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The user's gaze can provide important information for human–machine interaction, but the analysis of manual gaze data is extremely time-consuming, inhibiting wide adoption in usability studies. Existing methods for automated areas of interest (AOI) analysis cannot be applied to tangible products with a screen-based user interface (UI), which have become ubiquitous in everyday life. The objective of this paper is to present and evaluate a method to automatically map the user's gaze to dynamic AOIs on tangible screen-based UIs based on computer vision and deep learning. This paper presents an algorithm forautomated Dynamic AOI Mapping(aDAM), which allows the automated mapping of gaze data recorded with mobile eye tracking to the predefined AOIs on tangible screen-based UIs. The evaluation of the algorithm is performed using two medical devices, which represent two extreme examples of tangible screen-based UIs. The different elements of aDAM are examined for accuracy and robustness, as well as the time saved compared to manual mapping. The break-even point for an analyst's effort for aDAM compared to manual analysis is found to be 8.9 min gaze data time. The accuracy and robustness of both the automated gaze mapping and the screen matching indicate that aDAM can be applied to a wide range of products. aDAM allows, for the first time, automated AOI analysis of tangible screen-based UIs with AOIs that dynamically change over time. The algorithm requires some additional initial input for the setup and training, but analyzed gaze data duration and effort is only determined by computation time and does not require any additional manual work thereafter. The efficiency of the approach has the potential for a broader adoption of mobile eye tracking in usability testing for the development of new products and may contribute to a more data-driven usability engineering process in the future.

Introduction It is estimated that there are currently over 3 million patients receiving dialysis treatment worldwide. With effective pre-dialysis counselling, a majority of patients choose the home-based therapy peritoneal dialysis (PD) but only approximately 11% of prevalent dialysis patients use this modality. Connection-assist devices can overcome the challenges posed by decreased manual dexterity and/or visual acuity, and can allow more patients to be treated with home-based therapies. As part of the CE marking authorization, a connection device has been evaluated for safety and ease of use in a usability study. Methods Fifteen patients and nine carers volunteered in this study, ranging from 23 to 86 years in age and from 0.3 to 24 years in experience in the PD therapy. The operating cycle consisted of eight tasks, each having several handling steps. The data analysis focused on the task effectiveness and the subjects' subjective feedback from the NASA task load index (N-TLX) questionnaire and semi-structured interviews. Results Of 1248 handling steps performed in total, 38 use errors were observed and discussed with the subjects. This equates to 97% of all handling steps being performed safely and easily. In all six dimensions of the N-TLX, more than 50 percent of subjects rated the task load 50 points or less on the scale. Regarding the handling of the device, 13 of 15 of the patients and 8 of 9 of the carers gave positive feedback. Discussion Safety and ease of use was demonstrated by evaluating task effectiveness (97% SU), interviews and N-TLX. Additionally the study provided valuable individual user feedback, which will inform the final design of the system for PD. The majority of patients and carers gave positive feedback regarding use and handling of this connection device. Innovative connection devices in general promise to reduce the barriers to using this home-based dialysis treatment.

Background Patient safety is a top priority in healthcare. Little is known about the visual behaviour of professionals during high-risk procedures. The aim of this study was to assess feasibility, usability and safety of eye-tracking to analyse gaze patterns during the extubation-process in the intensive care unit. Methods Eye-tracking was used in this observational study to analyse the extubationprocess in 22 participants. Independent variables were average fixation time, dwell time, fixation count, hit ratio and revisit count for eighteen areas of interest. Primary outcome was dwell time for all areas of interest. Secondary outcomes were average fixation time, fixation count and revisits. In subgroup analyses, experienced and non-experienced physicians were compared. Results The most important area of interest was the patient, as analyzed by dwell time. Fixation of other areas of interest varied significantly among participants. Only 54% checked ventilator respiratory rate, despite declaring it as important in questionnaires. Other neglected areas of interest included tidal volume (59%), peak pressure (63.6%), CO2 (63.6%), temperature (18.2%), blood pressure (59%) and heart rate (68%). Experienced physicians gazed more frequently and longer at the patient while spending less time on monitor and ventilator parameters. Conclusions Eye-tracking can demonstrate that there is a mismatch between physicians' subjective evaluations and corresponding objective real-life measurements. Structured and standardized extubation-processes should be performed to improve patient safety. In the immediate post-extubation phase, long dwell time on the patient shows that clinical observation remains the most important cornerstone beyond monitoring devices.

