Design and fluid dynamic analysis of a custom drip chamber in a medical disposable device

Negli ultimi anni, parallelamente allo sviluppo di calcolatori elettronici sempre più performanti, la fluidodinamica computazionale è diventata uno strumento di notevole utilità nell’analisi dei flussi e nello sviluppo di dispositivi medici. Quando impiegate nello studio di flussi di fluidi fisiologici, come il sangue, il vantaggio principale delle analisi CFD è che permettono di caratterizzare il comportamento fluidodinamico senza dover eseguire test in-vivo/in-vitro, consentendo quindi notevoli vantaggi in termini di tempo, denaro e rischio derivante da applicazioni mediche. Inoltre, simulazioni CFD offrono una precisa e dettagliata descrizione di ogni parametro di interesse permettendo, già in fase di progettazione, di prevedere quali modifiche al layout garantiranno maggiori vantaggi in termini di funzionalità. Il presente lavoro di tesi si è posto l’obiettivo di valutare, tramite simulazioni CFD, le performances fluidodinamiche del comparto sangue “camera venosa” di un dispositivo medico monouso Bellco impiegato nella realizzazione di trattamenti di emodialisi. Dopo una panoramica del contesto, è presentata una breve descrizione della disfunzione renale e dei trattamenti sostitutivi. Notevole impegno è stato in seguito rivolto allo studio della letteratura scientifica in modo da definire un modello reologico per il fluido non-Newtoniano preso in considerazione e determinarne i parametri caratteristici. Il terzo capitolo presenta lo stato dell’arte delle apparecchiature Bellco, rivolgendosi con particolare attenzione al componente “cassette” del dispositivo monouso. L’analisi fluidodinamica del compartimento “camera venosa” della cassette, che sarà presa in considerazione nei capitoli quinto e sesto, si inserisce nell’ambito della riprogettazione del dispositivo attualmente in commercio: il quarto capitolo si incentra sul suo nuovo design, ponendo specifico interesse sul layout della camera venosa di nuova generazione. Per lo studio dei flussi che si sviluppano internamente ad essa ci si è avvalsi del modulo CFD del software COMSOL multiphysics® (versione 5.0); la definizione del modello implementato e della tipologia di studio effettuato sono presi in considerazione nel quinto capitolo. Le problematiche di maggior impatto nella realizzazione di un trattamento di emodialisi sono l’emolisi e la coagulazione del sangue. Nell'evenienza che si verifichino massivamente occorre infatti interrompere il trattamento con notevoli disagi per il paziente, per questo devono essere evitate. Nel sesto capitolo i risultati ottenuti sono stati esaminati rivolgendo particolare attenzione alla verifica dell’assenza di fenomeni che possano portare alle problematiche suddette.

Structure and thermodynamics of H3O+(H2O)8 clusters: A combined molecular dynamics and quantum mechanics approach

We have studied the structure and stability of (H3O+)(H2O)8 clusters using a combination of molecular dynamics sampling and high-level ab initio calculations. 20 distinct oxygen frameworks are found within 2 kcal/mol of the electronic or standard Gibbs free energy minimum. The impact of quantum zero-point vibrational corrections on the relative stability of these isomers is quite significant. The box-like isomers are favored in terms of electronic energy, but with the inclusion of zero-point vibrational corrections and entropic effects tree-like isomers are favored at higher temperatures. Under conditions from 0 to 298.15 K, the global minimum is predicted to be a tree-like structure with one dangling singly coordinated water molecule. Above 298.15 K, higher entropy tree-like isomers with two or more singly coordinated water molecules are favored. These assignments are generally consistent with experimental IR spectra of (H3O+)(H2O)8 obtained at 150 K.

Randomized, Double-Blind Trial of the Effect of Fluid Composition on Electrolyte, Acid-Base, and Fluid Homeostasis in Patients Early After Subarachnoid Hemorrhage.

Hyper- and hyponatremia are frequently observed in patients after subarachnoidal hemorrhage, and are potentially related to worse outcome. We hypothesized that the fluid regimen in these patients is associated with distinct changes in serum electrolytes, acid-base disturbances, and fluid balance.

