169 research outputs found

    A hydrodynamic study of a fast‐bed dual circulating fluidized bed for chemical looping combustion

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    This study explores the use of a dual interconnected circulating fluidized bed (CFB) for chemical looping combustion. This design can enhance gas–solid interactions, but it is difficult to control the solid transfer and circulation rates. With the use of a 1:1 scale cold-flow model, an investigation determining the hydrodynamic behavior of the dual CFB system has been conducted. The cold-flow system consists of two identical fast-bed risers, each with an internal diameter of 100 mm and a height of 7 m. The simplified cold-flow model is based on the chemical looping Pilot-Scale Advanced CO2 Capture Technology (PACT) facility at Cranfield. Here, we have determined the minimum fluidization and transport velocities, and we have assessed the solid density profiles, transport capacity, and potential for the dilution by air/N2 leakage into the CO2 stream exiting the fuel reactor. The experimental procedure uses two different bed materials, molochite (ceramic clay) and FE100 (iron particles), and it satisfies the dynamic scaling laws to model the bed inventory within the system. The results indicate that the two fast-bed risers share similar density and pressure profiles. Stable circulation can be achieved through pneumatic transport. The circulation rate of the system is flexible and can be adjusted by altering the fluidization velocity in the riser and by altering the bed inventory. The gas leakage from the loop seal to the cyclone was found to be sensitive to the bed height and fluidization velocity in the loop seal. However, by maintaining a loop-seal bed height above 600 mm during operation, the outlet stream remains undiluted

    Evaluation of Concussion Incidence and Modulating Factors in the 2013-2017 Australian Football League

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    The increasing awareness and popularization of concussions in the research realm over the last few years have begun to shed more light on the detrimental effects associated with repetitive head trauma. While the majority of the current literature focuses on the National Football League (NFL) and National Hockey League (NHL), several other high-impact sports have been implementing concussion management protocols to protect their players. The Australian Football League (AFL) is a prime example of a major contact sport that has undertaken recent changes to its concussion assessment and management modalities. We recognize the benefit of reporting potential changes in concussion rates over the 2013-2017 AFL seasons. We were interested in some of the factors not yet evaluated before, which may contribute to the overall concussion incidence such as “style-of-play” factors” (home/away, win/loss, points scored, time of season). We hope the results of this analysis shed light on the mechanisms by which concussion rates can be mitigated across major contact sports

    Incidence and etiology of omphalitis in Pakistan: a community-based cohort study

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    Introduction: Although omphalitis (umbilical infections) among newborns is common and a major cause of neonatal deaths in developing countries, information on its burden and etiology from community settings is lacking. This study aimed to determine the incidence and etiology of omphalitis in newborns in high neonatal mortality settings in Karachi, Pakistan. Methodology: Trained community health workers surveyed all new births in three low-income areas from September 2004 to August 2007. Pus samples from the umbilical stumps were obtained from babies with pre-defined signs of illness and subjected to culture and antimicrobial susceptibility testing. Results: Among 6904 births, 1501 (21.7%) newborns were diagnosed with omphalitis. Of these, 325 (21.6%) were classified as mild, 1042 (69.4%) as moderate, and 134 (8.9%) as severe, 141 (9.3%) were associated with clinical signs of sepsis. The incidence of omphalitis was 217.4/1000 live births, moderate-severe omphalitis 170.3 per 1000 live births, and associated with sepsis 20.4 per 1000 live births. Of 853 infants with purulent umbilical discharge, 64% yielded 583 isolates. The most common pathogens were Staphylococcus aureus, of which 291 (95.7%) were methicillin-susceptible Staphylococcus aureus (MSSA) and 13 (4.2%) methicillin-resistant S. aureus (MRSA), Streptococcus pyogenes 105 (18%), Group B beta-hemolytic streptococci 59 (10 %), Pseudomonas spp., 52 (8.9 %), Aeromonas spp. 19 (3.2%), and Klebsiella spp. 12 (2%). Conclusions: A high burden of omphalitis can be associated with sepsis among newborns in low-income communities in Pakistan. S. aureus is the most common pathogen isolated from umbilical pus. Appropriate low-cost prevention strategies need to be implemented