Introduction It is estimated that there are currently over 3 million patients receiving dialysis treatment worldwide. With effective pre-dialysis counselling, a majority of patients choose the home-based therapy peritoneal dialysis (PD) but only approximately 11% of prevalent dialysis patients use this modality. Connection-assist devices can overcome the challenges posed by decreased manual dexterity and/or visual acuity, and can allow more patients to be treated with home-based therapies. As part of the CE marking authorization, a connection device has been evaluated for safety and ease of use in a usability study. Methods Fifteen patients and nine carers volunteered in this study, ranging from 23 to 86 years in age and from 0.3 to 24 years in experience in the PD therapy. The operating cycle consisted of eight tasks, each having several handling steps. The data analysis focused on the task effectiveness and the subjects’ subjective feedback from the NASA task load index (N-TLX) questionnaire and semi-structured interviews. Results Of 1248 handling steps performed in total, 38 use errors were observed and discussed with the subjects. This equates to 97% of all handling steps being performed safely and easily. In all six dimensions of the N-TLX, more than 50 percent of subjects rated the task load 50 points or less on the scale. Regarding the handling of the device, 13 of 15 of the patients and 8 of 9 of the carers gave positive feedback. Discussion Safety and ease of use was demonstrated by evaluating task effectiveness (97% SU), interviews and N-TLX. Additionally the study provided valuable individual user feedback, which will inform the final design of the system for PD. The majority of patients and carers gave positive feedback regarding use and handling of this connection device. Innovative connection devices in general promise to reduce the barriers to using this home-based dialysis treatment.

For an in-depth, AOI-based analysis of mobile eye tracking data, a preceding gaze assignment step is inevitable. Current solutions such as manual gaze mapping or marker-based approaches are tedious and not suitable for applications manipulating tangible objects. This makes mobile eye tracking studies with several hours of recording difficult to analyse quantitatively. We introduce a new machine learning-based algorithm, the computational Gaze-Object Mapping (cGOM), that automatically maps gaze data onto respective AOIs. cGOM extends state-of-the-art object detection and segmentation by mask R-CNN with a gaze mapping feature. The new algorithm’s performance is validated against a manual fixation-by-fixation mapping, which is considered as ground truth, in terms of true positive rate (TPR), true negative rate (TNR) and efficiency. Using only 72 training images with 264 labelled object representations, cGOM is able to reach a TPR of approx. 80% and a TNR of 85% compared to the manual mapping. The break-even point is reached at 2 hours of eye tracking recording for the total procedure, respectively 1 hour considering human working time only. Together with a real-time capability of the mapping process after completed training, even hours of eye tracking recording can be evaluated efficiently., Journal of Eye Movement Research, 11 (6)

At times when the market demands strong active innovation, large industrial corporations with established R&D organizations benefit from screening and developing breakthrough innovation. The ability of established organizations to absorb for future technologies is a key to successfully recognize, explore and capture breakthrough innovations. R&D Venturing is a practical way of bringing about technology transfer and exploration of future technologies through R&D cooperation, which is described in this paper by a multiple case study in the energy sector. Existing literature has been reviewed and an R&D Venturing concept will be suggested with a number of propositions for implementation. The results of the case study strongly support that different perspectives of the concept from industry, academia and the ventures themselves have to be carefully understood. Based on the results of the case study, a conceptual framework and propositions for a successful implementation have been derived. A critical discussion of the R&D Venturing concept shows the need for further empirical investigation.

