Antiviral drug discovery : preparing for the next pandemic

Acknowledgements The authors also gratefully acknowledge financial support from the South African Medical Research Council (MRC) with funds received from the South African National Department of Health and the UK Government's Newton Fund (R. A. D., RL. M. G., K. C.), the UK Engineering and Physical Sciences Research Council EQATA (R. J. M. G.), the UK Global Challenge Research Fund (R. J. M. G., R. A. D.), the University of Cape Town (K. C.) and the South African Research Chairs Initiative of the Department of Science and Innovation, administered through the South African National Research Foundation (NRF) to K. C. (UID: 64767) and R. A. D. (UID: 87583). C. S. A. acknowledges financial support for SARS-CoV-2/Covid-19 research from UKMRC (CVG-1725-2020) and UKRI-DHSC (MR/Vo28464/1). The authors acknowledge Bronwyn Tweedie of the Rhodes University Print Services Unit who provided the graphics for Fig. 1 and thank Gordon Cragg for his insightful comments and encouragement during the preparation of this manuscript.Peer reviewedPublisher PD

Ashamed and Fused with Body Image and Eating: Binge Eating as an Avoidance Strategy

Binge Eating Disorder (BED) is currently recognized as a severe disorder associated with relevant psychiatric and physical comorbidity, and marked emotional distress. Shame is a specific negative emotion that has been highlighted as central in eating disorders. However, the effect of shame and underlying mechanisms on binge eating symptomatology severity remained unclear. This study examines the role of shame, depressive symptoms, weight and shape concerns and eating concerns, and body image-related cognitive fusion, on binge eating symptomatology severity. Participated in this study 73 patients with the diagnosis of BED, established through a clinical interview-Eating Disorder Examination 17.0D-who completed measures of external shame, body-image related cognitive fusion, depressive symptoms and binge eating symptomatology. Results revealed positive associations between binge eating severity and depressive symptoms, shame, weight and shape concerns, eating concerns and body image-related cognitive fusion. A path analysis showed that, when controlling for the effect of depressive symptoms, external shame has a direct effect on binge eating severity, and an indirect effect mediated by increased eating concern and higher levels of body image-related cognitive fusion. Results confirmed the plausibility of the model, which explained 43% of the severity of binge eating symptoms. The proposed model suggests that, in BED patients, perceiving that others see the self negatively may be associated with an entanglement with body image-related thoughts and concerns about eating, which may, in turn, fuel binge eating symptoms. Findings have important clinical implications supporting the relevance of addressing shame and associated processes in binge eating. Copyright © 2015 John Wiley & Sons, Ltd

Identification of ILK as a critical regulator of VEGFR3 signalling and lymphatic vascular growth

Vascular endothelial growth factor receptor-3 (VEGFR3) signalling promotes lymphangiogenesis. While there are many reported mechanisms of VEGFR3 activation, there is little understanding of how VEGFR3 signalling is attenuated to prevent lymphatic vascular overgrowth and ensure proper lymph vessel development. Here, we show that endothelial cell-specific depletion of integrin-linked kinase (ILK) in mouse embryos hyper-activates VEGFR3 signalling and leads to overgrowth of the jugular lymph sacs/primordial thoracic ducts, oedema and embryonic lethality. Lymphatic endothelial cell (LEC)-specific deletion of Ilk in adult mice initiates lymphatic vascular expansion in different organs, including cornea, skin and myocardium. Knockdown of ILK in human LECs triggers VEGFR3 tyrosine phosphorylation and proliferation. ILK is further found to impede interactions between VEGFR3 and β1 integrin in vitro and in vivo, and endothelial cell-specific deletion of an Itgb1 allele rescues the excessive lymphatic vascular growth observed upon ILK depletion. Finally, mechanical stimulation disrupts the assembly of ILK and β1 integrin, releasing the integrin to enable its interaction with VEGFR3. Our data suggest that ILK facilitates mechanically regulated VEGFR3 signalling via controlling its interaction with β1 integrin and thus ensures proper development of lymphatic vessels

Contextualizing the Global Nursing Care Chain: International Migration and the Status of Nursing in Kerala, India

In this article I explore the issue of nursing status in Kerala, India and how over time a colonial discourse of caste‐based pollution has given way to a discourse of sexual pollution under expanding migratory opportunities. Based on survey and qualitative research findings, I caution that the improving occupational status of nursing in India is not directly mapped onto social status, and this is particularly evident in the matrimonial market. In the light of these findings I argue that global nursing care chain (GNCC) analysis must assess more than just workplace contexts in order to conceptualize how global care chains (GCCs) interlock, and how they are differentiated from each other

