Search results for: decentralized trials

Authors: Adam N. Bell, Sarina J. Ergas, Michael Nystrom, Nathan P. Brennan, Kevan L. Main

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Integrated Multi-Trophic Aquaculture systems (IMTA) have the potential to improve the sustainability of seafood production, generate organic fertilizer and feed, remove waste discharges and reduce energy use. IMTA can include periphyton biofilters where algae and microbes grow on surfaces, along with caught detritus and amphipods. Periphyton biofilters provide many advantages: nitrification, denitrification, primary production and ecological diversity. The goal of this study was to determine how biofilter hydraulic residence time (τ) effects periphyton biomass production, dissolved oxygen (DO) and nutrient removal. A pilot scale recirculating aquaculture system (RAS) was designed, constructed and operated at different hydraulic residence times (τ= 1, 2, 4, 6, 8 hours per tank). For each τ, a conservative tracer study was conducted to investigate system hydrodynamics. Data on periphyton weights, pH, nitrogen species, phosphorus, temperature and DO were collected. The tracer study for τ =1 hour revealed that the normalized time < τ, indicating short-circuiting. Periphyton biomass production rate was relatively unaffected by τ (R_e<1 for all τ). Average ammonia nitrogen removal was > 75% for all trials. Nitrate and nitrite did not accumulate in the RAS for τ≥4 hours due to enhanced denitrification in anoxic zones. For τ≥4 hours DO concentration was at a maximum of 4 mg L-1 after 14:00, and decreased to 0 mg L-1 during nighttime. At τ=1 hour, the RAS stayed > 2 mg L-1 and DO was more evenly distributed. For the validation trial, the culture tank was stocked with Centropomus undecimalis (common snook) and the system was operated at τ= 1 hr. Preliminary results showed that a RAS with an integrated periphyton biofilter could support fish health with low nutrient concentrations DO > 6 mg L-1.

Keywords: sustainable aquaculture, resource recovery, nitrogen, microalgae, hydrodynamics, integrated multi-trophic aquaculture

Procedia PDF Downloads 119

Authors: G. Berhane, F. Kebede

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A feeding trial was conducted to enhance the utilization of locally produced full-fat soybean by the broiler industry. The study had three phases such as starter (1-14d), grower (15–28d), and finisher (29–49d) phases. A completely randomized design (CRD) was used in the starter phase with three treatments (commercial soybean meal (SBM) was replaced by raw full-fat soybean (RFSB) at 0, 10, or 20%), and each was replicated eight times. A total of 408 unsexed one-day-old Cobb-500 broiler chicks were randomly allocated to replicates. A 2 x 3 factorial arrangement was used in both second (grower) and third (finisher) phase trials, which had six experimental diets. These six treatments were formed by dividing the original three diets (containing 0, 10, or 20% of RFSB into two and then by pelleting anyone from each respective group and leaving the other as mash. Every treatment had four replications and 17 birds in each. Chemical compositions of feed ingredients were analyzed, and data on the initial body weight of chicks, feed offered, feed leftover, body weight (BW) of chickens, and mortality were collected. At the end of the experiment, two birds (one male and one female) per replicate were randomly selected and humanly slaughtered. Weights of dressed, eviscerated, cut parts of the carcass and visceral organs were weighed and recorded. Results indicated that feed intake (FI), body weight gain (BWG), BW, and feed conversion ratio (FCR) of broilers were not significantly affected (P=0.05) by supplementation of a leveled RFSB on diets at starter, grower, and finisher phases. The FI at the finisher stage was also significantly (P=0.05) influenced by the feed forms. However, weights of dressed, eviscerated, cut parts of the carcass and visceral organs were not significantly (P=0.05) affected by both RFSB supplementation, up to 20%, and feed forms. It is concluded that commercial SBM can be replaced by locally produced RFSB up to 20% without pelleting the diets.

Keywords: broilers, carcass characteristics, raw full-fat soybean, weight gain

Procedia PDF Downloads 121

Authors: Hannah K. M. Tang, Muhammad Ateeq, Mark J. Lake, Badr Abdullah, Frederic A. Bezombes

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There is little research applying virtual reality (VR) to the treatment of musculoskeletal injury in athletes. This is despite their prevalence, and the implications for physical and psychological health. Nevertheless, developments of wireless VR headsets better facilitate dynamic movement in VR environments (VREs), and more research is expected in this emerging field. This systematic review identified publications that used VR interventions for the analysis or treatment of lower-limb musculoskeletal injury of athletes. It established a search protocol, and through narrative discussion, identified existing trends. Database searches encompassed four term sets: 1) VR systems; 2) musculoskeletal injuries; 3) sporting population; 4) movement outcome analysis. Overall, a total of 126 publications were identified through database searching, and twelve were included in the final analysis and discussion. Many of the studies were pilot and proof of concept work. Seven of the twelve publications were observational studies. However, this may provide preliminary data from which clinical trials will branch. If specified, the focus of the literature was very narrow, with very similar population demographics and injuries. The trends in the literature findings emphasised the role of VR and attentional focus, the strategic manipulation of movement outcomes, and the transfer of skill to the real-world. Causal inferences may have been undermined by flaws, as most studies were limited by the practicality of conducting a two-factor clinical-VR-based study. In conclusion, by assessing the exploratory studies, and combining this with the use of numerous developments, techniques, and tools, a novel application could be established to utilise VR with dynamic movement, for the effective treatment of specific musculoskeletal injuries of athletes.

Keywords: athletes, lower-limb musculoskeletal injury, rehabilitation, return-to-sport, virtual reality

Procedia PDF Downloads 219

Authors: Xi Vivien Wu, Emily Neo Kim Ang, Yi Jung Tung, Wenru Wang

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Background and Objective: The increase in life expectancy and emphasis on self-reliance for the older adults are global phenomena. As such, lifelong learning in the community is considered a viable means of promoting successful and active aging. This systematic review aims to examine various lifelong learning programs for community-dwelling older adults and to synthesize the contents and outcomes of these lifelong learning programs. Methods: A systematic search was conducted in July to December 2016. Two reviewers were engaged in the process to ensure creditability of the selection process. Narrative description and analysis were applied with the support of a tabulation of key data including study design, interventions, and outcomes. Results: Eleven articles, which consisted of five randomized controlled trials and six quasi-experimental studies, were included in this review. Interventions included e-health literacy programs with the aid of computers and the Internet (n=4), computer and Internet training (n=3), physical fitness programs (n=2), music program (n=1), and intergenerational program (n=1). All studies used objective measurement tools to evaluate the outcomes of the study. Conclusion: The systematic review indicated lifelong learning programs resulted in positive outcomes in terms of physical health, mental health, social behavior, social support, self-efficacy and confidence in computer usage, and increased e-health literacy efficacy. However, the lifelong learning programs face challenges such as funding shortages, program cuts, and increasing costs. A comprehensive lifelong learning program could be developed to enhance the well-being of the older adults at a more holistic level. Empirical research can be done to explore the effectiveness of this comprehensive lifelong learning program.

