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It has long been established that the appropriate way of reslicing volume MR images is to use the method of sinc interpolation [2, 4]. We have recently needed to implement this method ourselves and have found, like other authors before us, that large convolution kernels are needed in order to produce accurate reslice data, suitable for subtraction. This requirement has led many groups to investigate the use of specialised hardware and software in order to perform data analysis within sensible timescales. However, we have found that the major component of the error introduced from interpolation with small kernels, is actually due to a first order normalisation problem introduced by truncation. In this paper we demonstrate the characteristics of this problem on real data and show how it can be eliminated, so that accurate reslice data can be obtained with small kernels. Unlike other recent suggestions for correcting such effects [3], the required changes in computation are simple and significantly reduce the processing requirement for a given interpolation accuracy. Renormalised Sinc Interpolation. There are several techniques that one can adopt to solve the problem of image interpolation. One is to assume a particular prior functional model for a local region of the image data, estimate the function parameters from a maximum likelihood metric and then recompute intermediate sites from the functiona

Opicapone Efficacy and Tolerability in Parkinson's Disease Patients Reporting Insufficient Benefit/Failure of Entacapone

Background: Opicapone, a recently introduced catechol‐o‐methyl transferase (COMT) inhibitor has the advantage of being administered once daily, and has pharmacokinetic data to indicate it offers a greater degree of COMT inhibition than entacapone. Although trial data indicate it is non‐inferior to entacapone, there are no data to indicate whether it offers any clinical advantages. / Methods: In this audit, we present data from 57 individuals prescribed opicapone at the National Hospital for Neurology and Neurosurgery, Queen Square who had either not tolerated or reported insufficient benefit following previous prescription of entacapone. / Results: A total of 20 of 57 patients switched directly from entacapone to opicapone (“entacapone switchers”) whereas 37 of 57 patients had previously discontinued entacapone because of lack of benefit or adverse events (“entacapone failures”). A total of 21 of 57 (37%) patients stopped opicapone prior to 6 months. A total of 7 of 20 (35%) “entacapone switchers” experienced adverse events with opicapone of which 5 stopped the drug prior to the 6 month evaluation of efficacy. A total of 23 of 37 (62%) “entacapone failures” reported adverse events of which 16 stopped the drug. Among 36 of 57 (63%) patients who continued to use opicapone at 6 months, there was an improvement in OFF time of ~2 hours per day as measured by interview. / Conclusions: We conclude that opicapone can be an effective additional treatment for wearing off in Parkinson's disease (PD) in a subgroup of patients. The use of opicapone in our cohort with prior entacapone exposure, however, was associated with higher rates of adverse effects and treatment discontinuation than reported in published trial data of COMT inhibitor naïve patients

Evidence for a lack of a direct transcriptional suppression of the iron regulatory peptide hepcidin by hypoxia-inducible factors.

BACKGROUND: Hepcidin is a major regulator of iron metabolism and plays a key role in anemia of chronic disease, reducing intestinal iron uptake and release from body iron stores. Hypoxia and chemical stabilizers of the hypoxia-inducible transcription factor (HIF) have been shown to suppress hepcidin expression. We therefore investigated the role of HIF in hepcidin regulation. METHODOLOGY/PRINCIPAL FINDINGS: Hepcidin mRNA was down-regulated in hepatoma cells by chemical HIF stabilizers and iron chelators, respectively. In contrast, the response to hypoxia was variable. The decrease in hepcidin mRNA was not reversed by HIF-1alpha or HIF-2alpha knock-down or by depletion of the HIF and iron regulatory protein (IRP) target transferrin receptor 1 (TfR1). However, the response of hepcidin to hypoxia and chemical HIF inducers paralleled the regulation of transferrin receptor 2 (TfR2), one of the genes critical to hepcidin expression. Hepcidin expression was also markedly and rapidly decreased by serum deprivation, independent of transferrin-bound iron, and by the phosphatidylinositol 3 (PI3) kinase inhibitor LY294002, indicating that growth factors are required for hepcidin expression in vitro. Hepcidin promoter constructs mirrored the response of mRNA levels to interleukin-6 and bone morphogenetic proteins, but not consistently to hypoxia or HIF stabilizers, and deletion of the putative HIF binding motifs did not alter the response to different hypoxic stimuli. In mice exposed to carbon monoxide, hypoxia or the chemical HIF inducer N-oxalylglycine, liver hepcidin 1 mRNA was elevated rather than decreased. CONCLUSIONS/SIGNIFICANCE: Taken together, these data indicate that hepcidin is neither a direct target of HIF, nor indirectly regulated by HIF through induction of TfR1 expression. Hepcidin mRNA expression in vitro is highly sensitive to the presence of serum factors and PI3 kinase inhibition and parallels TfR2 expression

