State of organic seeds in France

A comprehensive range of investigations carried out between 2010 and 2012 provided information on the state of organic seeds in France. Results fit with the hypothesis that the market is a significant factor influencing the choice of seeds and cultivars (local cultivars, landraces, modern cultivars). Expectations and practices of producers selling on a local market (i.e., direct sale) differ radically from those of producers selling to long food supply chains. This study showed that the availability and use of organic seeds have significantly improved over the last three years. A vast majority of organic producers willingly use organic seeds, with, on average, 45-70 % (cereals), and 75%-100 % (vegetables) of organic seeds being planted on farms. However, the total number of derogations remained quite high: there is still space for improvement in organic seed use and supply in France. Several limiting factors and levers were identified during the study, as well as farmers’ expectations for the future on cereals, forage crops and vegetables. This study described an action plan, which must be carefully implemented. The organic sector depends on the development of a wide and adapted range of organic seeds

A bio-inspired image coder with temporal scalability

We present a novel bio-inspired and dynamic coding scheme for static images. Our coder aims at reproducing the main steps of the visual stimulus processing in the mammalian retina taking into account its time behavior. The main novelty of this work is to show how to exploit the time behavior of the retina cells to ensure, in a simple way, scalability and bit allocation. To do so, our main source of inspiration will be the biologically plausible retina model called Virtual Retina. Following a similar structure, our model has two stages. The first stage is an image transform which is performed by the outer layers in the retina. Here it is modelled by filtering the image with a bank of difference of Gaussians with time-delays. The second stage is a time-dependent analog-to-digital conversion which is performed by the inner layers in the retina. Thanks to its conception, our coder enables scalability and bit allocation across time. Also, our decoded images do not show annoying artefacts such as ringing and block effects. As a whole, this article shows how to capture the main properties of a biological system, here the retina, in order to design a new efficient coder.Comment: 12 pages; Advanced Concepts for Intelligent Vision Systems (ACIVS 2011

A phase I and II study of 2-weekly irinotecan with capecitabine in advanced gastroesophageal adenocarcinoma

We investigated 2-weekly intravenous irinotecan combined with oral capecitabine in patients with advanced gastroesophageal adenocarcinoma. In phase I, doses were escalated in chemotherapy naïve or pretreated patients to establish maximum tolerated doses (MTD). In phase II, patients were treated at MTD as first-line therapy with the primary end point of RECIST response. Dose levels in phase I were as follows: Level 1: irinotecan 150 mg m−2 on day 1; capecitabine 850 mg m−2 12-hourly on days 1–9. Level 2: as level 1 but capecitabine 1000 mg m−2. Level 3: as level 2 but irinotecan 180 mg m−2. Level 4: as level 3 but capecitabine 1250 mg m−2. In phase I, 21 patients were entered. Maximum tolerated dose was level 3. Dose-limiting toxicities were lethargy, diarrhoea, vomiting and mucositis. In phase II, 31 patients were entered at level 3. During the first six cycles, 13 of these patients underwent dose reduction and three patients stopped treatment for toxicity. A further six patients stopped for progressive disease. The commonest grade 3–4 toxicities were lethargy (20%), diarrhoea (17%), nausea (10%) and anorexia (10%). There were no treatment-related deaths. The response rate was 32% (95% CI 16–52%). Median overall survival was 10 months. This regimen is active in gastroesophageal adenocarcinoma. However, using the MTD defined in phase I, fewer than 50% patients tolerated six cycles without modification in phase II; therefore, modification of these doses is recommended for further study

Insight into the origin of trapping in polymer/fullerene blends with a systematic alteration of the fullerene to higher adducts

