Phase 2 Study of Lutetium 177-Labeled Anti-Carbonic Anhydrase IX Monoclonal Antibody Girentuximab in Patients with Advanced Renal Cell Carcinoma.

Unlabelled Despite advances in the treatment of metastatic clear cell renal cell carcinoma (ccRCC), there is still an unmet need in the treatment of this disease. A phase 2 radioimmunotherapy (RIT) trial with lutetium 177 ((177)Lu)-girentuximab was initiated to evaluate the efficacy of this approach. In this nonrandomized single-arm trial, patients with progressive metastatic ccRCC who met the inclusion criteria received 2405 MBq/m(2) of (177)Lu-girentuximab intravenously. In the absence of persistent toxicity and progressive disease, patients were eligible for retreatment after 3 mo with 75% of the previous activity dose. A total of 14 patients were included. After the first therapeutic infusion, eight patients (57%) had stable disease (SD) and one (7%) had a partial regression. The treatment was generally well tolerated but resulted in grade 3-4 myelotoxicity in most patients. After the second cycle, continued SD was observed in five of six patients, but none were eligible for retreatment due to prolonged thrombocytopenia. In conclusion, RIT with (177)Lu-girentuximab resulted in disease stabilization in 9 of 14 patients with progressive metastatic ccRCC, but myelotoxicity prevented retreatment in some patients.Patient summary We investigated the efficacy of lutetium 177-girentuximab radioimmunotherapy in patients with metastatic kidney cancer. The treatment resulted in disease stabilization in 9 of 14 patients. The main toxicity was prolonged low blood cell counts.Trial registration ClinicalTrials.gov identifier: NCT02002312 (https://clinicaltrials.gov/ct2/show/NCT02002312)

Adaptation of eye and hand movements to target displacements of different size

Previous work has documented that the direction of eye and hand movements can be adaptively modified using the double-step paradigm. Here we report that both motor systems adapt not only to small direction steps (5° gaze angle) but also to large ones (28° gaze angle). However, the magnitude of adaptation did not increase with step size, and the relative magnitude of adaptation therefore decreased from 67% with small steps to 15% with large steps. This decreasing efficiency of adaptation may reflect the participation of directionally selective neural circuits in double-step adaptation

Fast and fine-tuned corrections when the target of a hand movement is displaced

To study the strategy in responding to target displacements during fast goal-directed arm movements, we examined how quickly corrections are initiated and how vigorously they are executed. We perturbed the target position at various moments before and after movement initiation. Corrections to perturbations before the movement started were initiated with the same latency as corrections to perturbations during the movement. Subjects also responded as quickly to a second perturbation during the same reach, even if the perturbations were only separated by 60 ms. The magnitude of the correction was minimized with respect to the time remaining until the end of the movement. We conclude that despite being executed after a fixed latency, these fast corrections are not stereotyped responses but are suited to the circumstances

Avoiding moving obstacles

To successfully move our hand to a target, we must consider how to get there without hitting surrounding objects. In a dynamic environment this involves being able to respond quickly when our relationship with surrounding objects changes. People adjust their hand movements with a latency of about 120 ms when the visually perceived position of their hand or of the target suddenly changes. It is not known whether people can react as quickly when the position of an obstacle changes. Here we show that quick responses of the hand to changes in obstacle position are possible, but that these responses are direct reactions to the motion in the surrounding. True adjustments to the changed position of the obstacle appeared at much longer latencies (about 200 ms). This is even so when the possible change is predictable. Apparently, our brain uses certain information exceptionally quickly for guiding our movements, at the expense of not always responding adequately. For reaching a target that changes position, one must at some time move in the same direction as the target did. For avoiding obstacles that change position, moving in the same direction as the obstacle is not always an adequate response, not only because it may be easier to avoid the obstacle by moving the other way, but also because one wants to hit the target after passing the obstacle. Perhaps subjects nevertheless quickly respond in the direction of motion because this helps avoid collisions when pressed for time. © 2008 Springer-Verlag

The Amsterdam Studies of Acute Psychiatry I (ASAP-I); A prospective cohort study of determinants and outcome of coercive versus voluntary treatment interventions in a metropolitan area

