Search results for: randomized controlled trial

Authors: Iris Vogeler, Rogerio Cichota, Armin Werner

Abstract:

Dairy farms are under pressure to increase productivity while reducing environmental impacts. Effective fertiliser management practices are critical to achieve this. Determination of optimum nitrogen (N) fertilisation rates which maximise pasture growth and minimise N losses is challenging due to variability in plant requirements and likely near-future supply of N by the soil. Remote sensing can be used for mapping N nutrition status of plants and to rapidly assess the spatial variability within a field. An algorithm is, however, lacking which relates the N status of the plants to the expected yield response to additions of N. The aim of this simulation study was to develop a multi-variate model for determining N fertilisation rate for a target percentage of the maximum achievable yield based on the pasture N concentration (ii) use of an algorithm for guiding fertilisation rates, and (iii) evaluation of the model regarding pasture yield and N losses, including N leaching, denitrification and volatilisation. A simulation study was carried out using the Agricultural Production Systems Simulator (APSIM). The simulations were done for an irrigated ryegrass pasture in the Canterbury region of New Zealand. A multi-variate model was developed and used to determine monthly required N fertilisation rates based on pasture N content prior to fertilisation and targets of 50, 75, 90 and 100% of the potential monthly yield. These monthly optimised fertilisation rules were evaluated by running APSIM for a ten-year period to provide yield and N loss estimates from both nonurine and urine affected areas. Comparison with typical fertilisation rates of 150 and 400 kg N/ha/year was also done. Assessment of pasture yield and leaching from fertiliser and urine patches indicated a large reduction in N losses when N fertilisation rates were controlled by the multi-variate model. However, the reduction in leaching losses was much smaller when taking into account the effects of urine patches. The proposed approach based on biophysical modelling to develop a multi-variate model for determining optimum N fertilisation rates dependent on pasture N content is very promising. Further analysis, under different environmental conditions and validation is required before the approach can be used to help adjust fertiliser management practices to temporal and spatial N demand based on the nitrogen status of the pasture.

Keywords: APSIM modelling, optimum N fertilization rate, pasture N content, ryegrass pasture, three dimensional surface response function.

Procedia PDF Downloads 130

Authors: Mandeep Kaur, K. C. Sharma, P. L. Sharma, R. S. Chandel

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Cauliflower is an important vegetable crop grown throughout the world and is attacked by a large number of insect pests at various stages of the crop growth. Amongst them, the cabbage aphid, Brevicoryne brassicae (Linnaeus) (Hemiptera: Aphididae) is an important insect pest. Continued feeding by both nymphs and adults of this aphid causes yellowing, wilting and stunting of plants. Amongst various management practices, the use of resistant cultivars is important and can be an effective method of reducing the population of this aphid. So it is imperative to know the complete record on various biological parameters and life table on specific cultivars. The biology and life fertility of the cabbage aphid were studied on five cauliflower cultivars viz. Megha, Shweta, K-1, PSB-1 and PSBK-25 under controlled temperature conditions of 20 ± 2°C, 70 ± 5% relative humidity and 16:8 h (Light: Dark) photoperiods. For studying biology; apterous viviparous adults were picked up from the laboratory culture of all five cauliflower cultivars after rearing them at least for two generations and placed individually on the desired plants of cauliflower cultivars grown in pots with ten replicates of each. Daily record on the duration of nymphal period, adult longevity, mortality in each stage and the total number of progeny produced per female was made. This biological data were further used to construct life fertility table on each cultivar. Statistical analysis showed that there was a significant difference ( P  < 0.05) between the different growth stages and the mean number of laid nymphs. The maximum and minimum growth periods were observed on Shweta and Megha (at par with K-1) cultivars, respectively. The maximum number of nymphs were laid on Shweta cultivar (26.40 nymphs per female) and minimum on Megha (at par with K-1) cultivar (15.20 nymphs per female). The true intrinsic rate of increase (rm) was found to be maximum on Shweta (0.233 nymphs/female/day) followed by PSB K-25 (0.207 nymphs/female/day), PSB-1 (0.203 nymphs/female/day), Megha (0.166 nymphs/female/day) and K-1 (0.153 nymphs/female/day). The finite rate of natural increase (λ) was also found to be in the order: K-1 < Megha < PSB-1 < PSBK-25 < Shweta whereas the doubling time (DT) was in the order of K-1 >Megha> PSB-1 >PSBk-25> Shweta. The aphids reared on the K-1 cultivar had the lowest values of rm & λ and the highest value of DT whereas on Shweta cultivar the values of rm & λ were the highest and the lowest value of DT. So on the basis of these studies, K-1 cultivar was found to be the least suitable and the Shweta cultivar was the most suitable for the cabbage aphid population growth. Although the cauliflower cultivars used in different parts of the world may be different yet the results of the present studies indicated that the application of cultivars affecting multiplication rate and reproductive parameters could be a good solution for the management of the cabbage aphid.

Keywords: biology, cauliflower, cultivars, fertility

Procedia PDF Downloads 184

Authors: Wissam Saliba, Mandy Nicholson

Abstract:

Secretory carcinoma (SC) is a rare type of salivary gland cancer. It was first realized as a distinct type of malignancy in 2010and wasinitially termed “mammary analogue secretory carcinoma” because of similarities with secretory breast cancer. The name was later changed to SC. Most SCs originate in parotid glands, and most harbour a rare gene mutation: ETV6-NTRK3. This mutation is rare in common cancers and common in rare cancers; it is present in most secretory carcinomas. Disease outcomes for SC are usually described as favourable as many cases of SC are lowgrade (LG), and cancer growth is slow. In early stages, localized therapy is usually indicated (surgery and/or radiation). Despitea favourable prognosis, a sub-set of casescan be much more aggressive.These cases tend to be of high-grade(HG).HG casesare associated with a poorer prognosis.Management of such cases can be challenging due to limited evidence for effective systemic therapy options. This case report describes the clinical management of a 46-year-oldmale patient with a unique case of SC. He was initially diagnosed with a low/intermediate grade carcinoma of the left parotid gland in 2009; he was treated with surgery and adjuvant radiation. Surgical pathology favoured primary salivary adenocarcinoma, and 2 lymph nodes were positive for malignancy. SC was not yet realized as a distinct type of cancerat the time of diagnosis, and the pathology reportvalidated this gap by stating that the specimen lacked features of the defined types of salivary carcinoma.Slow-growing pulmonary nodules were identified in 2017. In 2020, approximately 11 years after the initial diagnosis, the patient presented with malignant pleural effusion. Pathology from a pleural biopsy was consistent with metastatic poorly differentiated cancer of likely parotid origin, likely mammary analogue secretory carcinoma. The specimen was sent for Next Generation Sequencing (NGS); ETV6-NTRK3 gene fusion was confirmed, and systemic therapy was initiated.One cycle ofcarboplatin/paclitaxel was given in June 2020. He was switched to Larotrectinib (NTRK inhibitor (NTRKi)) later that month. Larotrectinib continued for approximately 9 months, with discontinuation in March 2021 due to disease progression. A second-generation NTRKi (Selitrectinib) was accessed and prescribedthrough a single patient study. Selitrectinib was well tolerated. The patient experienced a complete radiological response within~4 months. Disease progression occurred once again in October 2021. Progression was slow, and Selitrectinib continuedwhile the medical team performed a thorough search for additional treatment options. In January 2022, a liver lesion biopsy was performed, and NGS showed an NTRKG623R solvent-front resistance mutation. Various treatment pathways were considered. The patient pursuedanother investigational NTRKi through a clinical trial, and Selitrectinib was discontinued in July 2022. Excellent performance status was maintained throughout the entire course of treatment.It can be concluded that NTRK inhibitors provided satisfactory treatment efficacy and tolerance for this patient with high-grade transformation and NTRK gene fusion cancer. In the future, more clinical research is needed on systemic treatment options for high-grade transformations in NTRK gene fusion SCs.

Keywords: secretory carcinoma, high-grade transformations, NTRK gene fusion, NTRK inhibitor

Procedia PDF Downloads 108

Authors: Fatna Benmessaoud, Mohammed Cheikh, Vencent Velay, Vanessa Vidal, Farhad Rezai-Aria, Christine Boher

Abstract:

Ti-6Al-4V titanium alloy is one of the most widely used materials in aeronautical and aerospace industries. Because of its high specific strength, good fatigue, and corrosion resistance, this alloy is very suitable for moderate temperature applications. At room temperature, Ti-6Al-4V mechanical behavior is generally controlled by the behavior of alpha phase (beta phase percent is less than 8%). The plastic strain of this phase notably based on crystallographic slip can be hindered by various obstacles and mechanisms (crystal lattice friction, sessile dislocations, strengthening by solute atoms and grain boundaries…). The grains aspect of alpha phase (its morphology and texture) and the nature of its crystallographic lattice (which is hexagonal compact) give to plastic strain heterogeneous, discontinuous and anisotropic characteristics at the local scale. The aim of this work is to develop a multi-scale model for Ti-6Al-4V mechanical behavior using crystal plasticity approach; this multi-scale model is used then to investigate grains size, dispersion of grains size, crystallographic texture and slip systems activation effects on Ti-6Al-4V mechanical behavior under monotone quasi-static loading. Nine representative elementary volume (REV) are built for taking into account the physical elements (grains size, dispersion and crystallographic) mentioned above, then boundary conditions of tension test are applied. Finally, simulation of the mechanical behavior of Ti-6Al-4V and study of slip systems activation in alpha phase is reported. The results show that the macroscopic mechanical behavior of Ti-6Al-4V is strongly linked to the active slip systems family (prismatic, basal or pyramidal). The crystallographic texture determines which family of slip systems can be activated; therefore it gives to the plastic strain a heterogeneous character thus an anisotropic macroscopic mechanical behavior of Ti-6Al-4V alloy modeled. The grains size influences also on mechanical proprieties of Ti-6Al-4V, especially on the yield stress; by decreasing of the grain size, the yield strength increases. Finally, the grains' distribution which characterizes the morphology aspect (homogeneous or heterogeneous) gives to the deformation fields distribution enough heterogeneity because the crystallographic slip is easier in large grains compared to small grains, which generates a localization of plastic deformation in certain areas and a concentration of stresses in others.

