A random linear functional approach to efficiency bounds

This paper suggests a method for obtaining efficiency bounds in models containing either only infinite-dimensional parameters or both finite- and infinite-dimensional parameters (semiparametric models). The method is based on a theory of random linear functionals applied to the gradient of the log-likelihood functional and is illustrated by computing the lower bound for Cox's regression model

High capacity robust audio watermarking scheme based on FFT and linear regression

Peer-reviewed

Environmental data mining and modeling based on machine learning algorithms and geostatistics

The paper presents some contemporary approaches to spatial environmental data analysis. The main topics are concentrated on the decision-oriented problems of environmental spatial data mining and modeling: valorization and representativity of data with the help of exploratory data analysis, spatial predictions, probabilistic and risk mapping, development and application of conditional stochastic simulation models. The innovative part of the paper presents integrated/hybrid model-machine learning (ML) residuals sequential simulations-MLRSS. The models are based on multilayer perceptron and support vector regression ML algorithms used for modeling long-range spatial trends and sequential simulations of the residuals. NIL algorithms deliver non-linear solution for the spatial non-stationary problems, which are difficult for geostatistical approach. Geostatistical tools (variography) are used to characterize performance of ML algorithms, by analyzing quality and quantity of the spatially structured information extracted from data with ML algorithms. Sequential simulations provide efficient assessment of uncertainty and spatial variability. Case study from the Chernobyl fallouts illustrates the performance of the proposed model. It is shown that probability mapping, provided by the combination of ML data driven and geostatistical model based approaches, can be efficiently used in decision-making process. (C) 2003 Elsevier Ltd. All rights reserved.

Linear prediction application for modelling the relationships between a large number of stand characteristics of Norway spruce stands

Abstract

The need for combination antihypertensive therapy to reach target blood pressures: what has been learned from clinical practice and morbidity-mortality trials?

Pharmacological treatment of hypertension represents a cost-effective way for preventing cardiovascular and renal complications. To benefit maximally from antihypertensive treatment blood pressure (BP) should be brought to below 140/90 mmHg in every hypertensive patient, and even lower (< 130/80 mmHg) if diabetes or renal disease co-exists. Most of the time such targets cannot be reached using monotherapies. This is especially true in patients who exhibit a high cardiovascular risk. The co-administration of two agents acting by different mechanisms considerably increases BP control. Such preparations are not only efficacious, but also well tolerated, and some fixed low-dose combinations have a tolerability profile similar to placebo. This is for instance the case for the preparation containing the angiotensin-converting enzyme inhibitor perindopril (2 mg) and the diuretic indapamide (0.625 mg), a fixed low-dose combination that has recently been shown in controlled interventional trials to be more effective than monotherapies in reducing albuminuria, regressing cardiac hypertrophy and improving macrovascular stiffness. Fixed-dose combinations are becoming more and more popular and are even proposed by current hypertension guidelines as a first-line option to treat hypertensive patients.

Treatment of brain metastases from non-small cell lung cancer with whole-brain radiotherapy (wbrt) in combination with gefitinib (gft) or temozolomide (tmz): a randomized multicenter phase ii trial of the swiss group of clinical cancer research (sakk #70/03)

BACKGROUND: Patients with BM rarely survive .6 months and are commonly excluded from clinical trials. We aimed at improving outcome by exploring 2 combined modality regimens with at the time novel agents for which single-agent activity had been shown. METHODS: NSCLC patients with multiple BM were randomized to WBRT (10 × 3 Gy) and either GFT 250 mg p.o. daily or TMZ 75 mg/m2 p.o. daily ×21/28 days, starting on Day 1 of RT and to be continued until PD. Primary endpoint was overall survival, a Simon's optimal 2-stage design was based on assumptions for the 3-month survival rate. Cognitive functioning and quality of life were also evaluated. RESULTS: Fifty-nine patients (36 M, 23 F; 9 after prior chemo) were included. Median age was 61 years (range 46-82), WHO PS was 0 in 18 patients, 1 in 31 patients, and 2 in 10 patients. All but 1 patients had extracranial disease; 33 of 43 (TMZ) and 15 of 16 (GFT) had adenocarcinoma histology. GFT arm was closed early after stage 1 analysis when the prespecified 3-mo survival rate threshold (66%) was not reached, causes of death were not GFT related. Main causes of death were PD in the CNS 24%, systemic 41%, both 8%, and toxicity 10% [intestinal perforation (2 patients), pneumonia (2), pulmonary emboli (1), pneumonitis NOS (1), seizure (1)]. We summarize here other patients' characteristics for the 2 trial arms: TMZ (n ¼ 43)/GFT (n ¼ 16); median treatment duration: 1.6 /1.8 mo; Grade 3-4 toxicity: lymphopenia 5 patients (12%)/0; fatigue 8 patients (19%)/2 patients (13%). Survival data for TMZ/GFT arms: 3-month survival rate: 58.1% (95% CI 42.1-73)/62.5% (95% CI 35- 85); median OS: 4.9 months (95% CI 2.5-5.6)/6.3 months (95% CI 2.2- 14.6); median PFS: 1.8 months (95% CI 1.5-1.8)/1.8 (95% CI 1.1-3.9); median time to neurol. progr.: 8.0 months (95% CI 2.2-X)/4.8 (95% CI 3.9-10.5). In a model to predict survival time including the variables' age, PS, number of BM, global QL, total MMSE score, and subjective cognitive function, none of the variables accounted for a significant improvement in survival time. CONCLUSIONS: The combinations of WBRT with GFT or TMZ were feasible. However, in this unselected patient population, survival remains poor and a high rate of complication was observed. Four patients died as a result of high-dose corticosteroids. Preliminary evaluation of cognitive function andQL failed to show significant improvement. Indications and patient selection for palliative treatment should be revisited and careful monitoring and supportive care is required. Research and progress for this frequent clinical situation is urgently needed. Trial partly supported by AstraZeneca (Switzerland), Essex Chemie (Switzerland) and Swiss Federal Government.

