503 research outputs found
Visuospatial bootstrapping: spatialized displays enhance digit and nonword sequence learning
Visuospatial bootstrapping describes the observation that performance on a verbal memory task is enhanced by presenting the toâbeâremembered material in a format with additional embedded spatial information. Thus far, it has only been reported in shortâterm memory tasks. Here, we report two experiments assessing the impact of spatial information on the learning of sequences in longâterm memory. Experiment 1 used digits presented within a familiar numeric keypad as stimuli compared against single digits presented in one location. Experiment 2 used novel nonwords, which were either presented in an unchanging arrangement permitting the buildingâup of location knowledge or in a constantly changing arrangement. Both experiments demonstrated strong evidence that reliable spatial information facilitated sequence learning, particularly in later sequence positions. It is concluded that the incidental availability of spatialized information during study can facilitate learning of sequences of digits and nonwords. Furthermore, the spatial information can be learned during the task itself and does not need to be preexistent in longâterm knowledge
Erythropoietin and Anaemia in Patients with Chronic Renal Failure
Hyporegenerative anaemia is common complication of chronic renal failure CRF and responsible for fatigue and reduced general health condition among uremic patient. The main causes of anemia among patients with chronic renal failure are deficient production of erythropoietin (EPO), iron deficiency, and chronic disease with endogenous EPO resistance. This study confirmed on patients with chronic renal failure in Merjan Teaching Hospital and highlighted on the relationship between anaemia and erythropoiten level. The estimation of hemoglobin among patients with CRF revealed that 55% of patients suffered from severe anaemia and 45%suffered from moderate anaemia     Erythropoiten level estimated by ELISA technique and mean and standard deviation of erythropoietin level among patients and control groups were12.2 uU/ml ± 2.6, 7.3uU/ml± 1.8 respectively and comparism mean of erythropoietin between patients and control group  was indicated that there is significant difference between two groups at p value< 0.05 By study the correlation between hemoglobin and erythropoietin revealed that there is inverses relation ship between hemoglobin and erythropoietin , we concluded from this study although the level of erythropoietin increase in patients with CRF but the level of erythropoietin are not enough foe correction of anaemia and patient may required for exogenous source for erythropoietin with iron supplement in management of anaemia Keywords: erythropoiten Hyporegenerative anaemi
Wise Up To Cancer - can it make a difference?
This document reports the findings of 'Wise Up To Cancer' a Community Health Initiative, funded by Yorkshire Cancer Research. The aims of Wise Up To Cancer were to; decrease behaviours associated with cancer risk, increase awareness of cancer signs and symptoms,, increase cancer screening rates and increase signposting to other services
Wise Up To Cancer - can it make a difference? Executive Summary.
A summary of the evaluation of Wise Up To Cancer. A Community Health Initiative funded by Yorkshire Cancer Research, aiming to improve cancer outcomes
Blood RNA analysis can increase clinical diagnostic rate and resolve variants of uncertain significance
Purpose
Diagnosis of genetic disorders is hampered by large numbers of variants of uncertain significance (VUSs) identified through next-generation sequencing. Many such variants may disrupt normal RNA splicing. We examined effects on splicing of a large cohort of clinically identified variants and compared performance of bioinformatic splicing prediction tools commonly used in diagnostic laboratories.
Methods
Two hundred fifty-seven variants (coding and noncoding) were referred for analysis across three laboratories. Blood RNA samples underwent targeted reverse transcription polymerase chain reaction (RT-PCR) analysis with Sanger sequencing of PCR products and agarose gel electrophoresis. Seventeen samples also underwent transcriptome-wide RNA sequencing with targeted splicing analysis based on Sashimi plot visualization. Bioinformatic splicing predictions were obtained using Alamut, HSF 3.1, and SpliceAI software.
Results
Eighty-five variants (33%) were associated with abnormal splicing. The most frequent abnormality was upstream exon skipping (39/85 variants), which was most often associated with splice donor region variants. SpliceAI had greatest accuracy in predicting splicing abnormalities (0.91) and outperformed other tools in sensitivity and specificity.