Keywords: multi-scale modeling, Ti-6Al-4V alloy, crystal plasticity, grains size, crystallographic texture

Procedia PDF Downloads 157

Authors: Hellen L. De Castro e Silva, Ana A. Robles Aguilar, Erik Meers

Abstract:

Digestates are residual by-products, rich in nutrients and trace elements, which can be used as organic fertilisers on soils. However, due to the non-digestibility of these elements and reduced dry matter during the anaerobic digestion process, metal concentrations are higher in digestates than in feedstocks, which might hamper their use as fertilisers according to the threshold values of some country policies. Furthermore, there is uncertainty regarding the required assimilated amount of these elements by some crops, which might result in their bioaccumulation. Therefore, further processing of the digestate to obtain safe fertilizing products has been recommended. This research aims to analyze the effect of applying the hydrothermal carbonization process to manure-derived digestates as a thermal treatment to reduce the bioavailability of heavy metals in mono and co-digestates derived from pig manure and maize from contaminated land in France. This study examined pig manure collected from a novel stable system (VeDoWs, province of East Flanders, Belgium) that separates the collection of pig urine and feces, resulting in a solid fraction of manure with high up-concentration of heavy metals and nutrients. Mono-digestion and co-digestion processes were conducted in semi-continuous reactors for 45 days at mesophilic conditions, in which the digestates were dried at 105 °C for 24 hours. Then, hydrothermal carbonization was applied to a 1:10 solid/water ratio to guarantee controlled experimental conditions in different temperatures (180, 200, and 220 °C) and residence times (2 h and 4 h). During the process, the pressure was generated autogenously, and the reactor was cooled down after completing the treatments. The solid and liquid phases were separated through vacuum filtration, in which the solid phase of each treatment -hydrochar- was dried and ground for chemical characterization. Different fractions (exchangeable / adsorbed fraction - F1, carbonates-bound fraction - F2, organic matter-bound fraction - F3, and residual fraction – F4) of some heavy metals (Cd, Cr, Ni, and Cr) have been determined in digestates and derived hydrochars using the modified Community Bureau of Reference (BCR) sequential extraction procedure. The main results indicated a difference in the heavy metals fractionation between digestates and their derived hydrochars; however, the hydrothermal carbonization operating conditions didn’t have remarkable effects on heavy metals partitioning between the hydrochars of the proposed treatments. Based on the estimated potential ecological risk assessment, there was one level decrease (considerate to moderate) when comparing the HMs partitioning in digestates and derived hydrochars.

Keywords: heavy metals, bioavailability, hydrothermal treatment, bio-based fertilisers, agriculture

Procedia PDF Downloads 100

Authors: I. M. K. Ho, S. K. Y. Chan, K. H. P. Lam, G. M. W. Tong, N. C. Y. Yeung, J. T. C. Luk

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Low-dye taping (LDT) is commonly used for treating foot problems, such as plantar fasciitis, and supporting foot arch for runners and non-athletes patients with pes planus. The potential negative impact of pronated feet leading to tibial and femoral internal rotation via the entire kinetic chain reaction was postulated and identified. The changed lower limb biomechanics potentially leading to poor activation of hip and knee stabilizers, such as gluteus maximus and medius, may associate with higher risk of knee injuries including patellofemoral pain syndrome and ligamentous sprain in many team sports players. It is therefore speculated that foot arch correction with LDT might enhance the use of gluteal muscles. The purpose of this study was to investigate the effect of applying LDT on surface electromyographic (sEMG) activity of superior gluteus maximus (SGMax), inferior gluteus maximus (IGMax), gluteus medius (GMed) and tibialis anterior (TA) during double-leg squat. 12 male collegiate basketball players (age: 21.72.5 years; body fat: 12.43.6%; navicular drop: 13.72.7mm) with at least three years regular basketball training experience participated in this study. Participants were excluded if they had recent history of lower limb injuries, over 16.6% body fat and lesser than 10mm drop in navicular drop (ND) test. Recruited subjects visited the laboratory once for the within-subject crossover study. Maximum voluntary isometric contraction (MVIC) tests on all selected muscles were performed in randomized order followed by sEMG test on double-leg squat during LDT and non-LDT conditions in counterbalanced order. SGMax, IGMax, GMed and TA activities during the entire 2-second concentric and 2-second eccentric phases were normalized and interpreted as %MVIC. The magnitude of the difference between taped and non-taped conditions of each muscle was further assessed via standardized effect90% confidence intervals (CI) with non-clinical magnitude-based inference. Paired samples T-test showed a significant decrease (4.71.4mm) in ND (95% CI: 3.8, 5.6; p < 0.05) while no significant difference was observed between taped and non-taped conditions in sEMG tests for all muscles and contractions (p > 0.05). On top of traditional significant testing, magnitude-based inference showed possibly increase in IGMax activity (small standardized effect: 0.270.44), likely increase in GMed activity (small standardized effect: 0.340.34) and possibly increase in TA activity (small standardized effect: 0.220.29) during eccentric phase. It is speculated that the decrease of navicular drop supported by LDT application could potentially enhance the use of inferior gluteus maximus and gluteus medius especially during eccentric phase in this study. As the eccentric phase of double-leg squat is an important component of landing activities in basketball, further studies on the onset and amount of gluteal activation during jumping and landing activities with LDT are recommended. Since both hip and knee kinematics were not measured in this study, the underlying cause of the observed increase in gluteal activation during squat after LDT is inconclusive. In this regard, the investigation of relationships between LDT application, ND, hip and knee kinematics, and gluteal muscle activity during sports specific jumping and landing tasks should be focused in the future.

Keywords: flat foot, gluteus maximus, gluteus medius, injury prevention

Procedia PDF Downloads 155

Authors: Matthew Cardeiro, Amalia D. Ardeljan, Lexi Frankel, Dianela Prado Escobar, Catalina Molnar, Omar M. Rashid

Abstract:

Introduction: Enterococci comprise the natural flora of nearly all animals and are ubiquitous in food manufacturing and probiotics. However, its role in the microbiome remains controversial. The gut microbiome has shown to play an important role in immunology and cancer. Further, recent data has suggested a relationship between gut microbiota and breast cancer. These studies have shown that the gut microbiome of patients with breast cancer differs from that of healthy patients. Research regarding enterococcus infection and its sequala is limited, and further research is needed in order to understand the relationship between infection and cancer. Enterococcus may prevent the development of breast cancer (BC) through complex immunologic and microbiotic adaptations following an enterococcus infection. This study investigated the effect of enterococcus infection and the incidence of BC. Methods: A retrospective study (January 2010- December 2019) was provided by a Health Insurance Portability and Accountability Act (HIPAA) compliant national database and conducted using a Humans Health Insurance Database. International Classification of Disease (ICD) 9th and 10th codes, Current Procedural Terminology (CPT), and National Drug Codes were used to identify BC diagnosis and enterococcus infection. Patients were matched for age, sex, Charlson Comorbidity Index (CCI), antibiotic treatment, and region of residence. Chi-squared, logistic regression, and odds ratio were implemented to assess the significance and estimate relative risk. Results: 671 out of 28,518 (2.35%) patients with a prior enterococcus infection and 1,459 out of 28,518 (5.12%) patients without enterococcus infection subsequently developed BC, and the difference was statistically significant (p<2.2x10⁻¹⁶). Logistic regression also indicated enterococcus infection was associated with a decreased incidence of BC (RR=0.60, 95% CI [0.57, 0.63]). Treatment for enterococcus infection was analyzed and controlled for in both enterococcus infected and noninfected populations. 398 out of 11,523 (3.34%) patients with a prior enterococcus infection and treated with antibiotics were compared to 624 out of 11,523 (5.41%) patients with no history of enterococcus infection (control) and received antibiotic treatment. Both populations subsequently developed BC. Results remained statistically significant (p<2.2x10-16) with a relative risk of 0.57 (95% CI [0.54, 0.60]). Conclusion & Discussion: This study shows a statistically significant correlation between enterococcus infection and a decrease incidence of breast cancer. Further exploration is needed to identify and understand not only the role of enterococcus in the microbiome but also the protective mechanism(s) and impact enterococcus infection may have on breast cancer development. Ultimately, further research is needed in order to understand the complex and intricate relationship between the microbiome, immunology, bacterial infections, and carcinogenesis.

