Innovation and new business through mutually beneficial collaboration and proactive procurement

ABSTRACT This dissertation focuses on new technology commercialization, innovation and new business development. Industry-based novel technology may achieve commercialization through its transfer to a large research laboratory acting as a lead user and technical partner, and providing the new technology with complementary assets and meaningful initial use in social practice. The research lab benefits from the new technology and innovation through major performance improvements and cost savings. Such mutually beneficial collaboration between the lab and the firm does not require any additional administrative efforts or funds from the lab, yet requires openness to technologies and partner companies that may not be previously known to the lab- Labs achieve the benefits by applying a proactive procurement model that promotes active pre-tender search of new technologies and pre-tender testing and piloting of these technological options. The collaboration works best when based on the development needs of both parties. This means that first of all the lab has significant engineering activity with well-defined technological needs and second, that the firm has advanced prototype technology yet needs further testing, piloting and the initial market and references to achieve the market breakthrough. The empirical evidence of the dissertation is based on a longitudinal multiple-case study with the European Laboratory for Particle Physics. The key theoretical contribution of this study is that large research labs, including basic research, play an important role in product and business development toward the end, rather than front-end, of the innovation process. This also implies that product-orientation and business-orientation can contribute to basic re-search. The study provides practical managerial and policy guidelines on how to initiate and manage mutually beneficial lab-industry collaboration and proactive procurement.

Animal model to compare the effects of suture technique on cross-sectional compliance on end-to-side anastomoses.

OBJECTIVE: An animal model has been developed to compare the effects of suture technique on the luminal dimensions and compliance of end-to-side vascular anastomoses. METHODS: Carotid and internal mammalian arteries (IMAs) were exposed in three pigs (90 kg). IMAs were sectioned distally to perform end-to-side anastomoses on carotid arteries. One anastomosis was performed with 7/0 polypropylene running suture. The other was performed with the automated suture delivery device (Perclose/Abbott Labs Inc.) that makes a 7/0 polypropylene interrupted suture. Four piezoelectric crystals were sutured on toe, heel and both lateral sides of each anastomosis to measure anastomotic axes. Anastomotic cross-sectional area (CSAA) was calculated with: CSAA = pi x mM/4 where m and M are the minor and major axes of the elliptical anastomosis. Cross-sectional anastomotic compliance (CSAC) was calculated as CSAC=Delta CSAA/Delta P where Delta P is the mean pulse pressure and Delta CSAA is the mean CSAA during cardiac cycle. RESULTS: We collected a total of 1200000 pressure-length data per animal. For running suture we had a mean systolic CSAA of 26.94+/-0.4 mm(2) and a mean CSAA in diastole of 26.30+/-0.5 mm(2) (mean Delta CSAA was 0.64 mm(2)). CSAC for running suture was 4.5 x 10(-6)m(2)/kPa. For interrupted suture we had a mean CSAA in systole of 21.98+/-0.2 mm(2) and a mean CSAA in diastole of 17.38+/-0.3 mm(2) (mean Delta CSAA was 4.6+/-0.1 mm(2)). CSAC for interrupted suture was 11 x 10(-6) m(2)/kPa. CONCLUSIONS: This model, even with some limitations, can be a reliable source of information improving the outcome of vascular anastomoses. The study demonstrates that suture technique has a substantial effect on cross-sectional anastomotic compliance of end-to-side anastomoses. Interrupted suture may maximise the anastomotic lumen and provides a considerably higher CSAC than continuous suture, that reduces flow turbulence, shear stress and intimal hyperplasia. The Heartflo anastomosis device is a reliable instrument that facilitates performance of interrupted suture anastomoses.

Event-free survival at 24 months is a robust end point for disease-related outcome in diffuse large B-cell lymphoma treated with immunochemotherapy.