[Arterial pressure curve and fluid status.]

Fluid optimization is a major contributor to improved outcome in patients. Unfortunately, anesthesiologists are often in doubt whether an additional fluid bolus will improve the hemodynamics of the patient or not as excess fluid may even jeopardize the condition. This article discusses physiological concepts of liberal versus restrictive fluid management followed by a discussion on the respective capabilities of various monitors to predict fluid responsiveness. The parameter difference in pulse pressure (dPP), derived from heart-lung interaction in mechanically ventilated patients is discussed in detail. The dPP cutoff value of 13% to predict fluid responsiveness is presented together with several assessment techniques of dPP. Finally, confounding variables on dPP measurements, such as ventilation parameters, pneumoperitoneum and use of norepinephrine are also mentioned.

Neuromuscular disuse and atrophy: {\it In vivo\/} magnetic resonance studies of intramuscular lipid metabolism and fluid shift changes

We postulated that neuromuscular disuse results in deleteriously affected tissue-vascular fluid exchange processes and subsequently damages the important oxidative bioenergetic process of intramuscular lipid metabolism. The in-depth research reported in the literature is somewhat limited by the ex vivo nature and sporadic time-course characterization of disuse atrophy and recovery. Thus, an in vivo controlled, localized animal model of disuse atrophy was developed in one of the hindlimbs of laboratory rabbits (employing surgically implanted tetrodotoxin (TTX)-filled mini-osmotic pump-sciatic nerve superfusion system) and tested repeatedly with magnetic resonance (MR) throughout the 2-week period of temporarily induced disuse and during the recovery period (following explantation of the TTX-filled pump) for a period of 3 weeks. Controls consisted of saline/"sham"-implanted rabbit hindlimbs. The validity of this model was established with repeated electrophysiologic nerve conduction testing using a clinically appropriate protocol and percutaneously inserted small needle stimulating and recording electrodes. Evoked responses recorded from proximal (P) and distal (D) sites to the sciatic nerve cuff in the TTX-implanted group revealed significantly decreased (p $<$ 0.001) proximal-to-distal (P/D) amplitude ratios (as much as 50-70% below Baseline/pre-implanted and sham-implanted group values) and significantly increased (p $<$ 0.01) differential latency (PL-DL) values (as much as 1.5 times the pre- and sham-implanted groups). By Day 21 of recovery, observed P/D and PL-DL levels matched Baseline/sham-implemented levels. MRI-determined cross-sectional area (CSA) values of Baseline/pre-implanted, sham- or TTX-implanted, and recovering/explanted and the corresponding contralateral hindlimb tibialis anterior (TA) muscles normalized to tibial bone (TB) CSA (in TA/TB ratios) revealed that there was a significant decline (indicative of atrophic response) from pre- and sham-implanted controls by as much as 20% (p $<$ 0.01) at Day 7 and 50-55% (p $<$ 0.001) at Day 13 of TTX-implantation. In the non-implanted contralaterals, a significant increase (indicative of hypertrophic response) by as much as 10% (p $<$ 0.025) at Day 7 and 27% (p $<$ 0.001) at Day 13 + TTX was found. The induced atrophic/hypertrophic TA muscles were observed to be fully recovered by Day 21 post-explantation as evidenced by image TA/TB ratios. End-point biopsy results from a small group of rabbits revealed comprehensive atrophy of both Type I and Type II fibers, although the heterogeneity of the response supports the use of image-guided, volume-localized proton magnetic resonance spectroscopy (MRS) to noninvasively assess tissue-level metabolic changes. MRS-determined results of a 0.25cc volume of tissue within implanted limb TA muscles under resting/pre-ischemic, ischemic-stressed, and post-ischemic conditions at timepoints during and following disuse atrophy/recovery revealed significantly increased intramuscular spectral lipid levels, as much as 2-3 times (p $<$ 0.01) the Baseline/pre-implanted values at Day 7 and 6-7 times (p $<$ 0.001) at Day 13 + TTX, which approached normal levels (compared to pre- and sham-implanted groups) by Day 21 of post-explanation recovery. (Abstract shortened by UMI.) ^