Keywords: breast cancer, enterococcus, immunology, infection, microbiome

Procedia PDF Downloads 173

Authors: Dharshini Selvarajah, Nicula Lui, Karen Kong

Abstract:

Background: Uterine fibroids are a common benign gynaecologic neoplasm in reproductive-aged women. Fibroids may become symptomatic in a vast majority of nulliparous women. Their diagnosis and management is often coordinated between gyneacologists, radiologists and urologists depending on the anatomical location, growth, size and the fibroids sarcomatous evolvement. Some patients may develop obstructive uropathy symptoms, either uni or bilateral secondary urethral obstruction causing hydronephrosis. Uterine artery emoblisation (UAE) has previously shown to effectively resolve symptoms as well as relieve urethral obstruction and resolve the hydronephrosis. UAE has now established itself as an organ preserving and minimally invasive procedure in the management of symptomatic uterine fibroids. It is a safe and effective alternative to hysterectomy for resolving fibroid related pressure symptoms. The case presented examines the clinical manifestations and impact of uterine fibroids on the urinary tract system. The therapeutic options to relieve the urological symptoms as well as preserve fertility are explored and presented. Case: The case is a 29-year-old Nepalese female admitted to hospital with recurrent urosepsis with multiresistant organisms. This was on a background of an enlarged uterus (measuring 17cm x11cm) with multiple subserosal, intramural and exophytic fibroids- causing external ureteric compression. She had bilateral ureteric stents insitu and required bilateral right and left nephrostomies during repeated episodes of urosepsis and bilateral ureteric obstruction. The left nephrostomy was removed a month prior to admission and her most recent CT KUB demonstrated hypofunctioning ureteric stents with bilateral hydronephrosis. Options of hysterectomy versus uterine artery emoblisation (UAE) were extensively explored. The patient was keen to preserve fertility. Risks associated with UAE such as expulsion of the submucosal component of the fibroids and the possibilities of sepsis in the setting of ongoing ureteric colonisation were particularly high. The patient opted to trial UAE even though the risks of recurrent hospital admissions with urosepsis were going to be particularly high. In the event, the uterus fails to shrink adequately enough to relieve the obstructed ureters a hysterectomy would inevitably be required in future. Day 3 post UAE the patient developed fevers, was hypotensive and tachycardic post-receiving prophylactic meropenem and fluconazole pre emoblisation. She was noted to have a CRP of 293 with the most recent urine culture during this time growing Candida albicans. The patient was recommenced on oral fluconazole and IV meropenem, with good effect. Her repeat renal tract ultrasound post-UAE showed ongoing marked left hydronephrosis relatively unchanged from the scan one month prior to the procedure, however the right-sided hydronephrosis had resolved. The patient was discharged on a 2-week course of antibiotics. The patient will have a repeat renal tract ultrasound and MRI of the ureters to re-evaluate the degree of hydronephrosis and progress- this was unavailable at the time of abstract submission and will be presented at the conference. Conclusion: Fibroids are a common benign tumour of the uterus and can frequently impact the lower urinary system resulting in significant uropathy. They often enlarge and compress the urinary bladder, urethra and lower end of the ureters. The effectiveness of UAE as a fertility preserving option is described.

Keywords: Uterine leiomyomas and urological complications, uterine artery embolisation for fibroids, Uterine fibroids and complications, Management of uterine fibroids

Procedia PDF Downloads 223

Authors: Hemant Upadhyay, Tarun Kumar Kundu

Abstract:

It is utmost important for a blast furnace operator to understand the mechanisms governing the liquid flow, accumulation, drainage and heat transfer between various phases in blast furnace hearth for a stable and efficient blast furnace operation. Abnormal drainage behavior may lead to high liquid build up in the hearth. Operational problems such as pressurization, low wind intake, and lower material descent rates, normally be encountered if the liquid levels in the hearth exceed a critical limit when Hearth coke and Deadman start to float. Similarly, hot metal temperature is an important parameter to be controlled in the BF operation; it should be kept at an optimal level to obtain desired product quality and a stable BF performance. It is not possible to carry out any direct measurement of above due to the hostile conditions in the hearth with chemically aggressive hot liquids. The objective here is to develop a mathematical model to simulate the variation in hot metal / slag accumulation and temperature during the tapping of the blast furnace based on the computed drainage rate, production rate, mass balance, heat transfer between metal and slag, metal and solids, slag and solids as well as among the various zones of metal and slag itself. For modeling purpose, the BF hearth is considered as a pressurized vessel, filled with solid coke particles. Liquids trickle down in hearth from top and accumulate in voids between the coke particles which are assumed thermally saturated. A set of generic mass balance equations gives the amount of metal and slag intake in hearth. A small drainage (tap hole) is situated at the bottom of the hearth and flow rate of liquids from tap hole is computed taking in account the amount of both the phases accumulated their level in hearth, pressure from gases in the furnace and erosion behaviors of tap hole itself. Heat transfer equations provide the exchange of heat between various layers of liquid metal and slag, and heat loss to cooling system through refractories. Based on all that information a dynamic simulation is carried out which provides real time information of liquids accumulation in hearth before and during tapping, drainage rate and its variation, predicts critical event timings during tapping and expected tapping temperature of metal and slag on preset time intervals. The model is in use at JSPL, India BF-II and its output is regularly cross-checked with actual tapping data, which are in good agreement.

Keywords: blast furnace, hearth, deadman, hotmetal

Procedia PDF Downloads 184

Authors: Dharshini Selvarajah, Karen Kong

Abstract:

Background: Uterine fibroids are a common benign gynaecologic neoplasm in reproductive-aged women. Fibroids may become symptomatic in a vast majority of nulliparous women. Their diagnosis and management are often coordinated between gyneacologists, radiologists and urologists depending on the anatomical location, growth, size and the fibroids' sarcomatous evolvement. Some patients may develop obstructive uropathy symptoms, either uni or bilateral secondary urethral obstruction causing hydronephrosis. Uterine artery embolization (UAE) has previously been shown to effectively resolve symptoms as well as relieve urethral obstruction and resolve hydronephrosis. UAE has now established itself as an organ-preserving and minimally invasive procedure in the management of symptomatic uterine fibroids. It is a safe and effective alternative to hysterectomy for resolving fibroid-related pressure symptoms. The case presented examines the clinical manifestations and impact of uterine fibroids on the urinary tract system. The therapeutic options to relieve the urological symptoms as well as preserve fertility are explored and presented. Case: The case is a 29-year-old Nepalese female admitted to the hospital with recurrent urosepsis with multiresistant organisms. This was on a background of an enlarged uterus (measuring 17cm x11cm) with multiple subserosal, intramural and exophytic fibroids- causing external ureteric compression. She had bilateral ureteric stents in situ and required bilateral right and left nephrostomies during repeated episodes of urosepsis and bilateral ureteric obstruction. The left nephrostomy was removed a month prior to admission, and her most recent CT KUB demonstrated hypofunctioning ureteric stents with bilateral hydronephrosis. Options of hysterectomy versus uterine artery embolization (UAE) were extensively explored. The patient was keen to preserve fertility. Risks associated with UAE, such as the expulsion of the submucosal component of the fibroids and the possibilities of sepsis in the setting of ongoing ureteric colonisation were particularly high. The patient opted to trial UAE even though the risks of recurrent hospital admissions with urosepsis were going to be particularly high. In the event, the uterus fails to shrink adequately enough to relieve the obstructed ureters, a hysterectomy would inevitably be required in the future. Day 3 post-UAE the patient developed fevers, was hypotensive and tachycardic post-receiving prophylactic meropenem and fluconazole pre emoblisation. She was noted to have a CRP of 293 with the most recent urine culture during this time growing Candida albicans. The patient was recommenced on oral fluconazole and IV meropenum, with good effect. Her repeat renal tract ultrasound post-UAE showed ongoing marked left hydronephrosis relatively unchanged from the scan one month prior to the procedure; however, the right-sided hydronephrosis had resolved. The patient was discharged on a 2-week course of antibiotics. The patient will have a repeat renal tract ultrasound and MRI of the ureters to re-evaluate the degree of hydronephrosis and progress- this was unavailable at the time of abstract submission and will be presented at the conference. Conclusion: Fibroids are a common benign tumor of the uterus and can frequently impact the lower urinary system resulting in significant uropathy. They often enlarge and compress the urinary bladder, urethra and lower end of the ureters. The effectiveness of the UAE as a fertility-preserving option is described.

Keywords: uterine artery embolisation for fibroids, urological complications from fibroids, uropathy of fibroids, obstructive fibroid management

Procedia PDF Downloads 209

Authors: Alejandra Ben-Aissa, Martina Moreno, Luciano Sappia, Paul Lacharmoise, Ana Moya

Abstract:

Organ-on-Chip (OoC) stands out as a highly promising approach for drug testing, presenting a cost-effective and ethically superior alternative to conventional in vivo experiments. These cutting-edge devices emerge from the integration of tissue engineering and microfluidic technology, faithfully replicating the physiological conditions of targeted organs. Consequently, they offer a more precise understanding of drug responses without the ethical concerns associated with animal testing. When addressing the limitations of OoC due to conventional and time-consuming techniques, Lab-On-Chip (LoC) emerge as a disruptive technology capable of providing real-time monitoring without compromising sample integrity. This work develops LoC platforms that can be integrated within OoC platforms to monitor essential culture media parameters, including glucose, oxygen, and pH, facilitating the straightforward exchange of sensing units within a dynamic and controlled environment without disrupting cultures. This approach preserves the experimental setup, minimizes the impact on cells, and enables efficient, prolonged measurement. The LoC system is fabricated following the patented methodology protected by EU patent EP4317957A1. One of the key challenges of integrating sensors in a biocompatible, feasible, robust, and scalable manner is addressed through fully printed sensors, ensuring a customized, cost-effective, and scalable solution. With this technique, sensor reliability is enhanced, providing high sensitivity and selectivity for accurate parameter monitoring. In the present study, LoC is validated measuring a complete culture media. The oxygen sensor provided a measurement range from 0 mgO2/L to 6.3 mgO2/L. The pH sensor demonstrated a measurement range spanning 2 pH units to 9.5 pH units. Additionally, the glucose sensor achieved a measurement range from 0 mM to 11 mM. All the measures were performed with the sensors integrated in the LoC. In conclusion, this study showcases the impactful synergy of OoC technology with LoC systems using fully printed sensors, marking a significant step forward in ethical and effective biomedical research, particularly in drug development. This innovation not only meets current demands but also lays the groundwork for future advancements in precision and customization within scientific exploration.

