Search results for: population based research
15 A Case Study on Utility of 18FDG-PET/CT Scan in Identifying Active Extra Lymph Nodes and Staging of Breast Cancer
Authors: Farid Risheq, M. Zaid Alrisheq, Shuaa Al-Sadoon, Karim Al-Faqih, Mays Abdulazeez
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Breast cancer is the most frequently diagnosed cancer worldwide, and a common cause of death among women. Various conventional anatomical imaging tools are utilized for diagnosis, histological assessment and TNM (Tumor, Node, Metastases) staging of breast cancer. Biopsy of sentinel lymph node is becoming an alternative to the axillary lymph node dissection. Advances in 18-Fluoro-Deoxi-Glucose Positron Emission Tomography/Computed Tomography (18FDG-PET/CT) imaging have facilitated breast cancer diagnosis utilizing biological trapping of 18FDG inside lesion cells, expressed as Standardized Uptake Value (SUVmax). Objective: To present the utility of 18FDG uptake PET/CT scans in detecting active extra lymph nodes and distant occult metastases for breast cancer staging. Subjects and Methods: Four female patients were presented with initially classified TNM stages of breast cancer based on conventional anatomical diagnostic techniques. 18FDG-PET/CT scans were performed one hour post 18FDG intra-venous injection of (300-370) MBq, and (7-8) bed/130sec. Transverse, sagittal, and coronal views; fused PET/CT and MIP modality were reconstructed for each patient. Results: A total of twenty four lesions in breast, extended lesions to lung, liver, bone and active extra lymph nodes were detected among patients. The initial TNM stage was significantly changed post 18FDG-PET/CT scan for each patient, as follows: Patient-1: Initial TNM-stage: T1N1M0-(stage I). Finding: Two lesions in right breast (3.2cm2, SUVmax=10.2), (1.8cm2, SUVmax=6.7), associated with metastases to two right axillary lymph nodes. Final TNM-stage: T1N2M0-(stage II). Patient-2: Initial TNM-stage: T2N2M0-(stage III). Finding: Right breast lesion (6.1cm2, SUVmax=15.2), associated with metastases to right internal mammary lymph node, two right axillary lymph nodes, and sclerotic lesions in right scapula. Final TNM-stage: T2N3M1-(stage IV). Patient-3: Initial TNM-stage: T2N0M1-(stage III). Finding: Left breast lesion (11.1cm2, SUVmax=18.8), associated with metastases to two lymph nodes in left hilum, and three lesions in both lungs. Final TNM-stage: T2N2M1-(stage IV). Patient-4: Initial TNM-stage: T4N1M1-(stage III). Finding: Four lesions in upper outer quadrant area of right breast (largest: 12.7cm2, SUVmax=18.6), in addition to one lesion in left breast (4.8cm2, SUVmax=7.1), associated with metastases to multiple lesions in liver (largest: 11.4cm2, SUV=8.0), and two bony-lytic lesions in left scapula and cervicle-1. No evidence of regional or distant lymph node involvement. Final TNM-stage: T4N0M2-(stage IV). Conclusions: Our results demonstrated that 18FDG-PET/CT scans had significantly changed the TNM stages of breast cancer patients. While the T factor was unchanged, N and M factors showed significant variations. A single session of PET/CT scan was effective in detecting active extra lymph nodes and distant occult metastases, which were not identified by conventional diagnostic techniques, and might advantageously replace bone scan, and contrast enhanced CT of chest, abdomen and pelvis. Applying 18FDG-PET/CT scan early in the investigation, might shorten diagnosis time, helps deciding adequate treatment protocol, and could improve patients’ quality of life and survival. Trapping of 18FDG in malignant lesion cells, after a PET/CT scan, increases the retention index (RI%) for a considerable time, which might help localize sentinel lymph node for biopsy using a hand held gamma probe detector. Future work is required to demonstrate its utility.Keywords: axillary lymph nodes, breast cancer staging, fluorodeoxyglucose positron emission tomography/computed tomography, lymph nodes
Procedia PDF Downloads 31314 Using the UK as a Case Study to Assess the Current State of Large Woody Debris Restoration as a Tool for Improving the Ecological Status of Natural Watercourses Globally
Authors: Isabelle Barrett
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Natural watercourses provide a range of vital ecosystem services, notably freshwater provision. They also offer highly heterogeneous habitat which supports an extreme diversity of aquatic life. Exploitation of rivers, changing land use and flood prevention measures have led to habitat degradation and subsequent biodiversity loss; indeed, freshwater species currently face a disproportionate rate of extinction compared to their terrestrial and marine counterparts. Large woody debris (LWD) encompasses the trees, large branches and logs which fall into watercourses, and is responsible for important habitat characteristics. Historically, natural LWD has been removed from streams under the assumption that it is not aesthetically pleasing and is thus ecologically unfavourable, despite extensive evidence contradicting this. Restoration efforts aim to replace lost LWD in order to reinstate habitat heterogeneity. This paper aims to assess the current state of such restoration schemes for improving fluvial ecological health in the UK. A detailed review of the scientific literature was conducted alongside a meta-analysis of 25 UK-based projects involving LWD restoration. Projects were chosen for which sufficient information was attainable for analysis, covering a broad range of budgets and scales. The most effective strategies for river restoration encompass ecological success, stakeholder engagement and scientific advancement, however few projects surveyed showed sensitivity to all three; for example, only 32% of projects stated biological aims. Focus tended to be on stakeholder engagement and public approval, since this is often a key funding driver. Consequently, there is a tendency to focus on the aesthetic outcomes of a project, however physical habitat restoration does not necessarily lead to direct biodiversity increases. This highlights the significance of rivers as highly heterogeneous environments with multiple interlinked processes, and emphasises a need for a stronger scientific presence in project planning. Poor scientific rigour means monitoring is often lacking, with varying, if any, definitions of success which are rarely pre-determined. A tendency to overlook negative or neutral results was apparent, with unjustified focus often put on qualitative results. The temporal scale of monitoring is typically inadequate to facilitate scientific conclusions, with only 20% of projects surveyed reporting any pre-restoration monitoring. Furthermore, monitoring is often limited to a few variables, with biotic monitoring often fish-focussed. Due to their longer life cycles and dispersal capability, fish are usually poor indicators of environmental change, making it difficult to attribute any changes in ecological health to restoration efforts. Although the potential impact of LWD restoration may be positive, this method of restoration could simply be making short-term, small-scale improvements; without addressing the underlying symptoms of degradation, for example water quality, the issue cannot be fully resolved. Promotion of standardised monitoring for LWD projects could help establish a deeper understanding of the ecology surrounding the practice, supporting movement towards adaptive management in which scientific evidence feeds back to practitioners, enabling the design of more efficient projects with greater ecological success. By highlighting LWD, this study hopes to address the difficulties faced within river management, and emphasise the need for a more holistic international and inter-institutional approach to tackling problems associated with degradation.Keywords: biological monitoring, ecological health, large woody debris, river management, river restoration
