Search results for: internal damage
Commenced in January 2007
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Paper Count: 4667

Search results for: internal damage

17 Optical Coherence Tomography in Differentiation of Acute and Non-Healing Wounds

Authors: Ananya Barui, Provas Banerjee, Jyotirmoy Chatterjee

Abstract:

Application of optical technology in medicine and biology has a long track-record. In this endeavor, OCT is able to attract both engineers and biologists to work together in the field of photonics for establishing a striking non-invasive imaging technology. In contrast to other in vivo imaging modalities like Raman imaging, confocal imaging, two-photon microscopy etc. which can perform in vivo imaging upto 100-200 micron depth due to limitation in numerical aperture or scattering, however, OCT can achieve high-resolution imaging upto few millimeters of tissue structures depending on their refractive index in different anatomical location. This tomographic system depends on interference of two light waves in an interferometer to produce a depth profile of specimen. In wound healing, frequent collection of biopsies for follow-up of repair process could be avoided by such imaging technique. Real time skin OCT (the optical biopsy) has efficacy in deeper and faster illumination of cutaneou tissue to acquire high resolution cross sectional images of their internal micro-structure. Swept Source-OCT (SS-OCT), a novel imaging technique, can generate high-speed depth profile (~ 2 mm) of wound at a sweeping rate of laser with micron level resolution and optimum coherent length of 5-6 mm. Normally multi-layered skin tissue depicts different optical properties along with variation in thickness, refractive index and composition (i.e. keratine layer, water, fat etc.) according to their anatomical location. For instance, stratum corneum, the upper-most and relatively dehydrated layer of epidermis reflects more light and produces more lucid and a sharp demarcation line with rest of the hydrated epidermal region. During wound healing or regeneration, optical properties of cutaneous tissue continuously altered with maturation of wound bed. More mature and less hydrated tissue component reflects more light and becomes visible as a brighter area in comparison to immature region which content higher amount water or fat that depicts as a darker area in OCT image. Non-healing wound possess prolonged inflammation and inhibits nascent proliferative stage. Accumulation of necrotic tissues also prevents the repair of non-healing wounds. Due to high resolution and potentiality to reflect the compositional aspects of tissues in terms of their optical properties, this tomographic method may facilitate in differentiating non-healing and acute wounds in addition to clinical observations. Non-invasive OCT offers better insight regarding specific biological status of tissue in health and pathological conditions, OCT images could be associated with histo-pathological ‘gold standard’. This correlated SS-OCT and microscopic evaluation of the wound edges can provide information regarding progressive healing and maturation of the epithelial components. In the context of searching analogy between two different imaging modalities, their relative performances in imaging of healing bed were estimated for probing an alternative approach. Present study validated utility of SS-OCT in revealing micro-anatomic structure in the healing bed with newer information. Exploring precise correspondence of OCT images features with histo-chemical findings related to epithelial integrity of the regenerated tissue could have great implication. It could establish the ‘optical biopsy’ as a potent non-invasive diagnostic tool for cutaneous pathology.

Keywords: histo-pathology, non invasive imaging, OCT, wound healing

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16 Regional Metamorphism of the Loki Crystalline Massif Allochthonous Complex of the Caucasus

Authors: David Shengelia, Giorgi Chichinadze, Tamara Tsutsunava, Giorgi Beridze, Irakli Javakhishvili

Abstract:

The Loki pre-Alpine crystalline massif crops out within the Caucasus region. The massif basement is represented by the Upper Devonian gneissose quartz-diorites, the Lower-Middle Paleozoic metamorphic allochthonous complex, and different magmatites. Earlier, the metamorphic complex was considered as indivisible set represented by the series of different temperature metamorphits. The degree of metamorphism of separate parts of the complex is due to different formation conditions. This fact according to authors of the abstract was explained by the allochthonous-flaky structure of the complex. It was stated that the complex thrust over the gneissose quartz diorites before the intrusion of Sudetic granites. During the detailed mapping, the authors turned out that the metamorphism issues need to be reviewed and additional researches to be carried out. Investigations were accomplished by using the following methodologies: finding of key sections, a sampling of rocks, microscopic description of the material, analytical determination of elements in the rocks, microprobe analysis of minerals and new interpretation of obtained data. According to the author’s recent data within the massif four tectonic plates: Lower Gorastskali, Sapharlo-Lok-Jandari, Moshevani and “mélange” overthrust sheets have been mapped. They differ from each other by composition, the degree of metamorphism and internal structure. It is confirmed that the initial rocks of the tectonic plates formed in different geodynamic conditions during overthrusting due to tectonic compression form a thick tectonic sheet. Based on the detailed laboratory investigations additional mineral assemblages were established, temperature limits were specified, and a renewed trend of metamorphism facies and subfacies was elaborated. The results are the following: 1. The Lower Gorastskali overthrust sheet is a fragment of ophiolitic association corresponding to the Paleotethys oceanic crust. The main rock-forming minerals are carbonate, chlorite, spinel, epidote, clinoptilolite, plagioclase, hornblende, actinolite, hornblende, albite, serpentine, tremolite, talc, garnet, and prehnite. Regional metamorphism of rocks corresponds to the greenschist facies lowest stage. 2. The Sapharlo-Lok-Jandari overthrust sheet metapelites are represented by chloritoid, chlorite, phengite, muscovite, biotite, garnet, ankerite, carbonate, and quartz. Metabasites containing actinolite, chlorite, plagioclase, calcite, epidote, albite, actinolitic hornblende and hornblende are also present. The degree of metamorphism corresponds to the greenschist high-temperature chlorite, biotite, and low-temperature garnet subfacies. Later the rocks underwent the contact influence of Late Variscan granites. 3. The Moshevani overthrust sheet is represented mainly by metapelites and rarely by metabasites. Main rock-forming minerals of metapelites are muscovite, biotite, chlorite, quartz, andalusite, plagioclase, garnet and cordierite and of metabasites - plagioclase, green and blue-green hornblende, chlorite, epidote, actinolite, albite, and carbonate. Metamorphism level corresponds to staurolite-andalusite subfacies of staurolite facies and partially to facies of biotite muscovite gneisses and hornfelse facies as well. 4. The “mélange” overthrust sheet is built of different size rock fragments and blocks of Moshevani and Lower Gorastskali overthrust sheets. The degree of regional metamorphism of first and second overthrust sheets of the Loki massif corresponds to chlorite, biotite, and low-temperature garnet subfacies, but of the third overthrust sheet – to staurolite-andalusite subfacies of staurolite facies and partially to facies of biotite muscovite gneisses and hornfelse facies.