Comments on "On resistor-induced thermal noise in linear circuits"

Correspondència referida a l'article de R. Giannetti, publicat ibid. vol.49 p.87-88

Linear and nonlinear terrain deformation maps from a reduced set of interferometric SAR images

In this paper, an advanced technique for the generation of deformation maps using synthetic aperture radar (SAR) data is presented. The algorithm estimates the linear and nonlinear components of the displacement, the error of the digital elevation model (DEM) used to cancel the topographic terms, and the atmospheric artifacts from a reduced set of low spatial resolution interferograms. The pixel candidates are selected from those presenting a good coherence level in the whole set of interferograms and the resulting nonuniform mesh tessellated with the Delauney triangulation to establish connections among them. The linear component of movement and DEM error are estimated adjusting a linear model to the data only on the connections. Later on, this information, once unwrapped to retrieve the absolute values, is used to calculate the nonlinear component of movement and atmospheric artifacts with alternate filtering techniques in both the temporal and spatial domains. The method presents high flexibility with respect to the required number of images and the baselines length. However, better results are obtained with large datasets of short baseline interferograms. The technique has been tested with European Remote Sensing SAR data from an area of Catalonia (Spain) and validated with on-field precise leveling measurements.

Impulse response recovery of linear systems through weighted cumulant slice

Identifiability of the so-called ω-slice algorithm is proven for ARMA linear systems. Although proofs were developed in the past for the simpler cases of MA and AR models, they were not extendible to general exponential linear systems. The results presented in this paper demonstrate a unique feature of the ω-slice method, which is unbiasedness and consistency when order is overdetermined, regardless of the IIR or FIR nature of the underlying system, and numerical robustness.

Linear transceiver design in nonregenerative relays with channel state information

This paper deals with the design of nonregenerativerelaying transceivers in cooperative systems where channel stateinformation (CSI) is available at the relay station. The conventionalnonregenerative approach is the amplify and forward(A&F) approach, where the signal received at the relay is simplyamplified and retransmitted. In this paper, we propose an alternativelinear transceiver design for nonregenerative relaying(including pure relaying and the cooperative transmission cases),making proper use of CSI at the relay station. Specifically, wedesign the optimum linear filtering performed on the data to beforwarded at the relay. As optimization criteria, we have consideredthe maximization of mutual information (that provides aninformation rate for which reliable communication is possible) fora given available transmission power at the relay station. Threedifferent levels of CSI can be considered at the relay station: onlyfirst hop channel information (between the source and relay);first hop channel and second hop channel (between relay anddestination) information, or a third situation where the relaymay have complete cooperative channel information includingall the links: first and second hop channels and also the directchannel between source and destination. Despite the latter beinga more unrealistic situation, since it requires the destination toinform the relay station about the direct channel, it is useful as anupper benchmark. In this paper, we consider the last two casesrelating to CSI.We compare the performance so obtained with theperformance for the conventional A&F approach, and also withthe performance of regenerative relays and direct noncooperativetransmission for two particular cases: narrowband multiple-inputmultiple-output transceivers and wideband single input singleoutput orthogonal frequency division multiplex transmissions.

Hybrid turbo FEC/ARQ systems and distributed space-time coding for cooperative transmission

Cooperative transmission can be seen as a "virtual" MIMO system, where themultiple transmit antennas are in fact implemented distributed by the antennas both at the source and the relay terminal. Depending on the system design, diversity/multiplexing gainsare achievable. This design involves the definition of the type of retransmission (incrementalredundancy, repetition coding), the design of the distributed space-time codes, the errorcorrecting scheme, the operation of the relay (decode&forward or amplify&forward) and thenumber of antennas at each terminal. Proposed schemes are evaluated in different conditionsin combination with forward error correcting codes (FEC), both for linear and near-optimum(sphere decoder) receivers, for its possible implementation in downlink high speed packetservices of cellular networks. Results show the benefits of coded cooperation over directtransmission in terms of increased throughput. It is shown that multiplexing gains areobserved even if the mobile station features a single antenna, provided that cell wide reuse of the relay radio resource is possible.