Procedia PDF Downloads 21613 The Development of the Geological Structure of the Bengkulu Fore Arc Basin, Western Edge of Sundaland, Sumatra, and Its Relationship to Hydrocarbon Trapping Mechanism
Authors: Lauti Dwita Santy, Hermes Panggabean, Syahrir Andi Mangga
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The Bengkulu Basin is part of the Sunda Arc system, which is a classic convergent type margin that occur around the southern rim of the Eurasian continental (Sundaland) plate. The basin is located between deep sea trench (Mentawai Outer Arc high) and the volvanic/ magmatic Arc of the Barisan Mountains Range. To the northwest it is bounded by Padang High, to the northest by Barisan Mountains (Sumatra Fault Zone) to the southwest by Mentawai Fault Zone and to the southeast by Semangko High/ Sunda Strait. The stratigraphic succession and tectonic development can be broadly divided into four stage/ periods, i.e Late Jurassic- Early Cretaceous, Late Eocene-Early Oligocene, Late Oligocene-Early Miocene, Middle Miocene-Late Miocene and Pliocene-Plistocene, which are mainly controlled by the development of subduction activities. The Pre Tertiary Basement consist of sedimentary and shallow water limestone, calcareous mudstone, cherts and tholeiitic volcanic rocks, with Late Jurassic to Early Cretaceous in age. The sedimentation in this basin is depend on the relief of the Pre Tertiary Basement (Woyla Terrane) and occured into two stages, i.e. transgressive stage during the Latest Oligocene-Early Middle Miocene Seblat Formation, and the regressive stage during the Latest Middle Miocene-Pleistocene (Lemau, Simpangaur and Bintunan Formations). The Pre-Tertiary Faults were more intensive than the overlying cover, The Tertiary Rocks. There are two main fault trends can be distinguished, Northwest–Southwest Faults and Northeast-Southwest Faults. The NW-SE fault (Ketaun) are commonly laterally persistent, are interpreted to the part of Sumatran Fault Systems. They commonly form the boundaries to the Pre Tertiary basement highs and therefore are one of the faults elements controlling the geometry and development of the Tertiary sedimentary basins.The Northeast-Southwest faults was formed a conjugate set to the Northwest–Southeast Faults. In the earliest Tertiary and reactivated during the Plio-Pleistocene in a compressive mode with subsequent dextral displacement. The Block Faulting accross these two sets of faults related to approximate North–South compression in Paleogene time and produced a series of elongate basins separated by basement highs in the backarc and forearc region. The Bengkulu basin is interpreted having evolved from pull apart feature in the area southwest of the main Sumatra Fault System related to NW-SE trending in dextral shear.Based on Pyrolysis Yield (PY) vs Total Organic Carbon (TOC) diagram show that Seblat and Lemau Formation belongs to oil and Gas Prone with the quality of the source rocks includes into excellent and good (Lemau Formation), Fair and Poor (Seblat Formation). The fine-grained carbonaceous sediment of the Seblat dan Lemau Formations as source rocks, the coarse grained and carbonate sediments of the Seblat and Lemau Formations as reservoir rocks, claystone bed in Seblat and Lemau Formation as caprock. The source rocks maturation are late immature to early mature, with kerogen type II and III (Seblat Formation), and late immature to post mature with kerogen type I and III (Lemau Formation). The burial history show to 2500 m in depthh with paleo temperature reached 80oC. Trapping mechanism occur during Oligo–Miocene and Middle Miocene, mainly in block faulting system.Keywords: fore arc, bengkulu, sumatra, sundaland, hydrocarbon, trapping mechanism
Procedia PDF Downloads 55812 Microdiamond and Moissanite Inclusions in Garnets from Pohorje Mountains, Eastern Alps, Slovenia
Authors: Mirijam Vrabec, Marian Janak, Bojan Ambrozic, Angelja K. Surca, Nastja Rogan Smuc, Nina Zupancic, Saso Sturm
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Natural microdiamonds and moissanite (SiC) can form during the orogenic events under ultrahigh-pressure metamorphic conditions (UHP), when parts of Earth’s crust are subducted to extreme depths. So far, such processes were identified only in few places on the Earth, and therefore, represent unique opportunity to study the evolution of the Earth’s deep interior. An important discovery of microdiamonds and moissanite was reported from Pohorje, (Slovenia), where they occurred as single or polyphase inclusions in garnets. Metasedimentary rocks from Pohorje are predominantly gneisses representing parts of the Austroalpine metamorphic units of the Eastern Alps. During Cretaceous orogeny, (ca. 95–92 Ma) continental crustal rocks were deeply subducted to the mantle depths (below 100 km) and metamorphosed at pressures exceeding 3.5 GPa and temperatures between 800–850 °C. Microstructural and phase analysis of the inclusions as well as detailed elemental analysis of host garnets were carried out combining several analytical techniques: optical microscope in plane polarized transmitted light, electron probe microanalysis (EPMA) with wavelength-dispersive x-ray spectrometry (WDS) and field-emission scanning microscope (FEG-SEM) with energy-dispersive x-ray spectroscopy (EDS). Micro-Raman analysis revealed sharp, first order diamond bands sometimes accompanied by graphite bands implying that transformation of diamond back to graphite occurred. To study the chemical and crystallographic relationship between microdiamonds and co-inclusions, advanced techniques of transmission electron microscopy (TEM) were applied, which included high-angle annular dark-field scanning transmission electron microscopy (HAADF-STEM), combined with EDS and electron energy-loss spectroscopy (EELS). To prepare electron transparent TEM lamellae selectively a dual-beam Focused Ion Beam/SEM (FIB/SEM) was employed. Detailed study of TEM lamellae, which was cross-sectioned from the highly faceted inclusion body located within the host garnet crystal matrix, revealed rich and rather complex internal structure. Namely, the negative crystal facets of the main inclusion body were typically decorated with up to 1 μm thick amorphous layer, reflecting the general garnet composition with slight variations in Fe/Ca content. Within these layers, ELNES analysis revealed the presence of a 28–30 nm thick layer of amorphous carbon. The very last section of this layer corresponds to composition of SiO2. Within the inclusion, besides diamond and moissanite alumosilicate mineral with pronounced layered structure, iron sulfides and chlorine were identified under TEM and CO2 and CH4 using Raman. Moissanite is found as single crystal or composed from numerous highly textured nano-crystals with the average size of 10 nm. Moissanite inclusions were found embedded inside the amorphous crust implying that moissanite crystalized well before the deposition of the amorphous layer. From the microstructural, crystallographic and chemical observations so far we can deduce, that polyphase inclusions in diamond bearing garnets from Pohorje most probably crystallized from reduced supercritical fluids. Based on layered interface structure of the host mineral multiphase process of crystallization is possible. The presence of microdiamonds and moissanite in rocks from Pohorje demonstrates that these parts of the Eastern Alps were subducted to extreme depths, and were subsequently exhumed back to the Earth's surface without complete breakdown of UHP mineral phases, allowing a rear and exceptional opportunity to study them in-situ.Keywords: diamond, fluid inclusions, moissanite, TEM, UHP metamorphism.
