Abstract Measurements of cardiac conduction velocity provide valuable functional and structural insight into the initiation and perpetuation of cardiac arrhythmias, in both a clinical and laboratory ...context. The interpretation of activation wavefronts and their propagation can identify mechanistic properties of a broad range of electrophysiological pathologies. However, the sparsity, distribution and uncertainty of recorded data make accurate conduction velocity calculation difficult. A wide range of mathematical approaches have been proposed for addressing this challenge, often targeted towards specific data modalities, species or recording environments. Many of these algorithms require identification of activation times from electrogram recordings which themselves may have complex morphology or low signal-to-noise ratio. This paper surveys algorithms designed for identifying local activation times and computing conduction direction and speed. Their suitability for use in different recording contexts and applications is assessed.
Influenza viruses are thought to be spread by droplets, but the role of aerosol dissemination is unclear and has not been assessed by previous studies. Oxygen therapy, nebulised medication and ...ventilatory support are treatments used in clinical practice to treat influenzal infection are thought to generate droplets or aerosols.
Evaluation of the characteristics of droplet/aerosol dispersion around delivery systems during non-invasive ventilation (NIV), oxygen therapy, nebuliser treatment and chest physiotherapy by measuring droplet size, geographical distribution of droplets, decay in droplets over time after the interventions were discontinued.
Three groups were studied: (1) normal controls, (2) subjects with coryzal symptoms and (3) adult patients with chronic lung disease who were admitted to hospital with an infective exacerbation. Each group received oxygen therapy, NIV using a vented mask system and a modified circuit with non-vented mask and exhalation filter, and nebulised saline. The patient group had a period of standardised chest physiotherapy treatment. Droplet counts in mean diameter size ranges from 0.3 to > 10 µm were measured with an counter placed adjacent to the face and at a 1-m distance from the subject/patient, at the height of the nose/mouth of an average health-care worker.
NIV using a vented mask produced droplets in the large size range (> 10 µm) in patients (p = 0.042) and coryzal subjects (p = 0.044) compared with baseline values, but not in normal controls (p = 0.379), but this increase in large droplets was not seen using the NIV circuit modification. Chest physiotherapy produced droplets predominantly of > 10 µm (p = 0.003), which, as with NIV droplet count in the patients, had fallen significantly by 1 m. Oxygen therapy did not increase droplet count in any size range. Nebulised saline delivered droplets in the small- and medium-size aerosol/droplet range, but did not increase large-size droplet count.
NIV and chest physiotherapy are droplet (not aerosol)-generating procedures, producing droplets of > 10 µm in size. Due to their large mass, most fall out on to local surfaces within 1 m. The only device producing an aerosol was the nebuliser and the output profile is consistent with nebuliser characteristics rather than dissemination of large droplets from patients. These findings suggest that health-care workers providing NIV and chest physiotherapy, working within 1 m of an infected patient should have a higher level of respiratory protection, but that infection control measures designed to limit aerosol spread may have less relevance for these procedures. These results may have infection control implications for other airborne infections, such as severe acute respiratory syndrome and tuberculosis, as well as for pandemic influenza infection.
Saccadic eye rotations induce a flow in the vitreous humor of the eye. Any such flow is likely to have a significant influence on the dispersion of drugs injected into the vitreous chamber. The shape ...of this chamber deviates from a perfect sphere by up to 10–20% of the radius, which is predominantly due to an indentation caused by the lens. In this paper we investigate theoretically the effect of the domain shape upon the flow field generated by saccades by considering an idealized model. The posterior chamber geometry is assumed to be a sphere with a small indentation, undergoing prescribed small-amplitude sinusoidal torsional oscillations, and, as an initial step towards understanding the problem, we treat the vitreous humor as a Newtonian fluid filling the chamber. The latter assumption applies best in the case of a liquefied vitreous or a tamponade fluid introduced in the vitreous chamber after vitrectomy. We find the flow field in terms of vector spherical harmonics, focusing on the deviation from the flow that would be obtained in a perfect sphere. The flow induced by the departure of the domain geometry from the spherical shape has an oscillating component at leading order and a smaller-amplitude steady streaming flow. The oscillating component includes a circulation cell formed every half-period, which migrates from the indentation towards the center of the domain where it disappears. The steady component has two counter-rotating circulations in the anterior part of the domain. These findings are in good qualitative agreement with the experimental results of Stocchino et al. (Phys Med Biol 52:2021–2034, 2007). Our results predict a significant reduction in the expected time for drug dispersal across the eye compared with the situation in which there is no fluid flow present.
