High platelet content can increase storage lesion rates following Intercept pathogen inactivation primarily in platelet concentrates prepared by apheresis

Background: Pathogen inactivation methods for platelet concentrates are increasingly being used in blood banks worldwide. In vitro studies have demonstrated its effects on storage lesion, but little routine quality control data on blood banking outcomes have been reported. Materials and Methods: Swirling of distributed products was monitored before and after implementation of Intercept pathogen inactivation. Metabolic parameters pH, glucose and lactic acid were determined in a random cohort of expired pathogen-inactivated products. Storage lesion indicators in apheresis concentrates with premature low swirling were compared to concentrates with normal swirling. Results: During validation for implementing Intercept pathogen inactivation, pH and glucose levels decreased faster in apheresis platelet concentrates with high platelet content than with low platelet content or than in pathogen-inactivated pooled buffy coat-derived products. In routine products, glucose exhaustion was more often found in apheresis compared to buffy coat-derived platelet concentrates despite 3-7% more plasma carryover in the former. Annual incidence of premature low swirling increased significantly by 50% following implementation of pathogen inactivation implementation for apheresis but not for pooled buffy coat platelet concentrates. In addition, apheresis concentrates with premature low swirling had a significantly higher median platelet count (50 x 10(11)) than unaffected products (35 x 10(11)). Conclusion: The risk of increased storage lesion rates following Intercept pathogen inactivation is higher for apheresis than for buffy coat-derived platelet concentrates, especially when platelet contents are higher than 50 x 10(11)

Effect of a Physical Phase Plate on Contrast Transfer in an Aberration-Corrected Transmission Electron Microscope

In this theoretical study we analyze contrast transfer of weak-phase objects in a transmission electron microscope, which is equipped with an aberration corrector (Cs-corrector) in the imaging lens system and a physical phase plate in the back focal plane of the objective lens. For a phase shift of pi/2 between scattered and unscattered electrons induced by a physical phase plate, the sine-type phase contrast transfer function is converted into a cosine-type function. Optimal imaging conditions could theoretically be achieved if the phase shifts caused by the objective lens defocus and lens aberrations would be equal zero. In reality this situation is difficult to realize because of residual aberrations and varying, non-zero local defocus values, which in general result from an uneven sample surface topography. We explore the conditions - i.e. range of Cs-values and defocus - for most favourable contrast transfer as a function of the information limit, which is only limited by the effect of partial coherence of the electron wave in Cs-corrected transmission electron microscopes. Under high-resolution operation conditions we find that a physical phase plate improves strongly low- and medium-resolution object contrast, while improving tolerance to defocus and Cs-variations, compared to a microscope without a phase plate

Wafer-based aberration metrology for lithographic systems using overlay measurements on targets imaged from phase-shift gratings

In this paper, a new methodology is presented to derive the aberration state of a lithographic projection system from wafer metrology data. For this purpose, new types of phase-shift gratings (PSGs) are introduced, with special features that give rise to a simple linear relation between the PSG image displacement and the phase aberration function of the imaging system. By using the PSGs as the top grating in a diffraction-based overlay stack, their displacement can be measured as an overlay error using a standard wafer metrology tool. In this way, the overlay error can be used as a measurand based on which the phase aberration function in the exit pupil of the lithographic system can be reconstructed. In practice, the overlay error is measured for a set of different PSG targets, after which this information serves as input to a least-squares optimization problem that, upon solving, provides estimates for the Zernike coefficients describing the aberration state of the lithographic system. In addition to a detailed method description, this paper also deals with the additional complications that arise when the method is implemented experimentally and this leads to a number of model refinements and a required calibration step. Finally, the overall performance of the method is assessed through a number of experiments in which the aberration state of the lithographic system is intentionally detuned and subsequently estimated by the new method. These experiments show a remarkably good agreement, with an error smaller than 5¿¿m¿ , among the requested aberrations, the aberrations measured by the on-tool aberration sensor, and the results of the new wafer-based method

A new approach to high resolution, high contrast electron microscopy of macromolecular block copolymer assemblies

Determining the structure of macromolecular samples is vital for understanding and adapting their function. Transmission electron microscopy (TEM) is widely used to achieve this, but, owing to the weak electron scattering cross-section of carbon, TEM images of macromolecular samples are generally low contrast and low resolution. Here we implement a fast and practically simple routine to achieve high-contrast imaging of macromolecular samples using exit wave reconstruction (EWR), revealing a new level of structural detail. This is only possible using ultra-low contrast supports such as the graphene oxide (GO) used here and as such represents a novel application of these substrates. We apply EWR on GO membranes to study self-assembled block copolymer structures, distinguishing not only the general morphology or nanostructure, but also evidence for the substructure (i.e. the polymer chains) which gives insight into their formation mechanisms and functional properties

