Safety and preliminary efficacy of vorinostat with R-EPOCH in high-risk HIV-associated non-Hodgkin\u27s lymphoma (AMC-075)

We performed a phase I trial of vorinostat (VOR) given on days 1 to 5 with R-EPOCH (rituximab plus etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin hydrochloride) in patients with aggressive HIV-associated non-Hodgkin lymphoma. VOR was tolerable at 300 mg and seemingly efficacious with chemotherapy with complete response rate of 83% and 1-year event-free survival of 83%. VOR did not significantly alter chemotherapy steady-state concentrations, CD4+ cell counts, or HIV viral loads. Vorinostat (VOR), a histone deacetylase inhibitor, enhances the anti-tumor effects of rituximab (R) and cytotoxic chemotherapy, induces viral lytic expression and cell killing in Epstein-Barr virus-positive (EBV+) or human herpesvirus-8-positive (HHV-8+) tumors, and reactivates latent human immunodeficiency virus (HIV) for possible eradication by combination antiretroviral therapy (cART). We performed a phase I trial of VOR given with R-based infusional EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin hydrochloride) (n = 12) and cART in aggressive HIV-associated B-cell non-Hodgkin lymphoma (NHL) in order to identify safe dosing and schedule. VOR (300 or 400 mg) was given orally on days 1 to 5 with each cycle of R-EPOCH for 10 high-risk patients with diffuse large B-cell lymphoma (1 EBV+), 1 EBV+/HHV-8+ primary effusion lymphoma, and 1 unclassifiable NHL. VOR was escalated from 300 to 400 mg using a standard 3 + 3 design based on dose-limiting toxicity observed in cycle 1 of R-EPOCH. The recommended phase II dose of VOR was 300 mg, with dose-limiting toxicity in 2 of 6 patients at 400 mg (grade 4 thrombocytopenia, grade 4 neutropenia), and 1 of 6 treated at 300 mg (grade 4 sepsis from tooth abscess). Neither VOR, nor cART regimen, significantly altered chemotherapy steady-state concentrations. VOR chemotherapy did not negatively impact CD4+ cell counts or HIV viral loads, which decreased or remained undetectable in most patients during treatment. The response rate in high-risk patients with NHL treated with VOR(R)-EPOCH was 100% (complete 83% and partial 17%) with a 1-year event-free survival of 83% (95% confidence interval, 51.6%-97.9%). VOR combined with R-EPOCH was tolerable and seemingly efficacious in patients with aggressive HIV-NHL

Agglomeration Externalities and Localized Employment Growth

This paper addresses the question to what extent the performance of industrial sites is affected by their local economic structure and accessibility. For this aim, we test for the existence of statistically significant relationships between agglomeration externalities (specialization, diversity, and competition), accessibilty measures and the employment growth of a particular industry on a particular site. We use data on employment growth of site-industries on 68 formal industrial sites in the municipality of Amsterdam between 1998 and 2006. We show that at the site-industry level, specialization hampers growth. Furthermore, we find that industrial sites that are easily accessible from the highway grow relatively fast, as well as sites located in the Amsterdam harbour area

The impact of industrial sites on residential property values

Industrial sites cause several negative externalities, such as traffic noise disturbance, congestion, and obstruction of view. In order to quantify the negative effects stemming from industrial sites, we estimate – using a hedonic pricing model – the impact of distance to industrial sites on residential property values. We use data on houses sold in the Randstad region and the province of Noord-Brabant (both located in the Netherlands) in the year 2005, together with data on characteristics of a substantial number of industrial sites in the same regions and period. The results reveal that the distance to an industrial site has a statistically significant negative effect on the value of residential properties. However, the effect is largely localized within a relatively short distance from the nearest industrial site. Furthermore, we obtain statistical evidence for substantial localized price differentials, which vary according to the size of an industrial site

Financiële stabiliteit: de rol van DNB

DNB bewaakt de stabiliteit van ons financiële stelsel via het monetaire beleid, het toezicht en de zorg voor het betalingsverkeer. Deze gezamenlijke taakuitoefening biedt belangrijke voordelen.monetary policy, supervision, financial stability, central banking, payment system oversight

Ein bedeutender Schädling im ökologischen Landbau: Meloidogyne hapla Chitwood

Dieses Informationsblatt möchte Landwirte und Berater über den Nördlichen Wurzelgallennematoden Meloidogyne hapla informieren. Dieser Nematode verursacht vor allem im ökologischen Landbau zunehmend Schäden an Gemüse und Kartoffeln. M. hapla ist die in Mitteleuropa am häufigsten vorkommende Meloidogyne-Art. Sie kann vor allem auf leichten Böden beträchtliche Schäden verursachen

Studies of the horizontal vestibulo-ocular reflex on STS 7 and 8

Unpaced voluntary horizontal head oscillation was used to study the Vestibulo-Ocular Reflex (VOR) on Shuttle flights STS 7 and 8. Ten subjects performed head oscillations at 0.33 Hz + or - 30 deg amplitude under the followng conditions: VVOR (visual VOR), eyes open and fixed on a stationary target; VOR-EC, with eyes closed and fixed on the same target in imagination; and VOR-S (VOR suppression), with eyes open and fixed on a head-synchronized target. Effects of weightlessness, flight phase, and Space Motion Sickness (SMS) on head oscillation characteristics were examined. A significant increase in head oscillation frequency was noted inflight in subjects free from SMS. In subjects susceptible to SMS, frequency was reduced during their Symptomatic period. The data also suggest that the amplitude and peak velocity of head oscillation were reduced early inflight. No significant changes were noted in reflex gain or phase in any of the test conditions; however, there was a suggestion of an increase in VVOR and VOR-ES gain early inflight in asymptomatic subjects. A significant difference in VOR-S was found between SMS susceptible and non-susceptible subjects. There is no evidence that any changes in VOR characteristics contributed to SMS

Evaluation of Microwave Landing System (MLS) effect on the delivery performance of a fixed-path metering and spacing system

Metering and spacing (M & S) system's algorithms described assume an aircraft two dimensional are navigation capability. The three navigation systems compared were: very high frequency omnidirectional range/distance measuring equipment (VOR/DME) and ILS, VOR/DME and + or - 40 MLS, and VOR/DME and + or - 60 MLS. Other factors studied were M & S tentative schedule point location, route geometry effects, and approach gate location effects. Summarized results are: the MLS offers some improvement over VOR/DME and ILS if all approach routes contain computer assisted turns; pilot reaction to moving the gate closer to the runway threshold may adversely affect M & S performance; and coupling en route metering to terminal scheduling transfers most of the terminal holding to more full efficient, higher altitude en route delay

Improved navigation by combining VOR/DME information with air or inertial data

The improvement was determined in navigational accuracy obtainable by combining VOR/DME information (from one or two stations) with air data (airspeed and heading) or with data from an inertial navigation system (INS) by means of a maximum-likelihood filter. It was found that the addition of air data to the information from one VOR/DME station reduces the RMS position error by a factor of about 2, whereas the addition of inertial data from a low-quality INS reduces the RMS position error by a factor of about 3. The use of information from two VOR/DME stations with air or inertial data yields large factors of improvement in RMS position accuracy over the use of a single VOR/DME station, roughly 15 to 20 for the air-data case and 25 to 35 for the inertial-data case. As far as position accuracy is concerned, at most one VOR station need be used. When continuously updating an INS with VOR/DME information, the use of a high-quality INS (0.01 deg/hr gyro drift) instead of a low-quality INS (1.0 deg/hr gyro drift) does not substantially improve position accuracy