Effect of resting pressure on the estimate of cerebrospinal fluid outflow conductance

<p>Abstract</p> <p>Background</p> <p>A lumbar infusion test is commonly used as a predictive test for patients with normal pressure hydrocephalus and for evaluation of cerebrospinal fluid (CSF) shunt function. Different infusion protocols can be used to estimate the outflow conductance (<it>C</it>_out) or its reciprocal the outflow resistance (<it>R</it>_out), with or without using the baseline resting pressure, <it>P</it>_r. Both from a basic physiological research and a clinical perspective, it is important to understand the limitations of the model on which infusion tests are based. By estimating <it>C</it>_out using two different analyses, with or without <it>P</it>_r, the limitations could be explored. The aim of this study was to compare the <it>C</it>_out estimates, and investigate what effect <it>P</it>_rhad on the results.</p> <p>Methods</p> <p>Sixty-three patients that underwent a constant pressure infusion protocol as part of their preoperative evaluation for normal pressure hydrocephalus, were included (age 70.3 ± 10.8 years (mean ± SD)). The analysis was performed without (<it>C</it>_{excl Pr}) and with (<it>C</it>_{incl Pr}) P_r. The estimates were compared using Bland-Altman plots and paired sample <it>t</it>-tests (<it>p </it>< 0.05 considered significant).</p> <p>Results</p> <p>Mean <it>C</it>_out for the 63 patients was: <it>C</it>_{excl Pr}= 7.0 ± 4.0 (mean ± SD) μl/(s kPa) and <it>C</it>_{incl Pr} = 9.1 ± 4.3 μl/(s kPa) and <it>R</it>_out was 19.0 ± 9.2 and 17.7 ± 11.3 mmHg/ml/min, respectively. There was a positive correlation between methods (r = 0.79, n = 63, <it>p </it>< 0.01). The difference, Δ<it>C</it>_out= -2.1 ± 2.7 μl/(s kPa) between methods was significant (<it>p </it>< 0.01) and Δ<it>R</it>_outwas 1.2 ± 8.8 mmHg/ml/min). The Bland-Altman plot visualized that the variation around the mean difference was similar all through the range of measured values and there was no correlation between Δ<it>C</it>_outand <it>C</it>_out.</p> <p>Conclusions</p> <p>The difference between <it>C</it>_outestimates, obtained from analyses with or without <it>P</it>_r, needs to be taken into consideration when comparing results from studies using different infusion test protocols. The study suggests variation in CSF formation rate, variation in venous pressure or a pressure dependent <it>C</it>_outas possible causes for the deviation from the CSF absorption model seen in some patients.</p

Remotely acting SMCHD1 gene regulatory elements: in silico prediction and identification of potential regulatory variants in patients with FSHD

Background: Facioscapulohumeral dystrophy (FSHD) is commonly associated with contraction of the D4Z4 macro-satellite repeat on chromosome 4q35 (FSHD1) or mutations in the SMCHD1 gene (FSHD2). Recent studies have shown that the clinical manifestation of FSHD1 can be modified by mutations in the SMCHD1 gene within a given family. The absence of either D4Z4 contraction or SMCHD1 mutations in a small cohort of patients suggests that the disease could also be due to disruption of gene regulation. In this study, we postulated that mutations responsible for exerting a modifier effect on FSHD might reside within remotely acting regulatory elements that have the potential to interact at a distance with their cognate gene promoter via chromatin looping. To explore this postulate, genome-wide Hi-C data were used to identify genomic fragments displaying the strongest interaction with the SMCHD1 gene. These fragments were then narrowed down to shorter regions using ENCODE and FANTOM data on transcription factor binding sites and epigenetic marks characteristic of promoters, enhancers and silencers

High-cycle thermal fatigue in mixing tees. Large-eddy simulations compared to a new validation experiment

ABSTRACT The present paper describes new experimental data of thermal mixing in a T-junction compared with results from Large-Eddy Simulations (LES) and Detached Eddy Simulations (DES). The experimental setup was designed in order to provide data suitable for validation of CFD-calculations. The data is obtained from temperature measurements with thermocouples located near the pipe wall, velocity measurements with Laser Doppler Velocimetry (LDV) as well as single-point concentration measurements with Laser Induced Fluorescence (LIF). The LES showed good agreement with the experimental data also when fairly coarse computational meshes were used. However, grid refinement studies revealed a fairly strong sensitivity to the grid resolution, and a simulation using a fine mesh with nearly 10 million cells significantly improved the results in the entire flow domain. The sensitivity to different unsteady inlet boundary conditions was however small, which shows that the strong large-scale instabilities that are present in the mixing region are triggered independent of the applied inlet perturbations. A shortcoming in the performed simulations is insufficient near-wall resolution, which resulted in poor predictions of the near-wall mean velocity profiles and the wall-shear stress. Simulations using DES improved the near-wall velocity predictions, but failed to predict the temperature fluctuations due to high levels of modeled turbulent viscosity that restrained the formation of small scale turbulence