Carbonic anhydrase IX (CAIX) is a strictly membranous expressed metalloenzyme involved in cell adhesion, pH homeostasis, and cancer progression. The protein is specifically overexpressed in a wide variety of malignant tumors. This study was designed to assess the role of CAIX in primary vulvar cancer. One hundred forty-two well-characterized primary vulvar carcinomas were analyzed on a tissue microarray (TMA). Three tissue cores were sampled from each tumor. CAIX expression was determined by immunohistochemistry, using a four-step scoring system. To determine CAIX expression in benign vulvar tissue, we constructed a TMA with 120 samples of normal mucosa and non-neoplastic diseases. CAIX expression was found in 77/135 (57%) of all assessable vulvar cancer specimens and 48 (35.5%) exhibited a moderate or strong expression. CAIX expression in vulvar carcinomas was significantly stronger compared to non-neoplastic vulvar tissue (p < 0.001). High levels of CAIX expression were related to pT stage (p < 0.01), tumor size (p < 0.01), depth of invasion (p < 0.05), as well as inguinal lymph node metastases (p < 0.05). There was also a trend towards shorter recurrence-free patient survival in CAIX-positive compared to CAIX-negative vulvar cancers. CAIX staining results in different tissue cores from the same tumor were homogeneous, raising the possibility of a hypoxia-independent expression. In conclusion, CAIX is overexpressed in the majority of vulvar carcinomas with relationships to advanced tumor stages and development of lymph node metastases. Our data support the potential therapeutic benefit of newly developed targeting antibodies in advanced vulvar cancer.

ALSTOM Power Service delivers solutions not only to recover degradation, but also to increase the performance and efficiency of the installed global power generation fleet. Such performance improvements also reduce greenhouse gases, particularly CO2 emissions. The mechanisms of the Kyoto Protocol promote the implementation of CO2-reducing state-of-the-art technologies to developing and emerging economies. Having installed the world's largest power generation fleet, ALSTOM wants to make use of the Clean Development Mechanism (CDM) to make technology implementation economically attractive for non-Annex I countries. This paper gives an overview and outlook for environmental mechanisms and technologies, the value proposition and some experience in pioneering a CDM project with a gas turbine upgrade in a non-Annex I country. It is shown that in a crediting period of 10 years 3 million tons of CO2eq can be saved on a mid-sized power plant. Assuming a price of € 8 per ton of CO2eq for Certified Emission Reductions this would lead to an annual revenue of 20 % of the initial implementation cost, representing a very attractive business case for the plant operator. The described CDM application can be a decisive factor for proceeding with a fuel switch or an upgrade. The revenues earned from emission trading enables the plant operator to make the investment to reduce Kyoto-relevant emissions.

In patients on oral anticoagulation with warfarin, genetic variations of the cytochrome P 450–CYP2C9 have recently been associated with very low warfarin requirements. Patients needing low doses had an increased risk for bleeding complications. In Germany, phenprocoumon (having a similar metabolic pathway) is the most commonly employed vitamin K antagonist. Treatment is usually monitored by general practitioners (GPs). To determine whether CYP2C9 variant alleles can serve as risk markers in general-practice patients anticoagulated with phenprocoumon. All adult anticoagulated patients in 12 teaching general practices and one university outpatient clinic were to be recruited. Blood samples were taken from 185 patients during routine anticoagulation controls and tested for CYP2C9 mutations. Subjects answered a questionnaire concerning bleeding complications, drug intolerance, and personal and family medical history. Phenprocoumon dosages required for stable anticoagulation were recorded. Odds ratios (OR) with 95% confidence intervals (CI) were calculated based on 2-way cross-tabulations and multivariate logistic regression models, t-tests used where appropriate. Bleeding was reported by 19% of the patients, 2.2% of whom had suffered life-threatening bleeding. CYP2C9 variants were carried by 26.3% of 179 patients tested (17.9% *1/*2, 7.8% *1/*3, 0.6% *2/*3). While presence of a *2 allele was not associated with an increased risk (OR 0.35, CI 0.10–1.24), carriers of the rare *3 alleles had a higher risk of bleeding (OR 3.10, CI 1.02–9.40). With regard to bleeding, carrying CYP2C9*3 was highly specific (94%), though sensitivity was low at 17%; post-test probability of bleeding was 40%. CYP2C9*3 variants are associated with an increased bleeding risk in patients anticoagulated with phenprocoumon. Screening can identify patients with a high risk of bleeding. Appropriate clinical consequences (restricted indication for anticoagulation, careful induction, adjustment of target INR, closer monitoring or self-testing of INR) as well as the cost-effectiveness of screening for variant CYP2C9 with regard to patient outcomes should be subject of further research.