Keywords: community-dwelling older adults, e-health literacy program, lifelong learning program, the wellbeing of the older adults

Procedia PDF Downloads 151

Authors: Lakshmikanth Reddy, Bhavin Desai, Chandrakala Kari, Sanjay Sarkar, Pradeep Binu

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The sulphur dioxide gases generated as a by-product of smelting and converting operations of copper concentrate contain selenium apart from zinc, lead, copper, cadmium, bismuth, antimony, and arsenic. The gaseous stream is treated in waste heat boiler, electrostatic precipitator and scrubbers to remove coarse particulate matter in order to produce commercial grade sulfuric acid. The gas cleaning section of the acid plant uses water to scrub the smelting gases. After scrubbing, the sludge settled at the bottom of the scrubber, was analyzed in present investigation. It was found to contain 30 to 40 wt% copper and selenium up to 40 wt% selenium. The sludge collected during blow-down is directly recycled to the smelter for copper recovery. However, the selenium is expected to again vaporize due to high oxidation potential during smelting and converting, causing accumulation of selenium in sludge. In present investigation, a roasting process has been developed to recover the selenium before the copper recovery from the sludge at smelter. Selenium is associated with copper in sludge as copper selenide, as determined by X-ray diffraction and electron microscopy. The thermodynamic and thermos-gravimetry study revealed that the copper selenide phase present in the sludge was amenable to oxidation at 600°C forming oxides of copper and selenium (Cu-Se-O). However, the dissociation of selenium from the copper oxide was made possible by sulfatation using sulfur dioxide between 450 to 600°C, resulting into the formation of CuSO₄ (s) and SeO₂ (g). Lab scale trials were carried out in vertical tubular furnace to determine the optimum roasting conditions with respect to roasting time, temperature and molar ratio of O₂:SO₂. Using these optimum conditions, selenium up to 90 wt% in the form of SeO₂ vapors could be recovered from the sludge in a large-scale commercial roaster. Roasted sludge free from the selenium and containing oxides and sulfates of copper could now be recycled in the smelter for copper recovery.

Keywords: copper, selenium, copper selenide, sludge, roasting, SeO₂

Procedia PDF Downloads 194

Authors: Jacob Hatherell, Jason Matthews, Arnaud Marmier

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Anvil Staking is a cold-forming process that is used in the assembly of plain spherical bearings into a rod-end housing. This process ensures that the bearing outer lip conforms to the chamfer in the matching rod end to produce a lightweight mechanical joint with sufficient strength to meet the pushout load requirement of the assembly. Finite Element (FE) analysis is being used extensively to predict the behaviour of metal flow in cold forming processes to support industrial manufacturing and product development. On-going research aims to validate FE models across a wide range of bearing and rod-end geometries by systematically isolating and understanding the uncertainties caused by variations in, material properties, load-dependent friction coefficients and strain rate sensitivity. The improved confidence in these models aims to eliminate the costly and time-consuming process of experimental trials in the introduction of new bearing designs. Previous literature has shown that friction coefficients do not remain constant during cold forming operations, however, the understanding of this phenomenon varies significantly and is rarely implemented in FE models. In this paper, a new approach to evaluate the normal contact pressure versus friction coefficient relationship is outlined using friction calibration charts generated via iterative FE models and ring compression tests. When compared to previous research, this new approach greatly improves the prediction of forming geometry and the forming load during the staking operation. This paper also aims to standardise the FE approach to modelling ring compression test and determining the friction calibration charts.

Keywords: anvil staking, finite element analysis, friction coefficient, spherical plain bearing, ring compression tests

Procedia PDF Downloads 199

Authors: Wen Hsin Hsu, Pin Lin

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Objective: Thirst discomfort is the most common yet often overlooked symptom in patients in the intensive care unit (ICU), with an incidence rate of 69.8%. If not properly cared for, it can easily lead to irritability, affect sleep quality, and increase the incidence of delirium, thereby extending the length of hospital stay. Research points out that the sensation of coldness is an effective strategy to alleviate thirst. Using a combined care approach for thirst can prolong the sensation of coldness in the mouth and reduce thirst discomfort. Therefore, it needs to be further analyzed and its effectiveness reviewed. Methods: This study uses systematic literature review and meta-analysis methodologies and searched databases including PubMed, MEDLINE, EMBASE, Cochrane, CINAHL, and two Chinese databases (CEPS and CJTD) based on keywords. JBI was used to appraise the quality of the literature. RevMen 5.4 software package was used, and Fix Effect Model was applied for data analysis. We selected experimental articles, including those in English and Chinese, that met the inclusion and exclusion criteria. Three research articles were included in total, with a sample size of 416 people. Two were randomized controlled trials, and one was a quasi-experimental design. Results: The results show that the combined care for thirst, which includes ice water spray or oral swab wipes, menthol mouthwash, and lip balm, can significantly relieve thirst intensity MD=-1.36 (3 studies, 95% CI (-1.77, -0.95), p <0.001) and thirst distress MD=-0.71 (2 studies, 95% CI (-1.32, -0.10), p =0.02). Therefore, it is recommended that medical staff identify high-risk groups for thirst early on. Implications for Practice: For patients who cannot eat orally, providing combined care for thirst can increase oral comfort and improve the quality of care.

Keywords: thirst bundle care, intensive care units, meta-analysis, ice water spray, menthol

Procedia PDF Downloads 55

Authors: Massimo Mozzon, Nadia Raffaelli

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Proteases from herbs, woody plants, and trees are exploited for cheesemaking in several countries, especially in South Europe and West Africa. Particularly, “thistles” belonging to several genera within the Asteraceae family (Cynara, Silybum, Centaurea, Carlina, Cirsium, Onopordum) are traditionally used in Mediterranean countries for clotting raw ewe’s and goat’s milk. For the first time, the clotting performance of an aqueous extract from flowers of Onopordum tauricum Willd. (Taurian thistle, bull cottonthistle) were tested in milk of different origin (cow, goat, ewe). The vegetable material was collected in the Central Apennines range, between the Marche and Umbria regions. A response surface methodology (RSM) approach was used to study the effect of the curdling variables (temperature, pH, amount of enzymatic extract) on the technological performance of the thistle extract. A three-step procedure for the purification of the enzyme (ammonium sulphate precipitation, gel filtration and ion-exchange chromatography) was also carried out. The milk clotting activity (MCA) of O. tauricum crude extracts was strongly affected by temperature, pH and by the interaction between these two variables, according to a second-order response surface model, while the milk/coagulant ratio did not affect in a significant way the clotting properties. Experimental data showed that the addition of 10 mM CaCl2 reduced the clotting time of ewe’s, goat’s, and cow’s milk by about 3-fold, 8-fold, and 14-fold, respectively, at 35°C and pH 6.7-6.8. After purification, an enzymatic preparation very close to homogeneity was obtained, which showed a major band at about 30 kDa when analyzed by SDS-PAGE. The identity of the enzyme as an aspartic protease was confirmed by inhibition studies. Cheese-making trials were carried out to check the scale-up (1 to 5 L of milk; 37 °C; 10 mM CaCl2 fortification) and set the recipe: 35-45% of curd yields were recorded, according to curd cutting and pressing.

