 0.65 to 0.85; p0.0001). The manufacturer reported an incremental cost-effectiveness ratio (ICER) of 20,744 pounds per QALY gained for the target population. The probabilistic sensitivity analysis illustrated that for patients who are EGFR M+, gefitinib compared with doublet CTX was not likely to be cost-effective at what would usually be considered standard levels of willingness to pay for an additional QALY; the mean ICER for gefitinib EGFR M+ versus doublet CTX EGFR M+ was reported as 35,700 pounds per QALY. Additional analysis by the ERG included amendments to the base-case analysis, including an alternative approach to projecting survival, inclusion of two important additional comparators, sensitivity to EGFR M+ prevalence, and AE costs and disutilities. The manufacturer's submission provides clinical evidence to support the use of gefitinib in EGFR M+ patients with adenocarcinoma histology only. Before patients can be offered first-line treatment with gefitinib they must undergo EGFR mutation status testing which is currently not routinely available in the NHS. At the time of writing, the guidance document issued by NICE on 28 July 2010 states that 'Gefitinib is recommended as an option for the first-line treatment of people with locally advanced or metastatic non-small-cell lung cancer (NSCLC) if they test positive for the epidermal growth factor receptor tyrosine kinase (EGFR-TK) mutation and the manufacturer provides gefitinib at the fixed price agreed under the patient access scheme'.

Capecitabine provides an attractive alternative to intravenous (IV) 5-flourouracil (5-FU) in chemoradiation regimes for rectal cancer by avoiding the need for intravenous access and inpatient stay. We aimed to compare retrospectively the efficacy of concurrent capecitabine with IV 5-FU in preoperative pelvic chemoradiation schedules for rectal cancer in our centre.Patients treated from January 2005 to June 2007 were included. Information was collected on patient characteristics; treatment details; pathological response to treatment; recurrence and survival. All statistical analyses were performed using SPSS V17.All patients had pelvic radiation. Ninety-nine patients were treated with capecitabine and 97 with 5-FU. The two groups were well matched for age, sex and TNM stage. There were significantly more PS (performance status) 0 patients in the capecitabine group (51%vs 30%) (P = 0.001). Of the 99 patients in the capecitabine group, 91 (92%) were able to undergo surgery with 84 (93%) achieving R0 resection. In the 5-FU group, these proportions were 87 (90%) and 70 (80%). The difference in the rate of R0 resection was statistically significant (P = 0.024). The APR rate was 35% in the capecitabine group compared with 47% in the 5-FU group (P = 0.06). There was no significant difference in pathological complete response (pCR) rates between capecitabine (14%) and 5-FU(12%). A higher pCR rate (30%) was observed in patients who underwent a brachytherapy boost (P = 0.051). There were three local recurrences in the whole patient group, (capecitabine 1; 5-FU 2). Thirty-five patients had distant metastases, 14 in the capecitabine and 21 in the 5-FU group. There was no significant difference in the risk of recurrence between the two groups. Six patients in each group had grade 3 toxicity with diarrhoea being more common with capecitabine.Preoperative chemoradiotherapy with capecitabine for rectal cancer is efficacious and comparable to 5-FU (IV). It is more convenient, is well tolerated and avoids the need for inpatient admission.

Preoperative radiotherapy has been shown to improve local control in advanced rectal carcinoma compared with surgery alone. Several large randomized trials have confirmed that chemoradiotherapy (CRT) is better than radiotherapy alone. This pilot study was designed to increase the radiation dose using high-dose rate (HDR) brachytherapy boost following preoperative CRT to evaluate whether this strategy improves the outcome of surgery without increase in toxicity.Since October 2004, we have used the new rectal HDR applicator for brachytherapy boost in 68 patients following CRT. The patients had CT and MRI Scans as part of staging. All had locally advanced disease either bulky low T2 or T3 with threatened circumferential resection margin and multiple suspicious lymph nodes. They were offered preoperative CRT either by 5-FU infusion 1 g/m(2) day 1-4 (week 1 + 5) or by oral capecitabine 825 mg/m(2) Monday-Friday for 5 weeks together with CT planned external beam RT 45Gy in 25 fractions over 5 weeks (CRT). Those downstage on repeat MRI scan were offered additional HDR Boost 10Gy directly to the tumour followed by surgery 6-8 weeks later [group A]. Four patients proceeded directly to surgery but because of involved resection margin had a HDR brachytherapy boost as postoperative treatment [group B]. Thirty patients were not planned for immediate surgery after CRT and brachytherapy boost, as they were either elderly or considered high risk for anaesthesia [group C].There were 34 patients (median age 67 (range 39-81) years in group A, including 24 men). The PS was 0-1. The clinical stage at presentation was cT2 in five, cT3 in 23 and T4 in six patients and cN0 in 2, cN1 in 21 and N2 in 11. Thirty-three patients had CRT, and one had radiotherapy alone. All patients completed treatment without interruption. Twenty-nine patients had surgery following CRT and brachytherapy boost including anterior resection in 10 patients, Abdominoperineal excision (APR) in 18 and Hartmann's resection in one. Five patients did not have the intended surgery. Twenty-four (83%) patients had an RO resection compared with 63% having conventional preoperative CRT using bolus 5FU regimes. Pathological complete remission (pCR) was achieved in 9 (31%) compared with 12% patients having conventional CRT. There was no increase in G 3-4 toxicity from RT and no delay in wound healing or increase in anastomotic leakage. One of the four patients in group B developed local recurrence. The thirty patients in group C who had modified radical CRT followed by brachytherapy boost as a definitive treatment will be reported in a further communication.Increasing the dose of radiation by HDR brachytherapy boost appears to improve the RO resection and pCR rates compared with conventional CRT. The follow up is too short to judge its effect on disease-free survival. This study will be extended to compare this strategy in a randomized phase III trial with conventional CRT in patients who are not fit for more intensive CRT (HERCULES).