Search results for: Clinical Application

Authors: Gloria Pinilla, Jose Manuel Baena, Patricia Gálvez-Martín, Juan Antonio Marchad

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Cartilage is a dense connective tissue with limited self-repair properties. Currently, the therapeutic use of autologous or allogenic chondrocytes makes up an alternative therapy to the pharmacological treatment. The design of a bioprinted 3D cartilage with chondrocytes and biodegradable biomaterials offers a new therapeutic alternative able of bridging the limitations of current therapies in the field. We have developed an enhanced printing processes-Injection Volume Filling (IVF) to increase the viability and survival of the cells when working with high-temperature thermoplastics without the limitation of the scaffold geometry in contact with cells. We have demonstrated the viability of the printing process using chondrocytes for cartilage regeneration. This development will accelerate the clinical uptake of the technology and overcomes the current limitation when using thermoplastics as scaffolds. An alginate-based hydrogel combined with human chondrocytes (isolated from osteoarthritis patients) was formulated as bioink-A and the polylactic acid as bioink-B. The bioprinting process was carried out with the REGEMAT V1 bioprinter (Regemat 3D, Granada-Spain) through a IVF. The printing capacity of the bioprinting plus the viability and cell proliferation of bioprinted chondrociytes was evaluated after five weeks by confocal microscopy and Alamar Blue Assay (Biorad). Results showed that the IVF process does not decrease the cell viability of the chondrocytes during the printing process as the cells do not have contact with the thermoplastic at elevated temperatures. The viability and cellular proliferation of the bioprinted artificial 3D cartilage increased after 5 weeks. In conclusion, this study demonstrates the potential use of Regemat V1 for 3D bioprinting of cartilage and the viability of bioprinted chondrocytes in the scaffolds for application in regenerative medicine.

Keywords: cartilage regeneration, bioprinting, bioink, scaffold, chondrocyte

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Authors: Oscar Vega Camacho, Andrea Vargas Guevara, Ellery Rowina Ariza

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This paper presents the application of finite dynamic programming, specifically the "Markov Chain" model, as part of the decision making process of a company in the cosmetics sector located in the vicinity of Bogota DC. The objective of this process was to decide whether the company should completely reconstruct its wastewater treatment plant or instead optimize the plant through the addition of equipment. The goal of both of these options was to make the required improvements in order to comply with parameters established by national legislation regarding the treatment of waste before it is released into the environment. This technique will allow the company to select the best option and implement a solution for the processing of waste to minimize environmental damage and the acquisition and implementation costs.

Keywords: decision making, Markov chain, optimization, wastewater

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Authors: Lizelle Ramaccio Calvino

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Article 3 of the United Nations Convention on the Rights of Child states that 'The best interests of the child must be a top priority in all decisions and actions that affect children.' This stance is also echoed in terms of article 20 of the African Charter on the Rights and Welfare of the Child. South Africa, as a signatory of the aforesaid international and national conventions, constitutionalised the best interest of the child in terms of section 28(2) of the Republic of South Africa, 1996. Section 28(2) provides that '[A] child’s best interests are of paramount importance in every matter concerning the child.' The application of 'the best interests of the child' principle is consequently applicable in all fields of South African law, including matrimonial law. Two separate but equal Acts regulate civil marriages in South Africa, namely the Marriage Act 25 of 1961 and the Civil Union Act 17 of 2006. Customary marriages are regulated by the Recognition of Customary Marriages Act 120 of 1998. In terms of the Marriage Act and the Recognition of Customary Marriages Act, a minor may (provided he/she obtains the required consent) enter into a marriage. Despite the aforesaid, section 1 of the Civil Union Act categorically prohibits a minor from entering into a civil union. The article will first determine whether the ban of minors from entering into a civil union undermines the 'the best interests of the child' principle, and if so, whether it is in violation of the Constitution as well as international and national conventions. In addition, the article will critically analyse whether the application of the Marriage Act and the Civil Union Act (dual Acts) result in disparity within the South African marriage law framework, and if so, whether such discrepancy violates same-sex couples’ right (in particular a same-sex minor) to equality before the law and to have their dignity protected. The article intends, through the application of a qualitative research methodology and by way of a comparative analyses of international and domestic laws, consider whether a single well-defined structure such as the Dutch marriage law system would not be an improved alternative to address the existing paradox resulting from the application of an Act that undermines 'the best interest of the child' principle. Ultimately the article proposes recommendations for matrimonial law reform.

Keywords: best interests of the child, civil marriage, civil union, minor

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Authors: Parsa Mahdavi, M. Amin Hariri-Ardebili

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The development of accurate machine learning and deep learning models traditionally demands hands-on expertise and a solid background to fine-tune hyperparameters. With the continuous expansion of datasets in various scientific and engineering domains, researchers increasingly turn to machine learning methods to unveil hidden insights that may elude classic regression techniques. This surge in adoption raises concerns about the adequacy of the resultant meta-models and, consequently, the interpretation of the findings. In response to these challenges, automated machine learning (AutoML) emerges as a promising solution, aiming to construct machine learning models with minimal intervention or guidance from human experts. AutoML encompasses crucial stages such as data preparation, feature engineering, hyperparameter optimization, and neural architecture search. This paper provides a comprehensive overview of the principles underpinning AutoML, surveying several widely-used AutoML platforms. Additionally, the paper offers a glimpse into the application of AutoML on various engineering datasets. By comparing these results with those obtained through classical machine learning methods, the paper quantifies the uncertainties inherent in the application of a single ML model versus the holistic approach provided by AutoML. These examples showcase the efficacy of AutoML in extracting meaningful patterns and insights, emphasizing its potential to revolutionize the way we approach and analyze complex datasets.

