Field Induced Fragmentation (Fif) Spectra of Oxygen Containing Volatile Organic Compounds with Reactive Stage Tandem Ion Mobility Spectrometry and Functional Group Classification by Neural Network Analysis.

Mobility isolated spectra were obtained for protonated monomers of 42 volatile oxygen containing organic compounds at ambient pressure using a tandem ion mobility spectrometer with a reactive stage between drift regions. Fragment ions of protonated monomers of alcohols, acetates, aldehydes, ketones, and ethers were produced in the reactive stage using a 3.3 MHz symmetrical sinusoidal waveform with an amplitude of 1.4 kV and mobility analyzed in a 19 mm long drift region. The resultant field induced fragmentation (FIF) spectra included residual intensities for protonated monomers and fragment ions with characteristic drift times and peak intensities, associated with ion mass and chemical class. High efficiency of fragmentation was observed with single bond cleavage of alcohols and in six-member ring rearrangements of acetates. Fragmentation was not observed, or seen weakly, with aldehydes, ethers, and ketones due to their strained four-member ring transition states. Neural networks were trained to categorize spectra by chemical class and tested with FIF spectra of both familiar and unfamiliar compounds. Rates of categorization were class dependent with best performance for alcohols and acetates, moderate performance for ketones, and worst performance for ethers and aldehydes. Trends in the rates of categorization within a chemical family can be understood as steric influences on the energy of activation for ion fragmentation. Electric fields greater than 129 Td or new designs of reactive stages with improved efficiency of fragmentation will be needed to extend the practice of reactive stage tandem IMS to an expanded selection of volatile organic compounds.

Reactive Tandem Ion Mobility Spectrometry with Electric Field Fragmentation of Alcohols at Ambient Pressure.

A tandem ion mobility spectrometer at ambient pressure with a reactive stage produced fragment ions by water elimination from protonated monomers of alcohols with carbon numbers three to nine. Protonated monomers of individual alcohols were mobility isolated in a first drift region and were fragmented to carbocations at 64 to 128 Td and 45 to 89°C. Precursor and fragment ions were mobility characterized in a second drift region. Enthalpies for fragmentation of ROH2+ to primary carbocations were calculated as 76 to 97 kJ/mol and enthalpies for subsequent charge migration to 2° carbocations were -49 to -58 kJ/mol. Plots of drift times for pairs of protonated monomer and fragment ions from alcohols, esters, alkanes, and aldehydes produced distinctive trend lines attributed to fragmentation paths characteristic of chemical class. Specific combinations of drift times for fragments and precursor ions provide additional chemical information for spectral interpretation in ion mobility spectrometry.

Double Imprinted Nanoparticles for Sequential Membrane-to-Nuclear Drug Delivery.

Efficient and site-specific delivery of therapeutics drugs remains a critical challenge in cancer treatment. Traditional drug nanocarriers such as antibody-drug conjugates are not generally accessible due to their high cost and can lead to serious side effects including life-threatening allergic reactions. Here, these problems are overcome via the engineering of supramolecular agents that are manufactured with an innovative double imprinting approach. The developed molecularly imprinted nanoparticles (nanoMIPs) are targeted toward a linear epitope of estrogen receptor alfa (ERα) and loaded with the chemotherapeutic drug doxorubicin. These nanoMIPs are cost-effective and rival the affinity of commercial antibodies for ERα. Upon specific binding of the materials to ERα, which is overexpressed in most breast cancers (BCs), nuclear drug delivery is achieved via receptor-mediated endocytosis. Consequentially, significantly enhanced cytotoxicity is elicited in BC cell lines overexpressing ERα, paving the way for precision treatment of BC. Proof-of-concept for the clinical use of the nanoMIPs is provided by evaluating their drug efficacy in sophisticated three-dimensional (3D) cancer models, which capture the complexity of the tumor microenvironment in vivo without requiring animal models. Thus, these findings highlight the potential of nanoMIPs as a promising class of novel drug compounds for use in cancer treatment.

What do cost-effective health behaviour-change interventions contain? A comparison of six domains.