Procedia PDF Downloads 30411 Fabrication of Highly Stable Low-Density Self-Assembled Monolayers by Thiolyne Click Reaction
Authors: Leila Safazadeh, Brad Berron
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Self-assembled monolayers have tremendous impact in interfacial science, due to the unique opportunity they offer to tailor surface properties. Low-density self-assembled monolayers are an emerging class of monolayers where the environment-interfacing portion of the adsorbate has a greater level of conformational freedom when compared to traditional monolayer chemistries. This greater range of motion and increased spacing between surface-bound molecules offers new opportunities in tailoring adsorption phenomena in sensing systems. In particular, we expect low-density surfaces to offer a unique opportunity to intercalate surface bound ligands into the secondary structure of protiens and other macromolecules. Additionally, as many conventional sensing surfaces are built upon gold surfaces (SPR or QCM), these surfaces must be compatible with gold substrates. Here, we present the first stable method of generating low-density self assembled monolayer surfaces on gold for the analysis of their interactions with protein targets. Our approach is based on the 2:1 addition of thiol-yne chemistry to develop new classes of y-shaped adsorbates on gold, where the environment-interfacing group is spaced laterally from neighboring chemical groups. This technique involves an initial deposition of a crystalline monolayer of 1,10 decanedithiol on the gold substrate, followed by grafting of a low-packed monolayer on through a photoinitiated thiol-yne reaction in presence of light. Orthogonality of the thiol-yne chemistry (commonly referred to as a click chemistry) allows for preparation of low-density monolayers with variety of functional groups. To date, carboxyl, amine, alcohol, and alkyl terminated monolayers have been prepared using this core technology. Results from surface characterization techniques such as FTIR, contact angle goniometry and electrochemical impedance spectroscopy confirm the proposed low chain-chain interactions of the environment interfacing groups. Reductive desorption measurements suggest a higher stability for the click-LDMs compared to traditional SAMs, along with the equivalent packing density at the substrate interface, which confirms the proposed stability of the monolayer-gold interface. In addition, contact angle measurements change in the presence of an applied potential, supporting our description of a surface structure which allows the alkyl chains to freely orient themselves in response to different environments. We are studying the differences in protein adsorption phenomena between well packed and our loosely packed surfaces, and we expect this data will be ready to present at the GRC meeting. This work aims to contribute biotechnology science in the following manner: Molecularly imprinted polymers are a promising recognition mode with several advantages over natural antibodies in the recognition of small molecules. However, because of their bulk polymer structure, they are poorly suited for the rapid diffusion desired for recognition of proteins and other macromolecules. Molecularly imprinted monolayers are an emerging class of materials where the surface is imprinted, and there is not a bulk material to impede mass transfer. Further, the short distance between the binding site and the signal transduction material improves many modes of detection. My dissertation project is to develop a new chemistry for protein-imprinted self-assembled monolayers on gold, for incorporation into SPR sensors. Our unique contribution is the spatial imprinting of not only physical cues (seen in current imprinted monolayer techniques), but to also incorporate complementary chemical cues. This is accomplished through a photo-click grafting of preassembled ligands around a protein template. This conference is important for my development as a graduate student to broaden my appreciation of the sensor development beyond surface chemistry.Keywords: low-density self-assembled monolayers, thiol-yne click reaction, molecular imprinting
Procedia PDF Downloads 22610 Settlement Prediction in Cape Flats Sands Using Shear Wave Velocity – Penetration Resistance Correlations
Authors: Nanine Fouche
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The Cape Flats is a low-lying sand-covered expanse of approximately 460 square kilometres, situated to the southeast of the central business district of Cape Town in the Western Cape of South Africa. The aeolian sands masking this area are often loose and compressible in the upper 1m to 1.5m of the surface, and there is a general exceedance of the maximum allowable settlement in these sands. The settlement of shallow foundations on Cape Flats sands is commonly predicted using the results of in-situ tests such as the SPT or DPSH due to the difficulty of retrieving undisturbed samples for laboratory testing. Varying degrees of accuracy and reliability are associated with these methods. More recently, shear wave velocity (Vs) profiles obtained from seismic testing, such as continuous surface wave tests (CSW), are being used for settlement prediction. Such predictions have the advantage of considering non-linear stress-strain behaviour of soil and the degradation of stiffness with increasing strain. CSW tests are rarely executed in the Cape Flats, whereas SPT’s are commonly performed. For this reason, and to facilitate better settlement predictions in Cape Flats sand, equations representing shear wave velocity (Vs) as a function of SPT blow count (N60) and vertical effective stress (v’) were generated by statistical regression of site investigation data. To reveal the most appropriate method of overburden correction, analyses were performed with a separate overburden term (Pa/σ’v) as well as using stress corrected shear wave velocity and SPT blow counts (correcting Vs. and N60 to Vs1and (N1)60respectively). Shear wave velocity profiles and SPT blow count data from three sites masked by Cape Flats sands were utilised to generate 80 Vs-SPT N data pairs for analysis. Investigated terrains included sites in the suburbs of Athlone, Muizenburg, and Atlantis, all underlain by windblown deposits comprising fine and medium sand with varying fines contents. Elastic settlement analysis was also undertaken for the Cape Flats sands, using a non-linear stepwise method based on small-strain stiffness estimates, which was obtained from the best Vs-N60 model and compared to settlement estimates using the general elastic solution with stiffness profiles determined using Stroud’s (1989) and Webb’s (1969) SPT N60-E transformation models. Stroud’s method considers strain level indirectly whereasWebb’smethod does not take account of the variation in elastic modulus with strain. The expression of Vs. in terms of N60 and Pa/σv’ derived from the Atlantis data set revealed the best fit with R2 = 0.83 and a standard error of 83.5m/s. Less accurate Vs-SPT N relations associated with the combined data set is presumably the result of inversion routines used in the analysis of the CSW results showcasing significant variation in relative density and stiffness with depth. The regression analyses revealed that the inclusion of a separate overburden term in the regression of Vs and N60, produces improved fits, as opposed to the stress corrected equations in which the R2 of the regression is notably lower. It is the correction of Vs and N60 to Vs1 and (N1)60 with empirical constants ‘n’ and ‘m’ prior to regression, that introduces bias with respect to overburden pressure. When comparing settlement prediction methods, both Stroud’s method (considering strain level indirectly) and the small strain stiffness method predict higher stiffnesses for medium dense and dense profiles than Webb’s method, which takes no account of strain level in the determination of soil stiffness. Webb’s method appears to be suitable for loose sands only. The Versak software appears to underestimate differences in settlement between square and strip footings of similar width. In conclusion, settlement analysis using small-strain stiffness data from the proposed Vs-N60 model for Cape Flats sands provides a way to take account of the non-linear stress-strain behaviour of the sands when calculating settlement.Keywords: sands, settlement prediction, continuous surface wave test, small-strain stiffness, shear wave velocity, penetration resistance