Keywords: automated machine learning, uncertainty, engineering dataset, regression

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Authors: Choon Seong Ng, P. Petrick, C. L. Lau

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Background: Carbapenem-resistant isolates have been increasingly reported recently. Carbapenem stewardship is designed to optimize its usage particularly among medical wards with high prevalence of carbapenem prescriptions to combat such emerging resistance. Carbapenem stewardship programmes (CSP) can reduce antibiotic use but clinical outcome of such measures needs further evaluation. We examined this in a prospective manner using feedback mechanism. Methods: Our single-center prospective cohort study involved all carbapenem prescriptions across the medical wards (including medical patients admitted to intensive care unit) in a tertiary university hospital setting. The impact of such stewardship was analysed according to the accepted and the rejected groups. The primary endpoint was safety. Safety measure applied in this study was the death at 1 month. Secondary endpoints included length of hospitalisation and readmission. Results: Over the 19 months’ period, input from 144 carbapenem prescriptions was analysed on the basis of acceptance of our CSP recommendations on the use of carbapenems. Recommendations made were as follows : de-escalation of carbapenem; stopping the carbapenem; use for a short duration of 5-7 days; required prolonged duration in the case of carbapenem-sensitive Extended Spectrum Beta-Lactamases bacteremia; dose adjustment; and surgical intervention for removal of septic foci. De-escalation, shorten duration of carbapenem and carbapenem cessation comprised 79% of the recommendations. Acceptance rate was 57%. Those who accepted CSP recommendations had no increase in mortality (p = 0.92), had a shorter length of hospital stay (LOS) and had cost-saving. Infection-related deaths were found to be higher among those in the rejected group. Moreover, three rejected cases (6%) among all non-indicated cases (n = 50) were found to have developed carbapenem-resistant isolates. Lastly, Pitt’s bacteremia score appeared to be a key element affecting the carbapenem prescription’s behaviour in this trial. Conclusions: Carbapenem stewardship program in the medical wards not only saves money, but most importantly it is safe and does not harm the patients with added benefits of reducing the length of hospital stay. However, more time is needed to engage the primary clinical teams by formal clinical presentation and immediate personal feedback by senior Infectious Disease (ID) personnel to increase its acceptance.

Keywords: audit and feedback, carbapenem stewardship, medical wards, university hospital

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Authors: Mohhamed El Habib Labdouni

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Introduction: Co-infection with VIH and tuberculosis poses one of the major ongoing challenges for global TB and AIDS prevention and control. The objective of this study is to raise the issue of the resurgence of TB, in People living with VIH supported in a referent center in western Algeria. Its epidemiological, clinical, biological and radiological new trends, and to compare the mortality rate between early and delayed ART. Methods: It was a prospective study, during 36 months from the 01st/01/2012 to 31st/12/2014, by identifying and analyzing cases of TB-VIH co-infection. Our population was devised in two groups/ early ART and delayed ART. The primary and secondary endpoints were analyzed with Kaplan-Meier curves and log-rank test the period of follow up, which was fixed at 300 weeks. Results: Sixty cases of co-infection TB -VIH were enrolled in our study: 78.3% had pulmonary tuberculosis associated with extra-pulmonary, 13.3% had only pulmonary tuberculosis and 08.3% presented strictly extra-pulmonary TB. The clinical particularity of this co-infection is the frequency of serious localization such us: pleural 23.3%, peritoneal 31.7%, and meningeal suffusion 13.3%.y-.biologicaly we notice the predominance both of pancytopenia and leucoanemia, hyponatremia in 38,6% and hypokalemia in 19,3%. By analyzing Kaplan-Meier survival curves, we notice that early ART initiation is associated with a significant reduction of all-cause mortality (p = 0,000), and we have identified several prognostic factors such as hypokalemia hyponatremia, leukocytosis thrombopenemia leucothrombopenia (p = 0,005). Conclusion: Our study confirms most of the results reported in the literature. Early ART initiation reduces the rate of all-cause mortality, despite the probability of the occurrence of TB-IRIS.

Keywords: TB-HIV co-infection, early ART, hyponatremia, extrapulmonary tuberculosis

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Authors: Munir Rusan

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Municipal waste management (MWM) represents a cornerstone in the effort to preserve the environment, which guarantees a healthy living environment for communities. MWM is directly affected by population growth and population density, urbanization, and tourism. In Jordan, MWM is currently managed by transferring and dumping waste into landfills. Landfills are mostly saturated and cannot receive any more waste. Besides, the organic waste, which accounts for 50% of municipal waste, will be naturally fermented in the landfills creating an unpleasant odor and emits greenhouse gases as well as generate organic leachates that are harmful to the environment. Organic waste can be aerobically composted and generate organic fertilizer called compost. Compost is very beneficial to soil and plant growth and, in general, to the ecosystem. Home composting is very common in most developed countries, but unfortunately, in developing countries such as Jordan, such an approach is not practiced and is not even socially well acceptable. The objective of this study was to evaluate the physical and chemical properties of home composting materials and to produce compost for further use as a soil amendment. The effect of compost soil application on the soil-plant system was evaluated. The soil application of the compost resulted in enhancing soil organic matter and soil N, P, and K content. The plant growth was also improved quantitatively and qualitatively. It was concluded that composting of municipal organic solid waste and soil application of the compost has a significant positive impact on the environment and soil-plant productivity.

Keywords: composting, organic solid waste, soil, plant

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Authors: Wooseok Byon, Eunyoung Kim, Junseong Kwon, Byung Joo Song, Chan Heun Park

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Background/Purpose: Previous preclinical and clinical data suggest that increased lymphocytic infiltration would be associated with good prognosis and benefit from immunogenic chemotherapy especially in triple-negative breast cancer (TNBC). We investigated a single-center experience of TNBC and relationship with lymphocytic infiltration. Methods: From January 2004 to December 2012, at the Department of Surgery, Kangbuk Samsung Hospital, Sungkyunkwan University, School of Medicine, we retrospectively reviewed 897 breast cancer patients-clinical outcomes, clinicopathological characteristics, breast cancer subtypes. And we reviewed lymphocytic infiltration of TNBC specimens by two pathologists. Statistical analysis of risk factors associated with recurrence was performed. Results: A total of 897 patients, 76 were TNBC (8.47%). Mean age of TNBC patients were 50.95 (SD10.42) years, mean follow-up periods was 40.06 months. We reviewed 49 slides, and there were 8 recurrent breast cancer patients (16.32%), and 4 patients were expired (8.16%). There were 9 lymphocytic predominant breast cancers (LPBC)-carcinomas with either intratumoral lymphocytes in >60% of tumor cell nests. 1 patient of LPBC was recurred and 8 were not. In multivariate logistic regression, the odds ratio of lymphocytic infiltration was 0.59 (p=0.643). Conclusion: In a single-center experience of TNBC, the lymphocytic infiltration in tumor cell nest might be a good trend on the prognosis but there was not statistically significant.