Spectrum and characterisation of BRCA1 and BRCA2 deleterious mutations in high-risk Czech patients with breast and/or ovarian cancer

<p>Abstract</p> <p>Background</p> <p>The incidence of breast cancer has doubled over the past 20 years in the Czech Republic. Hereditary factors may be a cause of young onset, bilateral breast or ovarian cancer, and familial accumulation of the disease. <it>BRCA1 </it>and <it>BRCA2 </it>mutations account for an important fraction of hereditary breast and ovarian cancer cases. One thousand and ten unrelated high-risk probands with breast and/or ovarian cancer were analysed for the presence of a <it>BRCA1 </it>or <it>BRCA2 </it>gene mutation at the Masaryk Memorial Cancer Institute (Czech Republic) during 1999–2006.</p> <p>Methods</p> <p>The complete coding sequences and splice sites of both genes were screened, and the presence of large intragenic rearrangements in <it>BRCA1 </it>was verified. Putative splice-site variants were analysed at the cDNA level for their potential to alter mRNA splicing.</p> <p>Results</p> <p>In 294 unrelated families (29.1% of the 1,010 probands) pathogenic mutations were identified, with 44 different <it>BRCA1 </it>mutations and 41 different <it>BRCA2 </it>mutations being detected in 204 and 90 unrelated families, respectively. In total, three <it>BRCA1 </it>founder mutations (c.5266dupC; c.3700_3704del5; p.Cys61Gly) and two <it>BRCA2 </it>founder mutations (c.7913_7917del5; c.8537_8538del2) represent 52% of all detected mutations in Czech high-risk probands. Nine putative splice-site variants were evaluated at the cDNA level. Three splice-site variants in <it>BRCA1 </it>(c.302-3C>G; c.4185G>A and c.4675+1G>A) and six splice-site variants in <it>BRCA2 </it>(c.475G>A; c.476-2>G; c.7007G>A; c.8755-1G>A; c.9117+2T>A and c.9118-2A>G) were demonstrated to result in aberrant transcripts and are considered as deleterious mutations.</p> <p>Conclusion</p> <p>This study represents an evaluation of deleterious genetic variants in the <it>BRCA1 </it>and <it>2 </it>genes in the Czech population. The classification of several splice-site variants as true pathogenic mutations may prove useful for genetic counselling of families with high risk of breast and ovarian cancer.</p

High tie versus low tie in rectal surgery: comparison of anastomotic perfusion

Item does not contain fulltextPURPOSE: Both "high tie" (HT) and "low tie" (LT) are well-known strategies in rectal surgery. The aim of this study was to compare colonic perfusion after HT to colonic perfusion after LT. METHODS: Patients undergoing rectal resection for malignancy were included. Colonic perfusion was measured with laser Doppler flowmetry, immediately after laparotomy on the antimesenterial side of the colon segment that was to become the afferent loop (measurement A). This measurement was repeated after rectal resection (measurement B). The blood flow ratios (B/A) were compared between the HT group and the LT group. RESULTS: Blood flow was measured in 33 patients, 16 undergoing HT and 17 undergoing LT. Colonic blood flow slightly decreased in the HT group whereas the flow increased in the LT group. The blood flow ratio was significantly higher in the LT group (1.48 vs. 0.91; p = 0.04), independent of the blood pressure. CONCLUSION: This study shows the blood flow ratio to be higher in the LT group. This suggests that anastomoses may benefit from better perfusion when LT is performed

Linguistic assessment tools for the Digisonic® Dual electric-acoustic speech processor

Interdisciplinary domains LUC

Confirmation of a metastasis-specific microRNA signature in primary colon cancer

The identification of patients with high-risk stage II colon cancer who may benefit from adjuvant therapy may allow the clinical approach to be tailored for these patients based on an understanding of tumour biology. MicroRNAs have been proposed as markers of the prognosis or treatment response in colorectal cancer. Recently, a 2-microRNA signature (l et-7i and miR-10b) was proposed to identify colorectal cancer patients at risk of developing distant metastasis. We assessed the prognostic value of this signature and additional candidate microRNAs in an independent, clinically well-defined, prospectively collected cohort of primary colon cancer patients including stage I-II colon cancer without and stage III colon cancer with adjuvant treatment. The 2-microRNA signature specifically predicted hepatic recurrence in the stage I-II group, but not the overall ability to develop distant metastasis. The addition of miR-30b to the 2-microRNA signature allowed the prediction of both distant metastasis and hepatic recurrence in patients with stage I-II colon cancer who did not receive adjuvant chemotherapy. Available gene expression data allowed us to associate m iR-30b expression with axon guidance and l et-7i expression with cell adhesion, migration, and motility