Procedia PDF Downloads 1759 Climate Change Threats to UNESCO-Designated World Heritage Sites: Empirical Evidence from Konso Cultural Landscape, Ethiopia
Authors: Yimer Mohammed Assen, Abiyot Legesse Kura, Engida Esyas Dube, Asebe Regassa Debelo, Girma Kelboro Mensuro, Lete Bekele Gure
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Climate change has posed severe threats to many cultural landscapes of UNESCO world heritage sites recently. The UNESCO State of Conservation (SOC) reports categorized flooding, temperature increment, and drought as threats to cultural landscapes. This study aimed to examine variations and trends of rainfall and temperature extreme events and their threats to the UNESCO-designated Konso Cultural Landscape in southern Ethiopia. The study used dense merged satellite-gauge station rainfall data (1981-2020) with spatial resolution of 4km by 4km and observed maximum and minimum temperature data (1987-2020). Qualitative data were also gathered from cultural leaders, local administrators, and religious leaders using structured interview checklists. The spatial patterns, coefficient of variation, standardized anomalies, trends, and magnitude of change of rainfall and temperature extreme events both at annual and seasonal levels were computed using the Mann-Kendall trend test and Sen’s slope estimator under the CDT package. The standard precipitation index (SPI) was also used to calculate drought severity, frequency, and trend maps. The data gathered from key informant interviews and focus group discussions were coded and analyzed thematically to complement statistical findings. Thematic areas that explain the impacts of extreme events on the cultural landscape were chosen for coding. The thematic analysis was conducted using Nvivo software. The findings revealed that rainfall was highly variable and unpredictable, resulting in extreme drought and flood. There were significant (P<0.05) increasing trends of heavy rainfall (R10mm and R20mm) and the total amount of rain on wet days (PRCPTOT), which might have resulted in flooding. The study also confirmed that absolute temperature extreme indices (TXx, TXn, and TNx) and the percentile-based temperature extreme indices (TX90p, TN90p, TX10p, and TN10P) showed significant (P<0.05) increasing trends which are signals for warming of the study area. The results revealed that the frequency as well as the severity of drought at 3-months (katana/hageya seasons) was more pronounced than the 12-months (annual) time scale. The highest number of droughts in 100 years is projected at a 3-months timescale across the study area. The findings also showed that frequent drought has led to loss of grasses which are used for making traditional individual houses and multipurpose communal houses (pafta), food insecurity, migration, loss of biodiversity, and commodification of stones from terrace. On the other hand, the increasing trends of rainfall extreme indices resulted in destruction of terraces, soil erosion, loss of life and damage of properties. The study shows that a persistent decline in farmland productivity, due to erratic and extreme rainfall and frequent drought occurrences, forced the local people to participate in non-farm activities and retreat from daily preservation and management of their landscape. Overall, the increasing rainfall and temperature extremes coupled with prevalence of drought are thought to have an impact on the sustainability of cultural landscape through disrupting the ecosystem services and livelihood of the community. Therefore, more localized adaptation and mitigation strategies to the changing climate are needed to maintain the sustainability of Konso cultural landscapes as a global cultural treasure and to strengthen the resilience of smallholder farmers.Keywords: adaptation, cultural landscape, drought, extremes indices
Procedia PDF Downloads 268 Sandstone Petrology of the Kolhan Basin, Eastern India: Implications for the Tectonic Evolution of a Half-Graben
Authors: Rohini Das, Subhasish Das, Smruti Rekha Sahoo, Shagupta Yesmin
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The Paleoproterozoic Kolhan Group (Purana) ensemble constitutes the youngest lithostratigraphic 'outlier' in the Singhbhum Archaean craton. The Kolhan unconformably overlies both the Singhbhum granite and the Iron Ore Group (IOG). Representing a typical sandstone-shale ( +/- carbonates) sequence, the Kolhan is characterized by the development of thin and discontinuous patches of basal conglomerates draped by sandstone beds. The IOG-fault limits the western 'distal' margin of the Kolhan basin showing evidence of passive subsidence subsequent to the initial rifting stage. The basin evolved as a half-graben under the influence of an extensional stress regime. The assumption of a tectonic setting for the NE-SW trending Kolhan basin possibly relates to the basin opening to the E-W extensional stress system that prevailed during the development of the Newer Dolerite dyke. The Paleoproterozoic age of the Kolhan basin is based on the consideration of the conformable stress pattern responsible both for the basin opening and the development of the conjugate fracture system along which the Newer Dolerite dykes intruded the Singhbhum Archaean craton. The Kolhan sandstones show progressive change towards greater textural and mineralogical maturity in its upbuilding. The trend of variations in different mineralogical and textural attributes, however, exhibits inflections at different lithological levels. Petrological studies collectively indicate that the sandstones were dominantly derived from a weathered granitic crust under a humid climatic condition. Provenance-derived variations in sandstone compositions are therefore a key in unraveling regional tectonic histories. The basin axis controlled the progradation direction which was likely driven by climatically induced sediment influx, a eustatic fall, or both. In the case of the incongruent shift, increased sediment supply permitted the rivers to cross the basinal deep. Temporal association of the Kolhan with tectonic structures in the belt indicates that syn-tectonic thrust uplift, not isostatic uplift or climate, caused the influx of quartz. The sedimentation pattern in the Kolhan reflects a change from braided fluvial-ephemeral pattern to a fan-delta-lacustrine type. The channel geometries and the climate exerted a major control on the processes of sediment transfer. Repeated fault controlled uplift of the source followed by subsidence and forced regression, generated multiple sediment cyclicity that led to the fluvial-fan delta sedimentation pattern. Intermittent uplift of the faulted blocks exposed fresh bedrock to mechanical weathering that generated a large amount of detritus and resulted to forced regressions, repeatedly disrupting the cycles which may reflect a stratigraphic response of connected rift basins at the early stage of extension. The marked variations in the thickness of the fan delta succession and the stacking pattern in different measured profiles reflect the overriding tectonic controls on fan delta evolution. The accumulated fault displacement created higher accommodation and thicker delta sequences. Intermittent uplift of fault blocks exposed fresh bedrock to mechanical weathering, generated a large amount of detritus, and resulted in forced closure of the land-locked basin, repeatedly disrupting the fining upward pattern. The control of source rock lithology or climate was of secondary importance to tectonic effects. Such a retrograding fan delta could be a stratigraphic response of connected rift basins at the early stage of extension.Keywords: Kolhan basin, petrology, sandstone, tectonics
