Vaccination against Extracellular Vimentin for Treatment of Urothelial Cancer of the Bladder in Client-Owned Dogs.

It was recently shown that targeting extracellular vimentin (eVim) is safe and effective in preclinical models. Here, we report the safety and efficacy in client-owned dogs with spontaneous bladder cancer of CVx1, an iBoost technology-based vaccine targeting eVim in combination with COX-2 inhibition. This was a single-arm prospective phase 1/2 study with CVx1 in 20 client-owned dogs with spontaneous UC which involved four subcutaneous vaccinations with CVx1 at 2-week intervals for induction of antibody titers, followed by maintenance vaccinations at 2-month intervals. Additionally, daily cyclooxygenase (COX)-2 inhibition with meloxicam was given. The response was assessed by antibody titers, physical condition, abdominal ultrasound and thorax X-ray. The primary endpoints were the development of antibody titers, as well as overall survival compared to a historical control group receiving carboplatin and COX-2 inhibition with piroxicam. Kaplan-Meier survival analysis was performed. All dogs developed antibodies against eVim. Titers were adequately maintained for the duration of this study. A median overall survival of 374 days was observed, which was 196 days for the historical control group (p < 0.01). Short-term grade 1-2 toxicity at the injection site and some related systemic symptoms peri-vaccination were observed. No toxicity was observed related to the induced antibody response. A limitation of this study is the single-arm prospective setting. CVx1 plus meloxicam consistently induced efficient antibody titers, was well tolerated and showed prolonged survival. The results obtained merit further development for human clinical care.

Cancer Vaccination against Extracellular Vimentin Efficiently Adjuvanted with Montanide ISA 720/CpG.

Extracellular vimentin is a specific marker of the tumor vasculature, where it is secreted by tumor endothelial cells. Vaccination with a conjugate vaccine targeting extracellular vimentin was previously shown to induce a potent humoral immune response and tumor growth inhibition in mice. These data were obtained by vaccination using the toxic Freund's adjuvant (FA) and are therefore not directly translatable into the clinic. In the present study, we aimed to investigate the potential of the biodegradable Montanide ISA 720 adjuvant. We tested Montanide either alone (MN) or supplemented with CpG 1826 (MN-C). Both adjuvant compositions, as well as FA, resulted in a significant tumor growth inhibition and decreased vessel density in the B16F10 melanoma tumor model. Vaccination of mice with either FA or MN-C resulted in an equally potent humoral immune response towards vimentin, while the antibody titers obtained with MN alone were significantly lower compared to FA. Vaccination coincided with the infiltration of immune cells. The highest number of intratumoral immune cells was seen in tumors from the MN-C group. Therefore, we conclude that Montanide ISA 720 supplemented with CpG allows efficient vaccination against extracellular vimentin, which is a prerequisite for the transfer of the vaccine into the clinic.

Effect of AcrySof versus other intraocular lens properties on the risk of Nd:YAG capsulotomy after cataract surgery: A systematic literature review and network meta-analysis.