Keywords: tumor-infiltrating lymphocytes, triple negative breast cancer, medical and health sciences

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Authors: Selena Ferrian, Erin Mccaffrey, Toshie Saito, Aiqin Cao, Noah Greenwald, Mark Robert Nicolls, Trevor Bruce, Roham T. Zamanian, Patricia Del Rosario, Marlene Rabinovitch, Michael Angelo

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Recent experimental and clinical observations are advancing immunotherapies to clinical trials in pulmonary arterial hypertension (PAH). However, comprehensive mapping of the immune landscape in pulmonary arteries (PAs) is necessary to understand how immune cell subsets interact to induce pulmonary vascular pathology. We used multiplexed ion beam imaging by time-of-flight (MIBI-TOF) to interrogate the immune landscape in PAs from idiopathic (IPAH) and hereditary (HPAH) PAH patients. Massive immune infiltration in I/HPAH was observed with intramural infiltration linked to PA occlusive changes. The spatial context of CD11c+DCs expressing SAMHD1, TIM-3 and IDO-1 within immune-enriched microenvironments and neutrophils were associated with greater immune activation in HPAH. Furthermore, CD11c-DC3s (mo-DC-like cells) within a smooth muscle cell (SMC) enriched microenvironment were linked to vessel score, proliferating SMCs, and inflamed endothelial cells. Experimental data in cultured cells reinforced a causal relationship between neutrophils and mo-DCs in mediating pulmonary arterial SMC proliferation. These findings merit consideration in developing effective immunotherapies for PAH.

Keywords: pulmonary arterial hypertension, vascular remodeling, indoleamine 2-3-dioxygenase 1 (IDO-1), neutrophils, monocyte-derived dendritic cells, BMPR2 mutation, interferon gamma (IFN-γ)

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Authors: Pitchaporn Purngpiputtrakul, Suttasinee Petsakul, Sunisa Chatmongkolchart

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Nasogastric tube (NGT) insertion in anaesthetized and intubated patients can be challenging even for experienced anesthesiologists. Various techniques have been proposed to facilitate NGT insertion in these patients. This study aimed to compare the success rate and time required for NGT insertion between the GlideScope visualization and neck flexion with lateral neck pressure techniques. This randomized clinical trial was performed at a teaching hospital on 86 adult patients undergoing abdominal surgery under relaxant general anaesthesia who required intraoperative NGT insertion. The patients were randomized into two groups, the GlideScope group (group G) and the neck flexion with lateral neck pressure group (group F). The success rate of first and second attempts, duration of insertion, and complications were recorded. The total success rate was 79.1% in Group G compared with 76.7% in Group F (P=1) The median time required for NGT insertion was significantly longer in Group G, for both first and second attempts (97 vs 42 seconds P<0.001) and (70 vs 48.5 seconds P=0.015), respectively. Complications were reported in 23 patients (53.5%) in group G and 13 patients (30.2%) in group F. Bleeding and kinking were the most common complications in both techniques. Using GlideScope visualization to facilitate NGT insertion was comparable to neck flexion with lateral neck pressure technique in degree of success rate of insertion, while neck flexion with lateral neck pressure technique had fewer complications and was less time-consuming.

Keywords: anaesthesia, nasogastric tube, GlideScope, intubation

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Authors: Sidramappa Gaddnakeri, Lokanath Malligawad

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Any kind of research on production technology of individual crop / commodity /breed has not brought sustainability or stability in crop production. The sustainability of the system over years depends on the maintenance of the soil health. Organic production system includes use of organic manures, biofertilizers, green manuring for nutrient supply and biopesticides for plant protection helps to sustain the productivity even under adverse climatic condition. The study was initiated to evaluate the performance of different cropping systems under organic, inorganic and integrated production systems at The Institute of Organic Farming, University of Agricultural Sciences, Dharwad (Karnataka-India) under ICAR Network Project on Organic Farming. The trial was conducted for four years (2013-14 to 2016-17) on fixed site. Five cropping systems viz., sequence cropping of cowpea – safflower, greengram– rabi sorghum, maize-bengalgram, sole cropping of pigeonpea and intercropping of groundnut + cotton were evaluated under six nutrient management practices. The nutrient management practices are NM1 (100% Organic farming (Organic manures equivalent to 100% N (Cereals/cotton) or 100% P2O5 (Legumes), NM2 (75% Organic farming (Organic manures equivalent to 75% N (Cereals/cotton) or 100% P2O5 (Legumes) + Cow urine and Vermi-wash application), NM3 (Integrated farming (50% Organic + 50% Inorganic nutrients, NM4 (Integrated farming (75% Organic + 25% Inorganic nutrients, NM5 (100% Inorganic farming (Recommended dose of inorganic fertilizers)) and NM6 (Recommended dose of inorganic fertilizers + Recommended rate of farm yard manure (FYM). Among the cropping systems evaluated for different production systems indicated that the Groundnut + Hybrid cotton (2:1) intercropping system found more remunerative as compared to Sole pigeonpea cropping system, Greengram-Sorghum sequence cropping system, Maize-Chickpea sequence cropping system and Cowpea-Safflower sequence cropping system irrespective of the production systems. Production practices involving application of recommended rates of fertilizers + recommended rates of organic manures (Farmyard manure) produced higher net monetary returns and higher B:C ratio as compared to integrated production system involving application of 50 % organics + 50 % inorganic and application of 75 % organics + 25 % inorganic and organic production system only Both the two organic production systems viz., 100 % Organic production system (Organic manures equivalent to 100 % N (Cereals/cotton) or 100 % P2O5 (Legumes) and 75 % Organic production system (Organic manures equivalent to 75 % N (Cereals) or 100 % P2O5 (Legumes) + Cow urine and Vermi-wash application) are found to be on par. Further, integrated production system involving application of organic manures and inorganic fertilizers found more beneficial over organic production systems.