The bimolecular recombination characteristics of conjugated polymer poly[(4,4′-bis(2-ethylhexyl)dithieno[3,2-b:2′,3′-d]silole)-2,6-diyl-alt-(2,5-bis 3-tetradecylthiophen-2-yl thiazolo 5,4-d thiazole)-2,5diyl] (PDTSiTTz) blended with the fullerene series PC60BM, ICMA, ICBA, and ICTA have been investigated using microsecond and femtosecond transient absorption spectroscopy, in conjunction with electroluminescence measurements and ambient photoemission spectroscopy. The non-Langevin polymer PDTSiTTz allows an inspection of intrinsic bimolecular recombination rates uninhibited by diffusion, while the low oscillator strengths of fullerenes allow polymer features to dominate, and we compare our results to those of the well-known polymer Si-PCPDTBT. Using μs-TAS, we have shown that the trap-limited decay dynamics of the PDTSiTTz polaron becomes progressively slower across the fullerene series, while those of Si-PCPDTBT are invariant. Electroluminescence measurements showed an unusual double peak in pristine PDTSiTTz, attributed to a low energy intragap charge transfer state, likely interchain in nature. Furthermore, while the pristine PDTSiTTz showed a broad, low-intensity density of states, the ICBA and ICTA blends presented a virtually identical DOS to Si-PCPDTBT and its blends. This has been attributed to a shift from a delocalized, interchain highest occupied molecular orbital (HOMO) in the pristine material to a dithienosilole-centered HOMO in the blends, likely a result of the bulky fullerenes increasing interchain separation. This HOMO localization had a side effect of progressively shifting the polymer HOMO to shallower energies, which was correlated with the observed decrease in bimolecular recombination rate and increased “trap” depth. However, since the density of tail states remained the same, this suggests that the traditional viewpoint of “trapping” being dominated by tail states may not encompass the full picture and that the breadth of the DOS may also have a strong influence on bimolecular recombination

Modified FOLFOX-6 chemotherapy in advanced gastric cancer: Results of phase II study and comprehensive analysis of polymorphisms as a predictive and prognostic marker

<p>Abstract</p> <p>Background</p> <p>The objective of this study was to evaluate the efficacy and toxicity of infusional 5-fluorouracil (5-FU), folinic acid and oxaliplatin (modified FOLFOX-6) in patients with advanced gastric cancer (AGC), as first-line palliative combination chemotherapy. We also analyzed the predictive or prognostic value of germline polymorphisms of candidate genes associated with 5-FU and oxaliplatin.</p> <p>Methods</p> <p>Seventy-three patients were administered a 2 hour infusion of oxaliplatin (100 mg/m²) and folinic acid (100 mg/m²) followed by a 46 hour continuous infusion of 5-FU (2,400 mg/m²). Genomic DNA from the patients' peripheral blood mononuclear cells was extracted. Ten polymorphisms within five genes were investigated including TS, GSTP, ERCC, XPD and XRCC.</p> <p>Results</p> <p>The overall response rate (RR) was 43.8%. Median time to progression (TTP) and overall survival (OS) were 6.0 months and 12.6 months, respectively. Toxicities were generally tolerable and manageable. The RR was significantly higher in patients with a 6-bp deletion homozygote (-6 bp/-6 bp) in TS-3'UTR (55.0% <it>vs</it>. 30.3% in +6 bp/+6 bp or +6 bp/-6 bp, <it>p </it>= 0.034), and C/A or A/A in XPD156 (52.0% <it>vs</it>. 26.1% in C/C, <it>p </it>= 0.038). The -6 bp/-6 bp in TS-3'UTR was significantly associated with a prolonged TTP and OS. In a multivariate analysis, the 6-bp deletion in TS-3'UTR was identified as an independent prognostic marker of TTP (hazard ratio = 0.561, <it>p </it>= 0.032).</p> <p>Conclusion</p> <p>Modified FOLFOX-6 chemotherapy appears to be active and well tolerated as first line chemotherapy in AGC patients. The 6-bp deletion in TS-3'UTR might be a candidate to select patients who are likely to benefit from 5-FU based modified FOLFOX-6 in future large scale trial.</p

Cross talk between hedgehog and epithelial–mesenchymal transition pathways in gastric pit cells and in diffuse-type gastric cancers