    Integration of TTF, UTAUT, and ITM for mobile Banking Adoption

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    The introduction of mobile banking facility has enabled customers to carry out banking transactionswith the use of smartphones and other handheld devices from anywhere. It has become a luxurious and exclusive method of online payments. The recent growth of telecommunication sector and a tremendous increase in mobile USAge has opened new doors for sparking future of banking sector industry. The following research is aimed to find out the mobile banking adoption attitudes with the integration of TTF, UTAUT,and ITM models

    Characterisation of the Stromal Microenvironment in Lobular Breast Cancer

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    SIMPLE SUMMARY: Invasive lobular breast cancer (ILC) accounts for approximately 5–15% of breast cancers, and although response rates to treatments are initially good, an ILC diagnosis is associated with adverse long-term outcomes; better treatments, specifically targeted to this sub-type of breast cancer, are required to improve patient survival. The tumor microenvironment (TME) plays an important role in determining how cancers respond to treatment, and in this study, we carried out an in-depth analysis of the TME in ILC following laser-capture microdissection of the tumor stroma, and analysis of primary cancer-associated fibroblasts (CAFs), which comprise the majority of non-malignant cells within tumors. This identified changes in genes involved in regulation of the extracellular matrix and also growth factor signaling pathways that were differentially regulated in ILC. Further analysis of breast cancer datasets showed that two of these genes which encode a secreted metalloproteinase (PAPPA) and a metalloproteinase inhibitor (TIMP2) were associated with survival outcomes in ILC. ABSTRACT: Invasive lobular carcinoma (ILC) is the second most common histological subtype of breast cancer, and it exhibits a number of clinico-pathological characteristics distinct from the more common invasive ductal carcinoma (IDC). We set out to identify alterations in the tumor microenvironment (TME) of ILC. We used laser-capture microdissection to separate tumor epithelium from stroma in 23 ER+ ILC primary tumors. Gene expression analysis identified 45 genes involved in regulation of the extracellular matrix (ECM) that were enriched in the non-immune stroma of ILC, but not in non-immune stroma from ER+ IDC or normal breast. Of these, 10 were expressed in cancer-associated fibroblasts (CAFs) and were increased in ILC compared to IDC in bulk gene expression datasets, with PAPPA and TIMP2 being associated with better survival in ILC but not IDC. PAPPA, a gene involved in IGF-1 signaling, was the most enriched in the stroma compared to the tumor epithelial compartment in ILC. Analysis of PAPPA- and IGF1-associated genes identified a paracrine signaling pathway, and active PAPP-A was shown to be secreted from primary CAFs. This is the first study to demonstrate molecular differences in the TME between ILC and IDC identifying differences in matrix organization and growth factor signaling pathways

    Hypoxia promotes stem cell phenotypes and poor prognosis through epigenetic regulation of DICER

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    MicroRNAs are small regulatory RNAs that post-transcriptionally control gene expression. Reduced expression of DICER, the enzyme involved in microRNA processing, is frequently observed in cancer and is associated with poor clinical outcome in various malignancies. Yet the underlying mechanisms are not well understood. Here, we identify tumor hypoxia as a regulator of DICER expression in large cohorts of breast cancer patients. We show that DICER expression is suppressed by hypoxia through an epigenetic mechanism that involves inhibition of oxygen-dependent H3K27me3 demethylases KDM6A/B and results in silencing of the DICER promoter. Subsequently, reduced miRNA processing leads to derepression of the miR-200 target ZEB1, stimulates the epithelial to mesenchymal transition and ultimately results in the acquisition of stem cell phenotypes in human mammary epithelial cells. Our study uncovers a previously unknown relationship between oxygen-sensitive epigenetic regulators, miRNA biogenesis and tumor stem cell phenotypes that may underlie poor outcome in breast cancer

    A multi-gene signature predicts outcome in patients with pancreatic ductal adenocarcinoma.

