Room temperature spin filtering in epitaxial cobalt-ferrite tunnel barriers

We report direct experimental evidence of room temperature spin filtering in magnetic tunnel junctions (MTJs) containing CoFe2O4 tunnel barriers via tunneling magnetoresistance (TMR) measurements. Pt(111)/CoFe2O4(111)/gamma-Al2O3(111)/Co(0001) fully epitaxial MTJs were grown in order to obtain a high quality system, capable of functioning at room temperature. Spin polarized transport measurements reveal significant TMR values of -18% at 2 K and -3% at 290 K. In addition, the TMR ratio follows a unique bias voltage dependence that has been theoretically predicted to be the signature of spin filtering in MTJs containing magnetic barriers. CoFe2O4 tunnel barriers therefore provide a model system to investigate spin filtering in a wide range of temperatures.Comment: 6 pages, 3 figure

An innovative ethosuximide granule formulation designed for pediatric use: Comparative pharmacokinetics, safety, tolerability, and palatability profile versus reference syrup.

Ethosuximide, the first-line therapy for childhood absence epilepsy, is currently formulated as a syrup (Zarontin®, Pfizer) with a bitter taste and high sugar content, poorly adapted to children, and a ketogenic diet. The collaborative European FP7 project KIEKIDS aimed at developing an innovative sugar-free, tasteless formulation convenient for pediatric use. This dual Phase-I study evaluated two granule formulations based on lipid multiparticulate (LMP) technology. Two panels of 6 healthy adult volunteers underwent a randomized, placebo-controlled, partly blinded, 3-way cross-over trial, comparing ethosuximide granules A or B with placebo granules and syrup at single 10 mg/kg doses. Corresponding plasma pharmacokinetic profiles of ethosuximide were compared, along with palatability, safety, and tolerability. The LMP granule A proved suboptimal due to bitterness and adherence to beaker walls, while the optimized granule B revealed excellent palatability, similar to placebo granules, and low adherence to glass. The relative bioavailability of granules A versus syrup, based on dose-normalized C <sub>max</sub> and AUC <sub>0-∞</sub> was 93.7% [90% CI: 76.3-115.1] and 96.1% [91.0-101.5], respectively. For granules B it was 87.6% [81.6-94.0] and 92.5% [88.5-96.6], respectively, with slightly delayed t <sub>max</sub> of 0.75 h [0.5-4.05] compared to syrup 0.5 h [0.3-0.8]. Tolerability visual analog scales revealed a trend for statistically non-significant improvement versus syrup at peak (30 min) for transient dizziness (both granules), fatigue (granules A), and anxiety (granules B). The innovative ethosuximide granule formulation B achieves a suitable profile for pediatric use, being sugar-free, tasteless, bioequivalent, and well-tolerated while enabling precise adjustment to body weight

Evaluation of serum CEA, CYFRA21-1 and CA125 for the early detection of colorectal cancer using longitudinal preclinical samples

Blood-borne biomarkers for early detection of colorectal cancer (CRC) could markedly increase screening uptake. The aim of this study was to evaluate serum carcinoembryonic antigen (CEA), CYFRA21-1 and CA125 for the early detection of CRC in an asymptomatic cohort

Pediatr Nephrol

BACKGROUND: Distal renal tubular acidosis (dRTA), due to impaired acid secretion in the urine, can lead to severe long-term consequences. Standard of care (SoC) oral alkalizers, requiring several daily intakes, are currently used to restore normal plasma bicarbonate levels. A new prolonged-release formulation, ADV7103, has been developed to achieve a sustained effect with an improved dosing scheme. METHODS: In a multicenter, open-label, non-inferiority trial (n = 37), patients with dRTA were switched from SoC to ADV7103. Mean plasma bicarbonate values and proportion of responders during steady state therapy with both treatments were compared, as were other blood and urine parameters, as well as acceptability, tolerability, and safety. RESULTS: When switching from SoC to ADV7103, the number of daily intakes was reduced from a median of three to twice daily. Mean plasma bicarbonate was increased and non-inferiority of ADV7103 was demonstrated (p < 0.0001, per protocol), as was statistical superiority (p = 0.0008, intention to treat [ITT]), and the response rate increased from 43 to 90% with ADV7103 (p < 0.001, ITT). Urine calcium/citrate ratio was reduced below the threshold for risk of lithogenesis with ADV7103 in 56% of previously non-responders with SoC (p = 0.021, ITT). Palatability was improved (difference [95% CI] of 25 [10.7, 39.2] mm) and gastrointestinal discomfort was reduced (difference [95% CI] of - 14.2 [- 25.9, - 2.6] mm) with ADV7103. CONCLUSIONS: Plasma bicarbonate levels and response rate were significantly higher with ADV7103 than with SoC. Urine calcium/citrate ratio, palatability, and gastrointestinal safety were significantly improved, supporting the use of ADV7103 as first-line treatment for dRTA. TRIAL REGISTRATION: Registered as EudraCT 2013-002988-25 on the 1st July 2013 Graphical abstract

Screening for colorectal cancer: random comparison of guaiac and immunochemical faecal occult blood testing at different cut-off levels