Keywords: organ on chip, lab on chip, real time monitoring, biosensors

Procedia PDF Downloads 17

Authors: Yunjia Yang, Peng Li, Gordon Xu, Timothy Mahony, Bing Zhang, Neena Mitter, Karishma Mody

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Sheep flystrike is one of the most economically important diseases affecting the Australian sheep and wool industry (>356M/annually). Currently, control of Lucillia cuprina relies almost exclusively on chemicals controls, and the parasite has developed resistance to nearly all control chemicals used in the past. It is, therefore, critical to develop an alternative solution for the sustainable control and management of flystrike. RNA interference (RNAi) technologies have been successfully explored in multiple animal industries for developing parasites controls. This research project aims to develop a RNAi based biological control for sheep blowfly. Double-stranded RNA (dsRNA) has already proven successful against viruses, fungi, and insects. However, the environmental instability of dsRNA is a major bottleneck for successful RNAi. Bentonite polymer (BenPol) technology can overcome this problem, as it can be tuned for the controlled release of dsRNA in the gut challenging pH environment of the blowfly larvae, prolonging its exposure time to and uptake by target cells. To investigate the potential of BenPol technology for dsRNA delivery, four different BenPol carriers were tested for their dsRNA loading capabilities, and three of them were found to be capable of affording dsRNA stability under multiple temperatures (4°C, 22°C, 40°C, 55°C) in sheep serum. Based on stability results, dsRNA from potential targeted genes was loaded onto BenPol carriers and tested in larvae feeding assays, three genes resulting in knockdowns. Meanwhile, a primary blowfly embryo cell line (BFEC) derived from L. cuprina embryos was successfully established, aim for an effective insect cell model for testing RNAi efficacy for preliminary assessments and screening. The results of this study establish that the dsRNA is stable when loaded on BenPol particles, unlike naked dsRNA rapidly degraded in sheep serum. The stable nanoparticle delivery system offered by BenPol technology can protect and increase the inherent stability of dsRNA molecules at higher temperatures in a complex biological fluid like serum, providing promise for its future use in enhancing animal protection.

Keywords: lucilia cuprina, primary cell line establishment, RNA interference, insect cell transfection

Procedia PDF Downloads 73

Authors: Sanjay Shukla

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Excessive use of antibiotics is a main problem in the treatment of wounds and other chronic infections and antibiotic treatment is frequently non-curative, thus alternative treatment is necessary. Phage therapy is considered one of the most effective approaches to treat multi-drug resistant bacterial pathogens. Infections caused by Staphylococcus aureus are very efficiently controlled with phage cocktails, containing a different individual phages lysate infecting a majority of known pathogenic S. aureus strains. The aim of current study was to investigate the efficiency of a purified phage cocktail for prophylactic as well as therapeutic application in mouse model and in large animals with chronic septic infection of wounds. A total of 150 sewage samples were collected from various livestock farms. These samples were subjected for the isolation of bacteriophage by double agar layer method. A total of 27 sewage samples showed plaque formation by producing lytic activity against S. aureus in double agar overlay method out of 150 sewage samples. In TEM recovered isolates of bacteriophages showed hexagonal structure with tail fiber. In the bacteriophage (ØVS) had an icosahedral symmetry with the head size 52.20 nm in diameter and long tail of 109 nm. Head and tail were held together by connector and can be classified as a member of the Myoviridae family under the order of Caudovirale. Recovered bacteriophage had shown the antibacterial activity against the S. aureus in vitro. Cocktail (ØVS1, ØVS5, ØVS9 and ØVS 27) of phage lysate were tested to know in vivo antibacterial activity as well as the safety profile. Result of mice experiment indicated that the bacteriophage lysate was very safe, did not show any appearance of abscess formation which indicates its safety in living system. The mice were also prophylactically protected against S. aureus when administered with cocktail of bacteriophage lysate just before the administration of S. aureus which indicates that they are good prophylactic agent. The S. aureus inoculated mice were completely recovered by bacteriophage administration with 100% recovery which was very good as compere to conventional therapy. In present study ten chronic cases of wound were treated with phage lysate and follow up of these cases was done regularly up to ten days (at 0, 5 and 10 d). Result indicated that the six cases out of ten showed complete recovery of wounds within 10 d. The efficacy of bacteriophage therapy was found to be 60% which was very good as compared to the conventional antibiotic therapy in chronic septic wounds infections. Thus, the application of lytic phage in single dose proved to be innovative and effective therapy for treatment of septic chronic wounds.

Keywords: phage therapy, phage lysate, antimicrobial resistance, S. aureus

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Authors: Arkadiusz Gut, Robert Mirski

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The nativist-constructivist debate constitutes a considerable part of current research on mindreading. Peter Carruthers and his colleagues are known for their nativist position in the debate and take issue with constructivist views proposed by other researchers, with Henry Wellman, Alison Gopnik, and Ian Apperly at the forefront. More specifically, Carruthers together with Evan Westra propose a nativistic explanation of Theory of Mind Scale study results that Wellman et al. see as supporting constructivism. While allowing for development of the innate mindreading system, Westra and Carruthers base their argumentation essentially on a competence-performance gap, claiming that cross-cultural differences in Theory of Mind Scale progression as well as discrepancies between infants’ and toddlers’ results on verbal and non-verbal false-belief tasks are fully explainable in terms of acquisition of other, pragmatic, cognitive developments, which are said to allow for an expression of the innately present Theory of Mind understanding. The goal of the present paper is to bring together arguments against the view offered by Westra and Carruthers. It will be shown that even though Carruthers et al.’s interpretation has not been directly controlled for in Wellman et al.’s experiments, there are serious reasons to dismiss such nativistic views which Carruthers et al. advance. The present paper discusses the following issues that undermine Carruthers et al.’s nativistic conception: (1) The concept of innateness is argued to be developmentally inaccurate; it has been dropped in many biological sciences altogether and many developmental psychologists advocate for doing the same in cognitive psychology. Reality of development is a complex interaction of changing elements that is belied by the simplistic notion of ‘the innate.’ (2) The purported innate mindreading conceptual system posited by Carruthers ascribes adult-like understanding to infants, ignoring the difference between first- and second-order understanding, between what can be called ‘presentation’ and ‘representation.’ (3) Advances in neurobiology speak strongly against any inborn conceptual knowledge; neocortex, where conceptual knowledge finds its correlates, is said to be largely equipotential at birth. (4) Carruthers et al.’s interpretations are excessively charitable; they extend results of studies done with 15-month-olds to conclusions about innateness, whereas in reality at that age there has been plenty of time for construction of the skill. (5) Looking-time experiment paradigm used in non-verbal false belief tasks that provide the main support for Carruthers’ argumentation has been criticized on methodological grounds. In the light of the presented arguments, nativism in theory of mind research is concluded to be an untenable position.

Keywords: development, false belief, mindreading, nativism, theory of mind

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Authors: Ankita Singh

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Sex trafficking and child pornography are those kinds of borderless crimes which can not be effectively prevented only through the laws and efforts of one country because it requires a proper and smooth collaboration among countries. Eradication of international human trafficking syndicates, criminalisation of international cyber offenders, and effective ban on child pornography is not possible without applying effective universal laws; hence, continuous collaboration of all countries is much needed to adopt and routinely update these universal laws. Congregation of countries on an international platform is very necessary from time to time, where they can simultaneously adopt international agendas and create powerful universal laws to prevent sex trafficking and child pornography in this modern digital era. In the past, some international steps have been taken through The Convention on the Rights of the Child (CRC) and through The Optional Protocol to the Convention on the Rights of the Child on the Sale of Children, Child Prostitution, and Child Pornography, but in reality, these measures are quite weak and are not capable in effectively protecting children from sexual abuse in this modern & highly advanced digital era. The uncontrolled growth of artificial intelligence (AI) and its misuse, lack of proper legal jurisdiction over foreign child abusers and difficulties in their extradition, improper control over international trade of digital child pornographic content, etc., are some prominent issues which can only be controlled through some new, effective and powerful universal laws. Due to a lack of effective international standards and a lack of improper collaboration among countries, Indian laws are also not capable of taking effective actions against child abusers. This research will be conducted through both doctrinal as well as empirical methods. Various literary sources will be examined, and a questionnaire survey will be conducted to analyse the effectiveness of international standards and Indian laws against child pornography. Participants in this survey will be Indian University students. In this work, the existing international norms made for protecting children from sexual abuse will be critically analysed. It will explore why effective and strong collaboration between countries is required in modern times. It will be analysed whether existing international steps are enough to protect children from getting trafficked or being subjected to pornography, and if these steps are not found to be sufficient enough, then suggestions will be given on how international standards and protections can be made more effective and powerful in this digital era. The approach of India towards the existing international standards, the Indian laws to protect children from being subjected to pornography, and the contributions & capabilities of India in strengthening the international standards will also be analysed.