Keywords: milk clotting activity, Onopordum tauricum, plant proteases, vegetable rennet

Procedia PDF Downloads 149

Authors: Pankaj Kumar Jha, Saroj Sapkota, Dil Bahadur Gurung, Raju Kadel, Neena Amatya Gorkhali, Bhola Shankar Shrestha

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The study was conducted to evaluate the seminal attributes, effectiveness of cooling process and post-thawed semen quality of a Nepalese indigenous Khari buck. Thirty-two ejaculates, 16 from each buck were studied for seminal attributes of fresh semen: volume, color, mass activity, motility, viability, sperm concentration, and morphology. The pooled mean values for each seminal attributes were: volume 0.7±0.3 ml; colour 3.1±0.3 (milky white); mass activity 3.8±0.4 (rapid wave motion with formation of eddies at the end of waves to very rapid wave motion with distinct eddies formation); sperm motility 80.9±5.6%; sperm viability 94.6±2.0%; sperm concentration 2597.0±406.8x106/ml; abnormal acrosome, mid-piece and tail 10.7±1.8% and abnormal head 5±1.7%. For freezing semen, further 6 ejaculates from each buck were studied with Tris based egg yolk citrate extender. The pooled mean values of motility and viability of post diluted semen for 90 and 120 minutes each for cooling and glycerol equilibration were 73.8±4.8%, 88.1±2.6% and 69.2±6.0%, 85.0±1.7%, respectively. The pooled mean values of post thaw motility and viability with advancement of preservation time were: 0hour 49.0±4.6%, 81.2±1.9%; 2nd day 41±2.2%, 79±1%; 5th day 41±2.2%, 78.6±0.9% and 10th day 41±2.2%, 78.6±0.9%. We concluded from the above study that the seminal attributes and results of post-thaw semen quality were satisfactory and in accordance with other work in foreign countries, which indicated the feasibility of cryopreserving buck semen. For more validation, research with large number of bucks, different types of diluents and freezing trials by removing seminal plasma followed by pregnancy rate is recommended.

Keywords: cryopreservation, Nepalese indigenous Khari (Hill goat) buck, post-thaw semen quality, seminal attributes

Procedia PDF Downloads 388

Authors: Amrita Sen

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In the face of a growing insurgent movement and the perceived failure of the state and the market towards sustainable resource management, a range of decentralized forest management policies was formulated in the last two decades, which recognized the need for community representations within the statutory methods of forest management. The recognition conceded on the virtues of ecological sustainability and traditional environmental knowledge, which were considered to be the principal repositories of the forest dependent communities. The present study, in the light of empirical insights, reflects on the contemporary disjunctions between the preconceived communitarian ethic in environmentalism and the lived reality of forest based life-worlds. Many of the popular as well as dominant ideologies, which have historically shaped the conceptual and theoretical understanding of sociology, needs further perusal in the context of the emerging contours of empirical knowledge, which lends opportunities for substantive reworking and analysis. The image of the community appears to be one of those concepts, an identity which has for long defined perspectives and processes associated with people living together harmoniously in small physical spaces. Through an ethnographic account of the implementation of Joint Forest Management (JFM) in a forest fringe village in Sundarban, the study explores the ways in which the idea of ‘community’ gets transformed through the process of state-making, rendering the necessity of its departure from the standard, conventional definition of homogeneity and internal equity. The study necessitates an attention towards the anthropology of micro-politics, disaggregating an essentially constructivist anthropology of ‘collective identities’, which can render the visibility of political mobilizations plausible within the seemingly culturalist production of communities. The two critical questions that the paper seeks to ask in this context are: how the ‘local’ is constituted within community based conservation practices? Within the efforts of collaborative forest management, how accurately does the depiction of ‘indigenous environmental knowledge’, subscribe to its role of sustainable conservation practices? Reflecting on the execution of JFM in Sundarban, the study critically explores the ways in which the state ceases to be ‘trans-national’ and interacts with the rural life-worlds through its local factions. Simultaneously, the study attempts to articulate the scope of constructing a competing representation of community, shaped by increasing political negotiations and bureaucratic alignments which strains against the usual preoccupations with tradition primordiality and non material culture as well as the amorous construction of indigeneity.

Keywords: community, environmentalism, JFM, state-making, identities, indigenous

Procedia PDF Downloads 184

Authors: Rimel Mwamba, Mohan Gundeti

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Introduction: The use of robot-assisted laparoscopic surgeries (RALS) has largely increased in recent years, offering faster and safer treatment options for pediatric patients. In the field of urology, RALS has shown a significant advantage over laparoscopic and open surgeries but continues to be controversial in pediatric cases due to limited comprehensive data on its use. Methods: In this review, we aim to summarize the factors associated with RALS use in pediatric cases involving pyeloplasty, ureteral reimplantation, heminephrectomy, and lower urinary tract reconstruction. We used PubMed, EMBASE, and the Cochrane Database of Systematic Reviews to systematically search for literature on the topic. We then critically assessed and compiled data on RALS outcomes, complications, and associated factors. Results: To date, numerous comparative studies have been conducted on pediatric RALS, with only one randomized control trial investigating the nuances of robotic use against standard of care treatments. These robotic approaches have shown promise in post-surgical outcomes for pediatric patients undergoing upper and lower urinary tract reconstruction. Barriers to use still persist, however, showcasing a need to increase access to the technology, refine instruments for pediatric use, address cost barriers, and provide proper training for surgeons. Conclusion: RALS providesan opportunity to improve pediatric patient outcomes for numerous urologic complications. Additional studies are required to better compare the use of RALS with current standard practices. Due to the difficult nature of conducting randomized control trials, additional prospective observational studies are needed.