In the energy industry, a time of dynamic innovation and uncertainties drives R&D incumbents to extend their technology screening process to the early technology lifecycle. Many early breakthrough technology innovations stem from academia and are developed by academic spin-offs. In these situations an incumbent’s future technology organization (FTO), focused on open innovation, needs to expand its evaluation and development capabilities towards R&D alliances with academic technology spin-offs. In the light of the open innovation and real option frameworks this study analyzes R&D projects using the real options analysis (ROA) and discusses the critical decision of whether to develop technology internally or externally. It explores R&D alliances between academic spin-offs and a large power industry player and investigates the concept and role of a FTO in the open innovation process. A model will be introduced to operationalize the FTO concept and practically evaluate the risk of open innovation with R&D alliances for breakthrough technologies. Contrary to the common view that risks increase when open innovation is applied along with external development of a breakthrough technology in R&D alliances, the present study shows that the risks and uncertainties can be mitigated and controlled when applying ROA and the FTO model.

From previous thermal and photoinduced charge-transfer reactions in duplex DNA there is accumulative evidence for an attenuation parameter beta of the distance dependence in the range 0.6-0.8 A(-1), with the exception of one specific system exhibiting beta = 1.5 A(-1) which is reinvestigated in this paper. Femtosecond to nanosecond time-resolved pump-probe spectroscopy has been used to follow photoinduced charge-shift dynamics in DNA duplexes containing a covalently appended, protonated 9-alkylamino-6-chloro-2-methoxyacridine chromophore. This acridine derivative (X+) resides in the DNA duplex at a specific abasic site, which is highly defined as reflected in the monoexponentiality of the kinetics. In the presence of only neighboring A:T base pairs, no charge transfer occurs within the excited-state lifetime (18 ns) of the chromophore. However, the presence of a guanine nucleobase as either a nearest neighbor or with one interspersed A:T base pair does result in fluorescence quenching. In the case of nearest neighbors, the intermediate radical state X* is formed within 4 ps and decays on the 30 ps time scale. Placing one A:T base pair between the X+ and guanine slows down the forward transfer rate by 3 orders of magnitude, corresponding to an apparent beta value of2.0 A(-1). This dramatic decrease in the rate is due to a change in charge-transfer mechanism from a (nearly) activationless to a thermally activated regime in which the forward transfer is slower than the back transfer and the X* state is no longer observed. These observations indicate that the distance dependence of charge injection in the X+-labeled DNA duplex is not solely caused by a decrease in electronic couplings but also by a concomitant increase of the activation energy with increasing distance. This increase in activation energy may result from the loss of driving force due to excited-state relaxation competing with charge transfer, or reflect distance-dependent changes in the energetics, predominantly of the low-frequency reorganization energy in this charge-shift reaction, on purely electrostatic grounds. To test the hypothesis of distance-dependent activation energy, guanine has been replaced by 7-deazaguanine, its easier-to-oxidize purine analogue. In these duplexes, a similar change of charge-transfer mechanism is found. However, consistent with an a priori larger driving force this change occurs at a larger donor-acceptor separation than in the X+-guanine systems. Independent of the detailed contributions to the distance-dependent activation energy, this phenomenon illustrates the complex nature of experimental beta values.

