Superswelling Microneedle Arrays for Dermal Interstitial Fluid (Prote)Omics

The noninvasive sampling of dermal interstitial fluid (ISF) for the monitoring of clinical biomarkers is a greatly appealing area of research. The identification of molecular biomarkers in biological fluids has been accelerated with -omics analyses but remains limited in ISF because of its time-consuming and complex extraction process. Here, the generation of microneedle (MN) patches made of superabsorbent acrylate-based hydrogels for the rapid sampling of dermal ISF is described to explore its proteome. In depth, iterative optimization allows the identification of novel acrylate-based compositions with the required chemical, mechanical, and biocompatibility properties allowing proteomic analysis of the extracted ISF for the first time after sampling with swelling MNs. The generated MN arrays show no cytotoxic effect, successfully cross the stratum corneum, and can collect up to 6 µL of dermal ISF in 10 min in vivo. Proteomics lead to the detection of 176 clinically relevant biomarkers in the collected samples validating the use of ISF as a relevant bodily fluid for disease monitoring and diagnostic. Importantly, it is discovered that extraction fingerprint is strongly dependent on the MNs chemistry, and thus specific biomarkers could be selectively extracted by tuning the composition of the patch, making the system versatile and specific.     

The Critical Role of Passive Permeability in Designing Successful Drugs

Passive permeability is a key property in drug disposition and delivery. It is critical for gastrointestinal absorption, brain penetration, renal reabsorption, defining clearance mechanisms and drug-drug interactions. Passive diffusion rate is translatable across tissues and animal species, while the extent of absorption is dependent on drug properties, as well as in vivo physiology/pathophysiology. Design principles have been developed to guide medicinal chemistry to enhance absorption, which combine the balance of aqueous solubility, permeability and the sometimes unfavorable compound characteristic demanded by the target. Permeability assays have been implemented that enable rapid development of structure-permeability relationships for absorption improvement. Future advances in assay development to reduce nonspecific binding and improve mass balance will enable more accurately measurement of passive permeability. Design principles that integrate potency, selectivity, passive permeability and other ADMET properties facilitate rapid advancement of successful drug candidates to patients.     

p53 gene therapy in vivo of herpatocellular and liver metastatic colorectal cancer

Tumor suppressor genes such as p53 contribute to the oncogenic process via loss-of-function mechanisms such as genetic mutation or complex formation with other cellular or viral proteins. p53 is mutated in approximately 50% of human tumors and has an important role in the genesis or progression of both colorectal and hepatocellular cancers. Colorectal cancer is leading cause of cancer mortality in the United States, whereas hepatocellular cancer is the leading worldwide cause of cancer death; the liver is a primary site of morbidity in both diseases. Because systemic tumor suppressor gene therapy is currently not feasible, we have chosen to develop a regional form of such therapy directed at primary or metastatic liver neoplasms. Gene replacement therapy with p53 is a promising new strategy to treat advanced human cancers.     

PROBLEM-SOLVING SUPPORT FOR TQM A Hypertext Approach

New IS technology is contributing to continuous quality improvement throughout the organization. Hypertext and hypermedia offer new ways for decision makers to gain easy and relevant access to information. By combining hypertext with total quality tools, decision makers are able to explore the richness of data bases in more creative and useful ways. This article describes how you can develop a hypertext system that can help employees improve their job performance through better problem solving.     

Methodological issues in outcome studies of school-based interventions for the prevention of adolescent depression.

Several methodological and ethical issues are addressed in the context of 3 related school-based studies of the primary and targeted prevention of depressive symptoms and disorder in high school adolescents. These issues include obtaining S consent and the protection of confidentiality, minimizing attrition over long-term follow-up periods, the "unit of assignment" issue common to most school-based research, and ensuring therapist fidelity to the intervention protocol. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The ‘Hoare logic’ of concurrent programs

Summary Hoare's logical system for specifying and proving partial correctness properties of sequential programs is generalized to concurrent programs. The basic idea is to define the assertion {P} S {Q} to mean that if execution is begun anywhere in S with P true, then P will remain true until S terminates, and Q will be true if and when S terminates. The predicates P and Q may depend upon program control locations as well as upon the values of variables. A system of inference rules and axiom schemas is given, and a formal correctness proof for a simple program is outlined. We show that by specifying certain requirements for the unimplemented parts, correctness properties can be proved without completely implementing the program. The relation to Pnueli's temporal logic formalism is also discussed.     

Medical savings accounts: opportunities for cost savings?

Interest in medical savings accounts (MSAs) as a potential tool to reduce healthcare costs has been widespread. A small number of countries have either implemented or run pilot programs of MSAs, and vigorous policy debates have taken place in several other countries about the potential merits of introducing MSAs as a method of paying for health care. In this paper we develop a model to assess the cost saving potential of MSAs in a publicly funded healthcare system. We assume that the public healthcare payer may choose between reimbursing healthcare expenditures through an MSA or through a form of third‐party payer insurance. We use the model to identify the conditions under which MSAs may reduce costs. We illustrate using data on healthcare expenditures from Canada.