Keywords: pediatric urology, robot-assisted laparoscopic surgeries (RALS), pyeloplasty, ureteral reimplantation, heminephrectomy, and lower urinary tract reconstruction

Procedia PDF Downloads 85

Authors: Paul Lam, Kevin Wong, Chi Him Chan

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Constant practicing and accurate, immediate feedback are the keys to improving students’ speaking skills. However, traditional oral examination often fails to provide such opportunities to students. The traditional, face-to-face oral assessment is often time consuming – attending the oral needs of one student often leads to the negligence of others. Hence, teachers can only provide limited opportunities and feedback to students. Moreover, students’ incentive to practice is also reduced by their anxiety and shyness in speaking the new language. A mobile app was developed to use artificial intelligence (AI) to provide immediate feedback to students’ speaking performance as an attempt to solve the above-mentioned problems. Firstly, it was thought that online exercises would greatly increase the learning opportunities of students as they can now practice more without the needs of teachers’ presence. Secondly, the automatic feedback provided by the AI would enhance students’ motivation to practice as there is an instant evaluation of their performance. Lastly, students should feel less anxious and shy compared to directly practicing oral in front of teachers. Technically, the program made use of speech-to-text functions to generate feedback to students. To be specific, the software analyzes students’ oral input through certain speech-to-text AI engine and then cleans up the results further to the point that can be compared with the targeted text. The mobile app has invited English teachers for the pilot use and asked for their feedback. Preliminary trials indicated that the approach has limitations. Many of the users’ pronunciation were automatically corrected by the speech recognition function as wise guessing is already integrated into many of such systems. Nevertheless, teachers have confidence that the app can be further improved for accuracy. It has the potential to significantly improve oral drilling by giving students more chances to practice. Moreover, they believe that the success of this mobile app confirms the potential to extend the AI-assisted assessment to other language skills, such as writing, reading, and listening.

Keywords: artificial Intelligence, mobile learning, oral assessment, oral practice, speech-to-text function

Procedia PDF Downloads 95

Authors: Jocelyn Li, Xiangyang Li

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We have employed THINC-it® to study the acute effects of Spravato on the cognitive function of patients with severe major depression disorder (MDD). The scores of the four tasks (Spotter, Symbol Check, Code Breaker, Trails) found in THINC-it® were used to measure cognitive function throughout treatment. The patients who participated in this study have tried more than 3 antidepressants without significant improvement before they began Spravato treatment. All patients received 3 doses of 28 mg Spravato 5 minutes apart (84 mg total per treatment) during this study with THINC-it®. The data were collected before the first Spravato administration (T0), 1 hour after the first Spravato administration (T1), and 2 hours after the first Spravato administration (T2) during each treatment. The following data were from 13 patients, with a total of 226 trials in a 2-3 month period. Spravato at 84 mg reduced the scores of Trails, Code Breaker, Symbol Check, and Spotter at T1 by 10-20% in all patients with one exception for a minority of patients in Spotter. At T2, the scores of Trails, Symbol Check, and Spotter were back to 97% of T0 while the score of Code Breaker was back to 92%. Interestingly, we found that the score of Spotter was consistently increased by 17% at T1 in the same 30% of patients in each treatment. We called this change reverse response while the pattern of the other patients, a decline (T1) and then recovery (T2), was called non-reverse response. We also compared the scores at T0 between the first visit and the fifth visit. The T0 scores of all four tasks were improved at visit 5 when compared to visit 1. The scores of Trails, Code Breaker, and Symbol Check at T0 were increased by 14%, 33%, and 14% respectively at visit 5. The score of Code Breaker, which had two trends, improved by 9% in reverse response patients compared to a 27% improvement in non-reverse response patients. To our knowledge, this is the first study done on the impact of Spravato on cognitive function change in major depression patients at this time frame. Whether we can predict future responses to Spravato with THINC-it® merits further study.

Keywords: Spravato, THINC-it, major depressive disorder, cognitive function

Procedia PDF Downloads 108

Authors: Tamer M. Shehata

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Objective: Currently, mucoadhesive microparticles acquired a high interest in both research and pharmaceutical technology fields. Recently, BÜCHI lunched its latest fourth generation nano spray dryer B-90 used for nanoparticle production. B-90 offers an elegant technology combined particle engineering and drying in one step. In our laboratory, we successfully developed a new formulation for metformin hydrochloride, mucoadhesive microparticles utilizing B-90 technology for treatment of type 2-diabetis. Method: Gelatin or sodium alginate, natural occurring polymers with mucoadhesive properties, solely or in combination was used in our formulation trials. Preformulation studies (atomization head mesh size, flow rate, head temperature, polymer solution viscosity and surface tension) and postformulation characters (particle size, flowability, surface scan and dissolution profile) were evaluated. Finally, hypoglycemic effect of the selected formula was evaluated in streptozotocin-induced diabetic rats. Spray head with 7 µm hole, flow rate of 3.5 mL/min and head temperature 120 ºC were selected. Polymer viscosity was less than 11.5 cP with surface tension less than 70.1 dyne/cm. Result: Discrete, non aggregated particles and free flowing powders with particle size was less than 2000 nm were obtained. Gelatin and sodium alginate combination in ratio 1:3 were successfully sustained the in vitro release profile of the drug. Hypoglycemic evaluation of the previous formula, showed a significant reduction of blood glucose level over 24 h. Conclusion: B-90 technology can open a new era of , mucoadhesive microparticles preparation offering convenient dosage form that can enhance compliance of type 2 diabetic patients.

Keywords: mucoadhesive, microparticles, technology, diabetis

Procedia PDF Downloads 281

Authors: Maatouk Mohamed, Nouira Mariem, Hamdi Kbir Gh, Mahjoubi M. F., Ben Moussa M.

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Background and aim: Preoperative biliary drainage (PBD) has been introduced to lower bilirubin levels and to control the negative effects of obstructive jaundice in patients with malignant obstructive jaundice undergoing pancreaticoduodenectomy (PD). The optimal time interval between PBD and PD is still not clear. Delaying surgery by 4 to 6 weeks is the commonly accepted practice. However, delayed PD has been shown to decrease the rate of resection and adversely affect the tumor grading and prognosis. Thus, the purpose of our systematic review and meta-analysis was to evaluate the optimal period for PBD prior to PD: short or prolonged in terms of postoperative morbidity and survival outcomes. Methods: Trials were searched in PubMed, Science Direct, Google Scholar, and Cochrane Library until November 2022. Studies using PBD in patients with malignant obstructive jaundice that compared short duration group (SDG) (surgery performed within 3-4 weeks) with prolonged duration group (PDG) (at least 3-4 weeks after PBD) were included in this study. The risk of bias was assessed using the Rob v2 and Robins-I tools. The priori protocol was published in PROSPERO (ID: CRD42022381405). Results: Seven studies comprising 1625 patients (SDG 870, PDG 882) were included. All studies were non-randomized, and only one was prospective. No significant differences were observed between the SDG and PDG in mortality (OR= 0.59; 95% CI [0.30, 1.17], p=0.13), major morbidity (Chi² = 30.28, p <0.00001; I² = 87%), pancreatic fistula (Chi² = 6.61, p = 0.25); I² = 24%), post pancreatectomy haemorrhage (OR= 1.16; 95% CI [0.67, 2.01], p=0.59), positive drainage culture (OR= 0.36; 95% CI [0.10, 1.32], p=0.12), septic complications (OR= 0.78; 95% CI [0.23, 2.72], p=0.70), wound infection (OR= 0.08, p=0.07), operative time (MD= 0.21; p=0.21). Conclusion: Early surgery within 3 or 4 weeks after biliary drainage is both safe and effective. Thus, it is reasonable to suggest early surgery following PBD for patients having resectable periampullary cancers.