FOXC2 and fluid shear stress stabilize postnatal lymphatic vasculature

Biomechanical forces, such as fluid shear stress, govern multiple aspects of endothelial cell biology. In blood vessels, disturbed flow is associated with vascular diseases, such as atherosclerosis, and promotes endothelial cell proliferation and apoptosis. Here, we identified an important role for disturbed flow in lymphatic vessels, in which it cooperates with the transcription factor FOXC2 to ensure lifelong stability of the lymphatic vasculature. In cultured lymphatic endothelial cells, FOXC2 inactivation conferred abnormal shear stress sensing, promoting junction disassembly and entry into the cell cycle. Loss of FOXC2-dependent quiescence was mediated by the Hippo pathway transcriptional coactivator TAZ and, ultimately, led to cell death. In murine models, inducible deletion of Foxc2 within the lymphatic vasculature led to cell-cell junction defects, regression of valves, and focal vascular lumen collapse, which triggered generalized lymphatic vascular dysfunction and lethality. Together, our work describes a fundamental mechanism by which FOXC2 and oscillatory shear stress maintain lymphatic endothelial cell quiescence through intercellular junction and cytoskeleton stabilization and provides an essential link between biomechanical forces and endothelial cell identity that is necessary for postnatal vessel homeostasis. As FOXC2 is mutated in lymphedema-distichiasis syndrome, our data also underscore the role of impaired mechanotransduction in the pathology of this hereditary human disease.

Carbonate cements and fluid circulation of ODP Leg 116 samples

The carbonate cements found in Sites 717-719 of ODP Leg 116 correspond to the precipitation of inorganic calcite due to circulation of hot fluid associated with intraplate deformation in the central Indian Ocean. A first burst of hydrothermal activity may have occurred 7.5-9 Ma and a second burst less than 0.5 Ma. These fluids were probably derived from the basaltic basement and the immediately overlying sediments.

Stable isotope geochemistry of pore waters and marine sediments from the New Jersey shelf: Methane formation and fluid origin

Interstitial water and sediment samples of the Integrated Ocean Drilling Program (IODP) expedition 313 "New Jersey Shallow Shelf" were analyzed for chemical composition and stable isotope ratios. A total of 222 water samples were collected from the cores by Rhizon samplers and squeezing of fresh core material. Water was analyzed for its stable oxygen and hydrogen isotope geochemistry (d2H and d18O) at sites M0027A and M0029A, and the carbon isotope composition of the dissolved inorganic carbon (d13CDIC) (all sites). In addition, organic material (Corg) and inorganic carbonates from sediments were analyzed for their carbon ratios (d13Corg and d13Ccarb), and in case of the carbonates also for oxygen (d18Ocarb). Carbon isotopes were also analyzed in samples containing enough methane gas (d13Cmeth). Pore fluids from site M0027A were analyzed for the sulfur isotope composition of dissolved sulfate (d34S). The combination of isotope analyses of all phases (interstitial water, sediment, and gas) with pore water chemistry is expected to enable a better understanding of processes in the sediment and will help to identify the origin of fluids under the New Jersey shelf.

Geochemistry, isotopes, trace elements and fluid inclusion geothermometry at DSDP Hole 83-504B