Keywords: child pornography, prevention of children from sexual offences act, the optional protocol to the convention on the rights of the child on the sale of children, child prostitution and child pornography, the convention on the rights of the child

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Authors: Habib Alshuwaikhat, Nahid Hossain

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Residential sector consumes more than half of the produced electricity in Saudi Arabia, and fossil fuel is the main source of energy to meet growing household electricity demand in the Kingdom. Several studies forecasted and expressed concern that unless the domestic energy demand growth is controlled, it will reduce Saudi Arabia’s crude oil export capacity within a decade and the Kingdom is likely to be incapable of exporting crude oil within next three decades. Though the Saudi government has initiated to address the domestic energy demand growth issue, the demand side energy management policies and programs are focused on industrial and commercial sectors. It is apparent that there is an urgent need to develop a comprehensive energy efficiency strategy for addressing efficient energy use in residential sector in the Kingdom. Then again as Saudi Arabia is at its primary stage in addressing energy efficiency issues in its residential sector, there is a scope for the Kingdom to learn from global energy efficiency practices and design its own energy efficiency policies and programs. However, in order to do that sustainable, it is essential to address local contexts of energy efficiency. It is also necessary to find out the policies and programs that will fit to the local contexts. Thus the objective of this study was set to identify globally best practice energy efficiency policies and programs in residential sector that have replication potential in Saudi Arabia. In this regard two sets of multi-criteria decision analysis matrices were developed to evaluate the energy efficiency policies and programs. The first matrix was used to evaluate the global energy efficiency policies and programs, and the second matrix was used to evaluate the replication potential of global best practice energy efficiency policies and programs for Saudi Arabia. Wuppertal Institute’s guidelines for energy efficiency policy evaluation were used to develop the matrices, and the different attributes of the matrices were set through available literature review. The study reveals that the best practice energy efficiency policies and programs with good replication potential for Saudi Arabia are those which have multiple components to address energy efficiency and are diversified in their characteristics. The study also indicates the more diversified components are included in a policy and program, the more replication potential it has for the Kingdom. This finding is consistent with other studies, where it is observed that in order to be successful in energy efficiency practices, it is required to introduce multiple policy components in a cluster rather than concentrate on a single policy measure. The developed multi-criteria decision analysis matrices for energy efficiency policy and program evaluation could be utilized to assess the replication potential of other globally best practice energy efficiency policies and programs for the residential sector of the Kingdom. In addition it has potential to guide Saudi policy makers to adopt and formulate its own energy efficiency policies and programs for Saudi Arabia.

Keywords: Saudi Arabia, residential sector, energy efficiency, policy evaluation

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Authors: Zohar Manber, Ran Elkon

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Accumulation of somatic mutations (SMs) in the genome is a major driving force of cancer development. Most SMs in the tumor's genome are functionally neutral; however, some cause damage to critical processes and provide the tumor with a selective growth advantage (termed cancer driver mutations). Current research on functional significance of SMs is mainly focused on finding alterations in protein coding sequences. However, the exome comprises only 3% of the human genome, and thus, SMs in the noncoding genome significantly outnumber those that map to protein-coding regions. Although our understanding of noncoding driver SMs is very rudimentary, it is likely that disruption of regulatory elements in the genome is an important, yet largely underexplored mechanism by which somatic mutations contribute to cancer development. The expression of most human genes is controlled by multiple enhancers, and therefore, it is conceivable that regulatory SMs are distributed across different enhancers of the same target gene. Yet, to date, most statistical searches for regulatory SMs have considered each regulatory element individually, which may reduce statistical power. The first challenge in considering the cumulative activity of all the enhancers of a gene as a single unit is to map enhancers to their target promoters. Such mapping defines for each gene its set of regulating enhancers (termed "set of regulatory elements" (SRE)). Considering multiple enhancers of each gene as one unit holds great promise for enhancing the identification of driver regulatory SMs. However, the success of this approach is greatly dependent on the availability of comprehensive and accurate enhancer-promoter (E-P) maps. To date, the discovery of driver regulatory SMs has been hindered by insufficient sample sizes and statistical analyses that often considered each regulatory element separately. In this study, we analyzed more than 2,500 whole-genome sequence (WGS) samples provided by The Cancer Genome Atlas (TCGA) and The International Cancer Genome Consortium (ICGC) in order to identify such driver regulatory SMs. Our analyses took into account the combinatorial aspect of gene regulation by considering all the enhancers that control the same target gene as one unit, based on E-P maps from three genomics resources. The identification of candidate driver noncoding SMs is based on their recurrence. We searched for SREs of genes that are "hotspots" for SMs (that is, they accumulate SMs at a significantly elevated rate). To test the statistical significance of recurrence of SMs within a gene's SRE, we used both global and local background mutation rates. Using this approach, we detected - in seven different cancer types - numerous "hotspots" for SMs. To support the functional significance of these recurrent noncoding SMs, we further examined their association with the expression level of their target gene (using gene expression data provided by the ICGC and TCGA for samples that were also analyzed by WGS).

Keywords: cancer genomics, enhancers, noncoding genome, regulatory elements

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Authors: Abbas Ahmadi, Nasser Aliasgharzad, Ali Asghar Jafarzadeh

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Nowadays, drying of the Urmia Lake as a largest saline lake in the world and emerging its saline bed from water has caused the risk of salty dune storms, which threats the health of human society and also plants and animal communities living in the region. Biological soil crusts (BSCs) as a dust stabilizer attracted the attention of Soil conservation experts in recent years. Although the presence of water by the impenetrable lake bed and endorheic basin can be an advantage to create BSCs, but the extraordinary of the lake bed salinity is a factor for prevention of its establishment in the region. Therefore, the present research work has been carried out to investigate the effects of inoculating the Cyanobacteria, algae and their combination to create BSCs for dust control. In this study, an algae attributed to Chlamydomonas sp and a cyanobacteria attributed to Anabaena sp isolated from the soils of Urmia Lake margin were used to create BSC in four soil samples which collected from 0-10 cm of the current margin (A), the previous bed (B), affected lands by lake (C) and Quomtappe sand dune (D). The main characteristics of the A, B and C soil samples are their highly salinity (their ECe are 108, 140 and 118 dS/m, respectively) and sodicity. Also, texture class of the soil A was loamy sand, and other two soils had clay textures. Soil D was Non-saline, but it was sodic with a sandy texture class. This study was conducted separately in each soil in a completely randomized design under four inoculation treatments of non-inoculated (T0), Algae (T1), cyanobacteria (T2) and equal mixture of algae and cyanobacteria (T3) with three replications. In the experiment, the soil was placed into wind tunnel trays, and a suspension containing microorganisms mixed with the trays surface soil. During the experiment, water was sprayed to the trays at the morning and evening of every day. After passing the incubation period (30 days), some characteristics of samples such as pH, EC, cold water extractable carbohydrate (CWEC), hot water extractable carbohydrate (HWEC), sulfuric acid extractable carbohydrate (SAEC), organic matter, crust thickness, penetration resistance, wind erosion threshold velocity and soil loss in the wind tunnel were measured, and Correlation between the measured characteristics was obtained through the SPSS software. Analysis of variance and so comparison between the means of treatments were analyzed with MSTATC software. In this research, Chlorophyll, an amount, was used as an indicator of the microorganism's population in the samples. Based on obtained results, the amount of Chlorophyll a in the T2 treatment of soil A and all treatments of soil D was significantly increased in comparison to the control and crust thickness showed increase in all treatments by microorganism’s inoculation. But effect of the treatments was significant in soils A and D. At all treatment’s inoculation of microorganisms in soil A caused to increase %46, %34 and %55 of the wind erosion threshold velocity in T1, T2 and T3 treatments in comparison to the control, respectively, and in soil D all treatments caused wind erosion threshold velocity became two times more than control. However, soil loss in the wind tunnel experiments was significant in T2 and T3 treatments of these soils and T1 treatment had no effect in reducing soil loss. Correlation between Chlorophyll a and salinity shows the important role of salinity in microbial growth prevention and formation of BSCs in the studied samples. In general, according to the obtained results, it can be concluded that salinity reduces the growth of microorganisms in saline soils of the region, and in soils with fine textures, salinity role in prevention of the microbial growth is clear. Also, using the mix of algae and cyanobacteria together caused the synergistic growth of them and consequently, better protection of the soil against wind erosion was provided.