Keywords: preoperative biliary drainage, pancreatic cancer, pancreatic surgery, complication

Procedia PDF Downloads 60

Authors: B. Yermekbayeva, A. Gulyayaev, T. Nurgozhin, C. Bektur

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Cytisine aminophosphonate under the name "Cytafat" was approved for clinical trials in Republic of Kazakhstan as a putative liver protecting drug for the treatment of acute toxic hepatitis. A method of conducting the clinical trial is a double blind study. Total number of patients -71, aged from 16 to 56 years. Research on healthy volunteers determined the maximal tolerable doze of "Cytafat" as 200 mg/kg. Side effects when administered at high dozes (100-200 mg/kg) are tachycardia and increase of arterial blood pressure. The drug is tested in the treatment of 28 patients with a syndrome of hepatocellular failure (a poisoning with substitutes of alcohol, rat poison, or medical products). "Cytafat" was intravenously administered at a dose of 10 mg/kg in 200 ml of 5 % glucose solution once daily. The number of administrations: 1-3. In the comparison group, 23 patients were treated intravenously once a day with “Essenciale H” at a dose of 10 ml. 20 patients received a placebo (10 ml of glucose intravenously). In all cases of toxic hepatopathology the significant positive clinical effect of the testing drug distinguishable from placebo and surpassing the alternative was observed. Within a day after administration a sharp reduction of cytolitic syndrome parameters (ALT, AST, alkaline phosphatase, thymol turbidity test, GGT) was registered, a reduction of the severity of cholestatic syndrome (bilirubin decreased) was recorded, significantly decreased indices of lipid peroxidation. The following day, in all cases the positive dynamics was determined with ultrasound study (reduction of diffuse changes and events of reactive pancreatitis), hepatomegaly disappeared. Normalization of all parameters occurred in 2-3 times faster, than when using the drug "Essenciale H" and placebo. Average term of elimination of toxic hepatopathy when using the drug "Cytafat" -2,8 days, "Essenciale H" -7,2 days, and placebo -10,6 days. The new drug "Cytafat" has expressed cytoprotective properties.

Keywords: cytisine, cytoprotection, hepatopathy, hepatoprotection

Procedia PDF Downloads 355

Authors: Akshay Patil

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Objective: Mediation analysis identifies causal pathways by testing the relationships between the NCR, the OS, and an intermediate variable that mediates the relationship between the Nimotuzumab-cisplatin-radiation (NCR) and OS. Introduction: In randomized controlled trials, the primary interest is in the mechanisms by which an intervention exerts its effects on the outcomes. Clinicians are often interested in how the intervention works (or why it does not work) through hypothesized causal mechanisms. In this work, we highlight the value of understanding causal mechanisms in randomized trial by applying causal mediation analysis in a randomized trial in oncology. Methods: Data was obtained from a phase III randomized trial (Subgroup of HPVNOCP). NCR is reported to significantly improve the OS of patients locally advanced head and neck cancer patients undergoing definitive chemoradiation. Here, based on trial data, the mediating effect of NCR on patient overall survival was systematically quantified through progression-free survival(PFS), disease free survival (DFS), Loco-regional failure (LRF), and the disease control rate (DCR), Overall response rate (ORR). Effects of potential mediators on the HR for OS with NCR versus cisplatin-radiation (CR) were analyzed by Cox regression models. Statistical analyses were performed using R software Version 3.6.3 (The R Foundation for Statistical Computing) Results: Effects of potential mediator PFS was an association between NCR treatment and OS, with an indirect-effect (IE) 0.76(0.62 – 0.95), which mediated 60.69% of the treatment effect. Taking into account baseline confounders, the overall adjusted hazard ratio of death was 0.64 (95% CI: 0.43 – 0.96; P=0.03). The DFS was also a significant mediator and had an IE 0.77 (95% CI; 0.62-0.93), 58% mediated). Smaller mediation effects (maximum 27%) were observed for LRF with IE 0.88(0.74 – 1.06). Both DCR and ORR mediated 10% and 15%, respectively, of the effect of NCR vs. CR on the OS with IE 0.65 (95% CI; 0.81 – 1.08) and 0.94(95% CI; 0.79 – 1.04). Conclusion: Our findings suggest that PFS and DFS were the most important mediators of the OS with nimotuzumab to weekly cisplatin-radiation in HPVNOCP.

Keywords: mediation analysis, cancer data, survival, NCR, HPV negative oropharyngeal

Procedia PDF Downloads 131

Authors: Memoona Ramzan, Bushra Tabassum, Anwar Khan, Muhammad Tariq, Mudassar Fareed Awan, Idrees Ahmad Nasir, Zahida Qamar, Naila Shahid, Tayyab Husnain

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Biological control is a novel approach being used in crop protection nowadays. Bacteria like Bacillus and Pseudomonas are reported for this purpose and few of their products are commercially available too. Rhizosphere and phyllosphere of healthy cotton plants were used as a source to isolate bacteria capable of exhibiting properties worthy for selection as biocontrol agent. For this purpose all isolated strains were screened for the activities like phosphate solubilization, Indole acetic acid (IAA) production and biocontrol against fungi. Two strains S1HL3 and S1HL4 showed phosphate solubilization and IAA production simultaneously while two other JS2HR4 and JS3HR2 were good inhibitors of fungal pathogens. Through biochemical and molecular characterization these bacteria were identified as P. aeruginosa, Burkholderia and Bacillus respectively. In green house trials of these isolates against Cotton leaf curl virus (CLCuV), seven treatments including individual bacterial isolate and consortia were included. Treated plants were healthy as compared to control plants in which upto 74% CLCuV symptomatic plants exist. Maximum inhibition of CLCuV was observed in T7 treated plants where viral load was only 0.4% as compared to control where viral load was upto 74%. This treatment consortium included Bacillus and Pseudomonas isolates; S1HL3, S1HL4, JS2HR4 and JS3HR2. Principal Component Biplot depicted highly significant correlation between percentage viral load and the disease incidence.

Keywords: cotton leaf curl virus, biological control, bacillus, pseudomonas

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Authors: Anika Chebrolu

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Mono-targeted drugs can be of limited efficacy against complex diseases. Recently, multi-target drug design has been approached as a promising tool to fight against these challenging diseases. However, the scope of current computational approaches for multi-target drug design is limited. DeepLig presents a de-novo drug discovery platform that uses reinforcement learning to generate and optimize novel, potent, and multitargeted drug candidates against protein targets. DeepLig’s model consists of two networks in interplay: a generative network and a predictive network. The generative network, a Stack- Augmented Recurrent Neural Network, utilizes a stack memory unit to remember and recognize molecular patterns when generating novel ligands from scratch. The generative network passes each newly created ligand to the predictive network, which then uses multiple Graph Attention Networks simultaneously to forecast the average binding affinity of the generated ligand towards multiple target proteins. With each iteration, given feedback from the predictive network, the generative network learns to optimize itself to create molecules with a higher average binding affinity towards multiple proteins. DeepLig was evaluated based on its ability to generate multi-target ligands against two distinct proteins, multi-target ligands against three distinct proteins, and multi-target ligands against two distinct binding pockets on the same protein. With each test case, DeepLig was able to create a library of valid, synthetically accessible, and novel molecules with optimal and equipotent binding energies. We propose that DeepLig provides an effective approach to design multi-targeted drug therapies that can potentially show higher success rates during in-vitro trials.

