Pseudomonas aeruginosa (PA) is known to chronically infect airways of people with cystic fibrosis (CF) by early adulthood. PA infections can lead to increased airway inflammation and lung tissue ...damage, ultimately contributing to decreased lung function and quality of life. Existing models of PA infection in vitro commonly utilize 1-6-hour time courses. However, these relatively early time points may not encompass downstream airway cell signaling in response to the chronic PA infections observed in people with cystic fibrosis. To fill this gap in knowledge, the aim of this study was to establish an in vitro model that allows for PA infection of CF bronchial epithelial cells, cultured at the air liquid interface, for 24 hours. Our model shows with an inoculum of 2 x 102 CFUs of PA for 24 hours pro-inflammatory markers such as interleukin 6 and interleukin 8 are upregulated with little decrease in CF bronchial epithelial cell survival or monolayer confluency. Additionally, immunoblotting for phosphorylated phospholipase C gamma, a well-known downstream protein of fibroblast growth factor receptor signaling, showed significantly elevated levels after 24 hours with PA infection that were not seen at earlier timepoints. Finally, inhibition of phospholipase C shows significant downregulation of interleukin 8. Our data suggest that this newly developed in vitro "prolonged PA infection model" recapitulates the elevated inflammatory markers observed in CF, without compromising cell survival. This extended period of PA growth on CF bronchial epithelial cells will have impact on further studies of cell signaling and microbiological studies that were not possible in previous models using shorter PA exposures.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Educational institutions are increasingly turning to learning analytics to identify and intervene with students at risk of underperformance or discontinuation. However, the extent to which the ...current evidence base supports this investment is currently unclear, and particularly so in relation to the effectiveness of interventions based on predictive models. The aim of the present paper was to conduct a systematic review and quality assessment of studies on the use of learning analytics in higher education, focusing specifically on intervention studies. Search terms identified 689 papers, but only 11 studies evaluated the effectiveness of interventions based on learning analytics. These studies highlighted the potential of such interventions, but the general quality of the research was moderate, and left several important questions unanswered. The key recommendation based on this review is that more research into the implementation and evaluation of scientifically driven learning analytics is needed to build a solid evidence base for the feasibility, effectiveness and generalizability of such interventions. This is particularly relevant when considering the increasing tendency of educational institutions around the world to implement learning analytics interventions with only little evidence of their effectiveness.
Practitioner Notes
What is already known about this topic?
Drop‐out rates and underachivement is a significant issue at most Western universities.
Learning analytics have been shown to predict student performance and risk of dropping out.
Interventions based on learning analytics have emerged in recent years, some reportedly successful.
What this paper adds
The paper also reviews and synthesizes the evidence on the effectiveness of learning analytics interventions targeting student underperformance, experience and discontinuation.
The paper compares and contrasts past and current learning analytics methods and foci, and makes recommendations for the future research and practice.
It critically synthesizes the current evidence base on learning analytics interventions, which is a field that is in constant flux and development.
Implications for practice and/or policy
The paper focuses on an increasing part of higher education with the goal of validating learning analytics methods and usefulness.
The paper makes evidence‐based recommendations for institutions wishing to implement learning analytics programs and/or interventions.
The paper makes evidence‐based recommendations for instructors as well as researchers in the field.
Provides an in-depth analysis of Talk to Her, including both the formal elements of the film (its narrative, genre, and auteur study) and the themes and issues it raises.
Abstract
GPR61 is an orphan GPCR related to biogenic amine receptors. Its association with phenotypes relating to appetite makes it of interest as a druggable target to treat disorders of metabolism ...and body weight, such as obesity and cachexia. To date, the lack of structural information or a known biological ligand or tool compound has hindered comprehensive efforts to study GPR61 structure and function. Here, we report a structural characterization of GPR61, in both its active-like complex with heterotrimeric G protein and in its inactive state. Moreover, we report the discovery of a potent and selective small-molecule inverse agonist against GPR61 and structural elucidation of its allosteric binding site and mode of action. These findings offer mechanistic insights into an orphan GPCR while providing both a structural framework and tool compound to support further studies of GPR61 function and modulation.
Orbital pathologies can be broadly classified as ocular, extra-ocular soft-tissue (non-neoplastic and neoplastic), osseous, and traumatic. In part 1 of this orbital series, the authors will discuss ...the differential diagnosis and key imaging features of pediatric ocular pathologies. These include congenital and developmental lesions (microphthalmos, anophthalmos, persistent fetal vasculature, coloboma, morning glory disc anomaly, retinopathy of prematurity, Coats disease), optic disc drusen, infective and inflammatory lesions (uveitis, toxocariasis, toxoplasmosis), and ocular neoplasms (retinoblastoma, retinal hamartoma, choroidal melanoma, choroidal nevus). This pictorial review provides a practical approach to the imaging work-up of these anomalies with a focus on ocular US as the first imaging modality and additional use of CT and/or MRI for the evaluation of intracranial abnormalities. The characteristic imaging features of the non-neoplastic mimics of retinoblastoma, such as persistent fetal vasculature and Coats disease, are also highlighted.