PURPOSE: Studies of diffuse large B-cell lymphoma (DLBCL) are typically evaluated by using a time-to-event approach with relapse, re-treatment, and death commonly used as the events. We evaluated the timing and type of events in newly diagnosed DLBCL and compared patient outcome with reference population data. PATIENTS AND METHODS: Patients with newly diagnosed DLBCL treated with immunochemotherapy were prospectively enrolled onto the University of Iowa/Mayo Clinic Specialized Program of Research Excellence Molecular Epidemiology Resource (MER) and the North Central Cancer Treatment Group NCCTG-N0489 clinical trial from 2002 to 2009. Patient outcomes were evaluated at diagnosis and in the subsets of patients achieving event-free status at 12 months (EFS12) and 24 months (EFS24) from diagnosis. Overall survival was compared with age- and sex-matched population data. Results were replicated in an external validation cohort from the Groupe d'Etude des Lymphomes de l'Adulte (GELA) Lymphome Non Hodgkinien 2003 (LNH2003) program and a registry based in Lyon, France. RESULTS: In all, 767 patients with newly diagnosed DLBCL who had a median age of 63 years were enrolled onto the MER and NCCTG studies. At a median follow-up of 60 months (range, 8 to 116 months), 299 patients had an event and 210 patients had died. Patients achieving EFS24 had an overall survival equivalent to that of the age- and sex-matched general population (standardized mortality ratio [SMR], 1.18; P = .25). This result was confirmed in 820 patients from the GELA study and registry in Lyon (SMR, 1.09; P = .71). Simulation studies showed that EFS24 has comparable power to continuous EFS when evaluating clinical trials in DLBCL. CONCLUSION: Patients with DLBCL who achieve EFS24 have a subsequent overall survival equivalent to that of the age- and sex-matched general population. EFS24 will be useful in patient counseling and should be considered as an end point for future studies of newly diagnosed DLBCL.

A New Imaging Software To Evaluate The Centration Of Capsulorhexis And Intraocular Lens (IOL) After Cataract Surgery

Purpose: IOL centration and stability after cataract surgery is of high interest for cataract surgeons and IOL-producing companies. We present a new imaging software to evaluate the centration of the rhexis and the centration of the IOL after cataract surgery.Methods: We developed, in collaboration with the Biomedical Imaging Group (BIG), EPFL, Lausanne, a new working tool in order to assess precisely outcomes after IOL-implantation, such as ideal capsulorhexis and IOL-centration. The software is a plug-in of ImageJ, a general-purpose image processing and image-analysis package. The specifications of this software are: evaluation of the rhexis-centration and evaluation the position of the IOL in the posterior chamber. The end points are to analyze the quality of the centration of a rhexis after cataract surgery, the deformation of the rhexis with capsular bag retraction and the centration of the IOL after implantation.Results: This software delivers tools to interactively measure the distances between limbus, IOL and capsulorhexis and its changes over time. The user is invited to adjust nodes of three radial curves for the limbus, rhexis and the optic of the IOL. The radial distances of the curves are computed to evaluate the IOL implantation. The user is also able to define patterns for ideal capsulorhexis and optimal IOL-centration. We are going to present examples of calculations after cataract surgery.Conclusions: Evaluation of the centration of the rhexis and of the IOL after cataract surgery is an important end point for optimal IOL implantation after cataract surgery. Especially multifocal or accommodative lenses need a precise position in the bag with a good stability over time. This software is able to evaluate these parameters just after the surgery but also its changes over time. The results of these evaluations can lead to an optimizing of surgical procedures and materials.

Immunocytochemical and pharmacological characterization of metabotropic glutamate receptors of the vestibular end organs in the frog.

Using immunocytochemistry and multiunit recording of afferent activity of the whole vestibular nerve, we investigated the role of metabotropic glutamate receptors (mGluR) in the afferent neurotransmission in the frog semicircular canals (SCC). Group I (mGluR1alpha) and group II (mGluR2/3) mGluR immunoreactivities were distributed to the vestibular ganglion neurons, and this can be attributed to a postsynaptic locus of metabotropic regulation of rapid excitatory transmission. The effects of group I/II mGluR agonist (1S,3R)-1-aminocyclopentane-trans-1,3-dicarboxylic acid (ACPD) and antagonist (R,S)-alpha-methyl-4-carboxyphenylglycine (MCPG) on resting and chemically induced afferent activity were studied. ACPD (10-100 microM) enhanced the resting discharge frequency. MCPG (5-100 microM) led to a concentration-dependent decrease of both resting activity and ACPD-induced responses. If the discharge frequency had previously been restored by L-glutamate (L-Glu) in high-Mg2+ solution, ACPD elicited a transient increase in the firing rate in the afferent nerve suggesting that ACPD acts on postsynaptic receptors. The L-Glu agonists, alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) and N-methyl-D-aspartate (NMDA), were tested during application of ACPD. AMPA- and NMDA-induced responses were higher in the presence than absence of ACPD, implicating mGluR in the modulation of ionotropic glutamate receptors. These results indicate that activation of mGluR potentiates AMPA and NMDA responses through a postsynaptic interaction. We conclude that ACPD may exert modulating postsynaptic effects on vestibular afferents and that this process is activity-dependent.

Désir de mort, désir de vie et fin de vie [Desire to die, desire to live at the end of life]

Since a couple of years, physicians are confronted with an increasing request of end of life patients asking for a dying facilitated process. The reasons for this are multiple and complex. Existential suffering, increased by depression, a feeling of loss of meaning or dignity and/or being a burden, seems to be a significant factor. Social isolation and physical symptoms seem to be only contributory. The identification of "protecting elements" such as spiritual well-being or a preserved sense of dignity offers new opportunities for care. Providing a space for dialogue by exploring the patient's expectations and fears, his knowledge of care options available at the end of life, his own resources and difficulties frequently contribute to decrease suffering.