Keywords: regional metamorphism, crystalline massif, mineral assemblages, the Caucasus

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15 Human Bone Marrow Stem Cell Behavior on 3D Printed Scaffolds as Trabecular Bone Grafts

Authors: Zeynep Busra Velioglu, Deniz Pulat, Beril Demirbakan, Burak Ozcan, Ece Bayrak, Cevat Erisken

Abstract:

Bone tissue has the ability to perform a wide array of functions including providing posture, load-bearing capacity, protection for the internal organs, initiating hematopoiesis, and maintaining the homeostasis of key electrolytes via calcium/phosphate ion storage. The most common cause for bone defects is extensive trauma and subsequent infection. Bone tissue has the self-healing capability without a scar tissue formation for the majority of the injuries. However, some may result with delayed union or fracture non-union. Such cases include reconstruction of large bone defects or cases of compromised regenerative process as a result of avascular necrosis and osteoporosis. Several surgical methods exist to treat bone defects, including Ilizarov method, Masquelete technique, growth factor stimulation, and bone replacement. Unfortunately, these are technically demanding and come with noteworthy disadvantages such as lengthy treatment duration, adverse effects on the patient’s psychology, repeated surgical procedures, and often long hospitalization times. These limitations associated with surgical techniques make bone substitutes an attractive alternative. Here, it was hypothesized that a 3D printed scaffold will mimic trabecular bone in terms of biomechanical properties and that such scaffolds will support cell attachment and survival. To test this hypothesis, this study aimed at fabricating poly(lactic acid), PLA, structures using 3D printing technology for trabecular bone defects, characterizing the scaffolds and comparing with bovine trabecular bone. Capacity of scaffolds on human bone marrow stem cell (hBMSC) attachment and survival was also evaluated. Cubes with a volume of 1 cm³ having pore sizes of 0.50, 1.00 and 1.25 mm were printed. The scaffolds/grafts were characterized in terms of porosity, contact angle, compressive mechanical properties as well cell response. Porosities of the 3D printed scaffolds were calculated based on apparent densities. For contact angles, 50 µl distilled water was dropped over the surface of scaffolds, and contact angles were measured using ‘Image J’ software. Mechanical characterization under compression was performed on scaffolds and native trabecular bone (bovine, 15 months) specimens using a universal testing machine at a rate of 0.5mm/min. hBMSCs were seeded onto the 3D printed scaffolds. After 3 days of incubation with fully supplemented Dulbecco’s modified Eagle’s medium, the cells were fixed using 2% formaldehyde and glutaraldehyde mixture. The specimens were then imaged under scanning electron microscopy. Cell proliferation was determined by using EZQuant dsDNA Quantitation kit. Fluorescence was measured using microplate reader Spectramax M2 at the excitation and emission wavelengths of 485nm and 535nm, respectively. Findings suggested that porosity of scaffolds with pore dimensions of 0.5mm, 1.0mm and 1.25mm were not affected by pore size, while contact angle and compressive modulus decreased with increasing pore size. Biomechanical characterization of trabecular bone yielded higher modulus values as compared to scaffolds with all pore sizes studied. Cells attached and survived in all surfaces, demonstrating higher proliferation on scaffolds with 1.25mm pores as compared with those of 1mm. Collectively, given lower mechanical properties of scaffolds as compared to native bone, and biocompatibility of the scaffolds, the 3D printed PLA scaffolds of this study appear as candidate substitutes for bone repair and regeneration.

Keywords: 3D printing, biomechanics, bone repair, stem cell

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14 Assessing the Utility of Unmanned Aerial Vehicle-Borne Hyperspectral Image and Photogrammetry Derived 3D Data for Wetland Species Distribution Quick Mapping

Authors: Qiaosi Li, Frankie Kwan Kit Wong, Tung Fung

Abstract:

Lightweight unmanned aerial vehicle (UAV) loading with novel sensors offers a low cost approach for data acquisition in complex environment. This study established a framework for applying UAV system in complex environment quick mapping and assessed the performance of UAV-based hyperspectral image and digital surface model (DSM) derived from photogrammetric point clouds for 13 species classification in wetland area Mai Po Inner Deep Bay Ramsar Site, Hong Kong. The study area was part of shallow bay with flat terrain and the major species including reedbed and four mangroves: Kandelia obovata, Aegiceras corniculatum, Acrostichum auerum and Acanthus ilicifolius. Other species involved in various graminaceous plants, tarbor, shrub and invasive species Mikania micrantha. In particular, invasive species climbed up to the mangrove canopy caused damage and morphology change which might increase species distinguishing difficulty. Hyperspectral images were acquired by Headwall Nano sensor with spectral range from 400nm to 1000nm and 0.06m spatial resolution image. A sequence of multi-view RGB images was captured with 0.02m spatial resolution and 75% overlap. Hyperspectral image was corrected for radiative and geometric distortion while high resolution RGB images were matched to generate maximum dense point clouds. Furtherly, a 5 cm grid digital surface model (DSM) was derived from dense point clouds. Multiple feature reduction methods were compared to identify the efficient method and to explore the significant spectral bands in distinguishing different species. Examined methods including stepwise discriminant analysis (DA), support vector machine (SVM) and minimum noise fraction (MNF) transformation. Subsequently, spectral subsets composed of the first 20 most importance bands extracted by SVM, DA and MNF, and multi-source subsets adding extra DSM to 20 spectrum bands were served as input in maximum likelihood classifier (MLC) and SVM classifier to compare the classification result. Classification results showed that feature reduction methods from best to worst are MNF transformation, DA and SVM. MNF transformation accuracy was even higher than all bands input result. Selected bands frequently laid along the green peak, red edge and near infrared. Additionally, DA found that chlorophyll absorption red band and yellow band were also important for species classification. In terms of 3D data, DSM enhanced the discriminant capacity among low plants, arbor and mangrove. Meanwhile, DSM largely reduced misclassification due to the shadow effect and morphological variation of inter-species. In respect to classifier, nonparametric SVM outperformed than MLC for high dimension and multi-source data in this study. SVM classifier tended to produce higher overall accuracy and reduce scattered patches although it costs more time than MLC. The best result was obtained by combining MNF components and DSM in SVM classifier. This study offered a precision species distribution survey solution for inaccessible wetland area with low cost of time and labour. In addition, findings relevant to the positive effect of DSM as well as spectral feature identification indicated that the utility of UAV-borne hyperspectral and photogrammetry deriving 3D data is promising in further research on wetland species such as bio-parameters modelling and biological invasion monitoring.