Keywords: cropping systems, production systems, cowpea, safflower, greengram, pigeonpea, groundnut, cotton

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Authors: Dorsa Rahi, Arghavan Tonkanbonbi, Soheila Manifar, Behzad Jafvarnejad

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Background and Aim: Intraoral manipulation is performed during endotracheal intubation for general anesthesia, which can traumatize the soft and hard tissue in the oral cavity and cause postoperative pain and discomfort. Dental trauma is the most common complication of intubation. This study aimed to assess the prevalence of dental complications due to intubation in patients hospitalized in Imam Khomeini Hospital during 2018-2019. Materials and Methods: A total of 805 patients presenting to the Cancer Institute of Imam Khomeini Hospital for preoperative anesthesia consultation were randomly enrolled. A dentist interviewed the patients and performed a comprehensive clinical oral examination preoperatively. The patients underwent clinical oral examination by another dentist postoperatively. Results: No significant correlation was found between dental trauma (tooth fracture, tooth mobility, or soft tissue injury) after intubation with the age or gender of patients. According to the Wilcoxon test and McNemar-Bowker Test, the rate of mobility before the intubation was significantly different from that after the intubation (P=0.000). Maxillary central incisors, maxillary left canine and mandibular right and left central incisors had the highest rate of fracture. Conclusion: Mobile teeth before the intubation are at higher risk of avulsion and aspiration during the procedure. Patients with primary temporomandibular joint disorders are more susceptible to post-intubation trismus.

Keywords: oral trauma, dental trauma, intubation, anesthesia

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Authors: Kristen Erekson, Sarah Spendlove Caswell

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Nurse educators have the challenge of training future nurses that will provide compassionate care to an increasingly diverse population of patients in a culturally sensitive way. One approach to this challenge is an immersive public and global health experience as part of the nursing program curriculum. Undergraduate nursing students at our institution are required to participate in a Public and Global Health course. They participate in a didactic preparatory course followed by a 3-to-4-week program in one of the following locations: The Czech Republic, Ecuador, Finland/Poland, Ghana, India, Spain, Taiwan, Tonga, an Honor Flight to Washington D.C. with Veterans, or in local (Utah) communities working with marginalized populations (including incarcerated individuals, refugees, etc.). The students are required to complete 84 clinical hours and 84 culture hours (which involve exposure to local history, art, architecture, customs, etc.). As Faculty, we feel strongly that these public and global health experiences help cultivate cultural awareness in our students and prepare nurses who are better prepared to serve a diverse population of patients throughout their careers. This presentation will highlight our experiences and provide ideas for other nurse educators who have an interest in developing similar programs in their schools but do not know where to start. Suggestions about how to start building relationships that can lead to these opportunities, along with logistics for continuing the programs, will be highlighted.

Keywords: global health nursing, nursing education, clinical education, public health nursing

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Authors: Elena K. Schneider, Johnny X. Huang, Vincenzo Carbone, Mark Baker, Mohammad A. K. Azad, Matthew A. Cooper, Jian Li, Tony Velkov

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Ivacaftor is a novel CF trans-membrane conductance regulator (CFTR) potentiator that improves the pulmonary function for cystic fibrosis patients bearing a G551D CFTR-protein mutation. Because ivacaftor is highly bound (>97%) to plasma proteins, there is the strong possibility that co-administered CF drugs that compete for the same plasma protein binding sites and impact the free drug concentration. This in turn could lead to drastic changes in the in vivo efficacy of ivacaftor and therapeutic outcomes. This study compares the binding affinity of ivacaftor and co-administered CF drugs for human serum albumin (HSA) and α1-acid glycoprotein (AGP) using surface plasmon resonance and fluorimetric binding assays that measure the displacement of site selective probes. Due to their high plasma protein binding affinities, drug-drug interactions between ivacaftor are to be expected with ducosate, montelukast, ibuprofen, dicloxacillin, omeprazole and loratadine. The significance of these drug-drug interactions is interpreted in terms of the pharmacodynamic/pharmacokinetic parameters and molecular docking simulations. The translational outcomes of the data are presented as recommendations for a staggered treatment regimen for future clinical trials which aims to maximize the effective free drug concentration and clinical efficacy of ivacaftor.

Keywords: human α-1-acid glycoprotein, binding affinity, human serum albumin, ivacaftor, cystic fibrosis

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Authors: Hwang Kwon

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Objective: To assess the efficacy of embryo transfer (ET) of accumulated vitrified embryos and compare pregnancy outcomes between ET of thawed embryos following accumulation of vitrified embryos (frozen ET) and ET of fresh and thawed frozen embryos following accumulation of vitrified embryos (fresh ET + frozen ET). Study design: Patients were poor ovarian responders defined according to the Bologna criteria as well as a subgroup of women whose previous IVF-ET cycle through controlled ovarian stimulation (COS) yielded one or no embryos. Sixty-four frozen ETs were performed following accumulation of vitrified embryos (ACCE )(ACCE Frozen) and 51 fresh + frozen ETs were performed following accumulation of vitrified embryos (ACCE Fresh + Frozen). Positive βhCG rate, clinical pregnancy rate, ongoing pregnancy rate, and good quality embryos (%, ±SD) were compared between two groups. Results: There were more good quality embryos in the ACCE Fresh + Frozen group than in the ACCE Frozen group: 60±34.7 versus 42.9±28.9, respectively (p=0.03). Positive βhCG rate [18/64(28.2%) vs. 13/51(25.5%); p=0.75] and clinical pregnancy rate [12/64 (18.8%) vs. 11/51 (10.9%); p=0.71] were comparable between the two groups. Conclusion: Accumulation of vitrified embryos is an effective method in patients with poor ovarian response who fulfill the Bologna criteria. Pregnancy outcomes were comparable between the two groups.

Keywords: accumulation of embryos, frozen embryo transfer, poor responder, Bologna criteria

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Authors: Noor Ayuni Che Zakaria, Takashi Komeda, Cheng Yee Low, Kaoru Inoue, Fazah Akhtar Hanapiah

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Previous studies have shown that there are arguments regarding the reliability and validity of the Ashworth and Modified Ashworth Scale towards evaluating patients diagnosed with upper limb disorders. These evaluations depended on the raters’ experiences. This initiated us to develop an upper limb disorder part-task trainer that is able to simulate consistent upper limb disorders, such as spasticity and rigidity signs, based on the Modified Ashworth Scale to improve the variability occurring between raters and intra-raters themselves. By providing consistent signs, novice therapists would be able to increase training frequency and exposure towards various levels of signs. A total of 22 physiotherapists and occupational therapists participated in the study. The majority of the therapists agreed that with current therapy education, they still face problems with inter-raters and intra-raters variability (strongly agree 54%; n = 12/22, agree 27%; n = 6/22) in evaluating patients’ conditions. The therapists strongly agreed (72%; n = 16/22) that therapy trainees needed to increase their frequency of training; therefore believe that our initiative to develop an upper limb disorder training tool will help in improving the clinical education field (strongly agree and agree 63%; n = 14/22).

