To Kick Against the Pricks: An Examination of the Oresteia and the Acts of the Apostles

The major themes found in the Oresteia and the books of Luke and Acts of the Apostles are compared. By focusing on the similarities found in the themes of Justice, Religion, and New versus Old, the reader may determine if the phrase in question is being used as a literary allusion in the book of Acts of the Apostles to the Oresteia trilogy. The author believes this to be the case and believes that to arrive at a full understanding of the literary meaning of the phrase in question, an understanding of the major themes of the Oresteia is necessary

Comprehension as social and intellectual practice: Rebuilding curriculum in low socioeconomic and cultural minority schools

This article reframes the concept of comprehension as a social and intellectual practice. It reviews current approaches to reading instruction for linguistically and culturally diverse and low socioeconomic students, noting an emphasis on comprehension as autonomous skills. The Four Resources model (Freebody & Luke, 1990) is used to make the case for the integration of comprehension instruction with an emphasis on student cultural and community knowledge, and substantive intellectual and sociocultural content in elementary school curricula. Illustrations are drawn from research underway on the teaching of literacy in primary schools in low SES communities

The neighbourhood environment and profiles of the metabolic syndrome

Background There is a dearth of studies on how neighbourhood environmental attributes relate to the metabolic syndrome (MetS) and profiles of MetS components. We examined the associations of interrelated aspects of the neighbourhood environment, including air pollution, with MetS status and profiles of MetS components. Methods We used socio-demographic and MetS-related data from 3681 urban adults who participated in the 3rd wave of the Australian Diabetes, Obesity and Lifestyle Study. Neighbourhood environmental attributes included area socio-economic status (SES), population density, street intersection density, non-commercial land use mix, percentages of commercial land, parkland and blue space. Annual average concentrations of NO2 and PM2.5 were estimated using satellite-based land-use regression models. Latent class analysis (LCA) identified homogenous groups (latent classes) of participants based on MetS components data. Participants were then classified into five metabolic profiles according to their MetS-components latent class and MetS status. Generalised additive mixed models were used to estimate relationships of environmental attributes with MetS status and metabolic profiles. Results LCA yielded three latent classes, one including only participants without MetS (“Lower probability of MetS components” profile). The other two classes/profiles, consisting of participants with and without MetS, were “Medium-to-high probability of high fasting blood glucose, waist circumference and blood pressure” and “Higher probability of MetS components”. Area SES was the only significant predictor of MetS status: participants from high SES areas were less likely to have MetS. Area SES, percentage of commercial land and NO2 were associated with the odds of membership to healthier metabolic profiles without MetS, while annual average concentration of PM2.5 was associated with unhealthier metabolic profiles with MetS. Conclusions This study supports the utility of operationalising MetS as a combination of latent classes of MetS components and MetS status in studies of environmental correlates. Higher socio-economic advantage, good access to commercial services and low air pollution levels appear to independently contribute to different facets of metabolic health. Future research needs to consider conducting longitudinal studies using fine-grained environmental measures that more accurately characterise the neighbourhood environment in relation to behaviours or other mechanisms related to MetS and its components

Using OpenSim to predict knee joint moments during cycling

Cycling is a relatively low impact activity conventionally recommended as a rehabilitative or fitness sustaining exercise for patients at a high risk for knee osteoarthritis (OA) [1,2]. Expanding our understanding of knee joint loads is necessary to develop and improve evidence-based prescriptions for cycling as a rehabilitative and fitness therapy that limits the risk for knee OA. OpenSim (www.simtk.org) is an open source biomechanical analysis software that can partition predictions of external joint loads (or net muscle moments) into muscle and joint contact loads [3]. Joint contact loads more accurately represent cartilage tissue loading and hence risk for cartilage damage and/or OA [4]. As a first step towards predicting knee joint contact loads during cycling, we hypothesized that OpenSim can predict external knee joint moments that are consistent with published data [5,6]. To address this hypothesis, we conducted cycling experiments and used OpenSim’s scale tool, inverse kinematics (IK) solver, and inverse dynamics (ID) solver to model the recorded activity

Energy Flow in the Hadronic Final State of Diffractive and Non-Diffractive Deep-Inelastic Scattering at HERA

An investigation of the hadronic final state in diffractive and non--diffractive deep--inelastic electron--proton scattering at HERA is presented, where diffractive data are selected experimentally by demanding a large gap in pseudo --rapidity around the proton remnant direction. The transverse energy flow in the hadronic final state is evaluated using a set of estimators which quantify topological properties. Using available Monte Carlo QCD calculations, it is demonstrated that the final state in diffractive DIS exhibits the features expected if the interaction is interpreted as the scattering of an electron off a current quark with associated effects of perturbative QCD. A model in which deep--inelastic diffraction is taken to be the exchange of a pomeron with partonic structure is found to reproduce the measurements well. Models for deep--inelastic $ep$ scattering, in which a sizeable diffractive contribution is present because of non--perturbative effects in the production of the hadronic final state, reproduce the general tendencies of the data but in all give a worse description.Comment: 22 pages, latex, 6 Figures appended as uuencoded fil

