68 research outputs found
Anomalous diffusion in polymers: long-time behaviour
We study the Dirichlet boundary value problem for viscoelastic diffusion in
polymers. We show that its weak solutions generate a dissipative semiflow. We
construct the minimal trajectory attractor and the global attractor for this
problem.Comment: 13 page
Polymeric Micelles in Anticancer Therapy: Targeting, Imaging and Triggered Release
Micelles are colloidal particles with a size around 5β100Β nm which are currently under investigation as carriers for hydrophobic drugs in anticancer therapy. Currently, five micellar formulations for anticancer therapy are under clinical evaluation, of which Genexol-PM has been FDA approved for use in patients with breast cancer. Micelle-based drug delivery, however, can be improved in different ways. Targeting ligands can be attached to the micelles which specifically recognize and bind to receptors overexpressed in tumor cells, and chelation or incorporation of imaging moieties enables tracking micelles in vivo for biodistribution studies. Moreover, pH-, thermo-, ultrasound-, or light-sensitive block copolymers allow for controlled micelle dissociation and triggered drug release. The combination of these approaches will further improve specificity and efficacy of micelle-based drug delivery and brings the development of a βmagic bulletβ a major step forward
Recommended from our members
The burden of bacterial antimicrobial resistance in the WHO African region in 2019: a cross-country systematic analysis
Background
A critical and persistent challenge to global health and modern health care is the threat of antimicrobial resistance (AMR). Previous studies have reported a disproportionate burden of AMR in low-income and middle-income countries, but there remains an urgent need for more in-depth analyses across Africa. This study presents one of the most comprehensive sets of regional and country-level estimates of bacterial AMR burden in the WHO African region to date.
Methods
We estimated deaths and disability-adjusted life-years (DALYs) attributable to and associated with AMR for 23 bacterial pathogens and 88 pathogenβdrug combinations for countries in the WHO African region in 2019. Our methodological approach consisted of five broad components: the number of deaths in which infection had a role, the proportion of infectious deaths attributable to a given infectious syndrome, the proportion of infectious syndrome deaths attributable to a given pathogen, the percentage of a given pathogen resistant to an antimicrobial drug of interest, and the excess risk of mortality (or duration of an infection) associated with this resistance. These components were then used to estimate the disease burden by using two counterfactual scenarios: deaths attributable to AMR (considering an alternative scenario where infections with resistant pathogens are replaced with susceptible ones) and deaths associated with AMR (considering an alternative scenario where drug-resistant infections would not occur at all). We obtained data from research hospitals, surveillance networks, and infection databases maintained by private laboratories and medical technology companies. We generated 95% uncertainty intervals (UIs) for final estimates as the 25th and 975th ordered values across 1000 posterior draws, and models were cross-validated for out-of-sample predictive validity.
Findings
In the WHO African region in 2019, there were an estimated 1Β·05 million deaths (95% UI 829β000β1β316β000) associated with bacterial AMR and 250β000 deaths (192β000β325β000) attributable to bacterial AMR. The largest fatal AMR burden was attributed to lower respiratory and thorax infections (119β000 deaths [92β000β151β000], or 48% of all estimated bacterial pathogen AMR deaths), bloodstream infections (56β000 deaths [37β000β82β000], or 22%), intra-abdominal infections (26β000 deaths [17β000β39β000], or 10%), and tuberculosis (18β000 deaths [3850β39β000], or 7%). Seven leading pathogens were collectively responsible for 821β000 deaths (636β000β1β051β000) associated with resistance in this region, with four pathogens exceeding 100β000 deaths each: Streptococcus pneumoniae, Klebsiella pneumoniae, Escherichia coli, and Staphylococcus aureus. Third-generation cephalosporin-resistant K pneumoniae and meticillin-resistant S aureus were shown to be the leading pathogenβdrug combinations in 25 and 16 countries, respectively (53% and 34% of the whole region, comprising 47 countries) for deaths attributable to AMR.
Interpretation
This study reveals a high level of AMR burden for several bacterial pathogens and pathogenβdrug combinations in the WHO African region. The high mortality rates associated with these pathogens demonstrate an urgent need to address the burden of AMR in Africa. These estimates also show that quality and access to health care and safe water and sanitation are correlated with AMR mortality, with a higher fatal burden found in lower resource settings. Our cross-country analyses within this region can help local governments to leverage domestic and global funding to create stewardship policies that target the leading pathogenβdrug combinations.
Funding
Bill & Melinda Gates Foundation, Wellcome Trust, and Department of Health and Social Care using UK aid funding managed by the Fleming Fund
- β¦