Watson-Crick Base Pairing of N-Methoxy-1,3-Oxazinane (MOANA) Nucleoside Analogues within Double-Helical DNA.

Hairpin oligodeoxynucleotides incorporating a (2R,3S)-4-(methoxyamino)butane-1,2,3-triol residue in the middle of the double-helical stem and opposite to either one of the canonical nucleobases or an abasic 2-(hydroxymethyl)tetrahydrofuran-3-ol spacer were synthesized. Under mildly acidic conditions, aromatic aldehydes reacted reversibly with these oligonucleotides, converting the (2R,3S)-4-(methoxyamino)butane-1,2,3-triol unit into a 2-aryl-N-methoxy-1,3-oxazinane nucleoside analogue. The equilibrium of this reaction was found to be dependent on both the aldehyde and the nucleobase opposite to the modified residue. 9-Formyl-9-deazaadenine, combining a large stacking surface with an array of hydrogen bond donors and acceptors, showed the highest affinity as well as selectivity consistent with the rules of Watson-Crick base pairing. 5-Formyluracil or indole-3-carbaldehyde, lacking in either stacking or hydrogen bonding ability, were incorporated with a much lower affinity and selectivity.

N-Methoxy-1,3-oxazinane nucleic acids (MOANAs) - a configurationally flexible backbone modification allows post-synthetic incorporation of base moieties.

(2R,3S)-4-(Methoxyamino)butane-1,2,3-triol was converted into a protected phosphoramidite building block and incorporated into the middle of a short DNA oligonucleotide. O1 and O3 of the (2R,3S)-4-(methoxyamino)butane-1,2,3-triol were engaged in phosphodiester linkages, leaving O2 and the methoxyamino function available to form an N-methoxy-1,3-oxazinane ring through reaction with an aldehyde. In modified oligonucleotides thus obtained, the oxazinane ring formally replaces the furanose ring and the aldehyde, the base moiety of natural nucleosides. The feasibility of synthesizing base-modified oligonucleotides by this approach was demonstrated with several aromatic and aliphatic aldehydes featuring various functional groups.

3D simulation as a tool for improving the safety culture during remediation work at Andreeva Bay.

Andreeva Bay in northwest Russia hosts one of the former coastal technical bases of the Northern Fleet. Currently, this base is designated as the Andreeva Bay branch of Northwest Center for Radioactive Waste Management (SevRAO) and is a site of temporary storage (STS) for spent nuclear fuel (SNF) and other radiological waste generated during the operation and decommissioning of nuclear submarines and ships. According to an integrated expert evaluation, this site is the most dangerous nuclear facility in northwest Russia. Environmental rehabilitation of the site is currently in progress and is supported by strong international collaboration. This paper describes how the optimization principle (ALARA) has been adopted during the planning of remediation work at the Andreeva Bay STS and how Russian-Norwegian collaboration greatly contributed to ensuring the development and maintenance of a high level safety culture during this process. More specifically, this paper describes how integration of a system, specifically designed for improving the radiological safety of workers during the remediation work at Andreeva Bay, was developed in Russia. It also outlines the 3D radiological simulation and virtual reality based systems developed in Norway that have greatly facilitated effective implementation of the ALARA principle, through supporting radiological characterisation, work planning and optimization, decision making, communication between teams and with the authorities and training of field operators.

Elective surgical patients' narratives of hospitalization: the co-construction of safety.

This research explores how elective surgical patients make sense of their hospitalization experiences. We explore sensemaking using longitudinal narrative interviews (n=72) with 38 patients undergoing elective surgical procedures between June 2010 and February 2011. We consider patients' narratives, the stories they tell of their prior expectations, and subsequent post-surgery experiences of their care in a United Kingdom (UK) hospital. An emergent pre-surgery theme is that of a paradoxical position in which they choose to make themselves vulnerable by agreeing to surgery to enhance their health, this necessitating trust of clinicians (doctors and nurses). To make sense of their situation, patients draw on technical (doctors' expert knowledge and skills), bureaucratic (National Health Service as a revered institution) and ideological (hospitals as places of safety), discourses. Post-operatively, themes of 'chaos' and 'suffering' emerge from the narratives of patients whose pre-surgery expectations (and trust) have been violated. Their stories tell of unmet expectations and of inability to make shared sense of experiences with clinicians who are responsible for their care. We add to knowledge of how patients play a critical part in the co-construction of safety by demonstrating how patient-clinician intersubjectivity contributes to the type of harm that patients describe. Our results suggest that approaches to enhancing patients' safety will be limited if they fail to reflect patients' involvement in the negotiated process of healthcare. We also provide further evidence of the contribution narrative inquiry can make to patient safety.