Keywords: digital surface model (DSM), feature reduction, hyperspectral, photogrammetric point cloud, species mapping, unmanned aerial vehicle (UAV)

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13 Long-Term Subcentimeter-Accuracy Landslide Monitoring Using a Cost-Effective Global Navigation Satellite System Rover Network: Case Study

Authors: Vincent Schlageter, Maroua Mestiri, Florian Denzinger, Hugo Raetzo, Michel Demierre

Abstract:

Precise landslide monitoring with differential global navigation satellite system (GNSS) is well known, but technical or economic reasons limit its application by geotechnical companies. This study demonstrates the reliability and the usefulness of Geomon (Infrasurvey Sàrl, Switzerland), a stand-alone and cost-effective rover network. The system permits deploying up to 15 rovers, plus one reference station for differential GNSS. A dedicated radio communication links all the modules to a base station, where an embedded computer automatically provides all the relative positions (L1 phase, open-source RTKLib software) and populates an Internet server. Each measure also contains information from an internal inclinometer, battery level, and position quality indices. Contrary to standard GNSS survey systems, which suffer from a limited number of beacons that must be placed in areas with good GSM signal, Geomon offers greater flexibility and permits a real overview of the whole landslide with good spatial resolution. Each module is powered with solar panels, ensuring autonomous long-term recordings. In this study, we have tested the system on several sites in the Swiss mountains, setting up to 7 rovers per site, for an 18 month-long survey. The aim was to assess the robustness and the accuracy of the system in different environmental conditions. In one case, we ran forced blind tests (vertical movements of a given amplitude) and compared various session parameters (duration from 10 to 90 minutes). Then the other cases were a survey of real landslides sites using fixed optimized parameters. Sub centimetric-accuracy with few outliers was obtained using the best parameters (session duration of 60 minutes, baseline 1 km or less), with the noise level on the horizontal component half that of the vertical one. The performance (percent of aborting solutions, outliers) was reduced with sessions shorter than 30 minutes. The environment also had a strong influence on the percent of aborting solutions (ambiguity search problem), due to multiple reflections or satellites obstructed by trees and mountains. The length of the baseline (distance reference-rover, single baseline processing) reduced the accuracy above 1 km but had no significant effect below this limit. In critical weather conditions, the system’s robustness was limited: snow, avalanche, and frost-covered some rovers, including the antenna and vertically oriented solar panels, leading to data interruption; and strong wind damaged a reference station. The possibility of changing the sessions’ parameters remotely was very useful. In conclusion, the rover network tested provided the foreseen sub-centimetric-accuracy while providing a dense spatial resolution landslide survey. The ease of implementation and the fully automatic long-term survey were timesaving. Performance strongly depends on surrounding conditions, but short pre-measures should allow moving a rover to a better final placement. The system offers a promising hazard mitigation technique. Improvements could include data post-processing for alerts and automatic modification of the duration and numbers of sessions based on battery level and rover displacement velocity.

Keywords: GNSS, GSM, landslide, long-term, network, solar, spatial resolution, sub-centimeter.

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12 Exploratory Characterization of Antibacterial Efficacy of Synthesized Nanoparticles on Staphylococcus Isolates from Hospital Specimens in Saudi Arabia

Authors: Reham K. Sebaih, Afaf I. Shehata , Awatif A. Hindi, Tarek Gheith, Amal A. Hazzani Anas Al-Orjan

Abstract:

Staphylococci spp are ubiquitous gram-positive bacteria is often associated with infections, especially nosocomial infections, and antibiotic resistanceStudy pathogenic bacteria and its use as a tool in the technology of Nano biology and molecular genetics research of the latest research trends of modern characterization and definition of different multiresistant of bacteria including Staphylococci. The Staphylococci are widespread all over the world and particularly in Saudi Arabia The present work study was conducted to evaluate the effect of five different types of nanoparticles (biosynthesized zinc oxide, Spherical and rod of each silver and gold nanoparticles) and their antibacterial impact on the Staphylococcus species. Ninety-six isolates of Staphylococcus species. Staphylococcus aureus, Staphylococcus epidermidis, MRSA were collected from different sources during the period between March 2011G to June 2011G. All isolates were isolated from inpatients and outpatients departments at Royal Commission Hospital in Yanbu Industrial, Saudi Arabia. High percentage isolation from males(55%) than females (45%). Staphylococcus epidermidis from males was (47%), (28%), and(25%). For Staphylococcus aureus and Methicillin-resistant Staphylococcus aureus (MRSA. Isolates from females were Staphylococcus aureus with higher percent of (47%), (30%), and (23%) for MRSA, Staphylococcus epidermidis. Staphylococcus aureus from wound swab were the highest percent (51.42%) followed by vaginal swab (25.71%). Staphylococcus epidermidis were founded with higher percentage in blood (37.14%) and wound swab (34.21%) respectively related to other. The highest percentage of methicillin-resistant Staphylococcus aureus (MRSA)(80.77%) were isolated from wound swab, while those from nostrils were (19.23%). Staphylococcus species were isolates in highest percentage from hospital Emergency department with Staphylococcus aureus (59.37%), Methicillin-resistant Staphylococcus aureus (MRSA) (28.13%)and Staphylococcus epidermidis (12.5%) respectively. Evaluate the antibacterial property of Zinc oxide, Silver, and Gold nanoparticles as an alternative to conventional antibacterial agents Staphylococci isolates from hospital sources we screened them. Gold and Silver rods Nanoparticles to be sensitive to all isolates of Staphylococcus species. Zinc oxide Nanoparticles gave sensitivity impact range(52%) and (48%). The Gold and Silver spherical nanoparticles did not showed any effect on Staphylococci species. Zinc Oxide Nanoparticles gave bactericidal impact (25%) and bacteriostatic impact (75%) for of Staphylococci species. Detecting the association of nanoparticles with Staphylococci isolates imaging by scanning electron microscope (SEM) of some bacteriostatic isolates for Zinc Oxide nanoparticles on Staphylococcus aureus, Staphylococcus epidermidis and Methicillin resistant Staphylococcus aureus(MRSA), showed some Overlapping Bacterial cells with lower their number and appearing some appendages with deformities in external shape. Molecular analysis was applied by Multiplex polymerase chain reaction (PCR) used for the identification of genes within Staphylococcal pathogens. A multiplex polymerase chain reaction (PCR) method has been developed using six primer pairs to detect different genes using 50bp and 100bp DNA ladder marker. The range of Molecular gene typing ranging between 93 bp to 326 bp for Staphylococcus aureus and Methicillin resistant Staphylococcus aureus by TSST-1,mecA,femA and eta, while the bands border were from 546 bp to 682 bp for Staphylococcus epidermidis using icaAB and atlE. Sixteen isolation of Staphylococcus aureus and Methicillin resistant Staphylococcus aureus were positive for the femA gene at 132bp,this allowed the using of this gene as an internal positive control, fifteen isolates of Staphylococcus aureus and Methicillin resistant Staphylococcus aureus were positive for mecA gene at163bp.This gene was responsible for antibiotic resistant Methicillin, Two isolates of Staphylococcus aureus and Methicillin resistant Staphylococcus aureus were positive for the TSST-1 gene at326bp which is responsible for toxic shock syndrome in some Staphylococcus species, None were positive for eta gene at 102bpto that was responsible for Exfoliative toxins. Six isolates of Staphylococcus epidermidis were positive for atlE gene at 682 bp which is responsible for the initial adherence, three isolates of Staphylococcus epidermidis were positive for icaAB gene at 546bp that are responsible for mediates the formation of the biofilm. In conclusion, this study demonstrates the ability of the detection of the genes to discriminate between infecting Staphylococcus strains and considered biological tests, they may potentiate the clinical criteria used for the diagnosis of septicemia or catheter-related infections.

Keywords: multiplex polymerase chain reaction, toxic shock syndrome, Staphylococcus aureus, nosocomial infections

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11 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

Abstract:

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

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10 Development of a Core Set of Clinical Indicators to Measure Quality of Care for Thyroid Cancer: A Modified-Delphi Approach

Authors: Liane J. Ioannou, Jonathan Serpell, Cino Bendinelli, David Walters, Jenny Gough, Dean Lisewski, Win Meyer-Rochow, Julie Miller, Duncan Topliss, Bill Fleming, Stephen Farrell, Andrew Kiu, James Kollias, Mark Sywak, Adam Aniss, Linda Fenton, Danielle Ghusn, Simon Harper, Aleksandra Popadich, Kate Stringer, David Watters, Susannah Ahern

Abstract:

BACKGROUND: There are significant variations in the management, treatment and outcomes of thyroid cancer, particularly in the role of: diagnostic investigation and pre-treatment scanning; optimal extent of surgery (total or hemi-thyroidectomy); use of active surveillance for small low-risk cancers; central lymph node dissections (therapeutic or prophylactic); outcomes following surgery (e.g. recurrent laryngeal nerve palsy, hypocalcaemia, hypoparathyroidism); post-surgical hormone, calcium and vitamin D therapy; and provision and dosage of radioactive iodine treatment. A proven strategy to reduce variations in the outcome and to improve survival is to measure and compare it using high-quality clinical registry data. Clinical registries provide the most effective means of collecting high-quality data and are a tool for quality improvement. Where they have been introduced at a state or national level, registries have become one of the most clinically valued tools for quality improvement. To benchmark clinical care, clinical quality registries require systematic measurement at predefined intervals and the capacity to report back information to participating clinical units. OBJECTIVE: The aim of this study was to develop a core set clinical indicators that enable measurement and reporting of quality of care for patients with thyroid cancer. We hypothesise that measuring clinical quality indicators, developed to identify differences in quality of care across sites, will reduce variation and improve patient outcomes and survival, thereby lessening costs and healthcare burden to the Australian community. METHOD: Preparatory work and scoping was conducted to identify existing high quality, clinical guidelines and best practice for thyroid cancer both nationally and internationally, as well as relevant literature. A bi-national panel was invited to participate in a modified Delphi process. Panelists were asked to rate each proposed indicator on a Likert scale of 1–9 in a three-round iterative process. RESULTS: A total of 236 potential quality indicators were identified. One hundred and ninety-two indicators were removed to reflect the data capture by the Australian and New Zealand Thyroid Cancer Registry (ANZTCR) (from diagnosis to 90-days post-surgery). The remaining 44 indicators were presented to the panelists for voting. A further 21 indicators were later added by the panelists bringing the total potential quality indicators to 65. Of these, 21 were considered the most important and feasible indicators to measure quality of care in thyroid cancer, of which 12 were recommended for inclusion in the final set. The consensus indicator set spans the spectrum of care, including: preoperative; surgery; surgical complications; staging and post-surgical treatment planning; and post-surgical treatment. CONCLUSIONS: This study provides a core set of quality indicators to measure quality of care in thyroid cancer. This indicator set can be applied as a tool for internal quality improvement, comparative quality reporting, public reporting and research. Inclusion of these quality indicators into monitoring databases such as clinical quality registries will enable opportunities for benchmarking and feedback on best practice care to clinicians involved in the management of thyroid cancer.