Procedia PDF Downloads 5047 A Spatial Repetitive Controller Applied to an Aeroelastic Model for Wind Turbines
Authors: Riccardo Fratini, Riccardo Santini, Jacopo Serafini, Massimo Gennaretti, Stefano Panzieri
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This paper presents a nonlinear differential model, for a three-bladed horizontal axis wind turbine (HAWT) suited for control applications. It is based on a 8-dofs, lumped parameters structural dynamics coupled with a quasi-steady sectional aerodynamics. In particular, using the Euler-Lagrange Equation (Energetic Variation approach), the authors derive, and successively validate, such model. For the derivation of the aerodynamic model, the Greenbergs theory, an extension of the theory proposed by Theodorsen to the case of thin airfoils undergoing pulsating flows, is used. Specifically, in this work, the authors restricted that theory under the hypothesis of low perturbation reduced frequency k, which causes the lift deficiency function C(k) to be real and equal to 1. Furthermore, the expressions of the aerodynamic loads are obtained using the quasi-steady strip theory (Hodges and Ormiston), as a function of the chordwise and normal components of relative velocity between flow and airfoil Ut, Up, their derivatives, and section angular velocity ε˙. For the validation of the proposed model, the authors carried out open and closed-loop simulations of a 5 MW HAWT, characterized by radius R =61.5 m and by mean chord c = 3 m, with a nominal angular velocity Ωn = 1.266rad/sec. The first analysis performed is the steady state solution, where a uniform wind Vw = 11.4 m/s is considered and a collective pitch angle θ = 0.88◦ is imposed. During this step, the authors noticed that the proposed model is intrinsically periodic due to the effect of the wind and of the gravitational force. In order to reject this periodic trend in the model dynamics, the authors propose a collective repetitive control algorithm coupled with a PD controller. In particular, when the reference command to be tracked and/or the disturbance to be rejected are periodic signals with a fixed period, the repetitive control strategies can be applied due to their high precision, simple implementation and little performance dependency on system parameters. The functional scheme of a repetitive controller is quite simple and, given a periodic reference command, is composed of a control block Crc(s) usually added to an existing feedback control system. The control block contains and a free time-delay system eτs in a positive feedback loop, and a low-pass filter q(s). It should be noticed that, while the time delay term reduces the stability margin, on the other hand the low pass filter is added to ensure stability. It is worth noting that, in this work, the authors propose a phase shifting for the controller and the delay system has been modified as e^(−(T−γk)), where T is the period of the signal and γk is a phase shifting of k samples of the same periodic signal. It should be noticed that, the phase shifting technique is particularly useful in non-minimum phase systems, such as flexible structures. In fact, using the phase shifting, the iterative algorithm could reach the convergence also at high frequencies. Notice that, in our case study, the shifting of k samples depends both on the rotor angular velocity Ω and on the rotor azimuth angle Ψ: we refer to this controller as a spatial repetitive controller. The collective repetitive controller has also been coupled with a C(s) = PD(s), in order to dampen oscillations of the blades. The performance of the spatial repetitive controller is compared with an industrial PI controller. In particular, starting from wind speed velocity Vw = 11.4 m/s the controller is asked to maintain the nominal angular velocity Ωn = 1.266rad/s after an instantaneous increase of wind speed (Vw = 15 m/s). Then, a purely periodic external disturbance is introduced in order to stress the capabilities of the repetitive controller. The results of the simulations show that, contrary to a simple PI controller, the spatial repetitive-PD controller has the capability to reject both external disturbances and periodic trend in the model dynamics. Finally, the nominal value of the angular velocity is reached, in accordance with results obtained with commercial software for a turbine of the same type.Keywords: wind turbines, aeroelasticity, repetitive control, periodic systems
Procedia PDF Downloads 2496 Supply Side Readiness for Universal Health Coverage: Assessing the Availability and Depth of Essential Health Package in Rural, Remote and Conflict Prone District
Authors: Veenapani Rajeev Verma
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Context: Assessing facility readiness is paramount as it can indicate capacity of facilities to provide essential care for resilience to health challenges. In the context of decentralization, estimation of supply side readiness indices at sub national level is imperative for effective evidence based policy but remains a colossal challenge due to lack of dependable and representative data sources. Setting: District Poonch of Jammu and Kashmir was selected for this study. It is remote, rural district with unprecedented topographical barriers and is identified as high priority by government. It is also a fragile area as is bounded by Line of Control with Pakistan bearing the brunt of cease fire violations, military skirmishes and sporadic militant attacks. Hilly geographical terrain, rudimentary/absence of road network and impoverishment are quintessential to this area. Objectives: Objective of the study is to a) Evaluate the service readiness of health facilities and create a concise index subsuming plethora of discrete indicators and b) Ascertain supply side barriers in service provisioning via stakeholder’s analysis. Study also strives to expand analytical domain unravelling context and area specific intricacies associated with service delivery. Methodology: Mixed method approach was employed to triangulate quantitative analysis with qualitative nuances. Facility survey encompassing 90 Subcentres, 44 Primary health centres, 3 Community health centres and 1 District hospital was conducted to gauge general service availability and service specific availability (depth of coverage). Compendium of checklist was designed using Indian Public Health Standards (IPHS) in form of standard core questionnaire and scorecard generated for each facility. Information was collected across dimensions of amenities, equipment, medicines, laboratory and infection control protocols as proposed in WHO’s Service Availability and Readiness Assesment (SARA). Two stage polychoric principal component analysis employed to generate a parsimonious index by coalescing an array of tracer indicators. OLS regression method used to determine factors explaining composite index generated from PCA. Stakeholder analysis was conducted to discern qualitative information. Myriad of techniques like observations, key informant interviews and focus group discussions using semi structured