The early Miocene rotation of the Corso-Sardinian block. New paleomagnetic constraints for the end of the motion

The paleomagnetic investigations carried out in the 70's on Oligo-Miocene volcanics of Sardinia have demonstrated that the island was turned by 35-30 degrees clockwise from 33 Ma up to 3-1-20.5 Ma and rotated counterclockwise in a few million years [De Jong et al., 1969, 1973; Bobier et Coulon, 1970; Coulon et al., 1974; Manzoni, 1974, 1975; Bellon rr nl.. 1977: Edel et Lortscher, 1977; Edel, 1979, 1980]. Since then, the end of the rotation fixed at 19 Ma by Montigny er al. [1981] was the subject of discussions and several studies associating paleomagnetism and radiometric dating were undertaken [Assorgia er al., 1994: Vigliotti et Langenheim, 1995: Deino et al., 1997; Gattacceca rt Deino, 1999]. This is a contribution to this debate that is hampered by thr important secular variation recorded in the volcanics. The only way to get our of this problem is to sample series of successive flows as completely as possible, and to reduce the effect of secular variation by the calculation of means. Sampling was performed north of Bonorva in 5 pyroclastic flows that belong to the upper ignimbritic series SI2 according to Coulon rr nl. [1974] or LBLS according to Assorgia et al. [1997] (fig. I). Ar-40/Ar-39 dating of biotites from the debris flow (MDF) has yielded an age or 18.35 +/- 0.03 Ma [Dubois, 2000]. Five of the investigated sites are located beneath the debris flow ITV, TVB, TVD, SPM85, SPM86), one site was cured in the matrix of the debris flow (MDF) and one in 4 metric blocks included in the flow (DFC). Another site was sampled in the upper ash flow (PDM) that marks the end of the pyroclastic activity, just before the marine transgression. According to micropaleontological and radiometric dating this transgression has occurred between 18.35 and 17.6 Ma [Dubois, 2000]. After removal of a soft viscous component, the thermal demagnetization generally shows a univectorial behaviour of the remanent magnetization (fig. 2a). The maximum unblocking temperatures of 580-620 degrees (tab. I) and a rapid saturation below 100 mT (fig. 3) indicate that the carrier of the characteristic magnetization is magnetite. The exception comes: from the upper site PDM in which were found two characteristic components, one with a normal polarity and low unblocking temperatures up to 350 degreesC and one with a reversed polarity and maximum unblocking temperatures at 580-600 degreesC of magnetite. After calculation of a mean direction for each flow, the mean << Al >> direction 4 degrees /57 degrees (alpha (95) = 13 degrees) computed with the mean directions for the 5 flows may be considered as weakly affected by secular variation. But the results require a more careful examination. The declinations are N to NNW beneath the debris flow. NNW in the debris flow. and NNE (or SSW) above the debris flow, The elongated distribution of the directions obtained at sites TVB and TVD. scattered from the mean direction of TV to the mean direction of MDF is interpreted as due to partial overprinting during the debris How volcanic episode, The low temperature component PDMa is likely related to the alteration seen on thin sections and is also viewed as an overprint. As NNE/SSW directions occur as well below (mean direction << B >> : 5 degrees /58 degrees) as above the debris flow (PDMb : 200 degrees/-58 degrees). the NNW directions (<< C >> : 337 degrees /64 degrees) associated with the debris flow volcanism may be interpreted as resulting from a magnetic field excursion. According to the polarity scale of Cande and Kent [1992, 1995] and the radiometric age of MDF, the directions with normal polarity (TV, TVB, TVD, SPM85. SPM86a. MDF. DFC) may represent the period 5En. while the directions with reversed polarity PDMb and SPM86b were likely acquired during the period 5Dr. Using the mean << Al >> direction, the mean << B >>, or the PDM direction (tab. I). the deviation in declination with the direction of stable Europe 6.4 degrees /58.7 degrees (alpha (95) = 8 degrees) for a selection of 4 middle Tertiary poles by Besse et Courtillot [1991] or 7 degrees /56 degrees (alpha (95) = 3 degrees) for 19 poles listed by Edel [1980] can be considered as negligible. Using the results from the uppermost ignimbritic layer of Anglona also emplaced around 18.3 Ma [Odin rt al.. 1994]. the mean direction << E >> (3 degrees /51.5 degrees) leads to the same conclusion. On the contrary, when taking into account all dated results available for the period 5En (mean direction << D >> 353 degrees /56 degrees for 45 sites) (tab. II). the deviation 13 degrees is much more significant. As the rotation of Sardinia started around 21-20.5 Ma. the assumption of a constant velocity of rotation and the deviations of the Sardinia directions with respect to the stable Europe direction locate the end of the motion between 18.3 and 17.2 or 16.7 Ma (fig. 4). During the interval 18.35-17.5 Ma, the marine transgression took place. At the same period a NE-SW shortening interpreted as resulting from the collision of Sardinia with Apulia affected different parts of the island [Letouzey et al., 1982]. Consequently, the new paleomagnetic results and the tectono-sedimentary evolution are in favour of an end of the rotation at 17.5-18 Ma.

