Određivanje aflatoksina, okratoksina A, fumonizina i zearalenona u žitaricama i krmivu primjenom kompetetivnoga direktnog imunoenzimatskog testa (CD-ELISA) i tankoslojne kromatografije (TLC)

Aspergillus, Penicillium, and Fusarium species frequently contaminate crops. For this reason mycotoxins such as afl atoxins (AFs), ochratoxin A (OTA), fumonisins (FBs), and zearalenone (ZEA) are found in food and feed in a wide range of concentrations, depending on environmental and storage conditions. Consumption of mycotoxin-contaminated food and feed has been associated with acute and chronic poisoning and carcinoma. The aim of this study was to determine the incidence and co-occurrence of AFs (B1+B2+G1+G2), OTA, FBs (B1+B2+B3), and ZEA in 37 samples of cereals and feed randomly collected in 2007 from households of an endemic nephropathy (EN) area in Croatia. The mycotoxins were determined using the competitive direct ELISA test (CD-ELISA) in combination with thin-layer chromatography (TLC). The most frequent mycotoxin was ZEA (92 %, mean 318.3 μg kg-1), followed by FBs (27 %, 3690 μg kg-1), AFs (24.3 %, 4.6 μg kg-1), and OTA (16.2 %, 9.8 μg kg-1). Levels of AFs, ZEA, and FBs detected by CD-ELISA signifi cantly correlated with the TLC results. However, only one OTA-positive sample was confi rmed by TLC due to its high limit of detection. The levels of these mycotoxins were below the permissible limit for animal feed. Twenty-nine percent of cereals were contaminated with FBs, OTA, or ZEA in mass fractions above the permissible limit for humans. Co-occurrence of two toxins varied between 4.2 % and 54 % and of three between 4.2 % and 7.6 %. Prolonged co-exposure to AFs, OTA, FBs, and ZEA might increase the risk of various chronic diseases.Vrste plijesni iz rodova Aspergillus, Penicillium i Fusarium česti su kontaminanti usjeva te na takvim supstratima tvore mikotoksine. Stoga su žitarice i krmiva često kontaminirana afl atoksinima (AFs), okratoksinom A (OTA), fumonizinima (FBs) i zearalenonom (ZEA) u različitim koncentracijama ovisno o mikroklimatskim uvjetima na polju i u skladištu. Konzumiranje hrane kontaminirane mikotoksinima često je povezano s akutnim ili kroničnim trovanjima, ali i s razvojem karcinoma. Cilj ovog rada bio je odrediti istodobnu pojavnost AFs (B1+B2+G1+G2), OTA, FBs (B1+B2+B3) i ZEA u uzorcima žitarica i krme (N=37) koji su nasumično skupljeni u individualnim domaćinstvima na području endemske nefropatije (EN) u Hrvatskoj (2007). Za određivanje navedenih mikotoksina korišten je kompetitivni direktni ELISA-test (CD-ELISA) u kombinaciji s tankoslojnom kromatografi jom (TLC). Najzastupljeniji mikotoksin bio je ZEA (92 %, srednja koncentracija 318.3 μg kg-1), nakon čega slijede FBs (27 %, 3690 μg kg-1), AFs (24.3 %, 4.6 μg kg-1) te OTA (16.2 %, 9.8 μg kg-1). Koncentracije AFs, FBs i ZEA određene CD-ELISA-testom statistički značajno koreliraju s rezultatima dobivenim s TLC. OTA je potvrđen metodom TLC samo u jednom uzorku zbog visokog limita detekcije. Dokazane koncentracije su ispod razina dopuštenih za krmiva, dok je 29 % uzoraka žitarica sadržavalo FBs, OTA ili ZEA u koncentracijama iznad dopuštenih u hrani za ljude. Kokontaminacija s dvama odnosno trima toksinima varirala je između 4.2 % i 54 % odnosno između 4.2 % i 7.6 %. Dugotrajni unos AFs, OTA, FBs i ZEA putem hrane može povećati rizik od razvoja različitih kroničnih bolesti zbog njihova mogućega sinergističkog djelovanja

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

Finding Diagnostically Useful Patterns in Quantitative Phenotypic Data.

Trio-based whole-exome sequence (WES) data have established confident genetic diagnoses in ∼40% of previously undiagnosed individuals recruited to the Deciphering Developmental Disorders (DDD) study. Here we aim to use the breadth of phenotypic information recorded in DDD to augment diagnosis and disease variant discovery in probands. Median Euclidean distances (mEuD) were employed as a simple measure of similarity of quantitative phenotypic data within sets of ≥10 individuals with plausibly causative de novo mutations (DNM) in 28 different developmental disorder genes. 13/28 (46.4%) showed significant similarity for growth or developmental milestone metrics, 10/28 (35.7%) showed similarity in HPO term usage, and 12/28 (43%) showed no phenotypic similarity. Pairwise comparisons of individuals with high-impact inherited variants to the 32 individuals with causative DNM in ANKRD11 using only growth z-scores highlighted 5 likely causative inherited variants and two unrecognized DNM resulting in an 18% diagnostic uplift for this gene. Using an independent approach, naive Bayes classification of growth and developmental data produced reasonably discriminative models for the 24 DNM genes with sufficiently complete data. An unsupervised naive Bayes classification of 6,993 probands with WES data and sufficient phenotypic information defined 23 in silico syndromes (ISSs) and was used to test a "phenotype first" approach to the discovery of causative genotypes using WES variants strictly filtered on allele frequency, mutation consequence, and evidence of constraint in humans. This highlighted heterozygous de novo nonsynonymous variants in SPTBN2 as causative in three DDD probands