questionnaires on both leaders and laggards were administered for critical stakeholder’s analysis. Results: General readiness score of health facilities was found to be 0.48. Results indicated poorest readiness for subcentres and PHC’s (first point of contact) with composite score of 0.47 and 0.41 respectively. For primary care facilities; principal component was characterized by basic newborn care as well as preparedness for delivery. Results revealed availability of equipment and surgical preparedness having lowest score (0.46 and 0.47) for facilities providing secondary care. Presence of contractual staff, more than 1 hr walk to facility, facilities in zone A (most vulnerable) to cross border shelling and facilities inaccessible due to snowfall and thick jungles was negatively associated with readiness index. Nonchalant staff attitude, unavailability of staff quarters, leakages and constraint in supply chain of drugs and consumables were other impediments identified. Conclusions/Policy Implications: It is pertinent to first strengthen primary care facilities in this setting. Complex dimensions such as geographic barriers, user and provider behavior is not under precinct of this methodology.Keywords: effective coverage, principal component analysis, readiness index, universal health coverage
Procedia PDF Downloads 1215 Identification of the Antimicrobial Property of Double Metal Oxide/Bioactive Glass Nanocomposite Against Multi Drug Resistant Staphylococcus aureus Causing Implant Infections
Authors: M. H. Pazandeh, M. Doudi, S. Barahimi, L. Rahimzadeh Torabi
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The use of antibiotics is essential in reducing the occurrence of adverse effects and inhibiting the emergence of antibiotic resistance in microbial populations. The necessity for a novel methodology concerning local administration of antibiotics has arisen, with particular focus on dealing with localized infections prompted by bacterial colonization of medical devices or implant materials. Bioactive glasses (BG) are extensively employed in the field of regenerative medicine, encompassing a diverse range of materials utilized for drug delivery systems. In the present investigation, various drug carriers for imipenem and tetracycline, namely single systems BG/SnO2, BG/NiO with varying proportions of metal oxide, and nanocomposite BG/SnO2/NiO, were synthesized through the sol-gel technique. The antibacterial efficacy of the synthesized samples was assessed through the utilization of the disk diffusion method with the aim of neutralizing Staphylococcus aureus as the bacterial model. The current study involved the examination of the bioactivity of two samples, namely BG10SnO2/10NiO and BG20SnO2, which were chosen based on their heightened bacterial inactivation properties. This evaluation entailed the employment of two techniques: the measurement of the pH of simulated body fluid (SBF) solution and the analysis of the sample tablets through X-ray diffraction (XRD), scanning electron microscopy (SEM), and Fourier transform infrared (FTIR) spectroscopy. The sample tablets were submerged in SBF for varying durations of 7, 14, and 28 days. The bioactivity of the composite bioactive glass sample was assessed through characterization of alterations in its surface morphology, structure, and chemical composition. This evaluation was performed using scanning electron microscopy (SEM), Fourier-transform infrared (FTIR) spectroscopy, and X-ray diffraction spectroscopy. Subsequently, the sample was immersed in simulated liquids to simulate its behavior in biological environments. The specific body fat percentage (SBF) was assessed over a 28-day period. The confirmation of the formation of a hydroxyapatite surface layer serves as a distinct indicator of bioactivity. The infusion of antibiotics into the composite bioactive glass specimen was done separately, and then the release kinetics of tetracycline and imipenem were tested in simulated body fluid (SBF). Antimicrobial effectiveness against various bacterial strains have been proven in numerous instances using both melt and sol-gel techniques to create multiple bioactive glass compositions. An elevated concentration of calcium ions within a solution has been observed to cause an increase in the pH level. In aqueous suspensions, bioactive glass particles manifest a significant antimicrobial impact. The composite bioactive glass specimen exhibits a gradual and uninterrupted release, which is highly desirable for a drug delivery system over a span of 72 hours. The reduction in absorption, which signals the loss of a portion of the antibiotic during the loading process from the initial phosphate-buffered saline solution, indicates the successful bonding of the two antibiotics to the surfaces of the bioactive glass samples. The sample denoted as BG/10SnO2/10NiO exhibits a higher loading of particles compared to the sample designated as BG/20SnO2 in the context of bioactive glass. The enriched sample demonstrates a heightened bactericidal impact on the bacteria under investigation while concurrently preserving its antibacterial characteristics. Tailored bioactive glass that incorporates hydroxyapatite, with a regulated and efficient release of drugs targeting bacterial infections, holds promise as a potential framework for bone implant scaffolds following rigorous clinical evaluation, thereby establishing potential future biomedical uses. During the modification process, the introduction of metal oxides into bioactive glass resulted in improved antibacterial characteristics, particularly in the composite bioactive glass sample that displayed the highest level of efficiency.Keywords: antibacterial, bioactive glasses, implant infections, multi drug resistant
Procedia PDF Downloads 1004 From Core to Hydrocarbon: Reservoir Sedimentology, Facies Analysis and Depositional Model of Early Oligocene Mahuva Formation in Tapti Daman Block, Western Offshore Basin, India
Authors: Almas Rajguru
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The Oligocene succession of the Tapti- Daman area is one of the established petroleum plays in Tapti-Daman block of the Mumbai Offshore Basin. Despite good control and production history, the sand geometry and continuity of reservoir character of these sediments are less understood as most reservoirs are thin and fall below seismic resolution. The present work focuses on a detailed analysis of the Early Oligocene Mahuva Formation at the reservoir scale through laboratory studies (sedimentology and biostratigraphy) of core and sidewall cores in integration with electro logs for firming up facies’ distribution, micro-depositional environment and sequence stratigraphy, diagenesis and reservoir characterization from seventeen wells from North Tapti-C-37 area in Tapti Daman Block, WOB. The thick shale/claystone with thin interbeds of sandstone and siltstones of deeper marine in the lower part of Mahuva Fm represents deposition in a transgressive regime. The overlying interbedded sandstone, glauconitic-siltstone/fine-grained sandstone, and thin beds of packstone/grainstone within highly fissile shale were deposited in a prograding tide-dominated delta during late-rise normal regression. Nine litho facies (F1-F9) representing deposition in various microenvironments of the tide-dominated delta are identified based on their characteristic sediment texture, structure and microfacies. Massive, gritty sandstone (F1) with poorly sorted sands lithic fragments with calcareous and Fe-rich matrix represents channel fill sediments. High-angle cross-stratified sandstone (F2) deposited in rapidly shifting/migrating bars under strong tidal currents. F3 records the laterally accreted tidal-channel point bars. F3 (low-angle cross-stratified to