A direct comparison of strategies for combinatorial RNA interference

<p>Abstract</p> <p>Background</p> <p>Combinatorial RNA interference (co-RNAi) is a valuable tool for highly effective gene suppression of single and multiple-genes targets, and can be used to prevent the escape of mutation-prone transcripts. There are currently three main approaches used to achieve co-RNAi in animal cells; multiple promoter/shRNA cassettes, long hairpin RNAs (lhRNA) and miRNA-embedded shRNAs, however, the relative effectiveness of each is not known. The current study directly compares the ability of each co-RNAi method to deliver pre-validated siRNA molecules to the same gene targets.</p> <p>Results</p> <p>Double-shRNA expression vectors were generated for each co-RNAi platform and their ability to suppress both single and double-gene reporter targets were compared. The most reliable and effective gene silencing was achieved from the multiple promoter/shRNA approach, as this method induced additive suppression of single-gene targets and equally effective knockdown of double-gene targets. Although both lhRNA and microRNA-embedded strategies provided efficient gene knockdown, suppression levels were inconsistent and activity varied greatly for different siRNAs tested. Furthermore, it appeared that not only the position of siRNAs within these multi-shRNA constructs impacted upon silencing activity, but also local properties of each individual molecule. In addition, it was also found that the insertion of up to five promoter/shRNA cassettes into a single construct did not negatively affect the efficacy of each individual shRNA.</p> <p>Conclusions</p> <p>By directly comparing the ability of shRNAs delivered from different co-RNA platforms to initiate knockdown of the same gene targets, we found that multiple U6/shRNA cassettes offered the most reliable and predictable suppression of both single and multiple-gene targets. These results highlight some important strengths and pitfalls of the currently used methods for multiple shRNA delivery, and provide valuable insights for the design and application of reliable co-RNAi.</p

A multiplexed, confinable CRISPR/Cas9 gene drive can propagate in caged Aedes aegypti populations

Aedes aegypti is the main vector of several major pathogens including dengue, Zika and chikungunya viruses. Classical mosquito control strategies utilizing insecticides are threatened by rising resistance. This has stimulated interest in new genetic systems such as gene drivesHere, we test the regulatory sequences from the Ae. aegypti benign gonial cell neoplasm (bgcn) homolog to express Cas9 and a separate multiplexing sgRNA-expressing cassette inserted into the Ae. aegypti kynurenine 3-monooxygenase (kmo) gene. When combined, these two elements provide highly effective germline cutting at the kmo locus and act as a gene drive. Our target genetic element drives through a cage trial population such that carrier frequency of the element increases from 50% to up to 89% of the population despite significant fitness costs to kmo insertions. Deep sequencing suggests that the multiplexing design could mitigate resistance allele formation in our gene drive system

Antibody drug conjugates against the receptor for advanced glycation end products (RAGE), a novel therapeutic target in endometrial cancer

Background The treatment of endometrial cancer (EC), the most common gynecological cancer, is currently hampered by the toxicity of current cytotoxic agents, meaning novel therapeutic approaches are urgently required. Methods A cohort of 161 patients was evaluated for the expression of the receptor for advanced glycation end products (RAGE) in endometrial tissues. The present study also incorporates a variety of in vitro methodologies within multiple cell lines to evaluate RAGE expression and antibody-drug conjugate efficacy, internalisation and intercellular trafficking. Additionally, we undertook in vivo bio-distribution and toxicity evaluation to determine the suitability of our chosen therapeutic approach, together with efficacy studies in a mouse xenograft model of disease. Results We have identified an association between over-expression of the receptor for advanced glycation end products (RAGE) and EC (H-score = Healthy: 0.46, SD 0.26; Type I EC: 2.67, SD 1.39; Type II EC: 2.20, SD 1.34; ANOVA, p < 0.0001). Furthermore, increased expression was negatively correlated with patient survival (Spearman’s Rank Order Correlation: ρ = − 0.3914, p < 0.05). To exploit this association, we developed novel RAGE-targeting antibody drug conjugates (ADC) and demonstrated the efficacy of this approach. RAGE-targeting ADCs were up to 100-fold more efficacious in EC cells compared to non-malignant cells and up to 200-fold more cytotoxic than drug treatment alone. Additionally, RAGE-targeting ADCs were not toxic in an in vivo pre-clinical mouse model, and significantly reduced tumour growth in a xenograft mouse model of disease. Conclusions These data, together with important design considerations implied by the present study, suggest RAGE-ADCs could be translated to novel therapeutics for EC patients

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Relationships between supermicrometer particle concentrations and cloud water sea salt and dust concentrations, analysis of MONARC and ACTIVATE data

This study uses airborne field data from the MONterey Aerosol Research Campaign (MONARC northeast Pacific summer 2019) and Aerosol Cloud meTeorology Interactions oVer the western ATlantic Experiment (ACTIVATE: northwest Atlantic winter and summer 2020) to examine relationships between giant cloud condensation nuclei (GCCN) and cloud composition to advance knowledge of poorly characterized GCCNc loud interactions. The analysis compares cloud water composition data to particle concentration data with different minimum dry diameters between 1 and 10 mum (hereafter referred to as GCCN) collected below and above clouds adjacent to where cloud water samples were collected