Abstract
We measure the trajectories of macroscopic magnetic particles pulled against gravity between twisted alternating magnetic square patterns in a superposed homogeneous magnetic field normal to ...both patterns. The two patterns are built from a set of magentic cubes having a distribution of magnetization. The magnetic potential between the patterns is a sum of three contributions: two being periodic on two lattices with different magnitude and orientation, and the third random contribution arising from the distribution of magnetization of the cubes. As one varies the twist angle between the two patterns each time the twist angle coincides with a magic twist angle one of the two periodic lattices becomes a sublattice of the other lattice. Simulations of particles moving through patterns with a precise cube magnetization produce pronounced mobility peaks near magic twist angles that are associated with flat channels. Weak random fluctuations of the cube magnetization in the experiment and the simulations cause enhanced random disorder of the potential and reduce the mobility by scattering particles into the interior of the twisted Wigner Seitz cells. The mobility undergoes an Anderson transition from magic to generic behavior as the magnetization disorder increases beyond half of a percent of the cube magnetization.
Objective To determine whether children with calcium-deficiency rickets respond better to treatment with calcium as limestone or as ground fish. Study design Nigerian children with active rickets ...(n = 96) were randomized to receive calcium as powdered limestone (920 mg of elemental calcium) or ground fish (952 mg of elemental calcium) daily for 24 weeks. Radiographic healing was defined as achieving a score of 1.5 or less on a 10-point scale. Results The median (range) age of enrolled children was 35 (6-151) months. Of the 88 children who completed the study, 29 (66%) in the ground fish group and 24 (55%) in the limestone group achieved the primary outcome of a radiographic score of 1.5 or less within 6 months ( P = .39). The mean radiographic score improved from 6.2 ± 2.4 to 1.8 ± 2.2 in the ground fish group and from 6.3 ± 2.2 to 2.1 ± 2.4 in the limestone group ( P = .68 for group comparison). In an intention to treat analysis adjusted for baseline radiographic score, age, milk calcium intake, and serum 25-hydroxyvitamin D concentration, the response to treatment did not differ between the 2 groups ( P = .39). Younger age was associated with more complete radiographic healing in the adjusted model (aOR 0.74 95% CI 0.57-0.92). After 24 weeks of treatment, serum alkaline phosphatase had decreased, calcium and 25-hydroxyvitamin D increased, and bone mineral density increased in both groups, without significant differences between treatment groups. Conclusion In children with calcium-deficiency rickets, treatment with calcium as either ground fish or limestone for 6 months healed rickets in the majority of children.
Background Diastolic dysfunction with delayed relaxation and abnormal passive elastic properties has been described in patients with severe pressure overload hypertrophy. The purpose of this study ...was to evaluate the time course of rotational motion of the left ventricle in patients with aortic valve stenosis using myocardial tagging. Methods Myocardial tagging is a non-invasive method based on magnetic resonance which makes it possible to label (‘tag’) specific myocardial regions. From the motion of the tag’s cardiac rotation, radial displacement and translational motion can be determined. In 12 controls and 13 patients with severe aortic valve stenosis systolic and diastolic wall motion was assessed in an apical and basal short axis plane. Results The normal left ventricle performs a systolic wringing motion around the ventricular long axis with clockwise rotation at the base (−4·4±1·6°) and counterclockwise rotation at the apex (+6·8±2·5°) when viewed from the apex. During early diastole an untwisting motion can be observed which precedes diastolic filling. In patients with aortic valve stenosis systolic rotation is reduced at the base (−2·4±2·0°;P<0·01) but increased at the apex (+12·0±6·0°;P<0·05). Diastolic untwisting is delayed and prolonged with a decrease in normalized rotation velocity (−6·9±1·1s−1) when compared to controls (−10·7±2·2s−1;P<0·001). Maximal systolic torsion is 8·0±2·1° in controls and 14·1±6·4° (P<0·01) in patients with aortic valve stenosis. Conclusions Left ventricular pressure overload hypertrophy is associated with a reduction in basal and an increase in apical rotation resulting in increased torsion of the ventricle. Diastolic untwisting is delayed and prolonged. This may explain the occurrence of diastolic dysfunction in patients with severe pressure overload hypertrophy.