parallel bedded sandstone) and F4 (Clean sandstone) are often associated with F2 in a tidal bar complex. F5 (interbedded thin sand and mud) and F6 (bioturbated sandstone) represent tidal flat deposits. High energy open marine carbonate shoals (F8) and fossiliferous sandstone in offshore bars (F7) represent deepening up facies. Shallow marine standstill conditions facilitated the deposition of thick shale (F9) beds. The reservoir facies (F1-F6) are commonly poorly to moderately sorted; bimodal, immature sandstone represented by quartz-wacke. The framework grains are sub-angular to sub-rounded, medium to coarse-grained (occasionally gritty) embedded within argillaceous (kaolinite/chlorite/chamosite) to highly Fe-rich matrix (sideritic). The facies F7 and F8, representing the sandy packstone and grainstone facies, respectively, exhibit poor reservoir characteristics due to sanitization, diagenetic compaction and matrix-filled intergranular spaces. The various diagenetic features such as the presence of authigenic clays (kaolinite/dickite/smectite); ferruginous minerals like siderite, pyrite, hematite and other iron oxides; bioturbations; glauconite; calcite and quartz cementation, precipitation of gypsum, pressure solution and other compaction effects are identified. These diagenetic features, wherever present, have reduced porosity and permeability thereby adversely affecting reservoir quality. Tidal bar sandstones possess good reservoir characteristics such as moderate to good sorting, fair to good porosity and geometry that facilitates efficient lateral extension and vertical thickness of reservoir. The sand bodies of F2, F3 and F4 facies of Well L, M and Q deposited in a tidal bar complex exhibit good reservoir quality represented by relatively cleaner, poorly burrowed, loose, friable sandstone with good porosity. Sandstone facies around these wells could prove a potential hydrocarbon reservoir and could be considered for further exploration.Keywords: reservoir sedimentology, facies analysis, HST, tide dominated delta, tidal bars
Procedia PDF Downloads 913 “MaxSALIVA-II” Advancing a Nano-Sized Dual-Drug Delivery System for Salivary Gland Radioprotection, Regeneration and Repair in a Head and Neck Cancer Pre-Clinical Murine Model
Authors: Ziyad S. Haidar
Abstract:
Background: Saliva plays a major role in maintaining oral, dental, and general health and well-being; where it normally bathes the oral cavity acting as a clearing agent. This becomes more apparent when the amount and quality of saliva are significantly reduced due to medications, salivary gland neoplasms, disorders such as Sjögren’s syndrome, and especially ionizing radiation therapy for tumors of the head and neck, the 5th most common malignancy worldwide, during which the salivary glands are included within the radiation field/zone. Clinically, patients affected by salivary gland dysfunction often opt to terminate their radiotherapy course prematurely as they become malnourished and experience a significant decrease in their QoL. Accordingly, the formulation of a radio-protection/-prevention modality and development of an alternative Rx to restore damaged salivary gland tissue is eagerly awaited and highly desirable. Objectives: Assess the pre-clinical radio-protective effect and reparative/regenerative potential of layer-by-layer self-assembled lipid-polymer-based core-shell nanocapsules designed and fine-tuned for the sequential (ordered) release of dual cytokines, following a single local administration (direct injection) into a murine sub-mandibular salivary gland model of irradiation. Methods: The formulated core-shell nanocapsules were characterized by physical-chemical-mechanically pre-/post-loading with the drugs, followed by optimizing the pharmaco-kinetic profile. Then, nanosuspensions were administered directly into the salivary glands, 24hrs pre-irradiation (PBS, un-loaded nanocapsules, and individual and combined vehicle-free cytokines were injected into the control glands for an in-depth comparative analysis). External irradiation at an elevated dose of 18Gy was exposed to the head-and-neck region of C57BL/6 mice. Salivary flow rate (un-stimulated) and salivary protein content/excretion were regularly assessed using an enzyme-linked immunosorbent assay (3-month period). Histological and histomorphometric evaluation and apoptosis/proliferation analysis followed by local versus systemic bio-distribution and immuno-histochemical assays were then performed on all harvested major organs (at the distinct experimental end-points). Results: Monodisperse, stable, and cytocompatible nanocapsules capable of maintaining the bioactivity of the encapsulant within the different compartments with the core and shell and with controlled/customizable pharmaco-kinetics, resulted, as is illustrated in the graphical abstract (Figure) below. The experimental animals demonstrated a significant increase in salivary flow rates when compared to the controls. Herein, salivary protein content was comparable to the pre-irradiation (baseline) level. Histomorphometry further confirmed the biocompatibility and localization of the nanocapsules, in vivo, into the site of injection. Acinar cells showed fewer vacuoles and nuclear aberration in the experimental group, while the amount of mucin was higher in controls. Overall, fewer apoptotic activities were detected by a Terminal deoxynucleotidyl Transferase (TdT) dUTP Nick-End Labeling (TUNEL) assay and proliferative rates were similar to the controls, suggesting an interesting reparative and regenerative potential of irradiation-damaged/-dysfunctional salivary glands. The Figure below exemplifies some of these findings. Conclusions: Biocompatible, reproducible, and customizable self-assembling layer-by-layer core-shell delivery system is formulated and presented. Our findings suggest that localized sequential bioactive delivery of dual cytokines (in specific dose and order) can prevent irradiation-induced damage via reducing apoptosis and also has the potential to promote in situ proliferation of salivary gland cells; maxSALIVA is scalable (Good Manufacturing Practice or GMP production for human clinical trials) and patent-pending.Keywords: cancer, head and neck, oncology, drug development, drug delivery systems, nanotechnology, nanoncology
Procedia PDF Downloads 792 Tackling the Decontamination Challenge: Nanorecycling of Plastic Waste
Authors: Jocelyn Doucet, Jean-Philippe Laviolette, Ali Eslami
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The end-of-life management and recycling of polymer wastes remains a key environment issue in on-going efforts to increase resource efficiency and attaining GHG emission reduction targets. Half of all the plastics ever produced were made in the last 13 years, and only about 16% of that plastic waste is collected for recycling, while 25% is incinerated, 40% is landfilled, and 19% is unmanaged and leaks in the environment and waterways. In addition to the plastic collection issue, the UN recently published a report on chemicals in plastics, which adds another layer of challenge when integrating recycled content containing toxic products into new products. To tackle these important issues, innovative solutions are required. Chemical recycling of plastics provides new complementary alternatives to the current recycled plastic market by converting waste material into a high value chemical commodity that can be reintegrated in a variety of applications, making the total market size of the output – virgin-like, high value products - larger than the market size of the input – plastic waste. Access to high-quality feedstock also remains a major obstacle, primarily due to material contamination issues. Pyrowave approaches this challenge with its innovative