Keywords: upper limb disorder, clinical education tool, inter/intra-raters variability, spasticity, modified Ashworth scale

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Authors: Norimichi Nagano, Yoshio Hirano, Tsutomu Yasukawa

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Mesenchymal stem cells are thought to confer neuroprotection, facilitate tissue regeneration and exert their effects on retinal degenerative diseases, however, adverse events such as proliferative vitreoretinopathy and preretinal membrane disease associated with cell suspension transplantation have also been reported. We have recently developed human (allogeneic) adipose tissue-derived mesenchymal stem cell (adMSC) sheets through our proprietary sheet transformation technique, which could potentially mitigate these adverse events. To clarify the properties of our adMSC sheets named PAL-222, we performed in vitro studies such as viability testing, cytokine secretions by ELISA, immunohistochemical study, and migration assay. The viability of the cells exceeded 70%. Vascular Endothelial Growth Factor (VEGF) and Pigment Epithelium-Derived Factor (PEDF), which are quite important cytokines for the retinal area, were observed. PAL-222 expressed type I collagen, a strength marker, type IV collagen, a marker of the basement membrane, and elastin, an elasticity marker. Finally, the migration assay was performed and showed negative, which means that PAL-222 is stably kept in the topical area and does not come to pieces. Next, to evaluate the efficacy in vivo, we transplanted PAL-222 into the subretinal space of the eye of Royal College of Surgeons rats with congenital retinal degeneration and assessed it for three weeks after transplantation. We confirmed that PAL-222 suppressed the decrease in the thickness of the outer nuclear layer, which means that the photoreceptor protective effect treated with PAL-222 was significantly higher than that in the sham group. (p < 0.01). This finding demonstrates that PAL-222 showed their retinoprotective effect in a model of congenital retinal degeneration. As the study suggested the efficacy of PAL-222 in both in vitro and in vivo studies, we are presently engaged in clinical trials of PAL-222 for myopic chorioretinal atrophy, which is one of the retinal degenerative diseases, for the purpose of regenerative medicine.

Keywords: cell sheet, clinical trial, mesenchymal stem cell, myopic chorioretinal atrophy

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Authors: Mpai Mokoena, Nsenda Lukumwena

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South Africa is one of the driest countries in the world and is facing a water crisis. In addition to inadequate infrastructure and poor planning, the country is experiencing high rates of water wastage due to pipe leaks. This study outlines the level of water wastage and develops a smart solution to efficiently manage and reduce the effects of pipe leaks, while monitoring the situation before and after fixing the pipe leaks. To understand the issue in depth, a literature review of journal papers and government reports was conducted. A questionnaire was designed and distributed to the general public. Additionally, the municipality office was contacted from a managerial perspective. The analysis from the study indicated that the majority of the citizens are aware of the water crisis and are willing to participate positively to decrease the level of water wasted. Furthermore, the response from the municipality acknowledged that more practical solutions are needed to reduce water wastage, and resources to attend to pipe leaks swiftly. Therefore, this paper proposes a specific solution for municipalities, local plumbers and citizens to minimize the effects of pipe leaks. The solution provides web and mobile application platforms to report and manage leaks swiftly. The solution is beneficial to the country in achieving water security and would promote a culture of responsibility toward water usage.

Keywords: urban distribution networks, leak management, mobile application, responsible citizens, water crisis, water security

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Authors: Elizabeth M. Annoni, Elena G. Tolkacheva

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Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia that is a known prognostic marker for stroke, heart failure and death. Reentrant mechanisms of rotor formation, which are stable electrical sources of cardiac excitation, are believed to cause AF. No existing commercial mapping systems have been demonstrated to consistently and accurately predict rotor locations outside of the pulmonary veins in patients with persistent AF. There is a clear need for robust spatio-temporal techniques that can consistently identify rotors using unique characteristics of the electrical recordings at the pivot point that can be applied to clinical intracardiac mapping. Recently, we have developed four new signal analysis approaches – Shannon entropy (SE), Kurtosis (Kt), multi-scale frequency (MSF), and multi-scale entropy (MSE) – to identify the pivot points of rotors. These proposed techniques utilize different cardiac signal characteristics (other than local activation) to uncover the intrinsic complexity of the electrical activity in the rotors, which are not taken into account in current mapping methods. We validated these techniques using high-resolution optical mapping experiments in which direct visualization and identification of rotors in ex-vivo Langendorff-perfused hearts were possible. Episodes of ventricular tachycardia (VT) were induced using burst pacing, and two examples of rotors were used showing 3-sec episodes of a single stationary rotor and figure-8 reentry with one rotor being stationary and one meandering. Movies were captured at a rate of 600 frames per second for 3 sec. with 64x64 pixel resolution. These optical mapping movies were used to evaluate the performance and robustness of SE, Kt, MSF and MSE techniques with respect to the following clinical limitations: different time of recordings, different spatial resolution, and the presence of meandering rotors. To quantitatively compare the results, SE, Kt, MSF and MSE techniques were compared to the “true” rotor(s) identified using the phase map. Accuracy was calculated for each approach as the duration of the time series and spatial resolution were reduced. The time series duration was decreased from its original length of 3 sec, down to 2, 1, and 0.5 sec. The spatial resolution of the original VT episodes was decreased from 64x64 pixels to 32x32, 16x16, and 8x8 pixels by uniformly removing pixels from the optical mapping video.. Our results demonstrate that Kt, MSF and MSE were able to accurately identify the pivot point of the rotor under all three clinical limitations. The MSE approach demonstrated the best overall performance, but Kt was the best in identifying the pivot point of the meandering rotor. Artifacts mildly affect the performance of Kt, MSF and MSE techniques, but had a strong negative impact of the performance of SE. The results of our study motivate further validation of SE, Kt, MSF and MSE techniques using intra-atrial electrograms from paroxysmal and persistent AF patients to see if these approaches can identify pivot points in a clinical setting. More accurate rotor localization could significantly increase the efficacy of catheter ablation to treat AF, resulting in a higher success rate for single procedures.