Keywords: drug design, multitargeticity, de-novo, reinforcement learning

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Authors: Abhishek Pandey

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Ibuprofen and Acetaminophen is widely used as prescription & non-prescription medicine. Ibuprofen mainly used in the treatment of mild to moderate pain related to headache, migraine, postoperative condition and in the management of spondylitis, osteoarthritis and rheumatoid arthritis. Acetaminophen is used as an analgesic and antipyretic drug. Ibuprofen having high tendency of sticking to punches of tablet punching machine while Acetaminophen is not ordinarily compressible to tablet formulation because Acetaminophen crystals are very hard and brittle in nature and fracture very easily when compressed producing capping and laminating tablet defects therefore wet granulation method is used to make them compressible. The aim of study was to prepare Ibuprofen and Acetaminophen tablets by direct compression and top spray granulation technique. In this Investigation tablets were prepared by using directly compressible grade excipients. Dibasic calcium phosphate, lactose anhydrous (DCL21), microcrystalline cellulose (Avicel PH 101). In order to obtain best or optimized formulation, nine different formulations were generated among them batch F7, F8, F9 shows good results and within the acceptable limit. Formulation (F7) selected as optimize product on the basis of dissolution study. Furtherly, directly compressible granules of both drugs were prepared by using top spray granulation technique in fluidized bed processor equipment and compressed .In order to obtain best product process optimization was carried out by performing four trials in which various parameters like inlet air temperature, spray rate, peristaltic pump rpm, % LOD, properties of granules, blending time and hardness were optimized. Batch T3 coined as optimized batch on the basis physical & chemical evaluation. Finally formulations prepared by both techniques were compared.

Keywords: direct compression, top spray granulation, process optimization, blending time

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Authors: N. Seemuang, T. McLeay, T. Slatter

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Worn tools have a direct effect on the surface finish and part accuracy. Tool condition monitoring systems have been developed over a long period and used to avoid a loss of productivity resulting from using a worn tool. However, the majority of tool monitoring research has applied expensive sensing systems not suitable for production. In this work, the cutting sound in turning machine was studied using microphone. Machining trials using seven cutting conditions were conducted until the observable flank wear width (FWW) on the main cutting edge exceeded 0.4 mm. The cutting inserts were removed from the tool holder and the flank wear width was measured optically. A microphone with built-in preamplifier was used to record the machining sound of EN24 steel being face turned by a CNC lathe in a wet cutting condition using constant surface speed control. The sound was sampled at 50 kS/s and all sound signals recorded from microphone were transformed into the frequency domain by FFT in order to establish the frequency content in the audio signature that could be then used for tool condition monitoring. The extracted feature from audio signal was compared to the flank wear progression on the cutting inserts. The spectrogram reveals a promising feature, named as ‘spindle noise’, which emits from the main spindle motor of turning machine. The spindle noise frequency was detected at 5.86 kHz of regardless of cutting conditions used on this particular CNC lathe. Varying cutting speed and feed rate have an influence on the magnitude of power spectrum of spindle noise. The magnitude of spindle noise frequency alters in conjunction with the tool wear progression. The magnitude increases significantly in the transition state between steady-state wear and severe wear. This could be used as a warning signal to prepare for tool replacement or adapt cutting parameters to extend tool life.

Keywords: tool wear, flank wear, condition monitoring, spindle noise

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Authors: Hushyar Azari

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Aim and background: Deep brain stimulation (DBS) is regarded as an important therapeutic choice for Parkinson's disease (PD). The two most common targets for DBS are the subthalamic nucleus (STN) and globus pallidus (GPi). This review was conducted to compare the clinical effectiveness of these two targets. Methods: A systematic literature search in electronic databases: Embase, Cochrane Library and PubMed were restricted to English language publications 2010 to 2021. Specified MeSH terms were searched in all databases. Studies which evaluated the Unified Parkinson's Disease Rating Scale (UPDRS) III were selected by meeting the following criteria: (1) compared both GPi and STN DBS; (2) had at least three months follow-up period; (3)at least five participants in each group; (4)conducted after 2010. Study quality assessment was performed using the Modified Jadad Scale. Results: 3577 potentially relevant articles were identified, of these, 3569 were excluded based on title and abstract, duplicate and unsuitable article removal. Eight articles satisfied the inclusion criteria and were scrutinized (458 PD patients). According to Modified Jadad Scale, the majority of included studies had low evidence quality which was a limitation of this review. 5 studies reported no statistically significant between-group difference for improvements in UPDRS ш scores. At the same time, there were some results in terms of pain, action tremor, rigidity, and urinary symptoms, which indicated that STN DBS might be a better choice. Regarding the adverse effects, GPi was superior. Conclusion: It is clear that other larger randomized clinical trials with longer follow-up periods and control groups are needed to decide which target is more efficient for deep brain stimulation in Parkinson’s disease and imposes fewer adverse effects on the patients. Meanwhile, STN seems more reasonable according to the results of this systematic review.

Keywords: brain stimulation, globus pallidus, Parkinson's disease, subthalamic nucleus

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Authors: Muhammad Umer, Aishwariya Giri, Umaiyma Rakha

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Mimicked from the humpback whale flippers, the application of tubercle technology is seen to be particularly advantageous at high angles of attack. This particular advantage is of paramount importance when it comes to structures producing lift at high angles of attack. This characteristic of the technology makes it ideal for horizontal stabilizers and selecting the same as the subject of study to identify and exploit the advantage highlighted by researchers on airfoils, this project aims in establishing a foundation for the application of the bio-mimicked technology on an existing aircraft. Using a baseline and 2 tubercle configuration integrated models, the project targets to achieve the twin aim of highlighting the possibility and merits over the base model and also choosing the right configuration in providing the best characteristic suitable for high angles of attack. To facilitate this study, the required models are generated using Solidworks followed by trials in a virtual aerodynamic environment using Fluent in Ansys for resolving the project objectives. Following a structured plan, the aim is to initially identify the advantages mathematically and then selecting the optimal configuration, simulate the end configuration at angles mimicking the actual operation envelope for the particular structure. Upon simulating the baseline configuration at various angles of attack, the stall angle was determined to be 22 degrees. Thus, the tubercle configurations will be simulated and compared at 4 different angles of attacks: 0, 10, 20, and 24. Further, after providing the optimum configuration of horizontal stabilizers, this study aims at the integration of aircraft structure so that the results better imply the end deliverables of real life application. This draws the project scope closer at this point into longitudinal static stability considerations and improvements in the manoeuvrability characteristics. The objective of the study is to achieve a complete overview ready for real life application with marked benefits obtainable from bio morphing of the tubercle technology.