Keywords: wind erosion, algae, cyanobacteria, carbohydrate

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Authors: Raveena Naz

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The concept of ‘Corporate Social Responsibility’ (CSR) has often relied on firms thinking beyond their economic interest despite the larger debate of shareholder versus stakeholder interest. India gave legal recognition to CSR in the Companies Act, 2013 which promises better corporate governance. CSR in India is believed to be different for two reasons: the dominance of family business and the history of practice of social responsibility as a form of philanthropy (mainly among the family business). This paper problematises the actual structure of business houses in India and the role of CSR in India. When the law identifies each company as a separate business entity, the economics of institutions emphasizes the ‘business group’ consisting of a plethora of firms as the institutional organization of business. The capital owned or controlled by the family group is spread across the firms through the interholding (interlocked holding) structures. This creates peculiar implications for CSR legislation in India. The legislation sets criteria for individual firms to undertake liability of mandatory CSR if they are above a certain threshold. Within this framework, the largest family firms which are all part of family owned business groups top the CSR expenditure list. The interholding structures, common managers, auditors and series of related party transactions among these firms help the family to run the business as a ‘family business’ even when the shares are issued to the public. This kind of governance structure allows family owned business group to show mandatory compliance of CSR even when they actually spend much less than what is prescribed by law. This aspect of the family firms is not addressed by the CSR legislation in particular or corporate governance legislation in general in India. The paper illustrates this with an empirical study of one of the largest family owned business group in India which is well acclaimed for its CSR activities. The individual companies under the business group are identified, shareholding patterns explored, related party transactions investigated, common managing authorities are identified; and assets, liabilities and profit/loss accounting practices are analysed. The data has been mainly collected from mandatory disclosures in the annual reports and financial statements of the companies within the business group accessed from the official website of the ultimate controlling authority. The paper demonstrates how the business group through these series of shareholding network reduces its legally mandated CSR liability. The paper thus indicates the inadequacy of CSR legislation in India because the unit of compliance is an individual firm and it assumes that each firm is independent and only connected to each other through market dealings. The law does not recognize the inter-connections of firms in corporate governance structures of family owned business group and hence is inadequate in its design to effect the threshold level of CSR expenditure. This is the central argument of the paper.

Keywords: business group, corporate governance, corporate social responsibility, family firm

Procedia PDF Downloads 280

Authors: Mary-Ann N. Jallad, Dalal F. Jaber, Alexander M. Abdelnoor

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Introduction: Current evidence confirms that both innate and adaptive immune systems are capable of recognizing and abolishing malignant cells. The emergence of cancerous tumors in patients is, therefore, an indication that certain cancer cells can resist elimination by the immune system through a process known as “immune evasion”. In fact, cancer cells often exploit regulatory mechanisms to escape immunity. Such mechanisms normally exist to control the immune responses and prohibit exaggerated or autoimmune reactions. Recently, immunotherapies have shown promising yet limited results. Therefore this study investigates several immunotherapeutic combinations and devises a triple immunotherapy which harnesses the innate and acquired immune responses towards the annihilation of malignant cells through overcoming their ability of immune evasion, consequently hampering malignant progression and eliminating established tumors. The aims of the study are to rule out acute/chronic toxic effects of the proposed treatment combinations, to assess the effect of these combinations on tumor growth and survival rates, and to investigate potential mechanisms underlying the phenotypic results through analyzing serum levels of anti-tumor cytokines, angiogenic factors and tumor progression indicator, and the tumor-infiltrating immune-cells populations. Methodology: For toxicity analysis, cancer-free C57BL/6 mice are randomized into 9 groups: Group 1 untreated, group 2 treated with sterile saline (solvent of used treatments), group 3 treated with Monophosphoryl-lipid-A, group 4 with anti-CTLA4-antibodies, group 5 with 1-Methyl-Tryptophan (Indolamine-Dioxygenase-1 inhibitor), group 6 with both MPLA and anti-CTLA4-antibodies, group 7 with both MPLA and 1-MT, group 8 with both anti-CTLA4-antibodies and 1-MT, and group 9 with all three: MPLA, anti-CTLA4-antibodies and 1-MT. Mice are monitored throughout the treatment period and for three following months. At that point, histological sections from their main organs are assessed. For tumor progression and survival analysis, a murine melanoma model is generated by injecting analogous mice with B16F10 melanoma cells. These mice are segregated into the listed nine groups. Their tumor size and survival are monitored. For a depiction of underlying mechanisms, melanoma-bearing mice from each group are sacrificed at several time-points. Sera are tested to assess the levels of Interleukin-12 (IL-12), Vascular-Endothelial-Growth Factor (VEGF), and S100B. Furthermore, tumors are excised for analysis of infiltrated immune cell populations including T-cells, macrophages, natural killer cells and immune-regulatory cells. Results: Toxicity analysis shows that all treated groups present no signs of neither acute nor chronic toxicity. Their appearance and weights were comparable to those of control groups throughout the treatment period and for the following 3 months. Moreover, histological sections from their hearts, kidneys, lungs, and livers were normal. Work is ongoing for completion of the remaining study aims. Conclusion: Toxicity was the major concern for the success of the proposed comprehensive combinational therapy. Data generated so far ruled out any acute or chronic toxic effects. Consequently, ongoing work is quite promising and may significantly contribute to the development of more effective immunotherapeutic strategies for the treatment of cancer patients.

Keywords: cancer immunotherapy, check-point blockade, combination therapy, melanoma

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Authors: Shaine Mehta, Neelam Parmar, Patrick White, Mark Ashworth

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Patients with a history of substance have a high prevalence of comorbidities, including asthma and chronic obstructive pulmonary disease (COPD). Mortality rates are higher than that of the general population and the link to respiratory disease is reported. Randomised controlled trials (RCTs) support opioid substitution therapy as an effective means for harm reduction. However, whilst a high proportion of patients receiving opioid substitution therapy are smokers, to the author’s best knowledge there have been no studies of respiratory disease and smoking intensity in these patients. A cross sectional prevalence study was conducted using an anonymised patient-level database in primary care, Lambeth DataNet (LDN). We included patients aged 18 years and over who had records of ever having been prescribed methadone in primary care. Patients under 18 years old or prescribed buprenorphine (because of uncertainty about the prescribing indication) were excluded. Demographic, smoking, alcohol and asthma and COPD coding data were extracted. Differences between methadone and non-methadone users were explored with multivariable analysis. LDN contained data on 321, 395 patients ≥ 18 years; 676 (0.16%) had a record of methadone prescription. Patients prescribed methadone were more likely to be male (70.7% vs. 50.4%), older (48.9yrs vs. 41.5yrs) and less likely to be from an ethnic minority group (South Asian 2.1% vs. 7.8%; Black African 8.9% vs. 21.4%). Almost all those prescribed methadone were smokers or ex-smokers (97.3% vs. 40.9%); more were non-alcohol drinkers (41.3% vs. 24.3%). We found a high prevalence of COPD (12.4% vs 1.4%) and asthma (14.2% vs 4.4%). Smoking intensity data shows a high prevalence of ≥ 20 cigarettes per day (21.5% vs. 13.1%). Risk of COPD, adjusted for age, gender, ethnicity and deprivation, was raised in smokers: odds ratio 14.81 (95%CI 11.26, 19.47), and in the methadone group: OR 7.51 (95%CI: 5.78, 9.77). Furthermore, after adjustment for smoking intensity (number of cigarettes/day), the risk was raised in methadone group: OR 4.77 (95%CI: 3.13, 7.28). High burden of respiratory disease compounded by the high rates of smoking is a public health concern. This supports an integrated approach to health in patients treated for opiate dependence, with access to smoking cessation support. Further work may evaluate the current structure and commissioning of substance misuse services, including smoking cessation. Regression modelling highlights that methadone as a ‘risk factor’ was independently associated with COPD prevalence, even after adjustment for smoking intensity. This merits further exploration, as the association may be related to unexplored aspects of smoking (such as the number of years smoked) or may be related to other related exposures, such as smoking heroin or crack cocaine.

Keywords: methadone, respiratory disease, smoking cessation, substance misuse

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Authors: Sarah Alamolhoda, Kevin J. Smith, Xiaotao Bi, Naoko Ellis

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For millennials, biomass has been the most important source of fuel used to produce energy. Energy derived from biomass is renewable by re-growth of biomass. Various technologies are used to convert biomass to potential renewable products including combustion, gasification, pyrolysis and fermentation. Gasification is the incomplete combustion of biomass in a controlled environment that results in valuable products such as syngas, biooil and biochar. Syngas is a combustible gas consisting of hydrogen (H₂), carbon monoxide (CO), carbon dioxide (CO₂), and traces of methane (CH₄) and nitrogen (N₂). Cleaned syngas can be used as a turbine fuel to generate electricity, raw material for hydrogen and synthetic natural gas production, or as the anode gas of solid oxide fuel cells. In this work, syngas as a product of woody biomass gasification in British Columbia, Canada, was introduced to two consecutive fixed bed reactors to perform a catalytic water gas shift reaction followed by a catalytic methanation reaction. The water gas shift reaction is a well-established industrial process and used to increase the hydrogen content of the syngas before the methanation process. Catalysts were used in the process since both reactions are reversible exothermic, and thermodynamically preferred at lower temperatures while kinetically favored at elevated temperatures. The water gas shift reactor and the methanation reactor were packed with Cu-based catalyst and Ni-based catalyst, respectively. Simulated syngas with different percentages of CO, H₂, CH₄, and CO₂ were fed to the reactors to investigate the effect of operating conditions in the unit. The water gas shift reaction experiments were done in the temperature of 150 ˚C to 200 ˚C, and the pressure of 550 kPa to 830 kPa. Similarly, methanation experiments were run in the temperature of 300 ˚C to 400 ˚C, and the pressure of 2340 kPa to 3450 kPa. The Methanation reaction reached 98% of CO conversion at 340 ˚C and 3450 kPa, in which more than half of CO was converted to CH₄. Increasing the reaction temperature caused reduction in the CO conversion and increase in the CH₄ selectivity. The process was designed to be renewable and release low greenhouse gas emissions. Syngas is a clean burning fuel, however by going through water gas shift reaction, toxic CO was removed, and hydrogen as a green fuel was produced. Moreover, in the methanation process, the syngas energy was transformed to a fuel with higher energy density (per volume) leading to reduction in the amount of required fuel that flows through the equipment and improvement in the process efficiency. Natural gas is about 3.5 times more efficient (energy/ volume) than hydrogen and easier to store and transport. When modification of existing infrastructure is not practical, the partial conversion of renewable hydrogen to natural gas (with up to 15% hydrogen content), the efficiency would be preserved while greenhouse gas emission footprint is eliminated.