OBJECTIVE: The purpose of this study was to evaluate the impact of different intraocular lens materials (IOL) and optic edge designs on the incidence of Nd:YAG laser capsulotomy. METHODS: Randomized controlled trials (RCTs) reporting incidence of Nd:YAG capsulotomy in patients with monofocal IOLs were identified for systematic literature review (SLR) using Cochrane methodology. A network meta-analysis was conducted under a Bayesian framework. Mean hazard ratios (HRs), 95% credible intervals, and one-sided p-values were estimated for Nd:YAG capsulotomy incidence by comparing AcrySof IOLs with a group of non-AcrySof hydrophobic acrylic, hydrophilic acrylic, silicone, and PMMA IOLs. Sensitivity analysis was conducted comparing the risk of Nd:YAG capsulotomy between sharp- and round-edged designs of the above IOLs. RESULTS: AcrySof IOLs had a lower risk of Nd:YAG capsulotomy compared to hydrophobic acrylic (HR: 2.68; 95% CrI: 1.41, 4.77; p < 0.01), hydrophilic acrylic (HR: 7.54; 95% CrI: 4.24, 14.06; p < 0.001), PMMA (HR: 3.64, 95% CrI: 1.87, 6.33; p < 0.001), and silicone (HR: 1.13; 95% CrI: 0.59, 1.91; p <0.1) IOLs. The risk for Nd:YAG was highest among sharp-edged IOLs for hydrophilic acrylic IOLs (HR: 9.32; 95% CrI: 4.32, 19.29; p < 0.01), followed by other hydrophobic acrylic (HR: 2.91; 95% CrI: 1.27, 5.88; p < 0.01), silicone (HR: 0.838; 95% CrI: 0.328, 1.74; p = 0.69), and PMMA (HR: 0.39; 95% CrI: 0.042, 1.49; p = 0.93) IOLs, compared to AcrySof. Acrysof IOLs had a lower risk of Nd:YAG compared to PMMA (HR: 3.25; 95% CrI: 1.21, 7.37; p < 0.01) and silicone, round edge IOLs (HR: 3.84; 95% CrI: 1.08, 10.64; p = 0.015). CONCLUSION: The risk of Nd:YAG capsulotomy is lower in eyes implanted with AcrySof IOLs compared to non-AcrySof hydrophobic or hydrophilic acrylic IOLs. Sharp-edged AcrySof, PMMA, and silicone IOLs are comparable in terms of reducing the risk of Nd:YAG laser capsulotomy.

Personalized signal-independent beamforming for binaural hearing aids.

The effect of personalized microphone array calibration on the performance of hearing aid beamformers under noisy reverberant conditions is studied. The study makes use of a new, publicly available, database containing acoustic transfer function measurements from 29 loudspeakers arranged on a sphere to a pair of behind-the-ear hearing aids in a listening room when worn by 27 males, 14 females, and 4 mannequins. Bilateral and binaural beamformers are designed using each participant's hearing aid head-related impulse responses (HAHRIRs). The performance of these personalized beamformers is compared to that of mismatched beamformers, where the HAHRIR used for the design does not belong to the individual for whom performance is measured. The case where the mismatched HAHRIR is that of a mannequin is of particular interest since it represents current practice in commercially available hearing aids. The benefit of personalized beamforming is assessed using an intrusive binaural speech intelligibility metric and in a matrix speech intelligibility test. For binaural beamforming, both measures demonstrate a statistically signficant (p < 0.05) benefit of personalization. The benefit varies substantially between individuals with some predicted to benefit by as much as 1.5 dB.

Risks and interrelationships of subdistrict house prices: the case of Amsterdam.

This paper uses individual house transaction data from 1995 to 2014 in Amsterdam to explore the risks and interrelationships of the subdistrict house prices. Simple indicators suggest that house prices grow faster and are more risky in the central business district and its immediate surrounding areas than in the peripherals. Furthermore, we observe an over time decreasing intervariations between the subdistrict house price growth rates, whereas we find a lead-lag and house price causal flow from the more central to the peripheral subdistricts.

The mismatch between conventional house price modeling and regulated markets: insights from The Netherlands.

House price modeling has been frequently used to investigate the dynamics of housing markets, especially competitive markets; yet less attention has been given to markets that have experienced considerable interventions. The aim of this study is to demonstrate a mismatch between conventional house price models and the case of the Netherlands and to provide reasons of such mismatch. We first describe and classify the conventional house price models into asset-pricing house price model, stock-flow model, multi-period utility model, and repayment model. These models are subsequently applied to the Netherlands, where considerable government interventions took place. As expected, the empirical results are unsatisfactory to explain the Dutch house price development. The degree of mismatch of the repayment model and the multi-period utility model, however, seems to be fairly limited.

Call-duration and triage decisions in out of hours cooperatives with and without the use of an expert system.

