Attaining minimally disruptive medicine: context, challenges and a roadmap for implementation.

In this second of two papers on minimally disruptive medicine, we use the language of patient workload and patient capacity from the Cumulative Complexity Model to accomplish three tasks. First, we outline the current context in healthcare, comprised of contrasting problems: some people lack access to care and others receive too much care in an overmedicalised system, both of which reflect imbalances between patients' workloads and their capacity. Second, we identify and address five tensions and challenges between minimally disruptive medicine, the existing context, and other approaches to accessible and patient-centred care such as evidence-based medicine and greater patient engagement. Third, we outline a roadmap of three strategies toward implementing minimally disruptive medicine in practice, including large-scale paradigm shifts, mid-level add-ons to existing reform efforts, and a modular strategy using an existing 'toolkit' that is more limited in scope, but can fit into existing healthcare systems.

Matrix-induced fragmentation of P3'-N5' phosphoramidate-containing DNA: high-throughput MALDI-TOF analysis of genomic sequence polymorphisms.

Chemical and enzymatic approaches were used to produce polynucleotide fragments containing acid-labile internucleotide P3'-N5' phosphoramidate bonds, either in a surface-bound form or in solution. The primer extension reaction utilizing 5'-amino-5'-deoxynucleoside 5'-triphosphates generates polynucleotides that can be fragmented into short, easy-to-analyze pieces simply by being premixed with the acidic matrices typically used for MALDI-TOF mass spectrometry of nucleic acids. This leads to detection procedures that are simple, robust and easy to automate. Utilizing this approach, a polymorphic site in the human ADRB3 gene was interrogated. Primer extensions with phosphoramidate analogs of dNTPs allowed for unambiguous discrimination of all possible genotypes.