Werken aan meerwaarde van regionale landbouw en biodiversiteit : de oogst van vier jaar Echt Overijssel!

"Werken aan" heeft in Echt Overijssel! vele betekenissen. Livestock Research, CLM, Natuurmonumenten, Louis Bolk Instituut hebben gewerkt aan de ontwikkeling van duurzaamheid via de drie thema’s: (agro)biodiversiteit, regionale landbouw en markt. De werkvorm was er een met agrarische ondernemers, met kennisinstellingen, met terreinbeheerders, en vele andere partners in het keten- en kennisnetwerk. Kosten en opbrengsten voor biologische bedrijfsvoering zijn berekend voor verschillende bedrijfsvormen. Gebruikmakend van diverse teelten, die alternatief veevoer leveren. Vanuit teelt en beheerperspectief is het zoeken naar de balans tussen gewasopbrengst (productwaarde) en biodiversiteit (natuurwaarde)

HIRAX:A Probe of Dark Energy and Radio Transients

The Hydrogen Intensity and Real-time Analysis eXperiment (HIRAX) is a new 400-800MHz radio interferometer under development for deployment in South Africa. HIRAX will comprise 1024 six meter parabolic dishes on a compact grid and will map most of the southern sky over the course of four years. HIRAX has two primary science goals: to constrain Dark Energy and measure structure at high redshift, and to study radio transients and pulsars. HIRAX will observe unresolved sources of neutral hydrogen via their redshifted 21-cm emission line (`hydrogen intensity mapping'). The resulting maps of large-scale structure at redshifts 0.8-2.5 will be used to measure Baryon Acoustic Oscillations (BAO). HIRAX will improve upon current BAO measurements from galaxy surveys by observing a larger cosmological volume (larger in both survey area and redshift range) and by measuring BAO at higher redshift when the expansion of the universe transitioned to Dark Energy domination. HIRAX will complement CHIME, a hydrogen intensity mapping experiment in the Northern Hemisphere, by completing the sky coverage in the same redshift range. HIRAX's location in the Southern Hemisphere also allows a variety of cross-correlation measurements with large-scale structure surveys at many wavelengths. Daily maps of a few thousand square degrees of the Southern Hemisphere, encompassing much of the Milky Way galaxy, will also open new opportunities for discovering and monitoring radio transients. The HIRAX correlator will have the ability to rapidly and eXperimentciently detect transient events. This new data will shed light on the poorly understood nature of fast radio bursts (FRBs), enable pulsar monitoring to enhance long-wavelength gravitational wave searches, and provide a rich data set for new radio transient phenomena searches. This paper discusses the HIRAX instrument, science goals, and current status.Comment: 11 pages, 5 figure

Treatment strategies in primary vitreoretinal lymphoma: a 17-center European collaborative study.

IMPORTANCE: The best treatment option for primary vitreoretinal lymphoma (PVRL) without signs of central nervous system lymphoma (CNSL) involvement determined on magnetic resonance imaging or in cerebrospinal fluid is unknown. OBJECTIVE: To evaluate the outcomes of treatment regimens used for PVRL in the prevention of subsequent CNSL. DESIGN, SETTING, AND PARTICIPANTS: A retrospective cohort study was conducted at 17 referral ophthalmologic centers in Europe. We reviewed clinical, laboratory, and imaging data on 78 patients with PVRL who did not have CNSL on presentation between January 1, 1991, and December 31, 2012, with a focus on the incidence of CNS manifestations during the follow-up period. INTERVENTIONS: The term extensive treatment was used for various combinations of systemic and intrathecal chemotherapy, whole-brain radiotherapy, and peripheral blood stem cell transplantation. Therapy to prevent CNSL included ocular radiotherapy and/or ocular chemotherapy (group A, 31 patients), extensive systemic treatment (group B, 21 patients), and a combination of ocular and extensive treatment (group C, 23 patients); 3 patients did not receive treatment. A total of 40 patients received systemic chemotherapy. MAIN OUTCOMES AND MEASURES: Development of CNSL following the diagnosis of PVRL relative to the use or nonuse of systemic chemotherapy and other treatment regimens. RESULTS: Overall, CNSL developed in 28 of 78 patients (36%) at a median follow-up of 49 months. Specifically, CNSL developed in 10 of 31 (32%) in group A, 9 of 21 (43%) in group B, and 9 of 23 (39%) in group C. The 5-year cumulative survival rate was lower in patients with CNSL (35% [95% CI, 50% to 86%]) than in patients without CNSL (68% [95% CI, 19% to 51%]; P = .003) and was similar among all treatment groups (P = .10). Adverse systemic effects occurred in 9 of 40 (23%) patients receiving systemic chemotherapy; the most common of these effects was acute renal failure. CONCLUSIONS AND RELEVANCE: In the present series of patients with isolated PVRL, the use of systemic chemotherapy was not proven to prevent CNSL and was associated with more severe adverse effects compared with local treatment

A Rational Strategy for Reducing On-Target Off-Tumor Effects of CD38-Chimeric Antigen Receptors by Affinity Optimization

Chimeric antigen receptors (CARs) can effectively redirect cytotoxic T cells toward highly expressed surface antigens on tumor cells. The low expression of several tumor-associated antigens (TAAs) on normal tissues, however, hinders their safe targeting by CAR T cells due to on-target/off-tumor effects. Using the multiple myeloma (MM)-associated CD38 antigen as a model system, here, we present a rational approach for effective and tumor-selective targeting of such TAAs. Using “light-chain exchange” technology, we combined the heavy chains of two high-affinity CD38 antibodies with 176 germline light chains and generated ∼124 new antibodies with 10- to >1,000-fold lower affinities to CD38. After categorizing them into three distinct affinity classes, we incorporated the single-chain variable fragments of eight antibodies from each class into new CARs. T cells carrying these CD38-CARs were extensively evaluated for their on-tumor/off-tumor cytotoxicity as well as CD38-dependent proliferation and cytokine production. We identified CD38-CAR T cells of ∼1,000- fold reduced affinity, which optimally proliferated, produced Th1-like cytokines, and effectively lysed CD382+ MM cells, but spared CD38+ healthy hematopoietic cells in vitro and in vivo. Thus, this systematic approach is highly suitable for the generation of optimal CARs for effective and selective targeting of TAAs

Vincristine, doxorubicin and dexamethasone (VAD) administered as rapid intravenous infusion for first-line treatment in untreated multiple myeloma

We examined the feasibility of achieving a rapid response in patients with previously untreated multiple myeloma by administering vincristine 0.4 mR and doxorubicin 9 mg/m2 as a rapid intravenous infusion for 4 d together with intermittent high-dose dexamethasone 40 mg (VAD) for remission induction treatment in patients who were scheduled to receive high-dose therapy. 139 patients (86 male, 53 female; median age 53 years, range 32-65 years; Durie and Salmon stage IIA: 42, IIB: one, IIIA: 89, IIIB: seven) were included in a prospective multicentre study in which VAD was administered as remission induction treatment and was followed by intensified treatment. The response was evaluated according to the criteria of the Eastern Cooperative Oncology Group (ECOG). The results of treatment were evaluable in 134 patients. Five patients died before evaluation. 86 patients (62%) achieved a partial response (PR) and seven patients (5%) achieved a complete response (CR), which equates to a response rate of 67%. The main side-effect was mild neurotoxicity, which was observed in 18% of the patients. Fever or infections were reported in 27% of the patients. VAD administered as an outpatient regimen, based on rapid intravenous infusion, is an effective induction regimen for untreated myeloma with a 67% response rate and acceptable toxicity