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    © 2014 Haider et al.; licensee BioMed Central. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Improved usage of the repertoires of pancreatic ductal adenocarcinoma (PDAC) profiles is crucially needed to guide the development of predictive and prognostic tools that could inform the selection of treatment options

    Effects of antibiotic resistance, drug target attainment, bacterial pathogenicity and virulence, and antibiotic access and affordability on outcomes in neonatal sepsis: an international microbiology and drug evaluation prospective substudy (BARNARDS).

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    BACKGROUND: Sepsis is a major contributor to neonatal mortality, particularly in low-income and middle-income countries (LMICs). WHO advocates ampicillin-gentamicin as first-line therapy for the management of neonatal sepsis. In the BARNARDS observational cohort study of neonatal sepsis and antimicrobial resistance in LMICs, common sepsis pathogens were characterised via whole genome sequencing (WGS) and antimicrobial resistance profiles. In this substudy of BARNARDS, we aimed to assess the use and efficacy of empirical antibiotic therapies commonly used in LMICs for neonatal sepsis. METHODS: In BARNARDS, consenting mother-neonates aged 0-60 days dyads were enrolled on delivery or neonatal presentation with suspected sepsis at 12 BARNARDS clinical sites in Bangladesh, Ethiopia, India, Pakistan, Nigeria, Rwanda, and South Africa. Stillborn babies were excluded from the study. Blood samples were collected from neonates presenting with clinical signs of sepsis, and WGS and minimum inhibitory concentrations for antibiotic treatment were determined for bacterial isolates from culture-confirmed sepsis. Neonatal outcome data were collected following enrolment until 60 days of life. Antibiotic usage and neonatal outcome data were assessed. Survival analyses were adjusted to take into account potential clinical confounding variables related to the birth and pathogen. Additionally, resistance profiles, pharmacokinetic-pharmacodynamic probability of target attainment, and frequency of resistance (ie, resistance defined by in-vitro growth of isolates when challenged by antibiotics) were assessed. Questionnaires on health structures and antibiotic costs evaluated accessibility and affordability. FINDINGS: Between Nov 12, 2015, and Feb 1, 2018, 36 285 neonates were enrolled into the main BARNARDS study, of whom 9874 had clinically diagnosed sepsis and 5749 had available antibiotic data. The four most commonly prescribed antibiotic combinations given to 4451 neonates (77·42%) of 5749 were ampicillin-gentamicin, ceftazidime-amikacin, piperacillin-tazobactam-amikacin, and amoxicillin clavulanate-amikacin. This dataset assessed 476 prescriptions for 442 neonates treated with one of these antibiotic combinations with WGS data (all BARNARDS countries were represented in this subset except India). Multiple pathogens were isolated, totalling 457 isolates. Reported mortality was lower for neonates treated with ceftazidime-amikacin than for neonates treated with ampicillin-gentamicin (hazard ratio [adjusted for clinical variables considered potential confounders to outcomes] 0·32, 95% CI 0·14-0·72; p=0·0060). Of 390 Gram-negative isolates, 379 (97·2%) were resistant to ampicillin and 274 (70·3%) were resistant to gentamicin. Susceptibility of Gram-negative isolates to at least one antibiotic in a treatment combination was noted in 111 (28·5%) to ampicillin-gentamicin; 286 (73·3%) to amoxicillin clavulanate-amikacin; 301 (77·2%) to ceftazidime-amikacin; and 312 (80·0%) to piperacillin-tazobactam-amikacin. A probability of target attainment of 80% or more was noted in 26 neonates (33·7% [SD 0·59]) of 78 with ampicillin-gentamicin; 15 (68·0% [3·84]) of 27 with amoxicillin clavulanate-amikacin; 93 (92·7% [0·24]) of 109 with ceftazidime-amikacin; and 70 (85·3% [0·47]) of 76 with piperacillin-tazobactam-amikacin. However, antibiotic and country effects could not be distinguished. Frequency of resistance was recorded most frequently with fosfomycin (in 78 isolates [68·4%] of 114), followed by colistin (55 isolates [57·3%] of 96), and gentamicin (62 isolates [53·0%] of 117). Sites in six of the seven countries (excluding South Africa) stated that the cost of antibiotics would influence treatment of neonatal sepsis. INTERPRETATION: Our data raise questions about the empirical use of combined ampicillin-gentamicin for neonatal sepsis in LMICs because of its high resistance and high rates of frequency of resistance and low probability of target attainment. Accessibility and affordability need to be considered when advocating antibiotic treatments with variance in economic health structures across LMICs. FUNDING: The Bill & Melinda Gates Foundation