Background The overall number of involuntary admissions is increasing in many European countries. Patients with severe mental illnesses more often progress to stages in which acute, coercive treatment is warranted. The number of studies that have examined this development and possible consequences in terms of optimizing health care delivery in emergency psychiatry is small and have a number of methodological shortcomings. The current study seeks to examine factors associated with compulsory admissions in the Amsterdam region, taking into account a comprehensive model with four groups of predictors: patient vulnerability, social support, responsiveness of the health care system and treatment adherence. Methods/Design This paper describes the design of the Amsterdam Study of Acute Psychiatry-I (ASAP-I). The study is a prospective cohort study, with one and two-year follow-up, comparing patients with and without forced admission by means of a selected nested case-control design. An estimated total number of 4,600 patients, aged 18 years and over, consecutively coming into contact with the Psychiatric Emergency Service Amsterdam (PESA) are included in the study. From this cohort, a randomly selected group of 125 involuntary admitted subjects and 125 subjects receiving non-coercive treatment are selected for further evaluation and comparison. First, socio-demographic, psychopathological and network characteristics, and prior use of health services will be described for all patients who come into contact with PESA. Second, the in-depth study of compulsory versus voluntary patients will examine which patient characteristics are associated with acute compulsory admission, also taking into account social network and healthcare variables. The third focus of the study is on the associations between patient vulnerability, social support, healthcare characteristics and treatment adherence in a two-year follow-up for patients with or without involuntarily admittance at the index consultation. Discussion The current study seeks to establish a picture of the determinants of acute compulsory admissions in the Netherlands and tries to gain a better understanding of the association with the course of illness and patient's perception of services and treatment adherence. The final aim is to find specific patient and health care factors that can be influenced by adjusting treatment programs in order to reduce the number of involuntary admissions

Dutch measurement strategy for nuclear emergencies inside or outside the Netherlands

The intervention levels specified by the government serve as the starting-point for determining the necessary measurements for air, water, soil, foodstuffs and humans. A Technical Information Group (TIG) has been installed within the National Organisation for Nuclear Emergency Management to co-ordinate all measurement programs. The measurement strategy reported on here is meant primarily for the TIG, who represent different technical institutes. In the measurement strategy, the response phase is divided into an early measurement phase and an extensive measurement phase. The main goal of measurements in the early phase is to check model predictions of air and surface contamination. In the extensive phase measurements of foodstuffs and drinking water become important. Both the desired and existing measurement facilities have been compared. Bottlenecks are indicated in the areas of (fast) measurements of alpha and beta emitters in all compartments, possibilities for data analysis in the Information and Documentation Centre, sampling of grass and agricultural products, laboratory capacity for surface-water measurements, organisation of measuring imported foodstuffs, and the lack of measurement strategies for drinking water and personal decontamination.De door de overheid vastgestelde interventieniveaus voor het nemen van maatregelen vormen het uitgangspunt voor het beschrijven van de noodzakelijke metingen in lucht, water, bodem, voedingsmiddelen en aan personen. Om alle meetinspanningen te coordineren is binnen het Nationaal Plan voor de Kernongevallenbestrijding een Technische Informatie Groep (TIG) ingesteld. De beschreven meetstrategie is primair bedoeld voor de leden van de TIG, die de verschillende betrokken meetinstituten (de zogenaamde Steuncentra) vertegenwoordigen. In de meetstrategie wordt in de bestrijdingsfase onderscheid gemaakt tussen een vroege en een uitgebreide meetfase. Metingen in de vroege meetfase hebben als voornaamste doel om de gemodelleerde prognoses van lucht- en bodembesmetting te toetsen. In de uitgebreide meetfase ligt de nadruk op metingen aan voedingsmiddelen en drinkwater. In dit rapport worden de gewenste en bestaande meetfaciliteiten vergeleken. Knelpunten liggen op het gebied van (snelle) metingen aan alfa- en betastralers in alle matrices, mogelijkheden tot analyse van meetgegevens in het Informatie- en Documentatie Centrum, het bemonsteren van gras en landbouwgewassen, analysecapaciteit voor oppervlaktewatermetingen, de organisatie van metingen aan geimporteerde voedingswaren en het ontbreken van meetstrategieen voor drinkwater en persoonsontsmetting

Dutch measurement strategy for nuclear emergencies inside or outside the Netherlands