The capabilities of a automated theorem prover's interface are essential for the effective use of (interactive) proof systems. L Ω UI is the multi-modal interface that combines several features: a graphical display of information in a proof graph, a selective term browser with hypertext facilities, proof and proof plan presentation in natural language, and an editor for adding and maintaining the knowledge base. L Ω UI is realized in an agent-based client-server architecture and implemented in the concurrent constraint programming language Oz.

When the market demands strong, active innovation screening, the established industry needs to consider efficient technology transfers and development alliances across industry boundaries. The importance of academic spin-offs as a transfer channel for breakthrough technological innovations between academia and established industries is increasing. Consequently, cooperation between an established industry and academic spin-offs are of potential interest. This investigation at Swiss Federal Institute of Technology Zurich (ETHZ) aims to explore the alliances between academic technology spin-offs and an established industry. More specifically, parameters that can increase the chances of a successful alliance are explored in depth. An alliance model to develop breakthrough technologies will be presented, based on the results of a multiple case study.

Academia has established various technology transfer channels to support the technology transformation process. However, since universities are not expected to directly approach the market, either the established industry partners have to become involved, or new enterprises have to be developed. The established industry should be prepared for an efficient, early-stage technology transfer with development alliances right across boundaries. This paper looks at the preparation and implementation of the UTI at the Swiss Federal Institute of Technology Zurich (ETHZ) and aims to explore the specific strategic positioning and capabilities of a university technology incubator with focus on industry alliances. In a case study, the authors investigate technology screening, spin-off formation, and the alliance development phase as a collaborative innovation approach. The existing literature is reviewed and a university technology incubator method, as a “Broker of Technology”, is presented.

EGFR copy number increases have been frequently reported in cancer including vulvar carcinomas. Co-amplification of cancer genes plays an important role in the development of many tumour types. To better understand the effect of EGFR aberrations on vulvar cancer phenotype and patient prognosis, the authors analysed EGFR copy number changes using fluorescence in situ hybridisation and EGFR expression by immunohistochemistry in a tissue microarray containing 183 squamous cell carcinomas of vulva. Furthermore, the authors analysed the co-amplification frequency of EGFR with HER2, CCND1, MYC and PIK3CA, respectively. EGFR copy number increase was found in 39.3% of the tumours. Seventeen per cent of vulvar carcinomas showed EGFR high polysomy including 9% with amplification of the EGFR gene. Copy number gain of the EGFR locus was associated with non-basaloid phenotype (p=0.03), high-tumour stage (p0.001), human papillomaviruse negativity of tumours (p=0.04) and the number of lymph node metastases (p=0.02). EGFR protein expression was statistically correlated to EGFR copy number increase (p0.05). The observed co-amplification rate of EGFR with all four additionally examined oncogenes was much higher than statistically expected. There was a highly significant association between EGFR copy number increase and CCND1 amplifications (p0.001) as well as the total number of gene amplifications (p=0.04). EGFR copy number gains were significantly related to unfavourable patient outcome in univariate analysis and multivariate Cox regression analysis. In conclusion, EGFR copy number increases are detectable in a substantial proportion of vulvar carcinomas with relationships to advanced tumour stages and the development of lymph node metastases. EGFR copy number aberrations are connected to other gene amplifications and probably define an human papillomaviruses-independent pathway in the development of vulvar carcinomas. These data support the potential utility of EGFR inhibitors as a therapeutic alternative in a subset of vulvar carcinomas.