Introduction
We previously showed that pharmacokinetic‐guided prophylaxis (PKP) allows the dosing interval to be extended while maintaining a specific trough level. However, the associations of peak ...factor VIII (FVIII) levels and area under the curve (AUC) with breakthrough bleeding have not been investigated.
Aim
The aim of this study was to analyse data from the PKP arm to determine whether peak FVIII levels, AUC and time with FVIII levels in a haemostatically effective range are independent predictors of bleeding during prophylaxis.
Methods
Post hoc analysis of the association of FVIII levels and AUC with annualized bleeding rate in 34 patients on PKP.
Results
During 1 year of PKP, 131 bleeding episodes occurred in 24/34 patients. Average peak FVIII levels ranged from 24 to 168 IU dL−1, with higher values associated with a decreased risk for all bleeding (joint and non‐joint; P < 0.01) and joint bleeding (P < 0.01). Following rFVIII infusion, median percent of time spent with FVIII levels >20 IU dL−1 was 22%; median AUC was 1363. Both values were significantly associated with a lower ABR when targeting a 1% trough at 72 h.
Conclusion
When PKP was administered every third day, higher peak FVIII levels, higher AUC and more time spent per week with FVIII levels >20 IU dL−1 provided increased protection from joint and non‐joint bleeding. These data highlight the potential impact of variability in individual pharmacokinetic and bleeding risk and support the need for high peak levels and AUC in some patients treated every third day. The findings do not necessarily apply to alternate‐day or other prophylactic dosing regimens.
Abstract Objective To determine whether a single monthly supplement is as effective as a daily maternal supplement in increasing breast milk vitamin D to achieve vitamin D sufficiency in their ...infants. Patients and Methods Forty mothers with exclusively breast-fed infants were randomized to receive oral cholecalciferol (vitamin D3 ) 5000 IU/d for 28 days or 150,000 IU once. Maternal serum, breast milk, and urine were collected on days 0, 1, 3, 7, 14, and 28; infant serum was obtained on days 0 and 28. Enrollment occurred between January 7, 2011, and July 29, 2011. Results In mothers given daily cholecalciferol, concentrations of serum and breast milk cholecalciferol attained steady levels of 18 and 8 ng/mL, respectively, from day 3 through 28. In mothers given the single dose, serum and breast milk cholecalciferol peaked at 160 and 40 ng/mL, respectively, at day 1 before rapidly declining. Maternal milk and serum cholecalciferol concentrations were related (r=0.87). Infant mean serum 25-hydroxyvitamin D concentration increased from 17±13 to 39±6 ng/mL in the single-dose group and from 16±12 to 39±12 ng/mL in the daily-dose group ( P =.88). All infants achieved serum 25-hydroxyvitamin D concentrations of more than 20 ng/mL. Conclusion Either single-dose or daily-dose cholecalciferol supplementation of mothers provided breast milk concentrations that result in vitamin D sufficiency in breast-fed infants. Clinical Trial Registration clinicaltrials.gov NCT01240265
Background: Dose tailoring of coagulation factors requires reliably estimated and reproducible pharmacokinetics (PK) in the individual patient. Objectives: To investigate the contribution of both ...biological and methodological factors to the observed variability of factor VIII (FVIII) PK, with the focus on differences between children and adults, and to examine the implications for dosing. Patients: Data from 52 1–6‐year‐old and 100 10–65‐year‐old patients with hemophilia A (FVIII ≤ 2 IU dL−1) in three clinical studies were included. Results: In vivo recovery was lower, weight‐adjusted clearance was higher and FVIII half‐life was on average shorter in children than in adults. However, a reduced blood sampling schedule for children was estimated to account for up to one half of the total observed differences. Intrapatient variance in PK was smaller than interpatient variance in 10–65‐year‐olds. Age and ratio of actual to ideal weight only showed weak relationships with PK parameters. Variance in PK caused large variance in the calculated dose required to maintain a target FVIII trough level during prophylactic treatment. Conclusion: Differences in blood sampling schedules should be taken into account when results from different PK studies are compared. However, even with this consideration, PK cannot be predicted from observable patient characteristics but must be determined for the individual. Because the influence of reducing the blood sampling was minor in comparison to the true variance between patients, a reduced blood sampling protocol can be used. Low intrapatient variability supports the use of PK measurements for dose tailoring of FVIII.