nano-recycling technology, which purifies polymers at the molecular level, removing undesirable contaminants and restoring the resin to its virgin state without having to depolymerise it. This breakthrough approach expands the range of plastics that can be effectively recycled, including mixed plastics with various contaminants such as lead, inorganic pigments, and flame retardants. The technology allows yields below 100ppm, and purity can be adjusted to an infinitesimal level depending on the customer's specifications. The separation of the polymer and contaminants in Pyrowave's nano-recycling process offers the unique ability to customize the solution on targeted additives and contaminants to be removed based on the difference in molecular size. This precise control enables the attainment of a final polymer purity equivalent to virgin resin. The patented process involves dissolving the contaminated material using a specially formulated solvent, purifying the mixture at the molecular level, and subsequently extracting the solvent to yield a purified polymer resin that can directly be reintegrated in new products without further treatment. Notably, this technology offers simplicity, effectiveness, and flexibility while minimizing environmental impact and preserving valuable resources in the manufacturing circuit. Pyrowave has successfully applied this nano-recycling technology to decontaminate polymers and supply purified, high-quality recycled plastics to critical industries, including food-contact compliance. The technology is low-carbon, electrified, and provides 100% traceable resins with properties identical to those of virgin resins. Additionally, the issue of low recycling rates and the limited market for traditionally hard-to-recycle plastic waste has fueled the need for new complementary alternatives. Chemical recycling, such as Pyrowave's microwave depolymerization, presents a sustainable and efficient solution by converting plastic waste into high-value commodities. By employing microwave catalytic depolymerization, Pyrowave enables a truly circular economy of plastics, particularly in treating polystyrene waste to produce virgin-like styrene monomers. This revolutionary approach boasts low energy consumption, high yields, and a reduced carbon footprint. Pyrowave offers a portfolio of sustainable, low-carbon, electric solutions to give plastic waste a second life and paves the way to the new circular economy of plastics. Here, particularly for polystyrene, we show that styrene monomer yields from Pyrowave’s polystyrene microwave depolymerization reactor is 2,2 to 1,5 times higher than that of the thermal conventional pyrolysis. In addition, we provide a detailed understanding of the microwave assisted depolymerization via analyzing the effects of microwave power, pyrolysis time, microwave receptor and temperature on the styrene product yields. Furthermore, we investigate life cycle environmental impact assessment of microwave assisted pyrolysis of polystyrene in commercial-scale production. Finally, it is worth pointing out that Pyrowave is able to treat several tons of polystyrene to produce virgin styrene monomers and manage waste/contaminated polymeric materials as well in a truly circular economy.Keywords: nanorecycling, nanomaterials, plastic recycling, depolymerization
Procedia PDF Downloads 661 “MaxSALIVA”: A Nano-Sized Dual-Drug Delivery System for Salivary Gland Radioprotection and Repair in Head and Neck Cancer
Authors: Ziyad S. Haidar
Abstract:
Background: Saliva plays a major role in maintaining oral and dental health (consequently, general health and well-being). Where it normally bathes the oral cavity and acts as a clearing agent. This becomes more apparent when the amount and quality of salivare significantly reduced due to medications, salivary gland neoplasms, disorders such as Sjögren’s syndrome, and especially ionizing radiation therapy for tumors of the head and neck, the fifth most common malignancy worldwide, during which the salivary glands are included within the radiation field or zone. Clinically, patients affected by salivary gland dysfunction often opt to terminate their radiotherapy course prematurely because they become malnourished and experience a significant decrease in their quality of life. Accordingly, the development of an alternative treatment to restore or regenerate damaged salivary gland tissue is eagerly awaited. Likewise, the formulation of a radioprotection modality and early damage prevention strategy is also highly desirable. Objectives: To assess the pre-clinical radio-protective effect as well as the reparative/regenerative potential of layer-by-layer self-assembled lipid-polymer-based core-shell nanocapsules designed and fine-tuned in this experimental work for the sequential (ordered) release of dual cytokines, following a single local administration (direct injection) into a murine sub-mandibular salivary gland model of irradiation. Methods: The formulated core-shell nanocapsules were characterized by physical-chemical-mechanically pre-/post-loading with the drugs (in solution and powder formats), followed by optimizing the pharmaco-kinetic profile. Then, nanosuspensions were administered directly into the salivary glands, 24hrs pre-irradiation (PBS, un-loaded nanocapsules, and individual and combined vehicle-free cytokines were injected into the control glands for an in-depth comparative analysis). External irradiation at an elevated dose of 18Gy (revised from our previous 15Gy model) was exposed to the head-and-neck region of C57BL/6 mice. Salivary flow rate (un-stimulated) and salivary protein content/excretion were regularly assessed using an enzyme-linked immunosorbent assay (3-month period). Histological and histomorphometric evaluation and apoptosis/proliferation analysis followed by local versus systemic bio-distribution and immuno-histochemical assays were then performed on all harvested major organs (at the distinct experimental end-points). Results: Monodisperse, stable, and cytocompatible nanocapsules capable of maintaining the bioactivity of the encapsulant within the different compartments with the core and shell and with controlled/customizable pharmaco-kinetics, resulted, as is illustrated in the graphical abstract (Figure) below. The experimental animals demonstrated a significant increase in salivary flow rates when compared to the controls. Herein, salivary protein content was comparable to the pre-irradiation (baseline) level. Histomorphometry further confirmed the biocompatibility and localization of the nanocapsules, in vivo, into the site of injection. Acinar cells showed fewer vacuoles and nuclear aberration in the experimental group, while the amount of mucin was higher in controls. Overall, fewer apoptotic activities were detected by a Terminal deoxynucleotidyl Transferase (TdT) dUTP Nick-End Labeling (TUNEL) assay and proliferative rates were similar to the controls, suggesting an interesting reparative and regenerative potential of irradiation-damaged/-dysfunctional salivary glands. The Figure below exemplifies some of these findings. Conclusions: Biocompatible, reproducible, and customizable self-assembling layer-by-layer core-shell delivery system is formulated and presented. Our findings suggest that localized sequential bioactive delivery of dual cytokines (in specific dose and order) can prevent irradiation-induced damage via reducing apoptosis and also has the potential to promote in situ proliferation of salivary gland cells; maxSALIVA is scalable (Good Manufacturing Practice or GMP production for human clinical trials) and patent-pending.Keywords: saliva, head and neck cancer, nanotechnology, controlled drug delivery, xerostomia, mucositis, biopolymers, innovation
Procedia PDF Downloads 88