Keywords: renewable natural gas, methane, hydrogen, gasification, syngas, catalysis, fuel

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Authors: Anastasia Constantinou, Panayiotis Laouris, Stephen Morris

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Background: Climate change has been reported as one of the worst threats to healthcare. The healthcare sector is a significant contributor to greenhouse gas emissions with primary care being responsible for 23% of the NHS’ total carbon footprint. Digital interventions, primarily focusing on telemedicine, offer a route to change. This systematic review aims to quantify and characterize the carbon footprint savings associated with the implementation of digital interventions in the setting of primary care. Methods: A systematic review of published literature was conducted according to PRISMA (Preferred Reporting Item for Systematic Reviews and Meta-Analyses) guidelines. MEDLINE, PubMed, and Scopus databases as well as Google scholar were searched using key terms relating to “carbon footprint,” “environmental impact,” “sustainability”, “green care”, “primary care,”, and “general practice,” using citation tracking to identify additional articles. Data was extracted and analyzed in Microsoft Excel. Results: Eight studies were identified conducted in four different countries between 2010 and 2023. Four studies used interventions to address primary care services, three studies focused on the interface between primary and specialist care, and one study addressed both. Digital interventions included the use of mobile applications, online portals, access to electronic medical records, electronic referrals, electronic prescribing, video-consultations and use of autonomous artificial intelligence. Only one study carried out a complete life cycle assessment to determine the carbon footprint of the intervention. It estimate that digital interventions reduced the carbon footprint at primary care level by 5.1 kgCO2/visit, and at the interface with specialist care by 13.4 kg CO₂/visit. When assessing the relationship between travel-distance saved and savings in emissions, we identified a strong correlation, suggesting that most of the carbon footprint reduction is attributed to reduced travel. However, two studies also commented on environmental savings associated with reduced use of paper. Patient savings in the form of reduced fuel cost and reduced travel time were also identified. Conclusion: All studies identified significant reductions in carbon footprint following implementation of digital interventions. In the future, controlled, prospective studies incorporating complete life cycle assessments and accounting for double-consulting effects, use of additional resources, technical failures, quality of care and cost-effectiveness are needed to fully appreciate the sustainable benefit of these interventions

Keywords: carbon footprint, environmental impact, primary care, sustainable healthcare

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Authors: Anjana Rajput, Sandeep Chouksey, Bhaskar Bhandari, Shimpi Chourasia

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Ecologically, grassland is any plant community dominated by grasses, whether they exist naturally or because of management practices. Most forest grasslands are anthropogenic and established plant communities planted for forage production, though some are established for soil and water conservation and wildlife habitat. In Satpura Tiger Reserve, Madhya Pradesh, India, most of the grasslands have been established on evacuated village sites. Total of 42 villages evacuated, and study was carried out in 23 sites to evaluate habitat improvement. Grasslands were classified into three categories, i.e., evacuated sites, established sites, and controlled sites. During the present study impact of various management interventions on grassland health was assessed. Grasslands assessment was done for its composition, status of palatable and non-palatable grasses, the status of herbs and legumes, status of weeds species, and carrying capacity of particular grassland. Presence of wild herbivore species in the grasslands with their abundance, availability of water resources was also assessed. Grassland productivity is dependent mainly on the biotic and abiotic components of the area, but management interventions may also play an important role in grassland composition and productivity. Variation in the status of palatable and non-palatable grasses, legumes, and weeds was recorded and found effected by management intervention practices. Overall in all the studied grasslands, the most dominant grasses recorded are Themeda quadrivalvis, Dichanthium annulatum, Ischaemum indicum, Oplismenus burmanii, Setaria pumilla, Cynodon dactylon, Heteropogon contortus, and Eragrostis tenella. Presence of wild herbivores, i.e., Chital, Sambar, Bison, Bluebull, Chinkara, Barking deer in the grassland area has been recorded through the installation of camera traps and estimated their abundance. Assessment of developed grasslands was done in terms of habitat suitability for Chital (Axis axis) and Sambar (Rusa unicolor). The parameters considered for suitability modeling are biotic and abiotic life requisite components existing in the area, i.e., density of grasses, density of legumes, availability of water, site elevation, site distance from human habitation. Findings of the present study would be useful for further grassland management and animal translocation programmes.

Keywords: carrying capacity, dominant grasses, grassland, habitat suitability, management intervention, wild herbivore

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Authors: Clementine Colpaert, Boris L. Nikitenko

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The Upper Jurassic foraminiferal assemblages of the East European Platform have been strongly investigated through the 20th century with biostratigraphical and in smaller degree palaeoecological and palaeobiogeographical purposes. Over the Late Jurassic, the platform was a shallow epicontinental sea that extended from Tethys to the Artic through the Pechora Sea and further toward the northeast in the West Siberian Sea. Foraminiferal assemblages of the Russian Sea were strongly affected by sea-level changes and were controlled by alternated Boreal to Peritethyan influences. The central part of the East European Platform displays very rich and diverse foraminiferal assemblages. Two sections have been analyzed; the Makar'yev Section in the Moscow Depression and the Gorodishi Section in the Yl'yanovsk Depression. Based on the evolution of foraminiferal assemblages, palaeoenvironment has been reconstructed, and sea-level changes have been refined. The aim of this study is to understand palaeoceanographical changes throughout the Oxfordian – Kimmeridgian of the central part of the Russian Sea. The Oxfordian was characterized by a general transgressive event with intermittency of small regressive phases. The platform was connected toward the south with Tethys and Peritethys. During the Middle Oxfordian, opening of a pathway of warmer water from the North-Tethys region to the Boreal Realm favoured the migration of planktonic foraminifera and the appearance of new benthic taxa. It is associated with increased temperature and primary production. During the Late Oxfordian, colder water inputs associated with the microbenthic community crisis may be a response to the closure of this warm-water corridor and the disappearance of planktonic foraminifera. The microbenthic community crisis is probably due to the increased sedimentation rate in the transition from the maximum flooding surface to a second-order regressive event, increasing productivity and inputs of organic matter along with sharp decrease of oxygen into the sediment. It is following during the Early Kimmeridgian by a replacement of foraminiferal assemblages. The almost all Kimmeridgian is characterized by the abundance of many common with Boreal and Subboreal Realm. Connections toward the South began again dominant after a small regressive event recorded during the Late Kimmeridgian and associated with the abundance of many common taxa with Subboreal Realm and Peritethys such as Crimea and Caucasus taxa. Foraminiferal assemblages of the East European Platform are strongly affected by palaeoecological changes and may display a very good model for biofacies typification under Boreal and Subboreal environments. The East European Platform appears to be a key area for the understanding of Upper Jurassic big scale palaeoceanographical changes, being connected with Boreal to Peritethyan basins.

Keywords: foraminifera, palaeoceanography, palaeoecology, upper jurassic

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Authors: B. Salehi, D. Andrews, I. Chaer, A. Gillich, A. Chalk, D. Bush

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With the rapid increase of energy consumption in buildings in recent years, especially with the rise in population and growing economies, the importance of energy savings in buildings becomes more critical. One of the key factors in ensuring energy consumption is controlled and kept at a minimum is to utilise building energy modelling at the very early stages of the design. So, building modelling and simulation is a growing discipline. During the design phase of construction, modelling software can be used to estimate a building’s projected energy consumption, as well as building performance. The growth in the use of building modelling software packages opens the door for improvements in the design and also in the modelling itself by introducing novel methods such as building information modelling-based software packages which promote conventional building energy modelling into the digital building design process. To understand the most effective implementation tools, research projects undertaken should include elements of real-world experiments and not just rely on theoretical and simulated approaches. Upon review of the related studies undertaken, it’s evident that they are mostly based on modelling and simulation, which can be due to various reasons such as the more expensive and time-consuming nature of real-time data-based studies. Taking in to account the recent rise of building energy software modelling packages and the increasing number of studies utilising these methods in their projects and research, the accuracy and reliability of these modelling software packages has become even more crucial and critical. This Energy Performance Gap refers to the discrepancy between the predicted energy savings and the realised actual savings, especially after buildings implement energy-efficient technologies. There are many different software packages available which are either free or have commercial versions. In this study, IES VE (Integrated Environmental Solutions Virtual Environment) is used as it is a common Building Energy Modeling and Simulation software in the UK. This paper describes a study that compares real time results with those in a virtual model to illustrate this gap. The subject of the study is a north west facing north-west (345°) facing, naturally ventilated, conservatory within a domestic building in London is monitored during summer to capture real-time data. Then these results are compared to the virtual results of IES VE, which is a commonly used building energy modelling and simulation software in the UK. In this project, the effect of the wrong position of blinds on overheating is studied as well as providing new evidence of Performance Gap. Furthermore, the challenges of drawing the input of solar shading products in IES VE will be considered.