We previously reported hedgehog (Hh) signal activation in the mucus-secreting pit cell of the stomach and in diffuse-type gastric cancer (GC). Epithelial–mesenchymal transition (EMT) is known to be involved in tumour malignancy. However, little is known about whether and how both signallings cooperatively act in diffuse-type GC. By microarray and reverse transcription–PCR, we investigated the expression of those Hh and EMT signalling molecules in pit cells and in diffuse-type GCs. How both signallings act cooperatively in those cells was also investigated by the treatment of an Hh-signal inhibitor and siRNAs of Hh and EMT transcriptional key regulator genes on a mouse primary culture and on human GC cell lines. Pit cells and diffuse-type GCs co-expressed many Hh and EMT signalling genes. Mesenchymal-related genes (WNT5A, CDH2, PDGFRB, EDNRA, ROBO1, ROR2, and MEF2C) were found to be activated by an EMT regulator, SIP1/ZFHX1B/ZEB2, which was a target of a primary transcriptional regulator GLI1 in Hh signal. Furthermore, we identified two cancer-specific Hh targets, ELK1 and MSX2, which have an essential role in GC cell growth. These findings suggest that the gastric pit cell exhibits mesenchymal-like gene expression, and that diffuse-type GC maintains expression through the Hh–EMT pathway. Our proposed extensive Hh–EMT signal pathway has the potential to an understanding of diffuse-type GC and to the development of new drugs

Improved risk stratification of patients with atrial fibrillation: an integrated GARFIELD-AF tool for the prediction of mortality, stroke and bleed in patients with and without anticoagulation.

OBJECTIVES: To provide an accurate, web-based tool for stratifying patients with atrial fibrillation to facilitate decisions on the potential benefits/risks of anticoagulation, based on mortality, stroke and bleeding risks. DESIGN: The new tool was developed, using stepwise regression, for all and then applied to lower risk patients. C-statistics were compared with CHA2DS2-VASc using 30-fold cross-validation to control for overfitting. External validation was undertaken in an independent dataset, Outcome Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF). PARTICIPANTS: Data from 39 898 patients enrolled in the prospective GARFIELD-AF registry provided the basis for deriving and validating an integrated risk tool to predict stroke risk, mortality and bleeding risk. RESULTS: The discriminatory value of the GARFIELD-AF risk model was superior to CHA2DS2-VASc for patients with or without anticoagulation. C-statistics (95% CI) for all-cause mortality, ischaemic stroke/systemic embolism and haemorrhagic stroke/major bleeding (treated patients) were: 0.77 (0.76 to 0.78), 0.69 (0.67 to 0.71) and 0.66 (0.62 to 0.69), respectively, for the GARFIELD-AF risk models, and 0.66 (0.64-0.67), 0.64 (0.61-0.66) and 0.64 (0.61-0.68), respectively, for CHA2DS2-VASc (or HAS-BLED for bleeding). In very low to low risk patients (CHA2DS2-VASc 0 or 1 (men) and 1 or 2 (women)), the CHA2DS2-VASc and HAS-BLED (for bleeding) scores offered weak discriminatory value for mortality, stroke/systemic embolism and major bleeding. C-statistics for the GARFIELD-AF risk tool were 0.69 (0.64 to 0.75), 0.65 (0.56 to 0.73) and 0.60 (0.47 to 0.73) for each end point, respectively, versus 0.50 (0.45 to 0.55), 0.59 (0.50 to 0.67) and 0.55 (0.53 to 0.56) for CHA2DS2-VASc (or HAS-BLED for bleeding). Upon validation in the ORBIT-AF population, C-statistics showed that the GARFIELD-AF risk tool was effective for predicting 1-year all-cause mortality using the full and simplified model for all-cause mortality: C-statistics 0.75 (0.73 to 0.77) and 0.75 (0.73 to 0.77), respectively, and for predicting for any stroke or systemic embolism over 1 year, C-statistics 0.68 (0.62 to 0.74). CONCLUSIONS: Performance of the GARFIELD-AF risk tool was superior to CHA2DS2-VASc in predicting stroke and mortality and superior to HAS-BLED for bleeding, overall and in lower risk patients. The GARFIELD-AF tool has the potential for incorporation in routine electronic systems, and for the first time, permits simultaneous evaluation of ischaemic stroke, mortality and bleeding risks. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier for GARFIELD-AF (NCT01090362) and for ORBIT-AF (NCT01165710)

Two-year outcomes of patients with newly diagnosed atrial fibrillation: results from GARFIELD-AF.

