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Het concept waardegedreven zorg diept het verband uit tussen de kwaliteit van de zorg vanuit het perspectief van de patiënt en de kosten van die zorg. Santeon, vereniging van zeven topklinische ziekenhuizen, brengt het concept sinds een kleine drie jaar in de praktijk. De resultaten – betere zorg tegen gelijkblijvende of afnemende kosten – zijn hoopgevend. Directeur Pieter de Bey: ‘Vanuit alle kanten worden de principes van waardegedreven zorg omarmd. Nederland heeft de unieke kans op dit gebied voorloper te worden.’

We describe the synthesis of a series of phthalocyanine (Pc)–perylenediimide (PDI)8“octad” molecules, in which eight PDI moieties are attached to a Pc core through alkyl‐chain linkers. There is clear spectroscopic evidence that these octads can exist as non‐aggregated “monomers” or form aggregates along the Pc cores, depending on the type of Pc and the solvent medium. In the low dielectric constant solvents, into which the octads are soluble, photoexcitation of the PDI units leads to rapid energy transfer to the Pc centre, rather than a charge separation between moieties. In octad monomers, the Pc singlet excited‐state decays within tens of ps, whereas the excitons are stabilised in the aggregated form of the molecules, typically with lifetimes in the order of 1–10 ns. By contrast, in an octad design in which π–π interactions are suppressed by the steric hindrance of a corona of incompatible glycol tails around the molecule, a more straightforward photophysical interaction of Förster energy transfer between the PDI moieties and Pc core may be inferred. We consider these molecules as prototypical multichromophoric aggregates, giving delocalised states with considerable flexibility of design.

Sorption-enhanced reforming of methane is an attractive option for the combined production of electricity and capture of CO2. In this process, the steam-reforming catalyst is mixed with a CO2sorbent. During the reaction, CO2is adsorbed, leading to an increase of the hydrogen production rate. Once the sorbent is saturated, it must be regenerated using purge gas, usually steam. The amount of steam needed for CO2removal from the saturated sorbent determines the system efficiency of the process to a large extent. In this paper, several potassium-promoted hydrotalcite samples, both obtained commercially and prepared in-house, are tested for their suitability as a CO2sorbent for sorption-enhanced reforming of methane. In particular, the purge gas to adsorbed CO2ratio is determined under various operation conditions. It is shown that this ratio is still too large under the investigated conditions. Mixed with steam-reforming catalyst the hydrotalcite sorbent can adsorb sufficient CO2to enhance the CH4conversion to almost 100%.

Summary. The localization of the actin-monomer-binding protein profilin during the cell cycle of living Tradescantia virginiana stamen hair cells has been studied by microinjection of a fluorescently labeled analog of the protein. In contrast to previously published studies performed on chemically fixed animal cells, we do not find a specific colocalization of profilin with actin filament arrays. Our results show that, besides a general cytoplasmic distribution, profilin specifically accumulates in the nucleus in interphase and prophase cells. This nuclear localization was confirmed by means of electron microscopic immunolocalization of endogenous profilin (in Gibasis scheldiana stamen hair cells). During mitosis, as the nuclear envelope and nuclear matrix break down at the onset of prometaphase, the nuclear profilin redistributes equally into the accessible volume (cytosol) of the cell. During metaphase and anaphase no specific localization of profilin can be observed associated with the mitotic apparatus. However, during telophase, as nuclear envelopes and nuclear matrices re-form and the sister chromatids start to decondense, a subset of the microinjected profilin again localizes to the nucleus. No accumulation of profilin could be observed in the phragmoplast, where a distinct array of actin filaments exists. The function of profilin in the nucleus remains unclear.

Cytokinesis in higher plants involves the phragmoplast, a complex cytoplasmic structure that consists of microtubules (MTs), microfilaments (MFs) and membrane elements. Both MTs and MFs are essential for cell plate formation, although it is not clear which motor proteins are involved. Some candidate processes for motor proteins include transport of Golgi vesicles to the plane of the cell plate and the spatiotemporal organization of the cytoskeletal elements in order to achieve proper deposition and alignment of the cell plate. We have focused on the kinesin–like calmodulin binding protein (KCBP) and, more broadly, on myosins. Using an antibody that constitutively activates KCBP, we find that this MT motor, which is minus–end directed, contributes to the organization of the spindle and phragmoplast MTs. It does not participate in vesicle transport; rather, because of the orientation of the phragmoplast MTs, it is supposed that plus–end kinesins fill this role. Myosins, on the other hand, based on their inhibition with 2,3–butanedione monoxime and 1–(5–iodonaphthalene–1–sulphonyl)–1H–hexahydro–1,4–diazepine (ML–7), are associated with the process of post–mitotic spindle/phragmoplast alignment and with late lateral expansion of the cell plate. They are also not the principal motors involved in vesicle transport.

