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Abstract Background Previous research has demonstrated that the significant others of individuals with persistent back pain may have important influences on work participation outcomes. The aim of this study was to extend previous research by including individuals who have remained in work despite persistent back pain in addition to those who had become incapacitated for work, along with their significant others. The purpose of this research was to explore whether the illness beliefs of significant others differed depending on their relative’s working status, and to make some preliminary identification of how significant others may facilitate or hinder work participation for those with persistent back pain. Methods Interviews structured around the Illness Perception Questionnaire (chronic pain version) were conducted with back pain patients recruited from a hospital pain management clinic along with their significant others. Some patients had remained in work despite their back pain; others had ceased employment. Data were analysed using template analysis. Results There were clear differences between beliefs about, and reported responses to, back pain symptoms amongst the significant others of individuals who had remained in employment compared with the significant others of those who had ceased work. Three overarching themes emerged: perceived consequences of back pain, specific nature of employment and the impact of back pain on patient identity. Conclusions Significant others of employed individuals with back pain focused on the extent to which activity could still be undertaken despite back pain symptoms. Individuals out of work due to persistent back pain apparently self-limited their activity and were supported in their beliefs and behaviours by their significant others. To justify incapacity due to back pain, this group had seemingly become entrenched in a position whereby it was crucial that the individual with back pain was perceived as completely disabled. We suggest that significant others are clearly important, and potentially detrimental, sources of support to individuals with back pain. The inclusion of significant others in vocational rehabilitation programmes could potentially be a valuable way of mobilising readily accessible resources in a way that supports optimal functioning.

Abstract Background Individual illness perceptions have been highlighted as important influences on clinical outcomes for back pain. However, the illness perceptions of 'significant others' (spouse/partner/close family member) are rarely explored, particularly in relation to persistent back pain and work participation. The aim of this study was to initiate qualitative research in this area in order to further understand these wider influences on outcome. Methods Semi-structured interviews based on the chronic pain version of the Illness Perceptions Questionnaire-Revised were conducted with a convenience sample of UK disability benefit claimants, along with their significant others (n = 5 dyads). Data were analysed using template analysis. Results Significant others shared, and perhaps further reinforced, claimants' unhelpful illness beliefs including fear of pain/re-injury associated with certain types of work and activity, and pessimism about the likelihood of return to work. In some cases, significant others appeared more resigned to the permanence and negative inevitable consequences of the claimant's back pain condition on work participation, and were more sceptical about the availability of suitable work and sympathy from employers. In their pursuit of authenticity, claimants were keen to stress their desire to work whilst emphasising how the severity and physical limitations of their condition prevented them from doing so. In this vein, and seemingly based on their perceptions of what makes a 'good' significant other, significant others acted as a 'witness to pain', supporting claimants' self-limiting behaviour and statements of incapacity, often responding with empathy and assistance. The beliefs and responses of significant others may also have been influenced by their own experience of chronic illness, thus participants lives were often intertwined and defined by illness. Conclusions The findings from this exploratory study reveal how others and wider social circumstances might contribute both to the propensity of persistent back pain and to its consequences. This is an area that has received little attention to date, and wider support of these findings may usefully inform the design of future intervention programmes aimed at restoring work participation.

Abstract Background Hip and knee osteoarthritis is a common cause of pain and disability, which can be improved by exercise interventions. However, regular exercise is uncommon in this group because the low physical activity level in the general population is probably reduced even further by pain related fear of movement. The best method of encouraging increased activity in this patient group is not known. A booklet has been developed for patients with hip or knee osteoarthritis. It focuses on changing disadvantageous beliefs and encouraging increased physical activity. Methods/Design This paper describes the design of a Phase II randomised controlled trial (RCT) to test the effectiveness of this new booklet for patients with hip and knee osteoarthritis in influencing illness and treatment beliefs, and to assess the feasibility of conducting a larger definitive RCT in terms of health status and exercise behaviour. A computerised search of four general medical practice patients' record databases will identify patients older than 50 years of age who have consulted with hip or knee pain in the previous twelve months. A random sample of 120 will be invited to participate in the RCT comparing the new booklet with a control booklet, and we expect 100 to return final questionnaires. This trial will assess the feasibility of recruitment and randomisation, the suitability of the control intervention and outcome measurement tools, and will provide an estimate of effect size. Outcomes will include beliefs about hip and knee pain, beliefs about exercise, fear avoidance, level of physical activity, health status and health service costs. They will be measured at baseline, one month and three months. Discussion We discuss the merits of testing effectiveness in a phase II trial, in terms of intermediate outcome measures, whilst testing the processes for a larger definitive trial. We also discuss the advantages and disadvantages of testing the psychometric properties of the primary outcome measures concurrently with the trial. Trial registration Current Controlled Trials ISRCTN24554946