AIMS: The relationship between outcomes and time after diagnosis for patients with non-valvular atrial fibrillation (NVAF) is poorly defined, especially beyond the first year. METHODS AND RESULTS: GARFIELD-AF is an ongoing, global observational study of adults with newly diagnosed NVAF. Two-year outcomes of 17 162 patients prospectively enrolled in GARFIELD-AF were analysed in light of baseline characteristics, risk profiles for stroke/systemic embolism (SE), and antithrombotic therapy. The mean (standard deviation) age was 69.8 (11.4) years, 43.8% were women, and the mean CHA2DS2-VASc score was 3.3 (1.6); 60.8% of patients were prescribed anticoagulant therapy with/without antiplatelet (AP) therapy, 27.4% AP monotherapy, and 11.8% no antithrombotic therapy. At 2-year follow-up, all-cause mortality, stroke/SE, and major bleeding had occurred at a rate (95% confidence interval) of 3.83 (3.62; 4.05), 1.25 (1.13; 1.38), and 0.70 (0.62; 0.81) per 100 person-years, respectively. Rates for all three major events were highest during the first 4 months. Congestive heart failure, acute coronary syndromes, sudden/unwitnessed death, malignancy, respiratory failure, and infection/sepsis accounted for 65% of all known causes of death and strokes for <10%. Anticoagulant treatment was associated with a 35% lower risk of death. CONCLUSION: The most frequent of the three major outcome measures was death, whose most common causes are not known to be significantly influenced by anticoagulation. This suggests that a more comprehensive approach to the management of NVAF may be needed to improve outcome. This could include, in addition to anticoagulation, interventions targeting modifiable, cause-specific risk factors for death. CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

Recent progress towards development of effective systemic chemotherapy for the treatment of malignant brain tumors

Systemic chemotherapy has been relatively ineffective in the treatment of malignant brain tumors even though systemic chemotherapy drugs are small molecules that can readily extravasate across the porous blood-brain tumor barrier of malignant brain tumor microvasculature. Small molecule systemic chemotherapy drugs maintain peak blood concentrations for only minutes, and therefore, do not accumulate to therapeutic concentrations within individual brain tumor cells. The physiologic upper limit of pore size in the blood-brain tumor barrier of malignant brain tumor microvasculature is approximately 12 nanometers. Spherical nanoparticles ranging between 7 nm and 10 nm in diameter maintain peak blood concentrations for several hours and are sufficiently smaller than the 12 nm physiologic upper limit of pore size in the blood-brain tumor barrier to accumulate to therapeutic concentrations within individual brain tumor cells. Therefore, nanoparticles bearing chemotherapy that are within the 7 to 10 nm size range can be used to deliver therapeutic concentrations of small molecule chemotherapy drugs across the blood-brain tumor barrier into individual brain tumor cells. The initial therapeutic efficacy of the Gd-G5-doxorubicin dendrimer, an imageable nanoparticle bearing chemotherapy within the 7 to 10 nm size range, has been demonstrated in the orthotopic RG-2 rodent malignant glioma model. Herein I discuss this novel strategy to improve the effectiveness of systemic chemotherapy for the treatment of malignant brain tumors and the therapeutic implications thereof

A Diffusive Homeostatic Signal Maintains Neural Heterogeneity and Responsiveness in Cortical Networks

Gaseous neurotransmitters such as nitric oxide (NO) provide a unique and often overlooked mechanism for neurons to communicate through diffusion within a network, independent of synaptic connectivity. NO provides homeostatic control of intrinsic excitability. Here we conduct a theoretical investigation of the distinguishing roles of NO-mediated diffusive homeostasis in comparison with canonical non-diffusive homeostasis in cortical networks. We find that both forms of homeostasis provide a robust mechanism for maintaining stable activity following perturbations. However, the resulting networks differ, with diffusive homeostasis maintaining substantial heterogeneity in activity levels of individual neurons, a feature disrupted in networks with non-diffusive homeostasis. This results in networks capable of representing input heterogeneity, and linearly responding over a broader range of inputs than those undergoing non-diffusive homeostasis. We further show that these properties are preserved when homeostatic and Hebbian plasticity are combined. These results suggest a mechanism for dynamically maintaining neural heterogeneity, and expose computational advantages of non-local homeostatic processes