Medical futility at the end of life: the perspectives of intensive care and palliative care clinicians.

Objectives Medical futility at the end of life is a growing challenge to medicine. The goals of the authors were to elucidate how clinicians define futility, when they perceive life-sustaining treatment (LST) to be futile, how they communicate this situation and why LST is sometimes continued despite being recognised as futile. Methods The authors reviewed ethics case consultation protocols and conducted semi-structured interviews with 18 physicians and 11 nurses from adult intensive and palliative care units at a tertiary hospital in Germany. The transcripts were subjected to qualitative content analysis. Results Futility was identified in the majority of case consultations. Interviewees associated futility with the failure to achieve goals of care that offer a benefit to the patient's quality of life and are proportionate to the risks, harms and costs. Prototypic examples mentioned are situations of irreversible dependence on LST, advanced metastatic malignancies and extensive brain injury. Participants agreed that futility should be assessed by physicians after consultation with the care team. Intensivists favoured an indirect and stepwise disclosure of the prognosis. Palliative care clinicians focused on a candid and empathetic information strategy. The reasons for continuing futile LST are primarily emotional, such as guilt, grief, fear of legal consequences and concerns about the family's reaction. Other obstacles are organisational routines, insufficient legal and palliative knowledge and treatment requests by patients or families. Conclusion Managing futility could be improved by communication training, knowledge transfer, organisational improvements and emotional and ethical support systems. The authors propose an algorithm for end-of-life decision making focusing on goals of treatment.

Practical considerations for conducting ecotoxicity test methods with manufactured nanomaterials: what have we learnt so far?

This review paper reports the consensus of a technical workshop hosted by the European network, NanoImpactNet (NIN). The workshop aimed to review the collective experience of working at the bench with manufactured nanomaterials (MNMs), and to recommend modifications to existing experimental methods and OECD protocols. Current procedures for cleaning glassware are appropriate for most MNMs, although interference with electrodes may occur. Maintaining exposure is more difficult with MNMs compared to conventional chemicals. A metal salt control is recommended for experiments with metallic MNMs that may release free metal ions. Dispersing agents should be avoided, but if they must be used, then natural or synthetic dispersing agents are possible, and dispersion controls essential. Time constraints and technology gaps indicate that full characterisation of test media during ecotoxicity tests is currently not practical. Details of electron microscopy, dark-field microscopy, a range of spectroscopic methods (EDX, XRD, XANES, EXAFS), light scattering techniques (DLS, SLS) and chromatography are discussed. The development of user-friendly software to predict particle behaviour in test media according to DLVO theory is in progress, and simple optical methods are available to estimate the settling behaviour of suspensions during experiments. However, for soil matrices such simple approaches may not be applicable. Alternatively, a Critical Body Residue approach may be taken in which body concentrations in organisms are related to effects, and toxicity thresholds derived. For microbial assays, the cell wall is a formidable barrier to MNMs and end points that rely on the test substance penetrating the cell may be insensitive. Instead assays based on the cell envelope should be developed for MNMs. In algal growth tests, the abiotic factors that promote particle aggregation in the media (e.g. ionic strength) are also important in providing nutrients, and manipulation of the media to control the dispersion may also inhibit growth. Controls to quantify shading effects, and precise details of lighting regimes, shaking or mixing should be reported in algal tests. Photosynthesis may be more sensitive than traditional growth end points for algae and plants. Tests with invertebrates should consider non-chemical toxicity from particle adherence to the organisms. The use of semi-static exposure methods with fish can reduce the logistical issues of waste water disposal and facilitate aspects of animal husbandry relevant to MMNs. There are concerns that the existing bioaccumulation tests are conceptually flawed for MNMs and that new test(s) are required. In vitro testing strategies, as exemplified by genotoxicity assays, can be modified for MNMs, but the risk of false negatives in some assays is highlighted. In conclusion, most protocols will require some modifications and recommendations are made to aid the researcher at the bench. [Authors]