Keywords: flow simulation, horizontal stabilizer, stability enhancement, tubercle

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Authors: Kayode Fatokun, Nozipho N. Motsa

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Field experiments were carried out during the summer/autumn (first trial) and winter/spring (second trial) seasons of 2019 and 2021 inDlangubo, Ngwelezane, and Mtubatubaareas of KwaZulu-Natal Province of South Africa to study the drought amelioration effects and impact of 2 locally available organic wastes [filter cake (FC) and macadamia husk compost (MHC)] on the productivity, and physiological responses of 4 orange-fleshed sweet potato cultivars (Buregard cv., Impilo, W-119 and 199062.1). The effects of FC and MHC were compared with that of inorganic fertilizer (IF) [2:3:2 (30)], FC+IF, MHC+IF, and control. The soil amendments were applied in the first trials only. Climatic data such as humidity, temperature, and rainfall were taken via remote sensing. The results of the first trial indicated that filter cake and IF significantly performed better than MHC. While the strength of filter cake may be attributable to its rich array of mineral nutrients such as calcium, magnesium, potassium, sodium, zinc, copper, manganese, iron, and phosphorus. The little performance from MHC may be attributable to its water holding capacity. Also, a positive correction occurred between the yield of the test OFSP cultivars and climatic factors such as rainfall, NDVI, and NDWI values. Whereas the inorganic fertilizer did not have any significant effect on the growth and productivity of any of the tested sweet potato cultivars in the second trial; FC, and MHC largely maintained their significant performances. In conclusion, the use of FC is highly recommended in the production of the test orange-fleshed sweet potato cultivars. Also, the study indicated that both FC and MHC may not only supply the needed plant nutrients but has the capacity to reduce the impact of drought on the growth of the test cultivars. These findings are of great value to farmers, especially the resource-poorones.

Keywords: amendments, drought, filter cake, macadamia husk compost, sweet potato

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Authors: Paula Lopez-Arce, Hector Altamirano, Dimitrios Rovas, James Berry, Bryan Hindle, Steven Hodgson

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Efficient mould remediation and accurate moisture diagnostics leading to condensation and mould growth in dwellings are largely untapped. Number of factors are contributing to the rising trend of excessive moisture in homes mainly linked with modern living, increased levels of occupation and rising fuel costs, as well as making homes more energy efficient. Environmental monitoring by means of data collection though loggers sensors and survey forms has been performed in a range of buildings from different UK regions. Air and surface temperature and relative humidity values of residential areas affected by condensation and/or mould issues were recorded. Additional measurements were taken through different trials changing type, location, and position of loggers. In some instances, IR thermal images and ventilation rates have also been acquired. Results have been interpreted together with environmental key parameters by processing and connecting data from loggers and survey questionnaires, both in buildings with and without moisture issues. Monitoring exercises carried out during Winter and Spring time show the importance of developing and following accurate protocols for guidance to obtain consistent, repeatable and comparable results and to improve the performance of environmental monitoring. A model and a protocol are being developed to build a diagnostic tool with the goal of performing a simple but precise residential atmospheric moisture diagnostics to distinguish the cause entailing condensation and mould generation, i.e., ventilation, insulation or heating systems issue. This research shows the relevance of monitoring and processing environmental data to assign moisture risk levels and determine the origin of condensation or mould when dealing with a building atmospheric moisture excess.

Keywords: environmental monitoring, atmospheric moisture, protocols, mould

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Authors: Yu-Ju Tsai, Ching-Chun Wang, Wen-Tzu Tang, Huei-Ming Chai

Abstract:

A pronated foot is frequently associated with a hypermobile first ray, then developing further severe foot problems. Low-Dye taping with athletic tape has been widely used to restrict excessive first ray motion and re-build height of the medial longitudinal arch in general population with pronated foot. It is not the case, however, for sprinters since they feel too much restriction of foot motions. Currently, the kinesio tape, more elastic than the athletic tape, has been widely used to re-adjust joint positions. It was interesting whether modified low-Dye taping using kinesio tape was beneficial for altering first ray mobility and still giving enough arch support. The purpose of this study was to investigate the effect of modified low-Dye taping on first ray mobility test and 60-m sprint time for sprinters with pronated foot. The significance of this study provides new insight into a treatment alternative of modified low-Dye taping for sprinter with pronated foot. Ten young male sprinters, aged 20.8±1.6 years, with pronated foot were recruited for this study. The pronated foot was defined as the foot that the navicular drop test was greater than 1.0 cm. Three optic shutters were placed at the start, 30-m, and 60-m sites to record sprint time. All participants were asked to complete 3 trials of the 60-m dash with both taping and non-taping conditions in a random order. The low-Dye taping was applied using the method postulated by Ralph Dye in 1939 except the kinesio tape was used instead. All outcome variables were recorded for taping and non-taping conditions. Paired t-tests were used to analyze all outcome variables between 2 conditions. Although there were no statistically significant differences in dorsal and plantar mobility between taping and non-taping conditions, a statistical significance was found in a total range of motion (dorsiflexion plus plantarflexion angle) of the first ray when a modified low-Dye taping was applied (p < 0.05). Time to complete 60-m sprint was significantly increased with low-Dye taping (p < 0.05) while no significance was found for time to 30-m. it indicated that modified low-Dye taping changed maximum sprint speed of 60-m dash. Conclusively, modified low-Dye taping was capable of increasing first ray mobility and further altered maximum sprint speed.

Keywords: first ray mobility, kinesio taping, pronated foot, sprint time

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Authors: Denis Duagi, Ben Carter, Maria Farrelly, Stephen Lisk, June S. L. Brown

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Background: Adolescence represents a distinctive phase of development, and variables linked to this developmental period could affect the efficiency of prevention and treatment for depression and anxiety, as well as the long-term prognosis. The objectives of this study were to investigate the long-term effectiveness of psychosocial interventions for adolescents on depression and anxiety symptoms and to assess the influence of different intervention parameters on the long-term effects. Methods: Searches were carried out on the 11ᵗʰ of August 2022 using five databases (Cochrane Library, Embase, Medline, PsychInfo, Web of Science), as well as trial registers. Randomized controlled trials of psychosocial interventions targeting specifically adolescents were included if they assessed outcomes at 1-year post-intervention or more. The Cochrane risk of bias-2 quality assessment tool was used. The primary outcome was depression, and studies were pooled using a standardised mean difference, with an associated 95% confidence interval, p-value, and I². The study protocol was pre-registered (CRD42022348668). Findings: A total of 57 reports (n= 46,678 participants) were included in the review. Psychosocial interventions led to small reductions in depressive symptoms, with a standardised mean difference (SMD) at 1-year of -0.08 (95%CI -0.20, -0.03, p=0.002, I²=72%), 18-months SMD=-0.12, 95% CI -0.22, -0.01, p=0.03, I²=63%) and 2-years SMD=-0.12 (95% CI -0.20, -0.03, p=0.01, I²=68%). Sub-group analyses indicated that targeted interventions produced stronger effects, particularly when delivered by trained mental health professionals (K=18, SMD=-0.24, 95% CI -0.38, -0.10, p=0.001, I²=60%). No effects were detected for anxiety at any assessment. Conclusion: Psychosocial interventions specifically targeting adolescents were shown to have small but positive effects on depression symptoms but not anxiety symptoms, which were sustained for up to 2 years. These findings highlight the potential population-level preventive effects if such psychosocial interventions become widely implemented in accessible settings such as schools.