Conclusion
Splicing analysis of blood RNA identifies diagnostically important splicing abnormalities and clarifies functional effects of a significant proportion of VUSs. Bioinformatic predictions are improving but still make significant errors. RNA analysis should therefore be routinely considered in genetic disease diagnostics
Identification of diagnostic candidates in Mendelian disorders using an RNA sequencing-centric approach
Background: RNA sequencing (RNA-seq) is increasingly being used as a complementary tool to DNA sequencing in diagnostics where DNA analysis has been uninformative. RNA-seq enables the identification of aberrant splicing and aberrant gene expression, improving the interpretation of variants of unknown significance (VUSs), and provides the opportunity to scan the transcriptome for aberrant splicing and expression in relevant genes that may be the cause of a patientâs phenotype. This work aims to investigate the feasibility of generating new diagnostic candidates in patients without a previously reported VUS using an RNA-seq-centric approach. Methods: We systematically assessed the transcriptomic profiles of 86 patients with suspected Mendelian disorders, 38 of whom had no candidate sequence variant, using RNA from blood samples. Each VUS was visually inspected to search for splicing abnormalities. Once aberrant splicing was identified in cases with VUS, multiple open-source alternative splicing tools were used to investigate if they would identify what was observed in IGV. Expression outliers were detected using OUTRIDER. Diagnoses in cases without a VUS were explored using two separate strategies. Results: RNA-seq allowed us to assess 71% of VUSs, detecting aberrant splicing in 14/48 patients with a VUS. We identified four new diagnoses by detecting novel aberrant splicing events in patients with no candidate sequence variants from prior DNA testing (n = 32) or where the candidate VUS did not affect splicing (n = 23). An additional diagnosis was made through the detection of skewed X-inactivation. Conclusion: This work demonstrates the utility of an RNA-centric approach in identifying novel diagnoses in patients without candidate VUSs. It underscores the utility of blood-based RNA analysis in improving diagnostic yields and highlights optimal approaches for such analyses
Regional climate messages for South Asia
It was essential to understand the extent of climatic variability and the associated biophysical response to ascertain appropriate entry points for the RRP phase. To enhance our understanding of historical climate change and climate variability in the three ASSAR sub-regions, we investigated trends in temperature and precipitation in the broader landscape surrounding the sub-regions (hereafter ASSAR sub-region envelopes).International Development Research Centre (IDRC) - CanadaUK's Department for International Development (DFID) UKCollaborative Adaptation Research Initiative in Africa and Asia (CARIAA
Facile synthesis and proposed mechanism of α,Ïâoxetanyl-telechelic poly(3-nitratomethyl-3-methyl oxetane) by an SN2(i) nitrato displacement method in basic media
The synthesis of a novel heterocyclicâtelechelic polymer, α,Ï-oxetanyl-telechelic poly(3-nitratomethyl-3-methyl oxetane), is described. Infrared spectroscopy (IR), gel permeation chromatography (GPC), and nuclear magnetic resonance (NMR) spectroscopy have been used to confirm the successful synthesis, demonstrating the presence of the telechelic-oxetanyl moieties. Synthesis of the terminal functionalities has been achieved via displacement of nitrato groups, in a manner similar to that employed with other leaving groups such as azido, bromo, and nitro, initiated by nucleophiles. In the present case, displacement occurs on the ends of a nitrato-functionalized polymer driven by the formation of sodium nitrate, which is supported by the polar aprotic solvent N,N-dimethyl formamide. The formation of an alkoxide at the polymer chain ends is favored and allows internal back-biting to the nearest carbon bearing the nitrato group, intrinsically in an SN2(i) reaction, leading to α,Ï-oxetanyl functionalization. The telechelic-oxetanyl moieties have the potential to be cross-linked by chemical (e.g., acidic) or radiative (e.g., ultraviolet) curing methods without the use of high temperatures, usually below 100°C. This type of material was designed for future use as a contraband simulant, whereby it would form the predominant constituent of elastomeric composites comprising rubbery polymer with small quantities of solids, typically crystals of contraband substances, such as explosives or narcotics. This method also provides an alternative approach to ring closure and synthesis of heterocycles
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