Practice activity trends among oral and maxillofacial surgeons in Australia

BACKGROUND: The aim of this study was to describe practice activity trends among oral and maxillofacial surgeons in Australia over time. METHODS: All registered oral and maxillofacial surgeons in Australia were surveyed in 1990 and 2000 using mailed self-complete questionnaires. RESULTS: Data were available from 79 surgeons from 1990 (response rate = 73.8%) and 116 surgeons from 2000 (response rate = 65.1%). The rate of provision of services per visit changed over time with increased rates observed overall (from 1.43 ± 0.05 services per visit in 1990 to 1.66 ± 0.06 services per visit in 2000), reflecting increases in pathology and reconstructive surgery. No change over time was observed in the provision of services per year (4,521 ± 286 services per year in 1990 and 4,503 ± 367 services per year in 2000). Time devoted to work showed no significant change over time (1,682 ± 75 hours per year in 1990 and 1,681 ± 94 hours per year in 2000), while the number of visits per week declined (70 ± 4 visits per week in 1990 to 58 ± 4 visits per week in 2000). CONCLUSIONS: The apparent stability in the volume of services provided per year reflected a counterbalancing of increased services provided per visit and a decrease in the number of visits supplied

The Azithromycin to Prevent Wheezing following severe RSV bronchiolitis-II clinical trial: Rationale, study design, methods, and characteristics of study population

Severe respiratory syncytial virus (RSV) bronchiolitis in early life is a significant risk factor for future recurrent wheeze (RW) and asthma. The goal of the Azithromycin to Prevent Wheezing following severe RSV bronchiolitis II (APW-RSV II) clinical trial is to evaluate if azithromycin treatment in infants hospitalized with RSV bronchiolitis reduces the occurrence of RW during the preschool years. The APW-RSV II clinical trial is a double-blind, placebo-controlled, parallel-group, randomized trial, including otherwise healthy participants, ages 30 days-18 months, who are hospitalized due to RSV bronchiolitis. The study includes an active randomized treatment phase with azithromycin or placebo for 2 weeks, and an observational phase of 18-48 months. Two hundred participants were enrolled during three consecutive RSV seasons beginning in the fall of 2016 and were randomized to receive oral azithromycin 10 mg/kg/day for 7 days followed by 5 mg/kg/day for an additional 7 days, or matched placebo. The study hypothesis is that in infants hospitalized with RSV bronchiolitis, the addition of azithromycin therapy to routine bronchiolitis care would reduce the likelihood of developing post-RSV recurrent wheeze (≥3 episodes). The primary clinical outcome is the occurrence of a third episode of wheezing, which is evaluated every other month by phone questionnaires and during yearly in-person visits. A secondary objective of the APW-RSV II clinical trial is to examine how azithromycin therapy changes the upper airway microbiome composition, and to determine if these changes are related to the occurrence of post-RSV RW. Microbiome composition is characterized in nasal wash samples obtained before and after the study treatments. This clinical trial may identify the first effective intervention applied during severe RSV bronchiolitis to reduce the risk of post-RSV RW and ultimately asthma

Taking Ownership: Our Pledge to Educate All of Detroit's Children

Excellent Schools Detroit represents a broad and diverse cross section of Detroit's education, government, civic and community, parent, organized labor, and philanthropic leaders who are committed to ensuring that all Detroit children receive the great education they deserve. This citywide education plan reflects months of discussions and deliberations by coalition members, as well as a series of six community meetings in November and December, youth focus groups, small group discussions with multiple stakeholders, and other outreach efforts. We appreciate the thoughtful recommendations from the many Detroiters who are as passionate as we are about the need to prepare all students for college, careers, and life in the 21st century

Limits on WWZ and WW\gamma couplings from p\bar{p}\to e\nu jj X events at \sqrt{s} = 1.8 TeV

We present limits on anomalous WWZ and WW-gamma couplings from a search for WW and WZ production in p-bar p collisions at sqrt(s)=1.8 TeV. We use p-bar p -> e-nu jjX events recorded with the D0 detector at the Fermilab Tevatron Collider during the 1992-1995 run. The data sample corresponds to an integrated luminosity of 96.0+-5.1 pb^(-1). Assuming identical WWZ and WW-gamma coupling parameters, the 95% CL limits on the CP-conserving couplings are -0.33<lambda<0.36 (Delta-kappa=0) and -0.43<Delta-kappa<0.59 (lambda=0), for a form factor scale Lambda = 2.0 TeV. Limits based on other assumptions are also presented.Comment: 11 pages, 2 figures, 2 table

Search For Heavy Pointlike Dirac Monopoles

We have searched for central production of a pair of photons with high transverse energies in $p\bar p$ collisions at $\sqrt{s} = 1.8$ TeV using $70 pb^{-1}$ of data collected with the D\O detector at the Fermilab Tevatron in 1994--1996. If they exist, virtual heavy pointlike Dirac monopoles could rescatter pairs of nearly real photons into this final state via a box diagram. We observe no excess of events above background, and set lower 95% C.L. limits of $610, 870, or 1580 GeV/c^2$ on the mass of a spin 0, 1/2, or 1 Dirac monopole.Comment: 12 pages, 4 figure