Keywords: clinical registry, Delphi survey, quality indicators, quality of care

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9 Top Skills That Build Cultures at Organizations

Authors: Priyanka Botny Srinath, Alessandro Suglia, Mel McKendrick

Abstract:

Background: Organizational cultural studies integrate sociology and anthropology, portraying man as a creator of symbols, languages, beliefs, and ideologies -essentially, a creator and manager of meaning. In our research, we leverage analytical measures to discern whether an organization embodies a singular culture or a myriad of subcultures. Fast-forward to 2023, our research thesis focuses on digitally measuring culture, coining it as the "Work Culture Quotient." This entails conceptually mapping common experiential patterns to provide executives insights into the digital organization journey, aiding in understanding their current position and identifying future steps. Objectives: Finding the new age skills that help in defining the culture; understand the implications of post-COVID effects; derive a digital framework for measuring skillsets. Method: We conducted two comprehensive Delphi studies to distill essential insights. Delphi 1: Through a thematic analysis of interviews with 20 high-level leaders representing companies across diverse regions -India, Japan, the US, Canada, Morocco, and Uganda- we identified 20 key skills critical for cultivating a robust organizational culture. The skills are -influence, self-confidence, optimism, empathy, leadership, collaboration and cooperation, developing others, commitment, innovativeness, leveraging diversity, change management, team capabilities, self-control, digital communication, emotional awareness, team bonding, communication, problem solving, adaptability, and trustworthiness. Delphi 2: Subject matter experts were asked to complete a questionnaire derived from the thematic analysis in stage 1 to formalise themes and draw consensus amongst experts on the most important workplace skills. Results: The thematic analysis resulted in 20 workplace employee skills being identified. These skills were all included in the Delphi round 2 questionnaire. From the outputs, we analysed the data using R Studio for arriving at agreement and consensus, we also used sum of squares method to compare various agreements to extract various themes with a threshold of 80% agreements. This yielded three themes at over 80% agreement (leadership, collaboration and cooperation, communication) and three further themes at over 60% agreement (commitment, empathy, trustworthiness). From this, we selected five questionnaires to be included in the primary data collection phase, and these will be paired with the digital footprints to provide a workplace culture quotient. Implications: The findings from these studies bear profound implications for decision-makers, revolutionizing their comprehension of organizational culture. Tackling the challenge of mapping the digital organization journey involves innovative methodologies that probe not only external landscapes but also internal cultural dynamics. This holistic approach furnishes decision-makers with a nuanced understanding of their organizational culture and visualizes pivotal skills for employee growth. This clarity enables informed choices resonating with the organization's unique cultural fabric. Anticipated outcomes transcend mere individual cultural measurements, aligning with organizational goals to unveil a comprehensive view of culture, exposing artifacts and depth. Armed with this profound understanding, decision-makers gain tangible evidence for informed decision-making, strategically leveraging cultural strengths to cultivate an environment conducive to growth, innovation, and enduring success, ultimately leading to measurable outcomes.

Keywords: leadership, cooperation, collaboration, teamwork, work culture

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8 Flood Risk Management in the Semi-Arid Regions of Lebanon - Case Study “Semi Arid Catchments, Ras Baalbeck and Fekha”

Authors: Essam Gooda, Chadi Abdallah, Hamdi Seif, Safaa Baydoun, Rouya Hdeib, Hilal Obeid

Abstract:

Floods are common natural disaster occurring in semi-arid regions in Lebanon. This results in damage to human life and deterioration of environment. Despite their destructive nature and their immense impact on the socio-economy of the region, flash floods have not received adequate attention from policy and decision makers. This is mainly because of poor understanding of the processes involved and measures needed to manage the problem. The current understanding of flash floods remains at the level of general concepts; most policy makers have yet to recognize that flash floods are distinctly different from normal riverine floods in term of causes, propagation, intensity, impacts, predictability, and management. Flash floods are generally not investigated as a separate class of event but are rather reported as part of the overall seasonal flood situation. As a result, Lebanon generally lacks policies, strategies, and plans relating specifically to flash floods. Main objective of this research is to improve flash flood prediction by providing new knowledge and better understanding of the hydrological processes governing flash floods in the East Catchments of El Assi River. This includes developing rainstorm time distribution curves that are unique for this type of study region; analyzing, investigating, and developing a relationship between arid watershed characteristics (including urbanization) and nearby villages flow flood frequency in Ras Baalbeck and Fekha. This paper discusses different levels of integration approach¬es between GIS and hydrological models (HEC-HMS & HEC-RAS) and presents a case study, in which all the tasks of creating model input, editing data, running the model, and displaying output results. The study area corresponds to the East Basin (Ras Baalbeck & Fakeha), comprising nearly 350 km2 and situated in the Bekaa Valley of Lebanon. The case study presented in this paper has a database which is derived from Lebanese Army topographic maps for this region. Using ArcMap to digitizing the contour lines, streams & other features from the topographic maps. The digital elevation model grid (DEM) is derived for the study area. The next steps in this research are to incorporate rainfall time series data from Arseal, Fekha and Deir El Ahmar stations to build a hydrologic data model within a GIS environment and to combine ArcGIS/ArcMap, HEC-HMS & HEC-RAS models, in order to produce a spatial-temporal model for floodplain analysis at a regional scale. In this study, HEC-HMS and SCS methods were chosen to build the hydrologic model of the watershed. The model then calibrated using flood event that occurred between 7th & 9th of May 2014 which considered exceptionally extreme because of the length of time the flows lasted (15 hours) and the fact that it covered both the watershed of Aarsal and Ras Baalbeck. The strongest reported flood in recent times lasted for only 7 hours covering only one watershed. The calibrated hydrologic model is then used to build the hydraulic model & assessing of flood hazards maps for the region. HEC-RAS Model is used in this issue & field trips were done for the catchments in order to calibrated both Hydrologic and Hydraulic models. The presented models are a kind of flexible procedures for an ungaged watershed. For some storm events it delivers good results, while for others, no parameter vectors can be found. In order to have a general methodology based on these ideas, further calibration and compromising of results on the dependence of many flood events parameters and catchment properties is required.