The fetal intestinal mucosa is characterized by elevated Toll-like receptor 4 (TLR4) expression, which can lead to the development of necrotizing enterocolitis (NEC)—a devastating inflammatory ...disease of the premature intestine—upon exposure to microbes. To define endogenous strategies that could reduce TLR4 signaling, we hypothesized that amniotic fluid can inhibit TLR4 signaling within the fetal intestine and attenuate experimental NEC, and we sought to determine the mechanisms involved. We show here that microinjection of amniotic fluid into the fetal (embryonic day 18.5) gastrointestinal tract reduced LPS-mediated signaling within the fetal intestinal mucosa. Amniotic fluid is abundant in EGF, which we show is required for its inhibitory effects on TLR4 signaling via peroxisome proliferator-activated receptor, because inhibition of EGF receptor (EGFR) with cetuximab or EGF-depleted amniotic fluid blocked the inhibitory effects of amniotic fluid on TLR4, whereas amniotic fluid did not prevent TLR4 signaling in EGFR- or peroxisome proliferator-activated receptor γ–deficient enterocytes or in mice deficient in intestinal epithelial EGFR, and purified EGF attenuated the exaggerated intestinal mucosal TLR4 signaling in wild-type mice. Moreover, amniotic fluid-mediated TLR4 inhibition reduced the severity of NEC in mice through EGFR activation. Strikingly, NEC development in both mice and humans was associated with reduced EGFR expression that was restored upon the administration of amniotic fluid in mice or recovery from NEC in humans, suggesting that a lack of amniotic fluid-mediated EGFR signaling could predispose to NEC. These findings may explain the unique susceptibility of premature infants to the development of NEC and offer therapeutic approaches to this devastating disease.
Flow dynamics in a stented ureter Siggers, Jennifer H.; Waters, Sarah; Wattis, Jonathan ...
Mathematical medicine and biology,
03/2009, Letnik:
26, Številka:
1
Journal Article
Recenzirano
Vesicorenal reflux is a major side effect associated with ureteric stent placement. In a stented upper urinary tract when the bladder pressure rises, such as during bladder spasms (due to irritation ...caused by the stent) or voiding of the bladder, it drives urine reflux up the ureter, which, in turn, may be a contributory factor for infections in the renal pelvis. We develop a mathematical model to examine urine flow in a stented ureter, assuming that it remains axisymmetric and treating the wall as a non-linear elastic membrane. The stent is modelled as a rigid, permeable, hollow, circular cylinder lying coaxially inside the ureter. The renal pelvis is treated as an elastic bag, whose volume increases in response to an increased internal pressure. Fluid enters the renal pelvis from the kidney with a prescribed flux. The stent, ureter and renal pelvis are filled with urine, and the bladder pressure is prescribed. We use the model to calculate the total volume of reflux generated during rises in bladder pressure and investigate how it is affected by the stent and ureter properties.
The maintenance of mucosal barrier equilibrium in the intestine requires a delicate and dynamic balance between enterocyte loss by apoptosis and the generation of new cells by proliferation from stem ...cell precursors at the base of the intestinal crypts. When the balance shifts towards either excessive or insufficient apoptosis, a broad range of gastrointestinal diseases can manifest. Recent work from a variety of laboratories has provided evidence in support of a role for receptors of the innate immune system, including Toll-like receptors 2, 4, and 9 as well as the intracellular pathogen recognition receptor NOD2/CARD15, in the initiation of enterocyte apoptosis. The subsequent induction of enterocyte apoptosis in response to the activation of these innate immune receptors plays a key role in the development of various intestinal diseases, including necrotizing enterocolitis, Crohn’s disease, ulcerative colitis, and intestinal cancer. This review will detail the regulatory pathways that govern enterocyte apoptosis, and will explore the role of the innate immune system in the induction of enterocyte apoptosis in gastrointestinal disease.