OBJECTIVES: To help implement behaviour change interventions (BCIs) in practice it is important to be able to characterize their key components. This study compared broad features of cost-effective BCIs that addressed smoking, diet, physical activity, alcohol and sexual health. It also assessed the association of these with the magnitude of the cost-effectiveness estimates. METHODS: A content analysis of 79 interventions based on 338 intervention descriptions was conducted, using the Behaviour Change Wheel (BCW) to classify intervention content in terms of intervention functions, and the BCT taxonomy to identify and categorise component Behaviour Change Techniques (BCT). Regression analysis identified the association of these with upper (pessimistic) and lower (optimistic) cost-effectiveness estimates. RESULTS: The most and least common functions and BCT clusters were education (82.3%) and shaping knowledge (79.7%), and coercion (3.8%) and covert learning (2.5%). Smoking interventions contained the largest ([Formula: see text] = 12) number of BCTs and were most cost-effective. Several other factors were associated with worse (coercionfunction ßupper = 36551.24; shaping knowledgeBCT ßlower = 2427.78; comparison of outcomesBCT ßupper = 9067.32; repetition and substitutionBCT ßupper = 7172.47) and better (modellingfunction ßlower = -2905.3; environmental restructuringfunction ßupper = -8646.28; reward and threatBCT ßupper = -5577.59) cost-effectiveness (p<0.05). DISCUSSION: Cost-effective BCIs rely heavily on education with smoking interventions exhibiting the most comprehensive range of BCTs. Providing an example to aspire to, restructuring the environment and rewarding positive behaviour may be associated with greater cost-effectiveness.

What psychological and behaviour changes are initiated by 'expert patient' training and what training techniques are most helpful?

The Expert Patient Programme (EPP) is a lay-led, group-based, self-management training course available through the UK National Health Service for persons with long-term health conditions. Thirty-two patients who attended EPP courses in East London were interviewed about their experiences. Grounded theory coding of transcripts was employed to identify recurring accounts. Thematic analysis was used to theorise and organise participants' accounts, identifying commonly reported changes, helpful techniques and disappointments and frustrations. Results highlighted the role of information provision, especially face-to-face information exchange as well as the impact of in-class instruction and modelling of physical skills. Personal goal setting, using graded tasks, self-monitoring and goal review were regarded as the most useful techniques. Adoption and use of these self-management techniques depended on the establishment of an empathic and self-validating interpersonal context. Findings also imply that EPP may not be ideal for all participants and suggested modifications and improvements are discussed.

'OnePoint'--combining OneNote and SharePoint to facilitate knowledge transfer.

The identification and development of novel drugs requires a multidisciplinary team of individuals whose membership changes during the lifecycle of a project. Incomplete knowledge transfer across this team can be a barrier to effective decision-making and efficient drug discovery. We have deployed a new infrastructure supporting information storage and distribution within small teams using Microsoft's SharePoint server technology in conjunction with the desktop application OneNote. This delivers a user-friendly collaborative workspace that is fast, flexible and carries a low training burden. Demand from drug project teams for this 'solution' has now resulted in site-wide deployment to over 500 people across research.

Infrared atmospheric pressure MALDI ion trap mass spectrometry of frozen samples using a Peltier-cooled sample stage.

Infrared atmospheric pressure matrix-assisted laser desorption/ionization on an ion trap mass spectrometer is used to analyze frozen samples generated using a Peltier-cooled sample stage. This allows for the analysis of samples in water without the addition of matrix, in near-native conditions, and with minimal loss of water due to evaporation. Analysis of frozen samples is extended to study peptides, carbohydrates, and glycolipids.

Tandem time-of-flight mass spectrometry with a curved field reflectron.

The unique focusing properties of the curved-field reflectron provide a simple solution to the problem of compensating for the broad range of energies of product ions produced postsource in a time-of-flight mass spectrometer. This has been shown previously for the technique known as postsource decay, but in this report we demonstrate its use for tandem time-of-flight mass spectrometry using a high-performance MALDI time-of-flight instrument modified by the addition of a collision chamber to enable the recording of mass-selected product ions formed by collision-induced dissociation (CID). In particular, the curved-field reflectron enables the use of the full 20-keV kinetic energy provided by the ion source extraction voltage as the collision energy in the laboratory frame and obviates the need to reaccelerate the product ions, using a second "source" or "lift" cell. Results are presented for the collision-induced dissociation of fullerenes over a range of collision gas pressures and precursor ion attenuation. In addition, CID tandem mass spectra are obtained for several peptides.