Keywords: flood risk management, flash flood, semi arid region, El Assi River, hazard maps

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7 An Integrated Multisensor/Modeling Approach Addressing Climate Related Extreme Events

Authors: H. M. El-Askary, S. A. Abd El-Mawla, M. Allali, M. M. El-Hattab, M. El-Raey, A. M. Farahat, M. Kafatos, S. Nickovic, S. K. Park, A. K. Prasad, C. Rakovski, W. Sprigg, D. Struppa, A. Vukovic

Abstract:

A clear distinction between weather and climate is a necessity because while they are closely related, there are still important differences. Climate change is identified when we compute the statistics of the observed changes in weather over space and time. In this work we will show how the changing climate contribute to the frequency, magnitude and extent of different extreme events using a multi sensor approach with some synergistic modeling activities. We are exploring satellite observations of dust over North Africa, Gulf Region and the Indo Gangetic basin as well as dust versus anthropogenic pollution events over the Delta region in Egypt and Seoul through remote sensing and utilize the behavior of the dust and haze on the aerosol optical properties. Dust impact on the retreat of the glaciers in the Himalayas is also presented. In this study we also focus on the identification and monitoring of a massive dust plume that blew off the western coast of Africa towards the Atlantic on October 8th, 2012 right before the development of Hurricane Sandy. There is evidence that dust aerosols played a non-trivial role in the cyclogenesis process of Sandy. Moreover, a special dust event "An American Haboob" in Arizona is discussed as it was predicted hours in advance because of the great improvement we have in numerical, land–atmosphere modeling, computing power and remote sensing of dust events. Therefore we performed a full numerical simulation to that event using the coupled atmospheric-dust model NMME–DREAM after generating a mask of the potentially dust productive regions using land cover and vegetation data obtained from satellites. Climate change also contributes to the deterioration of different marine habitats. In that regard we are also presenting some work dealing with change detection analysis of Marine Habitats over the city of Hurghada, Red Sea, Egypt. The motivation for this work came from the fact that coral reefs at Hurghada have undergone significant decline. They are damaged, displaced, polluted, stepped on, and blasted off, in addition to the effects of climate change on the reefs. One of the most pressing issues affecting reef health is mass coral bleaching that result from an interaction between human activities and climatic changes. Over another location, namely California, we have observed that it exhibits highly-variable amounts of precipitation across many timescales, from the hourly to the climate timescale. Frequently, heavy precipitation occurs, causing damage to property and life (floods, landslides, etc.). These extreme events, variability, and the lack of good, medium to long-range predictability of precipitation are already a challenge to those who manage wetlands, coastal infrastructure, agriculture and fresh water supply. Adding on to the current challenges for long-range planning is climate change issue. It is known that La Niña and El Niño affect precipitation patterns, which in turn are entwined with global climate patterns. We have studied ENSO impact on precipitation variability over different climate divisions in California. On the other hand the Nile Delta has experienced lately an increase in the underground water table as well as water logging, bogging and soil salinization. Those impacts would pose a major threat to the Delta region inheritance and existing communities. There has been an undergoing effort to address those vulnerabilities by looking into many adaptation strategies.

Keywords: remote sensing, modeling, long range transport, dust storms, North Africa, Gulf Region, India, California, climate extremes, sea level rise, coral reefs

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6 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

Abstract:

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.

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5 A Comprehensive Study of Spread Models of Wildland Fires

Authors: Manavjit Singh Dhindsa, Ursula Das, Kshirasagar Naik, Marzia Zaman, Richard Purcell, Srinivas Sampalli, Abdul Mutakabbir, Chung-Horng Lung, Thambirajah Ravichandran

Abstract:

These days, wildland fires, also known as forest fires, are more prevalent than ever. Wildfires have major repercussions that affect ecosystems, communities, and the environment in several ways. Wildfires lead to habitat destruction and biodiversity loss, affecting ecosystems and causing soil erosion. They also contribute to poor air quality by releasing smoke and pollutants that pose health risks, especially for individuals with respiratory conditions. Wildfires can damage infrastructure, disrupt communities, and cause economic losses. The economic impact of firefighting efforts, combined with their direct effects on forestry and agriculture, causes significant financial difficulties for the areas impacted. This research explores different forest fire spread models and presents a comprehensive review of various techniques and methodologies used in the field. A forest fire spread model is a computational or mathematical representation that is used to simulate and predict the behavior of a forest fire. By applying scientific concepts and data from empirical studies, these models attempt to capture the intricate dynamics of how a fire spreads, taking into consideration a variety of factors like weather patterns, topography, fuel types, and environmental conditions. These models assist authorities in understanding and forecasting the potential trajectory and intensity of a wildfire. Emphasizing the need for a comprehensive understanding of wildfire dynamics, this research explores the approaches, assumptions, and findings derived from various models. By using a comparison approach, a critical analysis is provided by identifying patterns, strengths, and weaknesses among these models. The purpose of the survey is to further wildfire research and management techniques. Decision-makers, researchers, and practitioners can benefit from the useful insights that are provided by synthesizing established information. Fire spread models provide insights into potential fire behavior, facilitating authorities to make informed decisions about evacuation activities, allocating resources for fire-fighting efforts, and planning for preventive actions. Wildfire spread models are also useful in post-wildfire mitigation strategies as they help in assessing the fire's severity, determining high-risk regions for post-fire dangers, and forecasting soil erosion trends. The analysis highlights the importance of customized modeling approaches for various circumstances and promotes our understanding of the way forest fires spread. Some of the known models in this field are Rothermel’s wildland fuel model, FARSITE, WRF-SFIRE, FIRETEC, FlamMap, FSPro, cellular automata model, and others. The key characteristics that these models consider include weather (includes factors such as wind speed and direction), topography (includes factors like landscape elevation), and fuel availability (includes factors like types of vegetation) among other factors. The models discussed are physics-based, data-driven, or hybrid models, also utilizing ML techniques like attention-based neural networks to enhance the performance of the model. In order to lessen the destructive effects of forest fires, this initiative aims to promote the development of more precise prediction tools and effective management techniques. The survey expands its scope to address the practical needs of numerous stakeholders. Access to enhanced early warning systems enables decision-makers to take prompt action. Emergency responders benefit from improved resource allocation strategies, strengthening the efficacy of firefighting efforts.