BACKGROUND: Cooperatives delivering out of hours care in the Netherlands are hesitant about the use of expert systems during triage. Apart from the extra costs, cooperatives are not sure that quality of triage is sufficiently enhanced by these systems and believe that call duration will be prolonged drastically. No figures about the influence of the use of an expert system during triage on call duration and triage decisions in out of hours care in the Netherlands are available. METHODS: Electronically registered data concerning call duration and triage decisions were collected in two cooperatives. One in Tilburg, a cooperative in a Southern city of the Netherlands using an expert system, and one in Groningen, a cooperative in a Northern city not using an expert system. Some other relevant information about the care process was collected additionally. Data about call duration was compared using an independent sample t-test. Data about call decisions was compared using Chi Square. RESULTS: The mean call time in the cooperative using the TAS expert system is 4.6 minutes, in the cooperative not using the expert system 3.9 minutes. A significant difference of 0.7 minutes (0.4 - 1.0, 95% CI) minutes. In the cooperative with an expert system a larger percentage of patients is handled by the assistant, patients are less often referred to a telephone consultation with the GP and are less likely to be offered a visit by the GP.A quick interpretation of the impact of the difference in triage decisions, show that these may be large enough to support the hypothesis that longer call duration is compensated for by less contacts with the GP (by telephone or face-to-face). There is no proof, however, that these differences are caused by the use of the triage system. The larger amount of calls handled by the assistant may be partly caused by the fact that the assistants in the cooperative with an expert system more often consult the GP during triage. And it is not likely that the larger amount of home visits in Groningen can be attributed to the absence of an expert system. The expert system only offers advice whether a GP should be seen, not in which way (by consultation in the office or by home visit). CONCLUSION: The differences in call times between a cooperative using an expert system and a cooperative not using an expert system are small; 0.4 - 1.0 min. Differences in triage decisions were found, but it is not proven that these can be contributed to the use of an expert system.

Job satisfaction among general practitioners: a systematic literature review.

OBJECTIVE: In recent years, the incidence of being overworked and burnt out has increased among general practitioners (GPs). One of the factors that influences the development of burnout is the job satisfaction that physicians experience. Therefore, we conducted a literature review to answer the question: what factors influence the job satisfaction experienced by GPs? METHODS: We used two methods to retrieve citations. We searched four literature databases for citations from 1990 until July 2006, and we checked the reference lists of relevant articles. The inclusion criteria were: GPs had to be the subjects of the study, the study had to describe empirical research, the study had to focus on job satisfaction, and the number of subjects had to be greater than 30. RESULTS: We found 24 relevant citations. Factors increasing job satisfaction which were mentioned more than twice were: diversity of work, relations and contact with colleagues, and being involved in teaching medical students. Factors decreasing job satisfaction were: low income, too many working hours, administrative burdens, heavy workload, lack of time, and lack of recognition. CONCLUSION: Aspects of job satisfaction concerning the content of the profession seem to increase job satisfaction, and aspects concerning employment conditions seem to decrease job satisfaction.

The implementation of a call-back system reduces the doctor's workload, and improves accessibility by telephone in general practice.

BACKGROUND: In a general practice in The Netherlands, the demand for direct telephone consultation with the doctor became extreme, which resulted in poorly managed consultations, and poor telephone access due to busy lines. A call-back telephone appointment system was therefore introduced: all calls are answered and, when possible, managed by the practice assistant. If the assistant feels incapable, or if the patient prefers to speak to the doctor, a telephone appointment is scheduled, at which time the doctor returns the patient's call. OBJECTIVE: Our aim was to evaluate the effects of a call-back telephone appointment system on doctors' workload and patients' telephone access to doctors. METHODS: Telephone consultation data over 10 weeks were selected before and after the introduction of the call-back telephone appointment system. The outcomes measured were: number and duration of telephone calls to doctors, the reason for each call and how often telephone lines were engaged during the specified telephone hour. RESULTS: The number of calls requiring the doctor's attention was reduced by 59% and total time spent on the telephone by the GPs was reduced by 39%. This reduction is explained by a change in the reasons for calling. Telephone accessibility improved, as busy telephone lines were no longer an issue. CONCLUSION: The call-back telephone appointment system is superior to the previously used open access telephone hour.

Effect of Chain Length on the Adsorption Behavior of n-Alkanes in Ferrierite.

13 C NMR spectroscopy and computer simulations have shown that the chain length of hydrocarbons has a surprising effect on where these molecules reside in the zeolite FER. Propane and butane can access the entire two-dimensional channel structure, while hexane only the one-dimensional substructure. This difference has important consequences for the catalytic activity and explains some of the experimental observations.