31 research outputs found
Unleashing Mask: Explore the Intrinsic Out-of-Distribution Detection Capability
Out-of-distribution (OOD) detection is an indispensable aspect of secure AI
when deploying machine learning models in real-world applications. Previous
paradigms either explore better scoring functions or utilize the knowledge of
outliers to equip the models with the ability of OOD detection. However, few of
them pay attention to the intrinsic OOD detection capability of the given
model. In this work, we generally discover the existence of an intermediate
stage of a model trained on in-distribution (ID) data having higher OOD
detection performance than that of its final stage across different settings,
and further identify one critical data-level attribution to be learning with
the atypical samples. Based on such insights, we propose a novel method,
Unleashing Mask, which aims to restore the OOD discriminative capabilities of
the well-trained model with ID data. Our method utilizes a mask to figure out
the memorized atypical samples, and then finetune the model or prune it with
the introduced mask to forget them. Extensive experiments and analysis
demonstrate the effectiveness of our method. The code is available at:
https://github.com/tmlr-group/Unleashing-Mask.Comment: accepted by ICML 202
Optimization of Anti‐Pseudomonal Antibiotics for Cystic Fibrosis Pulmonary Exacerbations: IV. Colistimethate Sodium
Patients with cystic fibrosis (CF) often experience acute pulmonary exacerbations (APE) and may be treated with a wide variety of intravenous antibiotics. The aim of this review is to provide an evidence‐based summary of pharmacokinetic/pharmacodynamic (PK/PD), tolerability, and efficacy studies utilizing the intravenous (IV) polymixin antibiotic colistimethate sodium (CMS) in the treatment of APE and to identify areas where further study is warranted. Currently, there is not an international standard on the labeling of CMS products. As a result, this has lead to confusion in the interpretation of the literature with respect to efficacy, tolerance, and optimal dosing strategy. The dosing ranges of IV CMS from the literature are 5.3–12.9 mg/kg/day, maximum 480 mg per day for 60 kg patient (Colomycin® injection‐European product) and 8–21.3 mg/kg/day, maximum 800 mg per day for 60 kg patient (Coly‐Mycin M® parenteral‐US product).The literature supports a CMS dose of 8 mg/kg/day divided every 8 hr (maximum 480 mg/day) for the treatment of APE secondary to Pseudomonas aeruginosa. The maximum recommended CMS dose of 480 mg/day is less than is recommended by the FDA‐approved and CFF dosing guidelines but in agreement with UK CF Trust Antibiotic Working Group recommendations. There is debate over the frequency of CMS administration (once daily vs. thrice‐daily) and its impact on resistance and clinical efficacy. Further study is needed to determine the tolerability and efficacy of extended‐interval dosing of CMS in the treatment of APE. Pediatr Pulmonol. 2013; 48:1–7. © 2012 Wiley Periodicals, Inc
Combination and nanotechnology based pharmaceutical strategies for combating respiratory bacterial biofilm infections
Optimization of anti-pseudomonal antibiotics for cystic fibrosis pulmonary exacerbations: IV. colistimethate sodium
The Antibacterial Effects of an Antimicrobial Peptide Human β-Defensin 3 Fused with Carbohydrate-Binding Domain on Pseudomonas aeruginosa PA14
Pharmacokinetics/Pharmacodynamics of Pulmonary Delivery of Colistin against Pseudomonas aeruginosa in a Mouse Lung Infection Model
Mucoid Pseudomonas aeruginosa alters sputum viscoelasticity in patients with non-cystic fibrosis bronchiectasis
Searching for Novel Inhibitors of the S. aureus NorA Efflux Pump: Synthesis and Biological Evaluation of the 3-Phenyl-1,4-benzothiazine Analogues
Bacterial resistance to antimicrobial agents has become an increasingly serious health problem in recent years. Among the strategies by which resistance can be achieved, overexpression of efflux pumps such as NorA of S. aureus leads to a sub-lethal concentration of the antibacterial at the active site that in turn may predispose the organism to the development of high-level target-based resistance. With the aim to improve both the chemical stability and the potency of our previously reported 3-phenyl-1,4-benzothiazine NorA inhibitors, we replaced the benzothiazine core with different nuclei. None of the new synthesized compounds showed any appreciable intrinsic antibacterial activity and, in particular, the 2-phenylquinoline 6c was able to reduce, in a concentration-dependent manner, the ciprofloxacin MIC against the norA-overexpressing strains S. aureus SA-K2378 (norA++) and SA-1199B (norA+/ A116E GrlA)