Baseline characteristics of patients in the reduction of events with darbepoetin alfa in heart failure trial (RED-HF)

<p>Aims: This report describes the baseline characteristics of patients in the Reduction of Events with Darbepoetin alfa in Heart Failure trial (RED-HF) which is testing the hypothesis that anaemia correction with darbepoetin alfa will reduce the composite endpoint of death from any cause or hospital admission for worsening heart failure, and improve other outcomes.</p> <p>Methods and results: Key demographic, clinical, and laboratory findings, along with baseline treatment, are reported and compared with those of patients in other recent clinical trials in heart failure. Compared with other recent trials, RED-HF enrolled more elderly [mean age 70 (SD 11.4) years], female (41%), and black (9%) patients. RED-HF patients more often had diabetes (46%) and renal impairment (72% had an estimated glomerular filtration rate <60 mL/min/1.73 m2). Patients in RED-HF had heart failure of longer duration [5.3 (5.4) years], worse NYHA class (35% II, 63% III, and 2% IV), and more signs of congestion. Mean EF was 30% (6.8%). RED-HF patients were well treated at randomization, and pharmacological therapy at baseline was broadly similar to that of other recent trials, taking account of study-specific inclusion/exclusion criteria. Median (interquartile range) haemoglobin at baseline was 112 (106–117) g/L.</p> <p>Conclusion: The anaemic patients enrolled in RED-HF were older, moderately to markedly symptomatic, and had extensive co-morbidity.</p&gt

Combining farmers' decision rules and landscape stochastic regularities for landscape modelling

International audienceLandscape spatial organization (LSO) strongly impacts many environmental issues. Modelling agricultural landscapes and describing meaningful landscape patterns are thus regarded as key-issues for designing sustainable landscapes. Agricultural landscapes are mostly designed by farmers. Their decisions dealing with crop choices and crop allocation to land can be generic and result in landscape regularities, which determine LSO. This paper comes within the emerging discipline called "landscape agronomy", aiming at studying the organization of farming practices at the landscape scale. We here aim at articulating the farm and the landscape scales for landscape modelling. To do so, we develop an original approach consisting in the combination of two methods used separately so far: the identification of explicit farmer decision rules through on-farm surveys methods and the identification of landscape stochastic regularities through data-mining. We applied this approach to the Niort plain landscape in France. Results show that generic farmer decision rules dealing with sunflower or maize area and location within landscapes are consistent with spatiotemporal regularities identified at the landscape scale. It results in a segmentation of the landscape, based on both its spatial and temporal organization and partly explained by generic farmer decision rules. This consistency between results points out that the two modelling methods aid one another for land-use modelling at landscape scale and for understanding the driving forces of its spatial organization. Despite some remaining challenges, our study in landscape agronomy accounts for both spatial and temporal dimensions of crop allocation: it allows the drawing of new spatial patterns coherent with land-use dynamics at the landscape scale, which improves the links to the scale of ecological processes and therefore contributes to landscape ecology.L'organisation du paysage influe sur les problèmes environnementaux. Modéliser les paysages pour les décrire à l'aide de formes significatives est une étage clé. Les paysages agricoles sont principalement construits par les agriculteurs dont les décision d'assolement peuvent être génériques et déterminer des régularités dans l'organisation du paysage. Cet article contribue à l'agronomie des paysage qui est une discipline émergente. Nous cherchons à articuler les échelles du paysage et de l'exploitation agricole en développant deux méthodes : l'une consiste à identifier les décisions des agriculteurs par le bais d'enquêtes, l'autre consiste à retrouver des régularités stochastiques dans le paysage par le bais de fouille de données. Nous avons appliqué cette approche au paysage de la plaine de Niort en France. Les résultats montrent que les décisions des agriculteurs en matière de tournesol et maïs sont génériques et ont des effets sur le paysages que des méthodes de fouille de données révèlent et quantifient

Origin and timing of siderite cementation in Upper Ordovician glaciogenic sandstones from the Murzuq basin, SW Libya

The origin and timing of siderite cementation have been constrained in relation to depositional facies and sequence stratigraphy of Upper Ordovician glaciogenic sandstones from the Murzuq basin, SW Libya. Optical microscope, backscattered electron imagery, and carbon and oxygen stable isotope analysis have revealed that siderite is of eo- and mesogenetic origin. Eogenetic siderite is Mg-poor with a mean composition of (Fe91.7Mg1.5Ca0.3Mn6.5)CO3, and occurs in paraglacial, tide-dominated deltaic highstand systems tract (HST) sandstones, in paraglacial, foreshore to shoreface HST sandstones and in postglacial, Gilbert-type deltaic lowstand systems tract (LST) sandstones. This siderite is typically of meteoric water origin that influxed into the LST and HST sandstones during relative sea level fall and basinward shift of the strandline. Mesogenetic siderite, which engulfs and thus postdates quartz overgrowths and illite, is Mg-rich with a mean composition of (Fe72.2Mg21.7Ca0.8Mn5.3)CO3 and occurs in the paraglacial, tide-dominated deltaic HST sandstones, in paraglacial foreshore to shoreface HST sandstones, in glacial, tide-dominated estuarine transgressive systems tract (TST) sandstones, in postglacial, Gilbert-type deltaic LST sandstones, and in postglacial, shoreface TST sandstones. δ18OV-PDB values of this siderite, which range between −22.6 and −13.8‰, suggest that precipitation has occurred from evolved formation waters with δ18O values between −14.0 and +1.0‰ and was either meteoric, mixed marine–meteoric and/or marine in origin by assuming postdating quartz overgrowths and illite temperature between 80 and 130 °C