Methodological and empirical progress and challenges in integrated assessment of agricultural systems and policies

In this contribution we first present a methodology for integrated assessment of agricultural systems (SEAMLESS Integrated Framework), illustrate its application in an integrated assessment of high commodity prices and then discuss its flexibility and limitations. From there we take a broader view and reflect on key scientific and empirical questions with respect to the development of research tools for the integrated assessment of agricultural systems.agricultural systems, integrated assessment, modelling, Agricultural and Food Policy, Farm Management,

Analysis of N- and K-Ras Mutations in the Distinctive Tumor Progression Phases of Melanoma

Mutations in the ras genes are key events in the process of carcinogenesis; in particular, point mutations in codon 61 of exon 2 of the N-ras gene occur frequently in cutaneous melanoma. To investigate whether these mutations occur in early or late tumor progression phases, we searched for point mutations in the N- and K-ras genes in 69 primary cutaneous melanoma, 35 metastases, and seven nevocellular nevi in association with cutaneous melanoma. Lesions were microdissected in order to procure pure tumor samples from the distinctive growth phases of the cutaneous melanoma; the very sensitive denaturing gradient gel electrophoresis technique was used to visualize the mutations, and was followed by sequencing. Point mutations in the N-ras gene but not in the K-ras gene were detected on denaturing gradient gel electrophoresis. Twenty-three primary (33%) and nine metastatic (26%) melanomas showed bandshifts for N-ras. In the majority of cases, mutations occurring in early growth phases (i.e., the “intraepidermal” radial growth phase), were preserved in later growth phases (i.e., the invasive radial growth phase, vertical growth phase, and metastatic phase), which proves the clonal relationship between the successive growth phases. In three cases, however, the mutations differed between the distinctive growth phases within the same cutaneous melanoma, due to the occurrence of an additional mutation (especially in codon 61) in a later tumor progression phase. Our approach also permitted us to analyze the mutational status of nevi, associated with cutaneous melanoma. Six out of seven associated nevi carried the same sequence (mutated or wild-type) as the primary cutaneous melanoma, whereas in one case the sequence for N-ras differed between the primary melanoma and the associated nevus. In conclusion, this approach allowed us to demonstrate the clonal relationship between subsequent growth phases of melanoma and associated nevi; our results suggest that N-ras exon 1 mutations preferentially occur during early stages of tumor progression and hence may be involved in melanoma initiation, whereas those in N-ras exon 2 are found preferentially during later stages and hence are more probably involved in metastatic spread of cutaneous melanoma

Lebanese traders in Cotonou: A socio-cultural analysis of economic mobility and capital accumulation

Passenger cars and other small vehicles have for a long time been the backbone of transport in west Africa. The cars are usually second-hand, and they are sourced on overseas car markets, mostly in western Europe. During the 1990s the port town of Cotonou, Bénin, became one of the most prominent hubs in this car trade: car markets mushroomed, attracting large numbers and a wide variety of traders - including a prominent contingent of Lebanese. This article discusses the role of these Lebanese traders in the car trade through a reconstruction of their careers. It reveals that Lebanese business, which can go through a rapid succession of different economic activities, starts as kin-based enterprise, but gradually incorporates peers and friends. Close analysis of this practice suggests that Lebanese immigrant traders are to a large extent driven by the ideal of enjoying life by adopting an expatriate lifestyle

6-Mercaptopurine, still valuable for the palliative treatment of acute myeloid leukaemia

Although 6-mercaptopurine (6-MP) is frequently used in the treatment of acute myeloid leukaemia (AML), its effect on disease progression has not been studied systematically. In a small retrospective analysis, we found that 6-MP could induce marked haematological improvement in a considerable number of AML patients who were not treated with intensive remission induction courses. Due to the inherent limitations of retrospective analyses, we then investigated prospectively in 51 consecutive patients over a 3-year period in a single centre, to what extent, oral 6-MP 250 mg twice a week could be beneficial to AML patients who were not-or no longer-eligible for intensive chemotherapy. Clinical response was scored according to changes in blood cell counts and dependency on blood transfusions. Thirteen patients (25%) were considered responders since they showed an increased platelet count from the first month after initiation of 6-MP onwards and they became independent of blood transfusions after 3 months. This effect lasted for 13 (range 7-30+) months. Median overall survival of this subgroup was 16.5 (6-33+) months. Ten patients (20%) had a shorter or incomplete response and a survival of 12 (6-30) months. Seven patients were lost to follow-up. Twenty-one (41%) failed to respond and survived for 4 (1.5-17) months. The response seemed not to be affected by previous chemotherapy, history of myelodysplasia, or karyotype abnormalities, but high leukocyte count initially was unfavourable. 6-MP thus can induce marked improvement of blood cell counts in a considerable proportion of AML patients who are not eligible for intensive chemotherapy, leading to good quality of life and a significant prolongation of survival.</p