The well-being of hypertensive patients may be adversely affected by the disease itself, its complications, and other concomitant processes such as anxiety, sedation, and side effects of prescribed drugs. Some recently developed antihypertensive agents have been suggested to be devoid of these deleterious effects on well-being expressed as quality of life. We compared the effect on quality of life of the angiotensin-converting enzyme (ACE) inhibitor enalapril to the effect of bisoprolol as a representative of a new class of selective β1-adrenorecep-tor blocking agents. Fifty-seven patients with mild to moderate hypertension were eligible to enter an 18-week crossover study, consisting of a single-blind 2-week run-in period and two 8-week double-blind cross-over periods. At the end of the run-in period and the two crossover periods, both systolic and diastolic blood pressure (SBP, DBP) were assessed, as was quality of life perception by the Inventory of Subjective Health. During bisoprolol treatment, supine BP decreased from 163 ± 2/102 ± 1 to 144 ± 3/86 ± 1 mm Hg. The antihypertensive effect was at least as good with bisoprolol as with enalapril. Quality of life perception as measured with the Inventory of Subjective Health was comparable for the two drugs. Spontaneously mentioned adverse effects were more frequent (74) during enalapril than during bisoprolol treatment. At the end of the study, 69 of patients chose to continue antihypertensive treatment with bisoprolol. Our results show that the highly selective β1-adrenoreceptor blocking drug bisoprolol is at least as effective as enalapril and has no deleterious effects on well-being.

The well-being of hypertensive patients may be adversely affected by the disease itself, its complications, and other concomitant processes such as anxiety, sedation, and side effects of prescribed drugs. Some recently developed antihypertensive agents have been suggested to be devoid of these deleterious effects on wellbeing expressed as quality of life. We compared the effect on quality of life of the angiotensin-converting enzyme (ACE) inhibitor enalapril to the effect of bisoprolol as a representative of a new class of selective β1-adrenoreceptor blocking agents. Fifty-seven patients with mild to moderate hypertension were eligible to enter an 18-week cross-over study, consisting of a single-blind 2-week runin period and two 8-week double-blind cross-over periods. At the end of the run-in period and the two crossover periods, both systolic and diastolic blood pressure (SBP, DBP) were assessed, as was quality of life perception by the Inventory of Subjective Health. During bisoprolol treatment, supine BP decreased from 163 ± 2/102 ± 1 to 144 ± 3/86 ± 1 mm Hg. The antihypertensive effect was at least as good with bisoprolol as with enalapril. Quality of life perception as measured with the Inventory of Subjective Health was comparable for the two drugs. Spontaneously mentioned adverse effects were more frequent (74) during enalapril than during bisoprolol treatment. At the end of the study, 69 of patients chose to continue antihypertensive treatment with bisoprolol. Our results show that the highly selective β1-adrenoreceptor blocking drug bisoprolol is at least as effective as enalapril and has no deleterious effects on well-being

The well-being of hypertensive patients may be adversely affected by the disease itself, its complications, and other concomitant processes such as anxiety, sedation, and side effects of prescribed drugs. Some recently developed antihypertensive agents have been suggested to be devoid of these deleterious effects on well-being expressed as quality of life. We compared the effect on quality of life of the angiotensin-converting enzyme (ACE) inhibitor enalapril to the effect of bisoprolol as a representative of a new class of selective β1-adrenorecep-tor blocking agents. Fifty-seven patients with mild to moderate hypertension were eligible to enter an 18-week crossover study, consisting of a single-blind 2-week run-in period and two 8-week double-blind cross-over periods. At the end of the run-in period and the two crossover periods, both systolic and diastolic blood pressure (SBP, DBP) were assessed, as was quality of life perception by the Inventory of Subjective Health. During bisoprolol treatment, supine BP decreased from 163 ± 2/102 ± 1 to 144 ± 3/86 ± 1 mm Hg. The antihypertensive effect was at least as good with bisoprolol as with enalapril. Quality of life perception as measured with the Inventory of Subjective Health was comparable for the two drugs. Spontaneously mentioned adverse effects were more frequent (74) during enalapril than during bisoprolol treatment. At the end of the study, 69 of patients chose to continue antihypertensive treatment with bisoprolol. Our results show that the highly selective β1-adrenoreceptor blocking drug bisoprolol is at least as effective as enalapril and has no deleterious effects on well-being.