Stockwork-like metal sulfide mineralizations were found at 910-928 m below seafloor (BSF) in the pillow/dike transition zone of Hole 504B. This is the same interval where most physical properties of the 5.9-m.y.-old crust of the Costa Rica Rift change from those characteristic of Layer 2B to those of Layer 2C. The pillow lavas, breccias, and veins of the stockwork-like zone were studied by transmitted and reflected light microscopy, X-ray diffraction, and electron microprobe analysis. Bulk rock oxygen isotopic analyses as well as isolated mineral oxygen and sulfur isotopic analyses and fluid inclusion measurements were carried out. A complex alteration history was reconstructed that includes three generations of fissures, each followed by precipitation of characteristic hydrothermal mineral parageneses: (1) Minor and local deposition of quartz occurred on fissure walls; adjacent wall rocks were silicified, followed by formation of chlorite and minor pyrite I in the veins, whereas albite, sphene, chlorite and chlorite-expandable clay mixtures, actinolite, and pyrite replaced igneous phases in the host rocks. The hydrothermal fluids responsible for this first stage were probably partially reacted seawater, and their temperatures were at least 200-250° C. (2) Fissures filled during the first stage were reopened and new cracks formed. They were filled with quartz, minor chlorite and chlorite-expandable clay mixtures, traces of epidote, common pyrite, sphalerite, chalcopyrite, and minor galena. During the second stage, hydrothermal fluids were relatively evolved metal- and Si-rich solutions whose temperatures ranged from 230 to 340° C. The fluctuating chemical composition and temperature of the solutions produced a complex depositional sequence of sulfides in the veins: chalcopyrite I, ± Fe-rich sphalerite, chalcopyrite II ("disease"), Fe-poor sphalerite, chalcopyrite III, galena, and pyrite II. (3) During the last stage, zeolites and Mg-poor calcite filled up the remaining spaces and newly formed cracks and replaced the host rock plagioclase. Analcite and stilbite were first to form in veins, possibly at temperatures below 200°C; analcite and earlier quartz were replaced by laumontite at 250°C, whereas calcite formation temperature ranged from 135 to 220°C. The last stage hydrothermal fluids were depleted in Mg and enriched in Ca and 18O compared to seawater and contained a mantle carbon component. This complex alteration history paralleling a complex mineral paragenesis can be interpreted as the result of a relatively long-term evolution of a hydrothermal system with superimposed shorter term fluctuations in solution temperature and composition. Hydrothermal activity probably began close to the axis of the Costa Rica Rift with the overall cooling of the system and multiple fracturing stages due to movement of the crust away from the axis and/or cooling of a magmatic heat source.

Lithogeochemistry and fluid flow in the epithermal Veta Rublo base metal-silver deposit, Chonta Mine (Huancavelica, Perú)

The Chonta Mine (75º00’30” W & 13º04’30”S, 4495 to 5000 m absl), owned by Compañía Minera Caudalosa, operates a polymetallic Zn-Pb-Cu-Ag vein system of the low sulphidation epithermal type, hosted by cenozoic volcanics of dacitic to andesitic composition (Domos de Lava Formation). Veta Rublo, one of the main veins of the system, is worked underground to nearly 300 m. It strikes 60-80º NE and dips 60-70º SE; its width varies between 0.30 and 2.20m, and it crops out along 1 km, but is continued along strike by other veins, as Veta Caudalosa, for some 5 km. Typical metal contents are 7% Zn, 5% Pb, 0.4% Cu and 3 oz/t Ag, with quartz, sericite, sphalerite, galena, pyrite, chalcopyrite, fahlore as main minerals, and minor carbonate and sulphosalts.

Geothermometry, ore geochemistry and fluid flow in the Esperanza Vein, Huachocolpa District (Huancavelica, Peru)

The Esperanza Zn-Pb-Ag vein, owned by Compañía de Minas Buenaventura S.A.A., lies over 4000 to 4650 masl in the Western Cordillera of the Peruvian Central Andes. The Esperanza low sulphidation epithermal vein trends ~E-W along 1500 m; it dips to the South and can be followed to 350 m depth. As other veins of the district, like Teresita and Bienaventurada, it is hosted by intermediate to felsic volcanics (andesitic to dacitic compositions) of the Huachocolpa Group (Middle Miocene to Upper Pliocene). The mineralisation occurs mostly as open space filling related to fracture development during the Quechua III deformational event. Main ore minerals are sphalerite, galena, tetrahedrite, pyrite, chalcopyrite and Ag and Pb sulfosalts; quartz, barite and calcite are the main gangue minerals. Current production grades are ~5% Zn, ~8Oz/t Ag, ~3% Pb; usually very low Cu (mean ~0.04%).