De door de overheid vastgestelde interventieniveaus voor het nemen van maatregelen vormen het uitgangspunt voor het beschrijven van de noodzakelijke metingen in lucht, water, bodem, voedingsmiddelen en aan personen. Om alle meetinspanningen te coordineren is binnen het Nationaal Plan voor de Kernongevallenbestrijding een Technische Informatie Groep (TIG) ingesteld. De beschreven meetstrategie is primair bedoeld voor de leden van de TIG, die de verschillende betrokken meetinstituten (de zogenaamde Steuncentra) vertegenwoordigen. In de meetstrategie wordt in de bestrijdingsfase onderscheid gemaakt tussen een vroege en een uitgebreide meetfase. Metingen in de vroege meetfase hebben als voornaamste doel om de gemodelleerde prognoses van lucht- en bodembesmetting te toetsen. In de uitgebreide meetfase ligt de nadruk op metingen aan voedingsmiddelen en drinkwater. In dit rapport worden de gewenste en bestaande meetfaciliteiten vergeleken. Knelpunten liggen op het gebied van (snelle) metingen aan alfa- en betastralers in alle matrices, mogelijkheden tot analyse van meetgegevens in het Informatie- en Documentatie Centrum, het bemonsteren van gras en landbouwgewassen, analysecapaciteit voor oppervlaktewatermetingen, de organisatie van metingen aan geimporteerde voedingswaren en het ontbreken van meetstrategieen voor drinkwater en persoonsontsmetting.The intervention levels specified by the government serve as the starting-point for determining the necessary measurements for air, water, soil, foodstuffs and humans. A Technical Information Group (TIG) has been installed within the National Organisation for Nuclear Emergency Management to co-ordinate all measurement programs. The measurement strategy reported on here is meant primarily for the TIG, who represent different technical institutes. In the measurement strategy, the response phase is divided into an early measurement phase and an extensive measurement phase. The main goal of measurements in the early phase is to check model predictions of air and surface contamination. In the extensive phase measurements of foodstuffs and drinking water become important. Both the desired and existing measurement facilities have been compared. Bottlenecks are indicated in the areas of (fast) measurements of alpha and beta emitters in all compartments, possibilities for data analysis in the Information and Documentation Centre, sampling of grass and agricultural products, laboratory capacity for surface-water measurements, organisation of measuring imported foodstuffs, and the lack of measurement strategies for drinking water and personal decontamination.DGM/HIMH/C

Definition study of a spectrometer measurement system for ultraviolet radiation

Ultraviolet radiation has many, mostly harmful, effects on man and the environment. The stratospheric ozone layer offers an important protection against ultraviolet radiation because ozone absorbs the short-wave ultraviolet radiation. Therefore, a reduction in the ozone layer can cause an increased UV-radiation level on the earth's surface. In the Netherlands, a project to collect information on the current UV climatic conditions and changes has begun, which will include the development of an UV spectrometer system. In this report requirements for the system are formulated based on the project objectives. Several methods for UV-radiation measurement are presented, and monitoring networks in other countries are discussed. A specific UV-radiation measurement system in the Netherlands is proposed, consisting of a double monochromator for short-wave UV-B measurement, and a multichannel detection system for UV-A radiation measurement.DGM/

Research on the radioactivity of surfacewaters in the Netherlands. Results over 1990

Abstract niet beschikbaarthis report contains the results for 1990 of measurements of radioactivity in the rivers Meuse, Rhine, Roer, in the Westerscheldt, in the Channel of Sas van Gent to Terneuzen, and in het North Sea along the Dutch coast. The Sr-90-content in Meuse, Rhine and Roer varies between 2.4 Bq/m3 and 6.9 Bq/m3. In the Westerscheldt higher contents are found (between 9 Bq/m3 and 22 Bq/m3. The Sr-90-content of seawater varies between 7 Bq/m3 and 12 Bq/m3. Sr-89 was not found. As in previous ywars, the Ra-226- contents found in samples of the Roer (between 11 Bq/m3 and 14 Bq/m3) are higher than the ones measured in samples of the Meuse and of the Rhine (between 2.0 Bq/m3 and 6.1 Bq/m3). The Ra-226-content of the Westerscheldt varies between 6 Bq/m3 and 38 Bq/m3. The Po-210 and Pb-210-contents of the Meuse, Rhine and Roer are almost the same. The Po-210 and Pb-210-contents of the Westerscheldt are considerably higher than the contents of the rivers mentioned above: the yearly average of the Po-210-content is 26.3 Bq/m3 and of the Pb-210-content 24.2 Bq/m3. The Po-210 and Pb-210-contents of the Westerscheldt have increased during the last four years. Samples of suspended matter from the Meuse, Rhine, Roer, Westerscheldt and the Channel of Sas van Gent to Terneuzen were examined by means of gammaspectrometry. Natural as well as artificial radionuclides are found. The H-3-contents in the North Sea (between 1100 Bq/m3 and 3500 Bq/m3) are generally the same as in 1989. The Cs-137-contents measured vary between less than the detection limit (2 Bq/m3) and 25 Bq/m3.HIM