Cyclin D1 (CCND1) belongs to the family of D-type cyclins involved in cell cycle progression, transcriptional regulation, and cell migration. CCND1 was found to be amplified and overexpressed in a variety of cancers, including some vulvar carcinoma cell lines. To determine the relationship of CCND1 copy number changes and CCND1 protein expression with clinicopathologic features and prognosis, 183 vulvar carcinomas were analyzed on a tissue microarray. Amplification was observed in 32 (22.4%) vulvar cancer specimens and was statistically related to the presence of regional lymph node metastases (P < .001). Detectable CCND1 expression was found in 139 (83.2%) of vulvar carcinomas, and 76 (45.5%) exhibited a moderate or strong expression. Increased levels of CCND1 expression were significantly related to higher patient age (P = .013), positive pN category (P = .004), and negative human papillomavirus status (P < .001). Basaloid as well as verrucous, warty-type, and mixed vulvar carcinomas showed lower CCND1 expression levels than keratinizing or nonkeratinizing tumors (P < .001 and P = .032, respectively). Elevated CCND1 expression levels and amplification of the CCND1 gene were closely connected in the present analysis (P < .001). Patient prognosis was independent from CCND1 amplification status and expression level (P = .57 each). In conclusion, CCND1 is amplified and overexpressed in a substantial proportion of vulvar carcinomas and associated with the occurrence of locoregional lymph node metastases, especially in human papillomavirus-negative tumors.

Many thickening operations continue to be constrained by their ability to process consolidated underflows with high yield stress and associated rheological characteristics. The application of high molecular weight polymers (flocculants) is a prerequisite to maintain the operation integrity and dynamics of most gravity based solids/liquid separation processes. Such treatments are an effective means of consolidating solids and maximising clean water recovery. Unfortunately polymer/solids interaction at, and beyond, the gel point result in a significant increase the yield stress for a given solids content. BASF is developing a novel flocculant treatment (NFT) by which primary solid/liquid separation efficiency is maintained, and the subsequent consolidation process is enhanced, wherein higher underflow solids are associated with reduced yield stress. This paper will present application data to demonstrate the benefits associated with this NFT.

Colloidal suspensions are susceptible to gravitationally induced phase separation. This can be mitigated by the formation of a particle network caused by depletion attraction. The effectiveness of this network in supporting the buoyant weight of the suspension can be characterized by its compressional modulus. We measure the compressional modulus for emulsion networks induced by depletion attraction and present a model that quantitatively predicts their gravitational stability. We also determine the relationship between the strength of the depletion attraction and the magnitude of the compressional modulus.

A new class of fluorophores has been identified that can be imaged at the single-molecule level and offer additional beneficial properties such as a significant ground state dipole moment, moderate hyperpolarizability, and sensitivity to local rigidity. These molecules contain an amine donor and a dicyanodihydrofuran (DCDHF) acceptor linked by a conjugated unit (benzene, thiophene, alkene, styrene, etc.) and were originally designed to deliver both high polarizability anisotropy and dipole moment as nonlinear optical chromophores for photorefractive applications. Surprisingly, we have found that these molecules are also well-suited for single-molecule fluorescence imaging in polymers and other reasonably rigid environments. We report the bulk (ensemble) and single-molecule photophysical properties measured for six dyes in this new class of single-molecule reporters, with absorption maxima ranging from 486 to 614 nm.

The recent investigation of the apparently anomalous attenuation factor (beta1.5 A(-1)) for photoinduced hole injection into DNA duplexes modified by protonated 9-amino-6-chloro-2-methoxyacridine (X+) led to the conclusion that in addition to the electronic couplings, the activation energy must also be distance-dependent. In this communication we report the verification of this postulate by direct measurements of the activation energies for a series of (X+)-modified DNA duplexes which sample an appreciable range of donor-acceptor distances (approximately 4-11 A). The resulting changes in thermal activation energy can be explained within the framework of a distance-dependent reorganization energy.

The photophysics of intercalated chromophores is an important tool in studies of DNA structure and dynamics. detection of DNA hybridization, the fluorescent imaging of DNA in gels, and fluorescent staining of chromosomal DNA.1,2 The transfer of a conjugated chromophore from aqueous solution to an intercalation site in the duplex often significantly affects the photophysics of that species.