Keywords: artificial intelligence, deep learning, forest fire management, fire risk assessment, fire simulation, machine learning, remote sensing, wildfire modeling

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4 General Evaluation of a Three-Year Holistic Physical Activity Interventions Program in Qatar Campuses: Step into Health (SIH) in Campuses 2013- 2016

Authors: Daniela Salih Khidir, Mohamed G. Al Kuwari, Mercia V. Walt, Izzeldin J. Ibrahim

Abstract:

Background: University-based physical activity interventions aim to establish durable social patterns during the transition to adulthood. This study is a comprehensive evaluation of a 3-year intervention-based program to increase the culture of physical activity (PA) routine in Qatar campuses community, using a holistic approach. Methodology: General assessment methods: formative evaluation-SIH Campuses logic model design, stakeholders’ identification; process evaluation-members’ step counts analyze and qualitative Appreciative Inquiry session (4-D model); daily steps categorized as: ≤5,000, inactive; 5,000-7,499 low active; ≥7,500, physically active; outcome evaluation - records 3 years interventions. Holistic PA interventions methods: walking interventions - pedometers distributions and walking competitions for students and staff; educational interventions - in campuses implementation of bilingual educational materials, lectures, video related to PA in prevention of non-communicable diseases (NCD); articles published online; monthly emails and sms notifications for pedometer use; mass media campaign - radio advertising, yearly pre/post press releases; community stakeholders interventions-biyearly planning/reporting/achievements rewarding/ qualitative meetings; continuous follow-up communication, biweekly steps reports. Findings: Results formative evaluation - SIH in Campuses logic model identified the need of PA awareness and education within universities, resources, activities, health benefits, program continuity. Results process evaluation: walking interventions: Phase 1: 5 universities recruited, 2352 members, 3 months competition; Phase 2: 6 new universities recruited, 1328 members in addition, 4 months competition; Phase 3: 4 new universities recruited in addition, 1210 members, 6 months competition. Results phase 1 and 2: 1,299 members eligible for analyzes: 800 females (62%), 499 males (38%); 86% non-Qataris, 14% Qatari nationals, daily step count 5,681 steps, age groups 18–24 (n=841; 68%) students, 25–64; (n=458; 35.3%) staff; 38% - low active, 37% physically active and 25% inactive. The AI main themes engaging stakeholders: awareness/education - 5 points (100%); competition, multi levels of involvement in SIH, community-based program/motivation - 4 points each (80%). The AI points represent themes’ repetition within stakeholders’ discussions. Results education interventions: 2 videos implementation, 35 000 educational materials, 3 online articles, 11 walking benefits lectures, 40 emails and sms notifications. Results community stakeholders’ interventions: 6 stakeholders meetings, 3 rewarding gatherings, 1 focus meeting, 40 individual reports, 18 overall reports. Results mass media campaign: 1 radio campaign, 7 press releases, 52 campuses newsletters. Results outcome evaluation: overall 2013-2016, the study used: 1 logic model, 3 PA holistic interventions, partnerships 15 universities, registered 4890 students and staff (aged 18-64 years), engaged 30 campuses stakeholders and 14 internal stakeholders; Total registered population: 61.5% female (2999), 38.5% male (1891), 20.2% (988) Qatari nationals, 79.8% (3902) non-Qataris, 55.5% (2710) students aged 18 – 25 years, 44.5% (2180) staff aged 26 - 64 years. Overall campaign 1,558 members eligible for analyzes: daily step count 7,923; 37% - low active, 43% physically active and 20% inactive. Conclusion: The study outcomes confirm program effectiveness and engagement of young campuses community, specifically female, in PA. The authors recommend implementations of 'holistic PA intervention program approach in Qatar' aiming to impact the community at national level for PA guidelines achievement in support of NCD prevention.

Keywords: campuses, evaluation, Qatar, step-count

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3 Regenerative Agriculture Standing at the Intersection of Design, Mycology, and Soil Fertility

Authors: Andrew Gennett

Abstract:

Designing for fungal development means embracing the symbiotic relationship between the living system and built environment. The potential of mycelium post-colonization is explored for the fabrication of advanced pure mycelium products, going beyond the conventional methods of aggregating materials. Fruiting induction imparts desired material properties such as enhanced environmental resistance. Production approach allows for simultaneous generation of multiple products while scaling up raw materials supply suitable for architectural applications. The following work explores the integration of fungal environmental perception with computational design of built fruiting chambers. Polyporales, are classified by their porous reproductive tissues supported by a wood-like context tissue covered by a hard waterproofing coat of hydrobpobins. Persisting for years in the wild, these species represent material properties that would be highly desired in moving beyond flat sheets of arial mycelium as with leather or bacon applications. Understanding the inherent environmental perception of fungi has become the basis for working with and inducing desired hyphal differentiation. Working within the native signal interpretation of a mycelium mass during fruiting induction provides the means to apply textures and color to the final finishing coat. A delicate interplay between meeting human-centered goals while designing around natural processes of living systems represents a blend of art and science. Architecturally, physical simulations inform model design for simple modular fruiting chambers that change as fungal growth progresses, while biological life science principles describe the internal computations occurring within the fungal hyphae. First, a form filling phase of growth is controlled by growth chamber environment. Second, an initiation phase of growth forms the final exterior finishing texture. Hyphal densification induces cellular cascades, in turn producing the classical hardened cuticle, UV protective molecule production, as well, as waterproofing finish. Upon fruiting process completion, the fully colonized spent substrate holds considerable value and is not considered waste. Instead, it becomes a valuable resource in the next cycle of production scale-up. However, the acquisition of new substrate resources poses a critical question, particularly as these resources become increasingly scarce. Pursuing a regenerative design paradigm from the environmental perspective, the usage of “agricultural waste” for architectural materials would prove a continuation of the destructive practices established by the previous industrial regime. For these residues from fields and forests serve a vital ecological role protecting the soil surface in combating erosion while reducing evaporation and fostering a biologically diverse food web. Instead, urban centers have been identified as abundant sources of new substrate material. Diverting the waste from secondary locations such as food processing centers, papers mills, and recycling facilities not only reduces landfill burden but leverages the latent value of these waste steams as precious resources for mycelium cultivation. In conclusion, working with living systems through innovative built environments for fungal development, provides the needed gain of function and resilience of mycelium products. The next generation of sustainable fungal products will go beyond the current binding process, with a focus upon reducing landfill burden from urban centers. In final considerations, biophilic material builds to an ecologically regenerative recycling production cycle.