Can resistance to trastuzumab be reversed by endocrine therapy? Combination of trastuzumab and letrozole after resistance to sequential trastuzumab and aromatase inhibitor monotherapies in patients with ER-positive, HER-2 positive, advanced breast cancer: a proof-of-concept trial (SAKK 23/03)

Introduction: Trastuzumab (T) is a cornerstone in the treatment of patients with HER2-overexpressing advanced breast cancer and development of resistance to T is a major therapeutic problem. HER-2 is part of a highly interactive signaling network that may impair efficacy of endocrine therapy. A sequential treatment design was chosen in this trial to ensure complete resistance to single agent therapy before receiving both a non-steroidal aromatase inhibitor (AI) and T. Any kind of clinical activity with combined treatment of AI and T after progression of single agent treatments could indicate restoration of sensitivity as a consequence of cross-talking and networking between both pathways. Methods: Key eligibility criteria included postmenopausal patients (pts.) with advanced, measurable, HER-2 positive (assessed by FISH, ratio (≥2)), HR positive disease and progression on prior treatment with a non-steroidal AI, e.g. letrozole or anastrozole, either in an adjuvant or advanced setting. Pts. received standard dose T monotherapy either weekly or three-weekly in step 1 and upon disease progression, continued T in combination with letrozole in step 2. The primary endpoint was clinical benefit response (CBR: CR, PR or SD for at least 24 weeks (+/- 1 week) according to RECIST) in step 2. Results: Thirteen pts. were enrolled in five centers in Switzerland. In step 1, six pts. (46%) achieved CBR. Median time to progression (TTP) was 161 days (Range: 50 - 627). Based on data collected until the end of May 2010, CBR was observed in seven out of the eleven evaluable pts. (64%) in step 2, including one pt. with partial response. Four of the seven pts. within step 2 that achieved CBR also had CBR in step 1. Seven out of eleven pts. have documented tumor progression during step 2 treatment. Median TTP for all eleven pts. was 184 days (range 61 - 471). Mean time on study treatment (TTP in step 1 plus TTP in step 2) for pts. reaching step 2 was 380 days (range 174 - 864). Adverse events were generally mild. Conclusion: Results of this proof-of-principle trial suggest that complete resistance to both AI and T can be overcome in a proportion of pts. by combined treatment of AI and T, as all pts. served as their own control. Our results appear promising for a new treatment strategy which offers a chemotherapy-free and well-tolerated option for at least a subset of the pts. with HR positive, HER-2 positive breast cancer. Further trials will need to corroborate this finding.

Activity of dalbavancin, alone and in combination with rifampicin, against meticillin-resistant Staphylococcus aureus in a foreign-body infection model.

The activity of dalbavancin, a representative of the lipoglycopeptide antibiotics, alone and in combination with rifampicin, was investigated against meticillin-resistant Staphylococcus aureus (MRSA) in a foreign-body infection model in guinea pigs. The MIC, MBC and time-kill profile of dalbavancin were determined for MRSA ATCC 43300 in the logarithmic (MBClog) and stationary (MBCstat) growth phases. The pharmacokinetic profile of dalbavancin was determined in sterile cage fluid in guinea pigs. The activity of intraperitoneal dalbavancin (40, 60 or 80mg/kg as a single dose), rifampicin (12.5mg/kg/12h for 4 days) and their combination was assessed against planktonic and biofilm MRSA. The MIC of dalbavancin was 0.078mg/L; MBClog and MBCstat were both >128Ã- MIC. In time-kill studies, bacterial reduction of 3log10CFU/mL was achieved after 48h at â0/00¥32Ã- MIC (logarithmic growth) and at â0/00¥1Ã- MIC (stationary growth). Dalbavancin was neither synergistic nor antagonistic with rifampicin, and prevented the emergence of rifampicin resistance in vitro. The half-life of dalbavancin in cage fluid was 35.8-45.4h and the concentration remained above the MIC of MRSA during 7 days after a single dose. Dalbavancin reduced planktonic MRSA in cage fluid at high dose (60mg/kg and 80mg/kg) but failed to eradicate biofilm MRSA from cages. In combination with rifampicin, dalbavancin at 80mg/kg cured 36% of infected cages, and emergence of rifampicin resistance was completely prevented. Dalbavancin at 80mg/kg and in combination with rifampicin eradicated approximately one-third of cage-associated MRSA infections and prevented emergence of rifampicin resistance.