Keywords: psychosocial, adolescent, interventions, depression, anxiety, meta-analysis, randomized controlled trial

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Authors: Mohammed S. Mohammed, Asmaa M. S. Mohammed

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Background: To achieve the quality of cancer care, the oncologic academic programs should be continuously developed with establishing new ones. We highlighted three disciplines, Clinical nutrition, medical biophysics and radiobiology and Psycho-oncology programs; without a doubt, the Egyptian National Cancer Institute, in ‎the accreditation era, will be establishing them ‎ due to their importance in improving the skills of cancer practitioners. Methods: The first suggested program in Clinical Nutrition that is dealing with the assessment of the patient's well-being before, during and after treatment to avoid the defects in the metabolism resulting from the cancer disease and its treatment by giving the supplements in the patient's diet. The second program is Medical Biophysics and Radiobiology, which there's no denying that it ‎is ‎provided ‎in Cairo University as a good program in the faculty of science but lacks the clinical ‎practice. Hence, it is probably better to establish this program in our institute to ‎improve the ‎practitioner skills and introduce a tailored radiation therapy regimen for every patient according to ‎their characteristic profile.‎ While patients are receiving their treatment, the risk of post-traumatic stress disorder arises, so the importance of the third program, Psycho-Oncology, is clearly obtained. This program is concerned with the psychological, social, behavioral, and ethical aspects of cancer. The area of multi-disciplinary interest has boundaries with the major specialties in oncology: the clinical disciplines (surgery, medicine, pediatrics, and radiotherapy), epidemiology, immunology, endocrinology, biology, pathology, bioethics, palliative care, rehabilitation medicine, clinical trials research and decision making, as well as psychiatry and psychology. Results: It is a prospective academic plan which is compatible with the institutional vision and its strategic plan. Conclusion: In this context, evaluating and understanding the suggested academic programs has become a mandatory part of cancer care. And it is essential to be provided by the NCI.

Keywords: clinical nutrition, psycho-oncology, medical biophysics and radiobiology, medical education

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Authors: Abeer F. Almarzouki, Christopher A. Brown, Richard J. Brown, Anthony K. P. Jones

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Although relief is commonly assumed to be a direct reflection of pain reduction, it seems to be driven by complex emotional interactions in which pain reduction is only one component. For example, termination of a painful/aversive event may be relieving and rewarding. Accordingly, in this study, whether terminating an aversive negative prediction of pain would be reflected in a greater relief experience was investigated, with a view to separating apart the effects of the manipulation on pain and relief. We use aversive conditioning paradigm to investigate the perception of relief in an aversive (threat) vs. positive context. Participants received positive predictors of a non-painful outcome which were presented within either a congruent positive (non-painful) context or an incongruent threat (painful) context that had been previously conditioned; trials followed by identical laser stimuli on both conditions. Participants were asked to rate the perceived intensity of pain as well as their perception of relief in response to the cue predicting the outcome. Results demonstrated that participants reported more pain in the aversive context compared to the positive context. Conversely, participants reported more relief in the aversive context compares to the neutral context. The rating of relief in the threat context was not correlated with pain reports. The results suggest that relief is not dependant on pain intensity. Consistent with this, relief in the threat context was greater than that in the positive expectancy condition, while the opposite pattern was obtained for the pain ratings. The value of relief in this study is better appreciated in the context of an impending negative threat, which is apparent in the higher pain ratings in the prior negative expectancy compared to the positive expectancy condition. Moreover, the more threatening the context (as manifested by higher unpleasantness/higher state anxiety scores), the more the relief is appreciated. The importance of the study highlights the importance of exploring relief and pain intensity in monitoring separately or evaluating pain-related suffering. The results also illustrate that the perception of painful input may largely be shaped by the context and not necessarily stimulus-related.

Keywords: aversive context, pain, predictions, relief

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Authors: Xinxiu Li, Chuqian Zheng, Yanyan Qian, Hong Fan

Abstract:

Objectives: In hepatocellular carcinoma (HCC), oncogenes are continuously and robustly transcribed due to aberrant expression of essential components of the trans-acting super-enhancers (SE) complex. Preclinical and clinical trials are now being conducted on small-molecule inhibitors that target core-transcriptional components, including as transcriptional bromodomain protein 4 (BRD4) and cyclin-dependent kinase 7 (CDK7), in a number of malignant tumors. This study aims to explore whether co-overexpression of BRD4 and CDK7 is a potential marker of worse prognosis and a combined therapeutic target in HCC. Methods: The expression pattern of BRD4 and CDK7 and their correlation with prognosis in HCC were analyzed by RNA sequencing data and survival data of HCC patients from TCGA and GEO datasets. The protein levels of BRD4 and CDK7 were determined by immunohistochemistry (IHC), and survival data of patients were analyzed using the Kaplan-Meier method. The mRNA expression levels of genes in HCC cell lines were evaluated by quantitative PCR (q-PCR). CCK-8 and colony formation assays were conducted to assess cell proliferation of HCC upon treatment with BRD4 inhibitor JQ1 or/and CDK7 inhibitor THZ1. Results: It was shown that BRD4 and CDK7 were often overexpressed in HCCs and were associated with poor prognosis of HCC by analyzing the TCGA and GEO datasets. BRD4 or CDK7 overexpression was related to a lower survival rate. It's interesting to note that co-overexpression of CDK7 and BRD4 was a worse prognostic factor in HCC. Treatment with JQ1 or THZ1 alone had an inhibitory effect on cell proliferation; however, when JQ1 and THZ1 were combined, there was a more notable suppression of cell growth. At the same time, the combined use of JQ1 and THZ1 synergistically suppresses the expression of HCC driver genes. Conclusion: Our research revealed that BRD4 and CDK7 coupled can be a useful biomarker in HCC prognosis and the combination of JQ1 and THZ1 can be a promising therapeutic therapy against HCC.

Keywords: BRD4, CDK7, cell proliferation, combined inhibition

Procedia PDF Downloads 46