Golden Rule of Forecasting: Be Conservative

This article proposes a unifying theory, or the Golden Rule, or forecasting. The Golden Rule of Forecasting is to be conservative. A conservative forecast is consistent with cumulative knowledge about the present and the past. To be conservative, forecasters must seek out and use all knowledge relevant to the problem, including knowledge of methods validated for the situation. Twenty-eight guidelines are logically deduced from the Golden Rule. A review of evidence identified 105 papers with experimental comparisons; 102 support the guidelines. Ignoring a single guideline increased forecast error by more than two-fifths on average. Ignoring the Golden Rule is likely to harm accuracy most when the situation is uncertain and complex, and when bias is likely. Non-experts who use the Golden Rule can identify dubious forecasts quickly and inexpensively. To date, ignorance of research findings, bias, sophisticated statistical procedures, and the proliferation of big data, have led forecasters to violate the Golden Rule. As a result, despite major advances in evidence-based forecasting methods, forecasting practice in many fields has failed to improve over the past half-century

Phase structure of ceramics Al[2]O[3]-ZrW[2]O[8]

In the course of work the phase composition of the ceramic composite material Al[2]O[3] - 50 % ZrW[2]O[8] was studied. On the polished surface of the Al[2]O[3]-ZrW[2]O[8] sintered composite can be allocated three areas: dark gray matrix, white inclusions of an irregular form and spherical inclusions. The average size of spherical inclusions was equal to 15 [mu]m. The phase structure of ceramic composite was presented by trigonal modification of aluminum oxide, cubic zirconium tungstate, monoclinic modification of zirconium oxide and tungsten oxide

Physical and mechanical properties and deformation behavior of porous ceramics based on plasma chemical powders Al[2]O[3], ZrO[2](MgO)

This work investigates the behavior of porous alumina and zirconia stabilized with magnesium oxide (within the porosity range of 18% to 70%) ceramics when subjected to deformation by compression and shearing. The analysis of strain-deformation curves showed that there was a transition from a typically brittle state for relatively dense ceramics, to a pseudo-plastic one with a high rate of porosity. The values of the effective elasticity modulus, effective shear modulus and Poisson's ratio decrease with an increase in volume in the pore space of ceramics, which correlates with the appearance of plural cracking during the deformation of ceramics with a high level of porosity. There was made analysis of the nature of the destruction of ceramics with the same level of porosity. The difference in the deformation behavior of the ZrO[2]-MgO compared to the Al[2]O[3] ceramic was the fact that the transition from a typically brittle to tively dense ceramics to the pseudo -plastic at a high level of porosity is implemented with a lower level of porosity

SSR-Based Analysis of Genetic Diversity and Structure of Sweet Cherry (Prunus avium L.) from 19 Countries in Europe

Sweet cherry (Prunus avium L.) is a temperate fruit species whose production might be highly impacted by climate change in the near future. Diversity of plant material could be an option to mitigate these climate risks by enabling producers to have new cultivars well adapted to new environmental conditions. In this study, subsets of sweet cherry collections of 19 European countries were genotyped using 14 SSR. The objectives of this study were (i) to assess genetic diversity parameters, (ii) to estimate the levels of population structure, and (iii) to identify germplasm redundancies. A total of 314 accessions, including landraces, early selections, and modern cultivars, were monitored, and 220 unique SSR genotypes were identified. All 14 loci were confirmed to be polymorphic, and a total of 137 alleles were detected with a mean of 9.8 alleles per locus. The average number of alleles (N = 9.8), PIC value (0.658), observed heterozygosity (Ho = 0.71), and expected heterozygosity (He = 0.70) were higher in this study compared to values reported so far. Four ancestral populations were detected using STRUCTURE software and confirmed by Principal Coordinate Analysis (PCoA), and two of them (K1 and K4) could be attributed to the geographical origin of the accessions. A N-J tree grouped the 220 sweet cherry accessions within three main clusters and six subgroups. Accessions belonging to the four STRUCTURE populations roughly clustered together. Clustering confirmed known genealogical data for several accessions. The large genetic diversity of the collection was demonstrated, in particular within the landrace pool, justifying the efforts made over decades for their conservation. New sources of diversity will allow producers to face challenges, such as climate change and the need to develop more sustainable production systems