Keywords: regenerative agriculture, mycelium fabrication, growth chamber design, sustainable resource acquisition, fungal morphogenesis, soil fertility

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2 “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

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1 Glycyrrhizic Acid Inhibits Lipopolysaccharide-Stimulated Bovine Fibroblast-Like Synoviocyte, Invasion through Suppression of TLR4/NF-κB-Mediated Matrix Metalloproteinase-9 Expression

Authors: Hosein Maghsoudi

Abstract:

Rheumatois arthritis (RA) is progressive inflammatory autoimmune diseases that primarily affect the joints, characterized by synovial hyperplasia and inflammatory cell infiltration, deformed and painful joints, which can lead tissue destruction, functional disability systemic complications, and early dead and socioeconomic costs. The cause of rheumatoid arthritis is unknown, but genetic and environmental factors are contributory and the prognosis is guarded. However, advances in understanding the pathogenesis of the disease have fostered the development of new therapeutics, with improved outcomes. The current treatment strategy, which reflects this progress, is to initiate aggressive therapy soon after diagnosis and to escalate the therapy, guided by an assessment of disease activity, in pursuit of clinical remission. The pathobiology of RA is multifaceted and involves T cells, B cells, fibroblast-like synoviocyte (FLSc) and the complex interaction of many pro-inflammatory cytokine. Novel biologic agents that target tumor necrosis or interlukin (IL)-1 and Il-6, in addition T- and B-cells inhibitors, have resulted in favorable clinical outcomes in patients with RA. Despite this, at least 30% of RA patients are résistance to available therapies, suggesting novel mediators should be identified that can target other disease-specific pathway or cell lineage. Among the inflammatory cell population that might participated in RA pathogenesis, FLSc are crucial in initiaing and driving RA in concert of cartilage and bone by secreting metalloproteinase (MMPs) into the synovial fluid and by direct invasion into extracellular matrix (ECM), further exacerbating joint damage. Invasion of fibroblast-like synoviocytes (FLSc) is critical in the pathogenesis of rheumatoid-arthritis. The metalloproteinase (MMPs) and activator of Toll-like receptor 4 (TLR4)/nuclear factor- κB pthway play a critical role in RA-FLS invasion induced by lipopolysaccharide (LPS). The present study aimed to explore the anti-invasion activity of Glycyrrhizic Acid as a pharmacologically safe phytochemical agent with potent anti-inflammatory properties on IL-1beta and TNF-alpha signalling pathways in Bovine fibroblast-like synoviocyte ex- vitro, on LPS-stimulated bovine FLS migration and invasion as well as MMP expression and explored the upstream signal transduction. Results showed that Glycyrrhizic Acid suppressed LPS-stimulated bovine FLS migration and invasion by inhibition MMP-9 expression and activity. In addition our results revealed that Glycyrrhizic Acid inhibited the transcriptional activity of MMP-9 by suppression the nbinding activity of NF- κB in the MMP-9 promoter pathway. The extract of licorice (Glycyrrhiza glabra L.) has been widely used for many centuries in the traditional Chinese medicine as native anti-allergic agent. Glycyrrhizin (GL), a triterpenoidsaponin, extracted from the roots of licorice is the most effective compound for inflammation and allergic diseases in human body. The biological and pharmacological studies revealed that GL possesses many pharmacological effects, such as anti-inflammatory, anti-viral and liver protective effects, and the biological effects, such as induction of cytokines (interferon-γ and IL-12), chemokines as well as extrathymic T and anti-type 2 T cells. GL is known in the traditional Chinese medicine for its anti-inflammatory effect, which is originally described by Finney in 1959. The mechanism of the GL-induced anti-inflammatory effect is based on different pathways of the GL-induced selective inhibition of the prostaglandin E2 production, the CK-II- mediated activation of both GL-binding lipoxygenas (gbLOX; 17) and PLA2, an anti-thrombin action of GL and production of the reactive oxygen species (ROS; GL exerts liver protection properties by inhibiting PLA2 or by the hydroxyl radical trapping action, leading to the lowering of serum alanine and aspartate transaminase levels. The present study was undertaken to examine the possible mechanism of anti-inflammatory properties GL on IL-1beta and TNF-alpha signalling pathways in bovine fibroblast-like synoviocyte ex-vivo, on LPS-stimulated bovine FLS migration and invasion as well as MMP expression and explored the upstream signal transduction. Our results clearly showed that treatment of bovine fibroblast-like synoviocyte with GL suppressed LPS-induced cell migration and invasion. Furthermore, it revealed that GL inhibited the transcription activity of MMP-9 by suppressing the binding activity of NF-κB in the MM-9 promoter. MMP-9 is an important ECM-degrading enzyme and overexpression of MMPs in important of RA-FLSs. LPS can stimulate bovine FLS to secret MMPs, and this induction is regulated at the transcription and translational levels. In this study, LPS treatment of bovine FLS caused an increase in MMP-2 and MMP-9 levels. The increase in MMP-9 expression and secretion was inhibited by ex- vitro. Furthermore, these effects were mimicked by MMP-9 siRNA. These result therefore indicate the the inhibition of LPS-induced bovine FLS invasion by GL occurs primarily by inhibiting MMP-9 expression and activity. Next we analyzed the functional significance of NF-κB transcription of MMP-9 activation in Bovine FLSs. Results from EMSA showed that GL suppressed LPS-induced NF-κB binding to the MMP-9 promotor, as NF-κB regulates transcriptional activation of multiple inflammatory cytokines, we predicted that GL might target NF-κB to suppress MMP-9 transcription by LPS. Myeloid differentiation-factor 88 (MyD88) and TIR-domain containing adaptor protein (TIRAP) are critical proteins in the LPS-induced NF-κB and apoptotic signaling pathways, GL inhibited the expression of TLR4 and MYD88. These results demonstrated that GL suppress LPS-induced MMP-9 expression through the inhibition of the induced TLR4/NFκB signaling pathway. Taken together, our results provide evidence that GL exerts anti-inflammatory effects by inhibition LPS-induced bovine FLSs migration and invasion, and the mechanisms may involve the suppression of TLR4/NFκB –mediated MMP-9 expression. Although further work is needed to clarify the complicated mechanism of GL-induced anti-invasion of bovine FLSs, GL might be used as a further anti-invasion drug with therapeutic efficacy in the treatment of immune-mediated inflammatory disease such as RA.

Keywords: glycyrrhizic acid, bovine fibroblast-like synoviocyte, tlr4/nf-κb, metalloproteinase-9

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