Immunopotentiation by cytostatic drugs continuously released from osmotic minipumps, was investigated in a guinea-pig contact-sensitivity model. These pumps are designed to release their content within a period of 7 days. Vepesid (VP-16) and 5-fluorouracil were released into oxazolone-stimulated lymph nodes by subcutaneous implantation of pumps containing either of these drugs. The pumps were implanted at the intended sensitization site, 2 days before sensitization. Strong potentiation of T-cell-mediated immunity, evaluated by delayed-type hypersensitivity measurements, was observed with both drugs tested. Daily injections with VP-16 also caused an enhancement of the immune response. However, daily injections with 5-fluorouracil, a drug assumed to be cell-cycle-specific in its action, failed to potentiate delayed hypersensitivity to oxazolone. Intralesional administration of cytostatic drugs has been put forward as an effective treatment modality in various types of cancer. Therapeutic effects may depend on both local tumorcytotoxic and immunopotentiating activities. Our present results suggest that osmotic minipumps can be applied to broaden the applicability and effectiveness of local chemotherapy.

We report what we believe to be the first demonstration of a Kerr-lens mode-locked Cr^3+:LiSrAlF_6 laser that is pumped by a single narrow-stripe AlGaInP laser diode with a diffraction-limited output beam. A novel low-loss three-mirror laser cavity design is described in which strong, localized Kerr lensing was exploited such that 75-fs-duration pulses were obtained for only 36??mW of incident pump power. This pump power was maintained for 18??h by just three AA batteries as the electrical power source. We have shown that mode locking can be sustained for pump powers as low as 22??mW.

We report what we believe to be the first demonstration of a Kerr-lens mode-locked Cr^3+:LiSrAlF_6laser that is pumped by a single narrow-stripe AlGaInP laser diode with a diffraction-limited output beam. A novel low-loss three-mirror laser cavity design is described in which strong, localized Kerr lensing was exploited such that 75-fs-duration pulses were obtained for only 36mW of incident pump power. This pump power was maintained for 18h by just three AA batteries as the electrical power source. We have shown that mode locking can be sustained for pump powers as low as 22mW.

A tunable femtosecond solid-state amplifier system that uses only 3 W of 488-nm argon-ion pump power has been demonstrated to deliver microjoule pulses at repetition rates up to 20 kHz, with a maximum pulse energy of 14 μJ obtained at 5 kHz. An all-solid-state, tunable, diode-pumped Cr:LiSrAlF_6 regenerative amplifier has been demonstrated, for the first time to our knowledge, that amplifies femtosecond pulses to energies exceeding 1 μJ at up to a 16-kHz repetition rate.

An all-solid-state tunable diode-pumped Cr^3+:LiSrAlF _6 (Cr:LiSAF) regenerative amplifier, seeded by a tunable diode-pumped Cr:LiSAF femtosecond oscillator, has been demonstrated for the first time to our knowledge. The oscillator was tunable over 75 nm and generated pulses as short as 24 fs. As much as 70 mW average output power was obtained with pulses of 40-fs duration. The amplifier produced recompressed pulses of less than 200-fs duration with energies exceeding 1 μJ at a repetition rate as high as 25 kHz.

Several modifications of the InGaAsP double-channel buried-heterostructure laser diode are described with reduced parasitic capacitances in order to improve the modulation speed of the laser chip. The parasitic capacitances of the various devices are measured and the data are described in terms of an improved microwave circuit model for BH lasers. A modulation bandwidth of more than 3 GHz is experimentally obtained by means of proton isolation of the laser chip outside the active region.

Lugtenburg: Mundipharma: Consultancy; Servier: Consultancy; Janssen-Cilag: Consultancy; Roche: Consultancy; Celgene: Consultancy. Off Label Use: 90Ytrium-ibritumomab tiuxetan for diffuse large B-cell lymphoma. Zijlstra:Celgene: Consultancy; Roche: Consultancy. Doorduijn:Celgene: Consultancy; Janssen: Consultancy; Roche: Consultancy. Hoogendoorn:Gilead: Consultancy; Novartis: Consultancy.

Background:Patients with relapsed/ refractory diffuse large B-cell lymphoma (DLBCL) after- or not eligible for autologous stem cell transplantation (ASCT) have a poor prognosis. Treatment with salvage chemotherapy has generally been disappointing. In many centers in the Netherlands the oral PECC regimen is used for such patients. 90Y-ibritumomab tiuxetan (Zevalin®, Spectrum Pharmaceuticals) radioimmunotherapy (RIT) is clinically active as a single agent in relapsed DLBCL. We conducted a prospective multi-center phase II study evaluating salvage therapy with Rituximab (R)-PECC, in responsive patients followed by 90Y-ibritumomab tiuxetan consolidation.

GaInP/AlGaInP double heterostructure lasers can be obtained with either TE or TM polarised emission. In addition it is shown that, by using appropriate samples, TE or TM lasing can be selected by changing the temperature or the cavity length.

A record low threshold current density of 760 A/cm2 has been obtained for a compressively strained multiquantum well laser emitting at 632 nm. Narrow stripe gain guided lasers show a maximum continuous output power of 45 mW with normally passivated mirrors. Stable laser operation over more than 3000 h at 40°C and 2 mW output power is reported for the first time.