Keywords: Atrial Fibrillation, Optical Mapping, Signal Processing, Rotors

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Authors: Patrícia Pires, Renata Vaz, Bárbara Teles, Marco Pato, Pedro Beckert

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Introduction: The management of lateral third clavicle fractures can be challenging due to difficulty in distinguishing subtle variations in the fracture pattern, which may be suggestive of potential fracture instability. They occur most often in men between 30 and 50 years of age, and in individuals over 70 years of age, its distribution is equal between both men and women. These fractures account for 10%–30% of all clavicle fractures and roughly 30%–45% of all clavicle nonunion fractures. Lateral third clavicle fractures may be treated conservatively or surgically, and there is no gold standard, although the risk of nonunion or pseudoarthrosis impacts the recommendation of surgical treatment when these fractures are unstable. There are many strategies for surgical treatment, including locking plates, hook plates fixation, coracoclavicular fixation using suture anchors, devices or screws, tension band fixation with suture or wire, transacromial Kirschner wire fixation and arthroscopically assisted techniques. Whenever taking the hardware into consideration, we must not disregard that obtaining adequate lateral fixation of small fragments is a difficult task, and plates are more associated to local irritation. The aim of the appropriate treatment is to ensure fracture healing and a rapid return to preinjury activities of daily living but, as explained, definitive treatment strategies have not been established and the variety of techniques avalilable add up to the discussion of this topic. Methods and Results: We present a clinical case of a 43-year-old man with the diagnosis of a lateral third clavicle fracture (Neer IIC) in the sequence of a fall on his right shoulder after a bicycle fall. He was operated three days after the injury, and through K-wire temporary fixation and indirect reduction using a ZipTight, he underwent osteosynthesis with an interfragmentary figure-of-eight tension band with polydioxanone suture (PDS). Two weeks later, there was a good aligment. He kept the sling until 6 weeks pos-op, avoiding efforts. At 7-weeks pos-op, there was still a good aligment, starting the physiotherapy exercises. After 10 months, he had no limitation in mobility or pain and returned to work with complete recovery in strength. Conclusion: Some distal clavicle fractures may be conservatively treated, but it is widely accepted that unstable fractures require surgical treatment to obtain superior clinical outcomes. In the clinical case presented, the authors chose an osteosuture technique due to the fracture pattern, its location. Since there isn´t a consensus on the prefered fixation method, it is important for surgeons to be skilled in various techniques and decide with their patient which approach is most appropriate for them, weighting the risk-benefit of each method. For instance, with the suture technique used, there is no wire migration or breakage, and it doesn´t require a reoperation for hardware removal; there is also less tissue exposure since it requires a smaller approach in comparison to the plate fixation and avoids cuff tears like the hook plate. The good clinical outcome on this case report serves the purpose of expanding the consideration of this method has a therapeutic option.

Keywords: lateral third, clavicle, suture, fixation

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Authors: Ali Bolat, Ali Bayat, Mustafa Gullu

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Maize can be cultivated both under main and second crop conditions in Turkey. Main pests of maize under second crop conditions are Sesamia nonagrioides Lefebvre (Lepidoptera: Noctuidae) and Ostrinia nubilalis Hübner (Lepidoptera: Crambidae). Aerial spraying applications to control these two main maize pests can be carried out until 2006 in Turkey before it was banned due to environmental concerns like drifting of sprayed pestisides and low biological efficiency. In this context, pulverizers which can spray tall maize plants ( > 175 cm) from the ground have begun to be used. However, the biological efficiency of these sprayers is unknown. Some methods have been tested to increase the success of ground spraying in field experiments conducted in second crop maize in 2008 and 2009. For this aim, 6 spraying methods (air assisted spraying with TX cone jet, domestic cone nozzles, twinjet nozzles, air induction nozzles, standard domestic cone nozzles and tail booms) were used at two application rates (150 and 300 l.ha-1) by a sprayer. In the study, biological efficacy evaluations of each methods were measured in each parcel. Biological efficacy evaluations included counts of number of insect damaged plants, number of holes in stems and live larvae and pupa in stems of selected plants. As a result, the highest biological efficacy value (close to 70%) was obtained from Air Assisted Spraying method at 300 l / ha application volume.

Keywords: air assisted sprayer, drift nozzles, biological efficiency, maize plant

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Authors: David Oluwole Moses, Odeyemi Adebowale Toba, Olawale Adetunji Kola

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Candida auris, an emerging fungus, has been reported in more than 30 countries around the world since its first detection in 2009. Due to its several virulence factors, resistance to antifungals, and persistence in hospital settings, Candida auris has been reported to cause treatment-failure infections. This study was therefore carried out to determine the incidence of Candida auris in a tertiary hospital in Ekiti State, Nigeria. In this study, a total of 115 samples were screened for Candida species using cultural and molecular methods. The carriage of virulence factors and antifungal resistance among C. auris was detected using standard microbiological methods. Candida species isolated from the samples were 15 (30.0%) in clinical samples and 22 (33.85%) in hospital equipment screened. Non-albicans Candida accounted for 3 (20%) and 8 (36.36%) among the isolates from the clinical samples and equipment, respectively. Only five of the non-albicans Candida isolates were C. auris. All the isolates produced biofilm, gelatinase, and hemolysin, while none produced germ tubes. Two of the isolates were resistant to all the antifungals tested. Also, all the isolates were resistant to fluconazole and itraconazole. Nystatin appeared to be the most effective among the tested antifungals. The isolation of Candida auris is being reported for the second time in Nigeria, further confirming that the fungus has spread beyond Lagos and Ibadan, where it was first reported. The extent of the spread of the nosocomial fungus needed to be further investigated and curtailed in Nigeria before its outbreak in healthcare facilities.

Keywords: candida auris, virulence factors, antifungals, pathogen, hospital, infection

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Authors: M. Nemer, E. I. Konukseven

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In this paper, a motion generation algorithm for a six Degrees of Freedom (DoF) robotic hand in a static environment is presented. The purpose of developing this method is to be used in the path generation of the end-effector for edge finishing and inspection processes by utilizing the CAD model of the considered workpiece. Nonetheless, the proposed algorithm may be extended to be applicable for other similar manufacturing processes. A software package programmed in the application programming interface (API) of SolidWorks generates tool path data for the robot. The proposed method significantly simplifies the given problem, resulting in a reduction in the CPU time needed to generate the path, and offers an efficient overall solution. The ABB IRB2000 robot is chosen for executing the generated tool path.