Keywords: building energy modelling and simulation, integrated environmental solutions virtual environment, IES VE, performance gap, real time data, solar shading products

Procedia PDF Downloads 139

Authors: Peter. M. Kusen, Georg Wandrey, Christopher Probst, Dietrich Kohlheyer, Jochen Buchs, Jorg Pietruszkau

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Light as a stimulus provides the capability to develop regulation techniques for customizable gene expression. A great advantage is the extremely flexible and accurate dosing that can be performed in a non invasive and sterile manner even for high throughput technologies. Therefore, light regulation in a multiwell microbioreactor system was realized providing the opportunity to control gene expression with outstanding complexity. A light-regulated gene expression system in Saccharomyces cerevisiae was designed applying the strategy of caged compounds. These compounds are photo-labile protected and therefore biologically inactive regulator molecules which can be reactivated by irradiation with certain light conditions. The “caging” of a repressor molecule which is consumed after deprotection was essential to create a flexible expression system. Thereby, gene expression could be temporally repressed by irradiation and subsequent release of the active repressor molecule. Afterwards, the repressor molecule is consumed by the yeast cells leading to reactivation of gene expression. A yeast strain harboring a construct with the corresponding repressible promoter in combination with a fluorescent marker protein was applied in a Photo-BioLector platform which allows individual irradiation as well as online fluorescence and growth detection. This device was used to precisely control the repression duration by adjusting the amount of released repressor via different irradiation times. With the presented screening platform the regulation of complex expression procedures was achieved by combination of several repression/derepression intervals. In particular, a stepwise increase of temporally-constant expression levels was demonstrated which could be used to study concentration dependent effects on cell functions. Also linear expression rates with variable slopes could be shown representing a possible solution for challenging protein productions, whereby excessive production rates lead to misfolding or intoxication. Finally, the very flexible regulation enabled accurate control over the expression induction, although we used a repressible promoter. Summing up, the continuous online regulation of gene expression has the potential to synchronize gene expression levels to optimize metabolic flux, artificial enzyme cascades, growth rates for co cultivations and many other applications addicted to complex expression regulation. The developed light-regulated expression platform represents an innovative screening approach to find optimization potential for production processes.

Keywords: caged-compounds, gene expression regulation, optogenetics, photo-labile protecting group

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Authors: Michalina Aniola, Andrzej Katrusiak

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4,4-Bipyridine is an important compound often used in chemical practice and more recently frequently applied for designing new metal organic framework (MoFs). Here we present a systematic high-pressure study of its hydrobromide salt. 4,4-Bipyridine hydrobromide monohydrate, 44biPyHBrH₂O, at ambient-pressure is orthorhombic, space group P212121 (phase a). Its hydrostatic compression shows that it is stable to 1.32 GPa at least. However, the recrystallization above 0.55 GPa reveals a new hidden b-phase (monoclinic, P21/c). Moreover, when the 44biPyHBrH2O is heated to high temperature the chemical reactions of this compound in methanol solution can be observed. High-pressure experiments were performed using a Merrill-Bassett diamond-anvil cell (DAC), modified by mounting the anvils directly on the steel supports, and X-ray diffraction measurements were carried out on a KUMA and Excalibur diffractometer equipped with an EOS CCD detector. At elevated pressure, the crystal of 44biPyHBrH₂O exhibits several striking and unexpected features. No signs of instability of phase a were detected to 1.32 GPa, while phase b becomes stable at above 0.55 GPa, as evidenced by its recrystallizations. Phases a and b of 44biPyHBrH2O are partly isostructural: their unit-cell dimensions and the arrangement of ions and water molecules are similar. In phase b the HOH-Br- chains double the frequency of their zigzag motifs, compared to phase a, and the 44biPyH+ cations change their conformation. Like in all monosalts of 44biPy determined so far, in phase a the pyridine rings are twisted by about 30 degrees about bond C4-C4 and in phase b they assume energy-unfavorable planar conformation. Another unusual feature of 44biPyHBrH2O is that all unit-cell parameters become longer on the transition from phase a to phase b. Thus the volume drop on the transition to high-pressure phase b totally depends on the shear strain of the lattice. Higher temperature triggers chemical reactions of 44biPyHBrH2O with methanol. When the saturated methanol solution compound precipitated at 0.1 GPa and temperature of 423 K was required to dissolve all the sample, the subsequent slow recrystallization at isochoric conditions resulted in disalt 4,4-bipyridinium dibromide. For the 44biPyHBrH2O sample sealed in the DAC at 0.35 GPa, then dissolved at isochoric conditions at 473 K and recrystallized by slow controlled cooling, a reaction of N,N-dimethylation took place. It is characteristic that in both high-pressure reactions of 44biPyHBrH₂O the unsolvated disalt products were formed and that free base 44biPy and H₂O remained in the solution. The observed reactions indicate that high pressure destabilized ambient-pressure salts and favors new products. Further studies on pressure-induced reactions are carried out in order to better understand the structural preferences induced by pressure.

Keywords: conformation, high-pressure, negative area compressibility, polymorphism

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Authors: Fadi Saleh, Çığdem Sezer Zhmurov

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Biopharmaceuticals represent one of the wildest developing fields within biotechnology, and the biological macromolecules being produced inside cells have a variety of applications for therapies. In the past, mammalian cells, especially CHO cells, have been employed in the production of biopharmaceuticals. This is because these cells can achieve human-like completion of PTM. These systems, however, carry apparent disadvantages like high production costs, vulnerability to contamination, and limitations in scalability. This research is focused on the utilization of microalgae as a bioreactor system for the synthesis of biopharmaceutical glycoproteins in relation to PTMs, particularly N-glycosylation. The research points to a growing interest in microalgae as a potential substitute for more conventional expression systems. A number of advantages exist in the use of microalgae, including rapid growth rates, the lack of common human pathogens, controlled scalability in bioreactors, and the ability of some PTMs to take place. Thus, the potential of microalgae to produce recombinant proteins with favorable characteristics makes this a promising platform in order to produce biopharmaceuticals. The study focuses on the examination of the N-glycosylation pathways across different species of microalgae. This investigation is important as N-glycosylation—the process by which carbohydrate groups are linked to proteins—profoundly influences the stability, activity, and general performance of glycoproteins. Additionally, bioinformatics methodologies are employed to explain the genetic pathways implicated in N-glycosylation within microalgae, with the intention of modifying these organisms to produce glycoproteins suitable for human consumption. In this way, the present comparative analysis of the N-glycosylation pathway in humans and microalgae can be used to bridge both systems in order to produce biopharmaceuticals with humanized glycosylation profiles within the microalgal organisms. The results of the research underline microalgae's potential to help improve some of the limitations associated with traditional biopharmaceutical production systems. The study may help in the creation of a cost-effective and scale-up means of producing quality biopharmaceuticals by modifying microalgae genetically to produce glycoproteins with N-glycosylation that is compatible with humans. Improvements in effectiveness will benefit biopharmaceutical production and the biopharmaceutical sector with this novel, green, and efficient expression platform. This thesis, therefore, is thorough research into the viability of microalgae as an efficient platform for producing biopharmaceutical glycoproteins. Based on the in-depth bioinformatic analysis of microalgal N-glycosylation pathways, a platform for their engineering to produce human-compatible glycoproteins is set out in this work. The findings obtained in this research will have significant implications for the biopharmaceutical industry by opening up a new way of developing safer, more efficient, and economically more feasible biopharmaceutical manufacturing platforms.

Keywords: microalgae, glycoproteins, post-translational modification, genome

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Authors: Katharina Eberhardt, Florian Klaus Kaiser, Frank Schultmann

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Last-mile distribution is one of the most critical parts of a disaster relief operation. Various uncertainties, such as infrastructure conditions, resource availability, and fluctuating beneficiary demand, render last-mile distribution challenging in disaster relief operations. The need to balance critical performance criteria like response time, meeting demand and cost-effectiveness further complicates the task. The occurrence of disasters cannot be controlled, and the magnitude is often challenging to assess. In summary, these uncertainties create a need for additional flexibility, agility, and preparedness in logistics operations. As a result, strategic planning and efficient network design are critical for an effective and efficient response. Furthermore, the increasing frequency of disasters and the rising cost of logistical operations amplify the need to provide robust and resilient solutions in this area. Therefore, we formulate a scenario-based bi-objective optimization model that integrates pre-positioning, allocation, and distribution of relief supplies extending the general form of a covering location problem. The proposed model aims to minimize underlying logistics costs while maximizing demand coverage. Using a set of disruption scenarios, the model allows decision-makers to identify optimal network solutions to address the risk of disruptions. We provide an empirical case study of the public authorities’ emergency food storage strategy in Germany to illustrate the potential applicability of the model and provide implications for decision-makers in a real-world setting. Also, we conduct a sensitivity analysis focusing on the impact of varying stockpile capacities, single-site outages, and limited transportation capacities on the objective value. The results show that the stockpiling strategy needs to be consistent with the optimal number of depots and inventory based on minimizing costs and maximizing demand satisfaction. The strategy has the potential for optimization, as network coverage is insufficient and relies on very high transportation and personnel capacity levels. As such, the model provides decision support for public authorities to determine an efficient stockpiling strategy and distribution network and provides recommendations for increased resilience. However, certain factors have yet to be considered in this study and should be addressed in future works, such as additional network constraints and heuristic algorithms.

Keywords: humanitarian logistics, bi-objective optimization, pre-positioning, last mile distribution, decision support, disaster relief networks

Procedia PDF Downloads 79