A tunable diode-pumped Cr:LiSAF regenerative amplifier has been demonstrated for the first time. Femtosecond pulses have been amplified to pulse energies exceeding 1 µJ at repetition rates up to 16 kHz.

A three ridge type GaInP/AlGaInP visible light emitting laser diode array grown by AP-OMVPE has been achieved. A pulsed maximum output power of 108 mW is obtained from this laser array without the use of facet coatings. The pulsed threshold current is 290 mA and the external differential efficiency is 0.75 W/A.

A narrow linewidth has been obtained in a new 1.5 μm distributed feedback laser integrated monolithically with a tunable external cavity. The linewidth of 18 MHz has been achieved by tuning the current in the external cavity, and the FM response was flat from 100 kHz to 500 MHz.

Patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) after- or not eligible for autologous stem cell transplantation (ASCT) have a poor prognosis. The optimum salvage therapy for these patients is not known. Treatment results with second-line chemotherapy have generally been disappointing. In some centers in the Netherlands PECC (Prednisone, Etoposide, Chlorambucil and Lomustine) combination chemotherapy is used as salvage treatment for such patients. PECC is a completely oral schedule. The efficacy and toxicity of PECC in this patient category has not been evaluated systematically before. 90Y-ibritumomab tiuxetan (Zevalin®) showed clinical activity as a single agent in relapsed DLBCL. We conducted a prospective multi-center phase II study evaluating induction therapy with Rituximab (R)-PECC followed in responsive patients by 90Y-ibritumomab tiuxetan consolidation.Patients aged ≥ 18 years with refractory CD20 positive DLBCL or first or second relapse, more than one year after or not eligible for ASCT, were enrolled. Treatment consisted of R-PECC (Prednisone 40 mg/m2 po D1–5; Etoposide 100 mg/m2 po D1–5; Chlorambucil 8 mg/m2 po D1–5; Lomustine 80 mg/m2 po D1 and Rituximab 375 mg/m2 iv D1), every 28 days for 4 cycles. Patients with progressive disease after 2 cycles went off protocol. Patients in complete or partial remission after 4 cycles received consolidation treatment with 90Y-ibritumomab tiuxetan at the standard single dose of 15 MBq/kg (0.4 mCi/kg) 6 to 12 weeks after start of the last R-PECC cycle. Response to treatment was evaluated according to the revised 2007 Cheson criteria.Between November 2008 and February 2012 64 patients were enrolled. We report preliminary data for the first 50 patients evaluable for response and toxicity after the induction treatment with R-PECC. The median age was 70 years (range, 45–82) and median time since first diagnosis was 17 months (range 3–172). All patients had been treated with CHOP as first-line treatment and 8 patients (16%) had not been exposed to rituximab at first-line. Prior therapies consisted of (R)-CHOP (72%), R-CHOP and R-DHAP/VIM (16%) or R-CHOP and R-DHAP/VIM plus ASCT (12%). Eleven patients (22%) were refractory to their last prior systemic therapy. According to the secondary IPI, 26%, 28%, 34% and 8% of the patients belonged to the low-, low-intermediate-, high-intermediate-, and high risk group, respectively. Median relative dose intensities for the myelosuppressive agents of the PECC regimen were 93.7% (90% CI = 62.8–106.9%), 94.3% (90% CI = 71.6–104.7%) and 97.4% (90% CI 76.0–104.7%) for Lomustin, Etoposide and Chlorambucil, respectively. Progressive disease occurred in 14 patients (28%). Overall response rate (ORR) after induction treatment was 52%, including 34% complete response and 18% partial response. ORR of relapsed patients was significantly higher than that of patients refractory to their last prior treatment (64% vs. 9%, p=0.099). Patients more than one year from start of upfront treatment had a significant higher ORR than that of patients less than one year from start of upfront treatment (81% vs 21%, p=0.005). Median response duration was 13 months. One patient died because of treatment related toxicity due to sepsis and pneumonia after the first R-PECC cycle. The most common grade 3 or 4 adverse event was haematological toxicity (42%), followed by infection (14%), malaise (13%) and gastro-intestinal toxicity (6%). Eighteen serious adverse events (SAEs) occurred in 14 patients, 14 of the SAEs were possibly related to treatment (mainly hospitalisations because of infections). Approximately half of the patients (46%) have entered the 90Y-ibritumomab tiuxetan consolidation phase of the study.The R-PECC regimen shows good clinical activity in relapsed DLBCL patients. Its activity in refractory patients is low. This largely oral regimen provides patients not eligible for high-dose salvage treatment with a convenient treatment schedule with an acceptable safety profile.Off Label Use: 90Y-ibritumomab tiuxetan is not registered for DLBCL.

Abstract 2729