    Prevalence of Mistreatment or Belittlement among Medical Students – A Cross Sectional Survey at a Private Medical School in Karachi, Pakistan

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    Background: Mistreatment or belittlement of medical students either by faculty or fellow students has often been reported. Perception of mistreatment has also been associated with increased degree of psychological morbidity. There is a lack of such studies being conducted amongst the medical students of Pakistan. The aim of this study was to determine the prevalence and forms of perceived mistreatment and presence of mental health morbidity in a private medical school in Pakistan. Also, any association between mental health morbidity and mistreatment was to be identified. Methods: A cross sectional study was carried out on medical students from Aga Khan University Hospital, Karachi, Pakistan during the period of June-September 2007. A self administered questionnaire, adapted from Frank et al and Baldwin et al was distributed to a total of 350 students. The questionnaire consisted of three parts: the first dealing with the demographics of the population, the second concerning the various forms of mistreatment, while the third assessed the mental health of students using the General Health Questionnaire 12(GHQ12). Descriptive statistics were performed. The Chi-square test and Fisher\u27s exact tests were applied. Results: A total of 350 students were approached out of which 232 completed the questionnaire giving a response rate of 66.2%. Mistreatment was reported by 62.5% (145/232) of the respondents. Of these, 69.7% (83/145) were males and 54.9% (62/145) were females. There was a significant relationship between gender, year division, stress at medical school and possible use of drugs/alcohol and reported mistreatment but no statistical relationship was seen with psychiatric morbidity. The overall prevalence of psychological morbidity was 34.8% (77/221). Conclusion: This study suggests high prevalence of perceived mistreatment and psychological morbidity among Pakistani medical students. However, no association was found between these two aspects of medical student education. There is a need to bring about changes to make the medical education environment conducive to learning. Increased student feedback, support systems and guidance about progress throughout the year and the provision of adequate learning resources may provide help with resolving both of these issues

    Do International Health Partnerships contribute to reverse innovation? a mixed methods study of THET-supported partnerships in the UK

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    Background International health partnerships (IHPs) are changing, with an increased emphasis on mutual accountability and joint agenda setting for both the high- and the low- or middle-income country (LMIC) partners. There is now an important focus on the bi-directionality of learning however for the UK partners, this typically focuses on learning at the individual level, through personal and professional development. We sought to evaluate whether this learning also takes the shape of ‘Reverse Innovation’ –when an idea conceived in a low-income country is subsequently adopted in a higher-income country. Methods This mixed methods study used an initial scoping survey of all the UK-leads of the Tropical Health Education Trust (THET)-supported International Health Partnerships (n = 114) to ascertain the extent to which the IHPs are or have been vehicles for Reverse Innovation. The survey formed the sampling frame for further deep-dive interviews to focus on volunteers’ experiences and attitudes to learning from LMICs. Interviews of IHP leads (n = 12) were audio-recorded and transcribed verbatim. Survey data was analysed descriptively. Interview transcripts were coded thematically, using an inductive approach. Results Survey response rate was 27% (n = 34). The majority (70%) strongly agreed that supporting LMIC partners best described the mission of the partnership but only 13% of respondents strongly agreed that learning about new innovations and models was a primary mission of their partnership. Although more than half of respondents reported having observed innovative practice in the LMIC, only one IHP respondent indicated that this has led to Reverse Innovation. Interviews with a sample of survey respondents revealed themes primarily around how learning is conceptualised, but also a central power imbalance between the UK and LMIC partners. Paternalistic notions of knowledge could be traced to partnership power dynamics and latent attitudes to LMICs. Conclusions Given the global flow of innovation, if High-income countries (HICs) are to benefit from LMIC practices, it is paramount to keep an open mind about where such learning can come from. Making the potential for learning more explicit and facilitating innovation dissemination upon return will ultimately underpin the success of adoption