safety and efficacy of fidaxomicin and vancomycin in children and adolescents with clostridioides clostridium difficile infection a phase 3 multicenter randomized single blind clinical trial sunshine

Abstract Background Fidaxomicin, a narrow-spectrum antibiotic approved for Clostridioides (Clostridium) difficile infection (CDI) in adults, is associated with lower rates of recurrence than vancomycin; however, pediatric data are limited. This multicenter, investigator-blind, phase 3, parallel-group trial assessed the safety and efficacy of fidaxomicin in children. Methods Patients aged &lt;18 years with confirmed CDI were randomized 2:1 to 10 days of treatment with fidaxomicin (suspension or tablets, twice daily) or vancomycin (suspension or tablets, 4 times daily). Safety assessments included treatment-emergent adverse events. The primary efficacy end point was confirmed clinical response (CCR), 2 days after the end of treatment (EOT). Secondary end points included global cure (GC; CCR without CDI recurrence) 30 days after EOT (end of study; EOS). Plasma and stool concentrations of fidaxomicin and its active metabolite OP-1118 were measured. Results Of 148 patients randomized, 142 were treated (30 &lt;2 years old). The proportion of participants with treatment-emergent adverse events was similar with fidaxomicin (73.5%) and vancomycin (75.0%). Of 3 deaths in the fidaxomicin arm during the study, none were CDI or treatment related. The rate of CCR at 2 days after EOT was 77.6% (76 of 98 patients) with fidaxomicin and 70.5% (31 of 44) with vancomycin, whereas the rate of GC at EOS was significantly higher in participants receiving fidaxomicin (68.4% vs 50.0%; adjusted treatment difference, 18.8%; 95% confidence interval, 1.5%–35.3%). Systemic absorption of fidaxomicin and OP-1118 was minimal, and stool concentrations were high. Conclusions Compared with vancomycin, fidaxomicin was well tolerated and demonstrated significantly higher rates of GC in children and adolescents with CDI. ClinicalTrials.gov identifier NCT0221837

Use of agro-climatic zones to upscale simulated crop yield potential

Yield gap analysis, which evaluates magnitude and variability of difference between crop yield potential (Yp) or water limited yield potential (Yw) and actual farm yields, provides a measure of untapped food production capacity. Reliable location-specific estimates of yield gaps, either derived from research plots or simulation models, are available only for a limited number of locations and crops due to cost and time required for field studies or for obtaining data on long-term weather, crop rotations and management practices, and soil properties. Given these constraints, we compare global agro-climatic zonation schemes for suitability to up-scale location-specific estimates of Yp and Yw, which are the basis for estimating yield gaps at regional, national, and global scales. Six global climate zonation schemes were evaluated for climatic homogeneity within delineated climate zones (CZs) and coverage of crop area. An efficient CZ scheme should strike an effective balance between zone size and number of zones required to cover a large portion of harvested area of major food crops. Climate heterogeneity was very large in CZ schemes with less than 100 zones. Of the other four schemes, the Global Yield Gap Atlas Extrapolation Domain (GYGA-ED) approach, based on a matrix of three categorical variables (growing degree days, aridity index, temperature seasonality) to delineate CZs for harvested area of all major food crops, achieved reasonable balance between number of CZs to cover 80% of global crop area and climate homogeneity within zones. While CZ schemes derived from two climate-related categorical variables require a similar number of zones to cover 80% of crop area, within-zone heterogeneity is substantially greater than for the GYGA-ED for most weather variables that are sensitive drivers of crop production. Some CZ schemes are cropspecific, which limits utility for up-scaling location-specific evaluation of yield gaps in regions with crop rotations rather than single crop species