Keywords: CAD-based tools, edge deburring, edge scanning, offline programming, path generation

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Authors: Ashti Morovati, Hushyar Azari, Bahram Pourghassem Gargari

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Objectives and goals: The prevalence of metabolic syndrome (MetS), as a major health burden for societies, is increasing. This clinical trial was conducted to evaluate the effects of CuEO supplementation on anthropometric indices, systolic and diastolic blood pressure, blood glucose level, insulin resistance and serum lipid level in patients suffering from MetS. Methods: This was a randomized, triple‐blind, placebo‐controlled clinical trial in which 56 patients with MetS aged 18–60 years who fulfilled the eligibility criteria were randomly allocated to an intervention or a control group. Inclusion criteria for the study were comprised of diagnosis of MetS according to the new International Federation of Diabetes. The exclusion criteria were defined as: taking herbal supplements, use of drugs having evident interaction with cumin such as anti‐depressant drugs, vitamin D, omega 3, selenium, zinc, smoking, pregnancy, or breastfeeding, suffering from cancer, having any history of gastrointestinal and hepatic, cardiovascular, thyroid and kidney disorders, and menopause. 75 mg CuEO or placebo soft gels were administered three times daily to the participants for eight weeks. The soft gel consumption was checked by asking the participants to bring the medication containers in the follow‐up visits at the 4th and the 8th weeks of the study. Data pertaining to blood pressure, height, weight, waist circumference, hip circumference and BMI, as well as food consumption were collected at the beginning and end of the study. Fasting blood samples ( glucose, triglyceride, total cholesterol, HDL-cholesterol and LDL-cholesterol) were obtained and biochemical measurements were assessed at the beginning and end of the study. Results: At eight weeks, a total of 44 patients completed this study. Except for diastolic blood pressure (DBP), the other assessed variables were not significantly different between the two groups. In intra group analysis, placebo and CuEO groups both had insignificant decrements in DBP (mean difference [MD] with 95% CI: −3.31 [−7.11, 0.47] and −1.77 [−5.95, 2.40] mmHg, respectively). However, DBP was significantly lower in CuEO compared with the placebo group at the end of study (81.41 ± 5.88 vs. 84.09 ± 5.54 mmHg, MD with 95% CI: −3.98 [−7.60, −0.35] mmHg, p < .05). Conclusions: The results of this study indicated that CuEO does not have any effect on MetS components, except for DBP in patients with MetS.

Keywords: blood pressure, fasting blood glucose, lipid profile, waist circumference

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Authors: Ammar Ayad Issa Al-Rifaie, Zuhreya Muazu, Maysam Ali Abdulwahid, Dermot Gleeson

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The aim of this audit was to examine the efficiency of alcohol history documentation and screening for hazardous drinkers at the Medical Admission Unit (MAU) of Northern General Hospital (NGH), Sheffield, to identify any potential for enhancing clinical practice. Data were collected from medical clerking sheets, ICE system and directly from 82 patients by three junior medical doctors using both CAGE questionnaire and AUDIT-C tool for newly admitted patients to MAU in NGH, in the period between January and March 2015. Alcohol consumption was documented in around two-third of the patient sample and this was documented fairly accurately by health care professionals. Some used subjective words such as 'social drinking' in the alcohol units’ section of the history. CAGE questionnaire was applied to only four patients and none of the patients had documented advice, education or referral to an alcohol liaison team. AUDIT-C tool had identified 30.4%, while CAGE 10.9%, of patients admitted to the NGH MAU as hazardous drinkers. The amount of alcohol the patient consumes positively correlated with the score of AUDIT-C (Pearson correlation 0.83). Re-audit is planned to be carried out after integrating AUDIT-C tool as labels in the notes and presenting a brief teaching session to junior doctors. Alcohol misuse screening is not adequately undertaken and no appropriate action is being offered to hazardous drinkers. CAGE questionnaire is poorly applied to patients and when satisfactory and adequately used has low sensitivity to detect hazardous drinkers in comparison with AUDIT-C tool. Re-audit of alcohol screening practice after introducing AUDIT-C tool in clerking sheets (as labels) is required to compare the findings and conclude the audit cycle.

Keywords: alcohol screening, AUDIT-C, CAGE, hazardous drinking

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Authors: Philippe Dillien, Patrice Forget, Harald Engel, Olivier Cornu, Marc De Kock, Jean Cyr Yombi

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Introduction: Hip fracture precedes commonly death in elderly people. Identification of high-risk patients may contribute to target patients in whom optimal management, resource allocation and trials efficiency is needed. The aim of this study is to construct a predictive score of mortality after hip fracture on the basis of the objective prognostic factors available: Neutrophil-to-lymphocyte ratio (NLR), age, and sex. C-Reactive Protein (CRP), is also considered as an alternative to the NLR. Patients and methods: After the IRB approval, we analyzed our prospective database including 286 consecutive patients with hip fracture. A score was constructed combining age (1 point per decade above 74 years), sex (1 point for males), and NLR at postoperative day+5 (1 point if >5). A receiver-operating curve (ROC) curve analysis was performed. Results: From the 286 patients included, 235 were analyzed (72 males and 163 females, 30.6%/69.4%), with a median age of 84 (range: 65 to 102) years, mean NLR values of 6.47+/-6.07. At one year, 82/280 patients died (29.3%). Graphical analysis and log-rank test confirm a highly statistically significant difference (P<0.001). Performance analysis shows an AUC of 0.72 [95%CI 0.65-0.79]. CRP shows no advantage on NLR. Conclusion: We have developed a score based on age, sex and the NLR to predict the risk of mortality at one year in elderly patients after surgery for a hip fracture. After external validation, it may be included in clinical practice as in clinical research to stratify the risk of postoperative mortality.