An approximate model for cancellous bone screw fixation

This is the author's accepted manuscript. The final published article is available from the link below. Copyright @ 2013 Taylor & Francis.This paper presents a finite element (FE) model to identify parameters that affect the performance of an improved cancellous bone screw fixation technique, and hence potentially improve fracture treatment. In cancellous bone of low apparent density, it can be difficult to achieve adequate screw fixation and hence provide stable fracture fixation that enables bone healing. Data from predictive FE models indicate that cements can have a significant potential to improve screw holding power in cancellous bone. These FE models are used to demonstrate the key parameters that determine pull-out strength in a variety of screw, bone and cement set-ups, and to compare the effectiveness of different configurations. The paper concludes that significant advantages, up to an order of magnitude, in screw pull-out strength in cancellous bone might be gained by the appropriate use of a currently approved calcium phosphate cement

Associations between health-related quality of life, physical function and fear of falling in older fallers receiving home care

Falls and injuries in older adults have significant consequences and costs, both personal and to society. Although having a high incidence of falls, high prevalence of fear of falling and a lower quality of life, older adults receiving home care are underrepresented in research on older fallers. The objective of this study is to determine the associations between health-related quality of life (HRQOL), fear of falling and physical function in older fallers receiving home care

Capturing egocentric biases in reference reuse during collaborative dialogue

Words that are produced aloud—and especially self-produced ones—are remembered better than words that are not, a phenomenon labeled the production effect in the field of memory research. Two experiments were conducted to determine whether this effect can be generalized to dialogue, and how it might affect dialogue management. Triads (Exp. 1) or dyads (Exp. 2) of participants interacted to perform a collaborative task. Analyzing reference reuse during the interaction revealed that the participants were more likely to reuse the references that they had presented themselves, on the one hand, and those that had been accepted through verbatim repetition, on the other. Analyzing reference recall suggested that the greater accessibility of self-presented references was only transient. Moreover, among partner-presented references, those discussed while the participant had actively taken part in the conversation were more likely to be recalled than those discussed while the participant had been inactive. These results contribute to a better understanding of how individual memory processes might contribute to collaborative dialogue

The Mechanisms of Codon Reassignments in Mitochondrial Genetic Codes

Many cases of non-standard genetic codes are known in mitochondrial genomes. We carry out analysis of phylogeny and codon usage of organisms for which the complete mitochondrial genome is available, and we determine the most likely mechanism for codon reassignment in each case. Reassignment events can be classified according to the gain-loss framework. The gain represents the appearance of a new tRNA for the reassigned codon or the change of an existing tRNA such that it gains the ability to pair with the codon. The loss represents the deletion of a tRNA or the change in a tRNA so that it no longer translates the codon. One possible mechanism is Codon Disappearance, where the codon disappears from the genome prior to the gain and loss events. In the alternative mechanisms the codon does not disappear. In the Unassigned Codon mechanism, the loss occurs first, whereas in the Ambiguous Intermediate mechanism, the gain occurs first. Codon usage analysis gives clear evidence of cases where the codon disappeared at the point of the reassignment and also cases where it did not disappear. Codon disappearance is the probable explanation for stop to sense reassignments and a small number of reassignments of sense codons. However, the majority of sense to sense reassignments cannot be explained by codon disappearance. In the latter cases, by analysis of the presence or absence of tRNAs in the genome and of the changes in tRNA sequences, it is sometimes possible to distinguish between the Unassigned Codon and Ambiguous Intermediate mechanisms. We emphasize that not all reassignments follow the same scenario and that it is necessary to consider the details of each case carefully.Comment: 53 pages (45 pages, including 4 figures + 8 pages of supplementary information). To appear in J.Mol.Evo

Programming of adipose tissue miR-483-3p and GDF-3 expression by maternal diet in type 2 diabetes.

Nutrition during early mammalian development permanently influences health of the adult, including increasing the risk of type 2 diabetes and coronary heart disease. However, the molecular mechanisms underlying such programming are poorly defined. Here we demonstrate that programmed changes in miRNA expression link early-life nutrition to long-term health. Specifically, we show that miR-483-3p is upregulated in adipose tissue from low-birth-weight adult humans and prediabetic adult rats exposed to suboptimal nutrition in early life. We demonstrate that manipulation of miR-483-3p levels in vitro substantially modulates the capacity of adipocytes to differentiate and store lipids. We show that some of these effects are mediated by translational repression of growth/differentiation factor-3, a target of miR-483-3p. We propose that increased miR-483-3p expression in vivo, programmed by early-life nutrition, limits storage of lipids in adipose tissue, causing lipotoxicity and insulin resistance and thus increasing susceptibility to metabolic disease.This work was funded by the BBSRC (project grants BB/F-15364/1 and BB/F-14279/1). SEO is a British Heart Foundation Senior Fellow (FS/09/029/27902), MB is an MRC Senior Fellow and AEW is a BBSRC Professorial Fellow. KS and SEO are members of the MRC Centre for Obesity and Related Metabolic Diseases (MRC-CORD), which also provided a studentship for MW. KS is a member of the European Union COST Action BM0602

Crimean-Congo hemorrhagic fever: epidemiological trends and controversies in treatment

Crimean-Congo hemorrhagic fever (CCHF) virus has the widest geographic range of all tick-borne viruses and is endemic in more than 30 countries in Eurasia and Africa. Over the past decade, new foci have emerged or re-emerged in the Balkans and neighboring areas. Here we discuss the factors influencing CCHF incidence and focus on the main issue of the use of ribavirin for treating this infection. Given the dynamics of CCHF emergence in the past decade, development of new anti-viral drugs and a vaccine is urgently needed to treat and prevent this acute, life-threatening disease