Metal artefacts in PET/CT images hamper diagnostic accuracy in head and neck cancer (HNC). The aim of this study is to characterise the clinical effects of metal artefacts on PET/CT in HNC and to ...inform decision-making concerning implementation of MAR techniques. We study a combined dual energy CT and inpainting-based metal artefact reduction (DECT-I-MAR) technique for PET/CT in three settings: (A) A dental phantom with a removable amalgam-filled tooth to evaluate the PET error in comparison to a known reference. (B) PET-positive patients with metallic implants to demonstrate the relationship between CT metal artefacts and PET error. (C) Metabolic tumour volumes delineated in PET-positive patients with metal implants to evaluate the clinical impact. In (A) DECT-I-MAR reduced the PET error significantly. In (B) we demonstrate an increasing PET error with increasing CT artefact severity in patients. In (C) it is shown that the presence of artefacts in the same axial slices as the tumour significantly decreases biomarker stability and increase delineation variability. This work shows the practical feasibility of DECT-I-MAR-based PET/CT imaging, and indicates a positive clinical impact of using the technique routinely for HNC patients. The impact of CT artefacts on PET is considerable, especially in workflows where quantitative PET biomarkers and tumour volumes are used. In such cases, and for patients with tumours in proximity of metals, we recommend that a MAR technique for PET/CT is employed.
The peptide INFLORESCENCE DEFICIENT IN ABSCISSION (IDA), which signals through the leucine-rich repeat receptor-like kinases HAESA (HAE) and HAESA-LIKE2 (HSL2), controls different cell separation ...events in Arabidopsis thaliana. We hypothesize the involvement of this signaling module in abscission processes in other plant species even though they may shed other organs than A. thaliana. As the first step toward testing this hypothesis from an evolutionarily perspective we have identified genes encoding putative orthologs of IDA and its receptors by BLAST searches of publically available protein, nucleotide and genome databases for angiosperms. Genes encoding IDA or IDA-LIKE (IDL) peptides and HSL proteins were found in all investigated species, which were selected as to represent each angiosperm order with available genomic sequences. The 12 amino acids representing the bioactive peptide in A. thaliana have virtually been unchanged throughout the evolution of the angiosperms; however, the number of IDL and HSL genes varies between different orders and species. The phylogenetic analyses suggest that IDA, HSL2, and the related HSL1 gene, were present in the species that gave rise to the angiosperms. HAE has arisen from HSL1 after a genome duplication that took place after the monocot-eudicots split. HSL1 has also independently been duplicated in the monocots, while HSL2 has been lost in gingers (Zingiberales) and grasses (Poales). IDA has been duplicated in eudicots to give rise to functionally divergent IDL peptides. We postulate that the high number of IDL homologs present in the core eudicots is a result of multiple whole genome duplications (WGD). We substantiate the involvement of IDA and HAE/HSL2 homologs in abscission by providing gene expression data of different organ separation events from various species.
Background
Intravenous immunoglobulins (IVIG) are an attractive therapeutic tool for therapy of toxic epidermal necrolysis and severe forms of certain autoimmune diseases, including dermatomyositis, ...autoimmune blistering diseases, systemic vasculitis and lupus erythematodes.
Objectives
Prompted by a case of IVIG‐associated haemolytic anaemia, the effects of IVIG administrations on haematological parameters in patients with dermatological conditions were investigated.
Methods
Erythrocyte and leucocyte parameters were retrospectively analysed in 16 patients who had received IVIG at doses from 1 to 3 g/kg bodyweight (n = 35 cycles). The influence of IVIG on leucocyte survival was determined in vitro.
Results
Decreased absolute erythrocyte numbers, haemoglobin and haematocrit levels and a case of haemolytic anaemia were linked to transfusion of high‐, but not low‐dose IVIG. In contrast, leucopenia post‐IVIG occurred in the vast majority of the recipients, unrelated to the administered IVIG amounts. In vitro investigations revealed a dose‐dependent impairment of cell survival by IVIG in the neutrophil and monocyte, but not in the lymphocyte subpopulations. In several IVIG preparations, substantial amounts of blood group anti‐A/anti‐B antibodies were detected which could have accounted for the observed changes in the haematological parameters in our study cohort.
Conclusions
IVIG products should be administered strictly according to indications. Commercially available IVIG products can contain blood group‐specific antibodies that may induce haemolysis in some recipients. Monitoring of blood counts during applied IVIG therapy, especially when high doses are administered, is recommended.
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