Keywords: neutrophil-to-lymphocyte ratio, hip fracture, postoperative mortality, medical and health sciences

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Authors: Zakia Belhadj, Bing He, Hua Zhang, Xueqing Wang, Wenbing Dai, Qiang Zhang

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Mononuclear phagocyte system (MPS) forms an abominable obstacle hampering the tumor delivery efficiency of nanoparticles. Passively targeted nanocarriers have received clinical approval over the past 20 years. However, none of the actively targeted nanocarriers have entered clinical trials. Thus it is important to endue effective targeting ability to actively targeted approaches by overcoming biological barriers to nanoparticle drug delivery. Here, it presents that an Esomeprazole-based preconditioning strategy for regulating nanocarrier-MPS interaction to substantially prolong circulation time and enhance tumor targeting of nanoparticles. In vitro, the clinically approved proton pump inhibitor Esomeprazole “ESO” was demonstrated to reduce interactions between macrophages and subsequently injected targeted vesicles by interfering with their lysosomal trafficking. Of note, in vivo studies demonstrated that ESO pretreatment greatly decreased the liver and spleen uptake of c(RGDm7)-modified vesicles, highly enhanced their tumor accumulation, thereby provided superior therapeutic efficacy of c(RGDm7)-modified vesicles co-loaded with Doxorubicin (DOX) and Gefitinib (GE). This MPS-preconditioning strategy using ESO provides deeper insights into regulating nanoparticles interaction with the phagocytic system and enhancing their cancer cells' accessibility for anticancer therapy.

Keywords: esomeprazole (ESO), mononuclear phagocyte system (MPS), preconditioning strategy, targeted lipid vesicles

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Authors: K. Genise, S. Murthy

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Introductory Statement: The results of this retrospective chart review suggest the effects of bacterial colonization in critically ill children with viral bronchiolitis, currently unproven, are clinically insignificant. Background: Viral bronchiolitis is one of the most prevalent causes of illness requiring hospitalization among children worldwide and one of the most common reasons for admission to pediatric intensive care. It has been hypothesized that co-infection with bacteria results in more severe clinical outcomes. Conversely, the effects of bacterial colonization in critically ill patients with bronchiolitis are poorly defined. Current clinical management of colonized patients consists primarily of supportive therapies with the role of antibiotics remaining controversial. Methods: A retrospective review of all critically ill children admitted to the BC Children’s Hospital Pediatric Intensive Care Unit (PICU) from 2014-2017 with a diagnosis of bronchiolitis was performed. Routine testing in this time frame consisted of complete pathogen testing, including PCR for Streptococcus pneumoniae. Analyses were performed to determine the impact of bacterial colonization and antibiotic use on a primary outcome of PICU length-of-stay, with secondary outcomes of hospital length-of-stay and duration of ventilation. Results: There were 92 patients with complete pathogen testing performed during the assessed timeframe. A comparison between children with detected Streptococcus pneumoniae (n=22) and those without (n=70) revealed no significant (p=0.20) differences in severity of illness on presentation as per Pediatric Risk of Mortality III scores (mean=3.0). Patients colonized with S. pneumoniae had significantly shorter PICU stays (p=0.002), hospital stays (p=0.0001) and duration of non-invasive ventilation (p=0.002). Multivariate analyses revealed that these effects on length of PICU stay and duration of ventilation do not persist after controlling for antibiotic use, presence of radiographic consolidation, age, and severity of illness (p=0.15, p=0.32). The relationship between colonization and duration of hospital stay persists after controlling for these variables (p=0.008). Conclusions: Children with viral bronchiolitis colonized with S. pneumoniae do not appear to have significantly different PICU length-of-stays or duration of ventilation compared to children who are not colonized. Colonized children appear to have shorter hospital stays. The results of this study suggest bacterial colonization is not associated with increased severity of presenting illness or negative clinical outcomes.

Keywords: bronchiolitis, colonization, critical care, pediatrics, pneumococcal, infection

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Authors: Arshad Mehmood Ch, Riaz Ahmad, Imran Ali Ch, Waqas Durrani

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This study deals with the application of Ant Colony Optimization (ACO) approach to solve no-wait flowshop scheduling problem (NW-FSSP). ACO algorithm so developed has been coded on Matlab computer application. The paper covers detailed steps to apply ACO and focuses on judging the strength of ACO in relation to other solution techniques previously applied to solve no-wait flowshop problem. The general purpose approach was able to find reasonably accurate solutions for almost all the problems under consideration and was able to handle a fairly large spectrum of problems with far reduced CPU effort. Careful scrutiny of the results reveals that the algorithm presented results better than other approaches like Genetic algorithm and Tabu Search heuristics etc; earlier applied to solve NW-FSSP data sets.

Keywords: no-wait, flowshop, scheduling, ant colony optimization (ACO), makespan

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Authors: Qi En Han, Si En Wai, Eugene Quek

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As one of the two Academic Medical Centres (AMCs) in Singapore, SingHealth Duke-NUS AMC strives to improve patients’ lives through excellent clinical care, research and education. These efforts are enhanced with the establishment of Academic Clinical Programmes (ACPs). Each ACP brings together specialists in a particular discipline from different institutions to maximize the power of shared knowledge and resources. Initiated by Surgery ACP, the student research mentorship programme is a programme designed to facilitate engagement between medical students and the surgical faculty. The programme offers mentors not only the opportunity to supervise research but also to nurture future clinician scientists. In turn, medical students acquire valuable research experience which may be useful in their future careers. The programme typically lasts one year, depending on the students’ commitment. Surgery ACP matches students’ research interests with the mentor's area of expertise whenever possible. Surgery ACP organizes informal tea sessions to bring students and prospective mentors together. Once a match is made, the pair is required to submit a project proposal which includes the title, proposed start and end dates, ethical and biosafety considerations and project details. The mentees either think of their own research question with guidance from the mentors or join an existing project. The mentees may participate in data collection, data analysis, manuscript writing and conference presentation. The progress of each research project is monitored through half-yearly progress report. The mentees report problems encountered or changes made to existing proposal on top of the progress made. A total of 18 mentors were successfully paired with 36 mentees since 2013. Currently, there are 23 on-going and 13 completed projects. The mentees are encouraged to present their projects at conferences and to publish in peer-reviewed journals. Six mentees have presented their completed projects at local or international conferences and one mentee has her work published. To further support student research, Surgery ACP organized a Research Day in 2015 to recognize their research efforts and to showcase their wide-range of research. Surgery ACP recognizes that early exposure of medical students to research is important in developing them into clinician scientists. As interest in research take time to develop and are usually realized during various research attachments, it is crucial that programmes such as the student research mentorship programme exist. Surgery ACP will continue to build on this programme.

Keywords: academic clinical programme, clinician scientist, medical student, mentoring

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