Graphical Abstract
Orbital pathologies can be broadly classified as ocular, extraocular soft-tissue (non-neoplastic and neoplastic), osseous, and traumatic. In this paper, we discuss the key imaging features and ...differential diagnoses of congenital and developmental lesions (dermoid cyst, dermolipoma), infective and inflammatory pathologies (pre-septal cellulitis, orbital cellulitis, optic neuritis, chalazion, thyroid ophthalmopathy, orbital pseudotumor), and non-neoplastic vascular anomalies (venous malformation, lymphatic malformation, carotid-cavernous fistula), emphasizing the key role of CT and MRI in the imaging work-up. In addition, we highlight the adjunctive role of ocular ultrasound in the diagnosis of dermoid cyst and chalazion, and discuss the primary role of ultrasound in the diagnosis of vascular malformations.
Graphical abstract
Pediatric neoplastic extraocular soft-tissue lesions in the orbit are uncommon. Early multimodality imaging work-up and recognition of the key imaging features of these lesions allow narrowing of the ...differential diagnoses in order to direct timely management. In this paper, the authors present a multimodality approach to the imaging work-up of these lesions and highlight the use of ocular ultrasound as a first imaging modality where appropriate. We will discuss vascular neoplasms (congenital hemangioma, infantile hemangioma), optic nerve lesions (meningioma, optic nerve glioma), and other neoplastic lesions (plexiform neurofibroma, teratoma, chloroma, rhabdomyosarcoma, infantile fibrosarcoma, schwannoma).
Graphical Abstract
Orbital pathologies can be broadly classified as ocular lesions, extraocular soft-tissue pathologies (non-neoplastic and neoplastic), and bony and traumatic lesions. In this paper, we discuss the key ...imaging features and differential diagnoses of bony and traumatic lesions of the pediatric orbit and globe, emphasizing the role of CT and MRI as the primary imaging modalities. In addition, we highlight the adjunctive role of ocular sonography in the diagnosis of intraocular foreign bodies and discuss the primary role of sonography in the diagnosis of traumatic retinal detachment.
Graphical abstract
Research in the social identity tradition acknowledges the multiplicity of our identities and the implications that identity compatibility has for our health and well‐being. However, current measures ...of multiple group membership have not yet captured the richness and complexity of our social identity networks at the wider sample level, and data regarding the different behaviours typically associated with different group memberships are scarce. Adopting a network approach, we explore the co‐occurrence of different group memberships within an individual (identity‐by‐identity network), the behaviours that are shared among identities (behaviour‐by‐identity network), and whether identities that are shared also share common behaviours (identity‐by‐behaviour network). An online survey asked participants (N = 286) to list the groups they are part of, as well as the behaviours viewed to be typical of group members. The networks identified several identities and behaviours to significantly co‐occur at a rate both higher and lower than chance. Networks were found to be low in modularity; there was no evidence of clustering within the data. Permutation analyses demonstrated the overall structure of the networks to be significantly different than expected by chance. The co‐occurrences identified serve as a meaningful resource for those conducting research into identities, group norms and their associated behaviours.
Childhood cancer is increasing in prevalence whilst survival rates are improving. The prevalence of adult survivors of childhood cancer is consequently increasing. Many survivors suffer long‐term ...consequences of their cancer treatment. Whilst many of these are well documented, relatively little is known about the mental health of survivors of childhood cancer. This article aimed to describe the prevalence and spectrum of mental health problems found in adult survivors of childhood cancer using a systematic review methodology. Our review included 67 articles, describing a number of problems, including depression, anxiety, behavioural problems and drug misuse. Factors increasing the likelihood of mental health problems included treatment with high‐dose anthracyclines, cranial irradiation, diagnoses of sarcoma or central nervous system tumours and ongoing physical ill health. There were numerous limitations to the studies we found, including use of siblings of survivors as a control group, self‐report methodology and lack of indications for prescriptions when prescribing data were used. This review has identified many mental health problems experienced by survivors of childhood cancer; however, the exact incidence, prevalence and risk‐factors for their development remain unclear. Further work to identify childhood cancer patients who are at risk of developing late mental health morbidity is essential.
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