The development of novel Lewis acids derived from bipyridinium and phenanthrolinium dications is reported. Calculations of Hydride Ion Affinity (HIA) values indicate high carbon-based Lewis acidity at the ortho and para positions. This arises in part from extensive LUMO delocalization across the aromatic backbones. Species [C 10 H 6 R 2 N 2 CH 2 CH 2 ] 2+ (R=H [1 a] 2+ , Me [1 f] 2+ , tBu [1 g] 2+ ), and [C 12 H 4 R 4 N 2 CH 2 CH 2 ] 2+ (R=H [2 a] 2+ , Me [2 b] 2+ ) were prepared and evaluated for use in the initiation of hydrodefluorination (HDF) catalysis. Compound [2 a] 2+ proved highly effective towards generating catalytically active silylium cations via Lewis acid-mediated hydride abstraction from silane. This enabled the HDF of a range of aryl- and alkyl- substituted sp 3 (C-F) bonds under mild conditions. The protocol was also adapted to effect the deuterodefluorination of cis-2,4,6-(CF 3 ) 3 C 6 H 9 . The dications are shown to act as hydride acceptors with the isolation of neutral species C 16 H 14 N 2 (3 a) and C 16 H 10 Me 4 N 2 (3 b) and monocationic species [C 14 H 13 N 2 ] + ([4 a] + ) and [C 18 H 21 N 2 ]+ ([4 b] + ). Experimental and computational data provide further support that the dications are initiators in the generation of silylium cations., (© 2021 Wiley-VCH GmbH.)

Our ongoing search for underdeveloped functional group combinations has brought to light α-fluorinated aminoalkylboronic acids, a new class of molecules featuring the B-CF linkage. These compounds can now be generated from secondary amines and α-boryl aldehydes through electrophilic fluorination of boryl enamines or enamides. Fluorinated β-aminoalkylboronic acids show no signs of degradation under ambient conditions. We present evidence for the involvement of chair-like motifs, favored over the acyclic forms by up to 1.7±0.1 kcal mol -1 in water and held together by an amine-boronate hydrogen bond. Fluorinated β-aminoalkylboronic acids are stable over a wide pH range and are characterized by a pK a of 3.4, which is the lowest of any alkylboronic acid., (© 2021 Wiley-VCH GmbH.)

A series of thirty-three N,N'-diaryl, dialkyl, and alkyl-aryl ureas have been prepared in pyridine or toluene by reaction of silylamines with CO 2 . This protocol is shown to provide facile access to 13 C-labeled ureas, as well as chiral and macrocyclic ureas. These reactions proceed through initial generation of the corresponding silylcarbamates, which subsequently react with silylamine under thermal conditions to afford the thermodynamically favored urea and disilyl ether., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Increasing the success rate and throughput of drug discovery will require efficiency improvements throughout the process that is currently used in the pharmaceutical community, including the crucial step of identifying hit compounds to act as drivers for subsequent optimization. Hit identification can be carried out through large compound collection screening and often involves the generation and testing of many hypotheses based on available knowledge. In practice, hypothesis generation can involve the selection of promising chemical structures from compound collections using predictive models built from previous screening/assay results. Available physical collections, typically used during hit identification, are of the order of 10 6 compounds but represent only a small fraction of the small molecule drug-like chemical space. In an effort to survey a larger portion of chemical space and eliminate inefficiencies during hit identification, we introduce a new process, termed Idea2Data (I2D) that tightly integrates computational and experimental components of the drug discovery process. I2D provides the ability to connect a vast virtual collection of compounds readily synthesizable on automated synthesis systems with computational predictive models for the identification of promising structures. This new paradigm enables researchers to process billions of virtual molecules and select structures that can be prepared on automated systems and made available for biological testing, allowing for timely hypothesis testing and follow-up. Since its introduction, I2D has positively impacted several portfolio efforts through identification of new chemical scaffolds and functionalization of existing scaffolds. In this Innovations paper, we describe the I2D process and present an application for the discovery of new ULK inhibitors., Competing Interests: The authors declare no competing financial interest.

The use of ammonium halide salts as metal hydride precursors in a new Pd-catalyzed cycloisomerization of 1,6-diynes, which affords unexplored silylated 2-azafluorenes, is reported. This cascade process includes the addition of a Pd-hydride species to a π-system, intramolecular carbopalladation, and C(sp 2 )-H bond activation. A variety of functional groups are tolerated, and the synthetic utility of the resulting products has been demonstrated by a series of derivatizations.

An enantioselective copper-catalyzed intramolecular borylacylation is reported. The reaction proceeds through an initial enantioselective borylcupration of the styrene, followed by a nucleophilic attack on the tethered carbamoyl chloride. The products, chiral borylated 3,3-disubstituted oxindoles, were generated in excellent yields and enantioselectivities. The versatile carbon-boron bond provides a platform for a wide array of diversification., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

High performance liquid chromatography has been coupled simultaneously to high field NMR and MS detectors, giving UV, NMR and mass spectra for each component in a mixture, after on-line separation. This powerful new tool for the structure elucidation of components in mixtures without isolation has been successfully applied to the analysis of the metabolites of paracetamol in human urine.

The ease of use of the newer liquid chromatography-mass spectrometry interfaces has made possible the automated acquisition of spectra from large batch queues of samples. This fact, combined with the realization that unit molecular mass determination was the only datum desired by a majority of drug discovery synthetic chemists, led us to develop open access mass spectrometry in the early 1990s. Open access spectrometers now scan over 100,000 samples per year from synthesis laboratories at Pfizer. Our experiences with this novel use of mass spectrometry in a large research facility are discussed and we detail some of the pitfalls we believe to be common to this approach. In addition, we offer some reflection on the cultural changes we have observed in our research environment since this experiment began.