Immunochemical faecal occult blood testing (FIT) provides quantitative test results, which allows optimisation of the cut-off value for follow-up colonoscopy. We conducted a randomised population-based trial to determine test characteristics of FIT (OC-Sensor micro, Eiken, Japan) screening at different cut-off levels and compare these with guaiac-based faecal occult blood test (gFOBT) screening in an average risk population. A representative sample of the Dutch population (n=10 011), aged 50–74 years, was 1 : 1 randomised before invitation to gFOBT and FIT screening. Colonoscopy was offered to screenees with a positive gFOBT or FIT (cut-off 50 ng haemoglobin/ml). When varying the cut-off level between 50 and 200 ng ml−1, the positivity rate of FIT ranged between 8.1% (95% CI: 7.2–9.1%) and 3.5% (95% CI: 2.9–4.2%), the detection rate of advanced neoplasia ranged between 3.2% (95% CI: 2.6–3.9%) and 2.1% (95% CI: 1.6–2.6%), and the specificity ranged between 95.5% (95% CI: 94.5–96.3%) and 98.8% (95% CI: 98.4–99.0%). At a cut-off value of 75 ng ml−1, the detection rate was two times higher than with gFOBT screening (gFOBT: 1.2%; FIT: 2.5%; P<0.001), whereas the number needed to scope (NNscope) to find one screenee with advanced neoplasia was similar (2.2 vs 1.9; P=0.69). Immunochemical faecal occult blood testing is considerably more effective than gFOBT screening within the range of tested cut-off values. From our experience, a cut-off value of 75 ng ml−1 provided an adequate positivity rate and an acceptable trade-off between detection rate and NNscope

Comparison of a guaiac based and an immunochemical faecal occult blood test in screening for colorectal cancer in a general average risk population

BACKGROUND: The guaiac faecal occult blood test (G‐FOBT) is recommended as a screening test for colorectal cancer but its low sensitivity has prevented its use throughout the world. METHODS: We compared the performances of the reference G‐FOBT (non‐rehydrated Hemoccult II test) and the immunochemical faecal occult blood test (I‐FOBT) using different positivity cut‐off values in an average risk population sample of 10 673 patients who completed the two tests. Patients with at least one test positive were asked to undergo colonoscopy. RESULTS: Using the usual cut‐off point of 20 ng/ml haemoglobin, the gain in sensitivity associated with the use of I‐FOBT (50% increase for cancer and 256% increase for high risk adenoma) was balanced by a decrease in specificity. The number of extra false positive results associated with the detection of one extra advanced neoplasia (cancer or high risk adenoma) was 2.17 (95% confidence interval 1.65–2.85). With a threshold of 50 ng/ml, I‐FOBT detected more than twice as many advanced neoplasias as the G‐FOBT (ratio of sensitivity = 2.33) without any loss in specificity (ratio of false positive rate = 0.99). With a threshold of 75 ng/ml, associated with a similar positivity rate to G‐FOBT (2.4%), the use of I‐FOBT allowed a gain in sensitivity of 90% and a decrease in the false positive rate of 33% for advanced neoplasia. CONCLUSIONS: Evidence in favour of the substitution of G‐FOBT by I‐FOBT is increasing, the gain being more important for high risk adenomas than for cancers. The automated reading technology allows choice of the positivity rate associated with an ideal balance between sensitivity and specificity

Crystalline structure of oxide-based epitaxial tunnel junctions

Epitaxial metal/oxide based magnetic tunnel-junctions (MTJ) are valuable model systems to investigate the influence of the crystallinity of individual layers on the magnetic properties. We have non-destructively studied the effect of the optical lithography procedure on the crystalline structure of MTJ's with lateral spatial resolution by performing local x-ray diffraction experiments using a microfocused x-ray spot. We demonstrate that the lithography process produces distortion effects on the crystalline structure of the layers near the edges of the lithographed junction. These distortions are present on all the constituent layers and are most probably driven by the elastic constants of the materials. They translate into tilts of the crystalline planes in the vicinity of the edges and propagate towards the center of the junction; the tilt's amplitude (up to several degrees) and sign (concave or convex) depend on the junction's shape, size and the type of materials (interfaces) used. We report results for junctions made with two types of metal-oxide interfaces (Co/CoFe2O4 and Co/Fe3O4), with sizes from 10 to 150 μm and various shapes (square-, rectangle- and disk-like)

Comparison of a guaiac and an immunochemical faecal occult blood test for the detection of colonic lesions according to lesion type and location.

International audienceWe investigated variations in sensitivity of an immunochemical (I-FOBT) and a guaiac (G-FOBT) faecal occult blood test according to type and location of lesions in an average-risk 50- to 74-year-old population. Screening for colorectal cancer by both non-rehydrated Haemoccult II G-FOBT and Magstream I-FOBT was proposed to a sample of 20 322 subjects. Of the 1615 subjects with at least one positive test, colonoscopy results were available for 1277. A total of 43 invasive cancers and 270 high-risk adenomas were detected. The gain in sensitivity associated with the I-FOBT was calculated using the ratio of sensitivities (RSN) according to type and location of lesions, and amount of bleeding. The gain in sensitivity by using I-FOBT increased from invasive cancers (RSN=1.48 (1.16-4.59)) to high-risk adenomas (RSN=3.32 (2.70-4.07)), and was inversely related to the amount of bleeding. Among cancers, the gain in sensitivity was confined to rectal cancer (RSN=2.09 (1.36-3.20)) and concerned good prognosis cancers, because they involve less bleeding. Among high-risk adenomas, the gain in sensitivity was similar whatever the location. This study suggests that the gain in sensitivity by using an I-FOBT instead of a G-FOBT greatly depends on the location of lesions and the amount of bleeding. Concerning cancer, the gain seems to be confined to rectal cancer