Background & Aims:
Preterm birth and formula feeding are key risk factors associated with necrotizing enterocolitis (NEC) in infants, but little is known about intestinal conditions that predispose ...to disease. Thus, structural, functional, and microbiologic indices were used to investigate the etiology of spontaneous NEC development in preterm pigs.
Methods:
Piglets were delivered by cesarean section at 92% gestation, reared in infant incubators, and fed infant formula or colostrum every 3 hours (n = 120) until tissue collection at 1–2 days of age.
Results:
Clinical and histopathologic signs of NEC were observed in 57% of pigs fed FORMULA (26/46) and in 5% of pigs fed COLOSTRUM (2/38) (
P < .05). Relative to COLOSTRUM, both healthy and sick FORMULA pigs had reduced intestinal villous heights, enzyme activities, nutrient absorption, and antioxidant levels and higher inducible nitric oxide synthetase activity (
P < .05). In healthy pigs, mucosal microbial diversity remained low and diet independent. NEC pigs showed bacterial overgrowth, and a high mucosal density of
Clostridium perfringens was detected in some but not all pigs. Germ-free conditions and antiserum against
Clostridium perfringens toxin prevented intestinal dysfunction and NEC in formula-fed pigs, whereas the gut trophic factors, epidermal growth factor, and glucagon-like peptide 2 had limited effects.
Conclusions:
A subclinical, formula-induced mucosal atrophy and dysfunction predispose to NEC and bacterial overgrowth. The adverse feeding effects are colonization dependent and may be reduced by factors in colostrum that include antibodies against aggressive toxins such as those of
Clostridium perfringens.
One-dimensional (1D) models are useful to study pressure and flow waves in large arteries in cases where clinical measurements are not available. Using a simplified 1D model (1) we have modelled the ...pressure waveform in the brachial artery with and without occlusion, which is relevant to non-invasive measurement of blood pressure with cuff-based devices. The results show that occlusion of the brachial artery leads to superposed high frequency oscillations in local brachial blood pressure of up to 10mmHg (Fig.). A modelling study of brachial occlusion done independently by a group from Swansea University (2) has also shown similar results.
Preliminary data made with a fluid-filled catheter by collaborators in New Zealand (unpublished data) show much smaller pressure fluctuations during cuff occlusion, but the use of a fluid-filled catheter may have damped out the relatively high frequency waves that are predicted. Therefore, measurements of blood pressure using a high-fidelity catheter are being made in patients undergoing routine cardiac catheterization. Pressure waveforms recorded in the brachial, subclavian arteries and the ascending aorta with and without brachial artery occlusion are compared to the predictions of the 1D models.
Figure 1
Predicted pressure waveforms for an occluded and non-occluded brachial artery.
Ureteric stents: investigating flow and encrustation Waters, S L; Heaton, K; Siggers, J H ...
Proceedings of the Institution of Mechanical Engineers. Part H, Journal of engineering in medicine,
05/2008, Letnik:
222, Številka:
4
Journal Article
Recenzirano
Blockages of the ureter, e.g. due to calculi (kidney stones), can result in an increase in renal pelvic pressure. This may be relieved by inserting a stent (essentially a permeable hollow tube). ...However, a number of complications are associated with stent use. Stents can result in reflux (backflow of urine along the ureter), which will promote recurrent urinary infection and possible renal parenchymal damage. Furthermore, long-term stent use is associated with infection and precipitation of salts from the urine, which can lead to a build-up of crystalline deposits on the stent surface, making stent removal difficult and painful. This paper examines factors governing urine flow in a stented ureter, the implications for reflux, and the processes by which the stent surface encrusts, in particular focusing on the influence of bacterial infection. An interdisciplinary approach is adopted, involving a combination of theoretical investigations and novel experiments.
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