Evaluation of the current use of MRI to aid the diagnosis of axial spondyloarthritis in the UK: results from a freedom of information request.

AIM: To evaluate the impact of recommendations from the 2019 consensus exercise conducted by radiologists and rheumatologists on the use of magnetic resonance imaging (MRI) to investigate axial spondyloarthritis (axSpA) in clinical practice. MATERIALS AND METHODS: A freedom of information (FOI) request was used to assess the use of MRI in the diagnosis of axSpA and radiologists' awareness of the 2019 guidance across all NHS Trusts and Health Boards in the UK, including England, Scotland, Northern Ireland, and Wales. RESULTS: The FOI request was sent to 150 Trusts/Health Boards, and 93 full responses were received. Of the 93 respondents (97%), 90 reported familiarity with the term axSpA and 70/93 (75%) reported familiarity with the 2019 recommendations. Awareness of recommendations regarding specific MRI features supportive of the diagnosis of axSpA was 74/93 (80%) for the sacroiliac joints (SIJs) and 66/93 (71%) for the spine. The median wait for MRI acquisition was 2-3 months. Fifty-two of the 93 (56%) reported at least some outsourcing of axSpA MRI (33%/29% for specialist/non-specialist outsourcing respectively); 32/93 (34%) reported some scans being reported in-house by non-musculoskeletal radiologists. CONCLUSION: There have been several positive developments in the understanding and use of MRI for the diagnosis of axSpA in the UK since the 2017 survey, although substantial scope for further improvement remains. Several new challenges have also emerged, including the increase in waiting times, reliance on outsourcing, and the reporting of MRI by non-musculoskeletal radiologists.

Orbital-specific mapping of the ligand exchange dynamics of Fe(CO)5 in solution.

Transition-metal complexes have long attracted interest for fundamental chemical reactivity studies and possible use in solar energy conversion. Electronic excitation, ligand loss from the metal centre, or a combination of both, creates changes in charge and spin density at the metal site that need to be controlled to optimize complexes for photocatalytic hydrogen production and selective carbon-hydrogen bond activation. An understanding at the molecular level of how transition-metal complexes catalyse reactions, and in particular of the role of the short-lived and reactive intermediate states involved, will be critical for such optimization. However, suitable methods for detailed characterization of electronic excited states have been lacking. Here we show, with the use of X-ray laser-based femtosecond-resolution spectroscopy and advanced quantum chemical theory to probe the reaction dynamics of the benchmark transition-metal complex Fe(CO)5 in solution, that the photo-induced removal of CO generates the 16-electron Fe(CO)4 species, a homogeneous catalyst with an electron deficiency at the Fe centre, in a hitherto unreported excited singlet state that either converts to the triplet ground state or combines with a CO or solvent molecule to regenerate a penta-coordinated Fe species on a sub-picosecond timescale. This finding, which resolves the debate about the relative importance of different spin channels in the photochemistry of Fe(CO)5 (refs 4, 16 - 20), was made possible by the ability of femtosecond X-ray spectroscopy to probe frontier-orbital interactions with atom specificity. We expect the method to be broadly applicable in the chemical sciences, and to complement approaches that probe structural dynamics in ultrafast processes.

Initial metal-metal bond breakage detected by fs X-ray scattering in the photolysis of Ru3(CO)12 in cyclohexane at 400 nm.

Using femtosecond resolution X-ray solution scattering at a free electron laser we were able to directly observe metal-metal bond cleavage upon photolysis at 400 nm of Ru3(CO)12, a prototype for the photochemistry of transition metal carbonyls. This leads to the known single intermediate Ru3(CO)11(µ-CO)*, with a bridging ligand (µCO) and where the asterisk indicates an open Ru3-ring. This loses a CO ligand on a picosecond time scale yielding a newly observed triple bridge intermediate, Ru3(CO)8(µ-CO)3*. This loses another CO ligand to form the previously observed Ru3(CO)10, which returns to Ru3(CO)12via the known single-bridge Ru3(CO)10(µ-CO). These results indicate that contrary to long standing hypotheses, metal-metal bond breakage is the only chemical reaction immediately following the photolysis of Ru3(CO)12 at 400 nm. Combined with previous picosecond resolution X-ray scattering data and time resolved infrared spectroscopy these results yield a new mechanism for the photolysis of Ru3(CO)12.

Consistency of fish-shoal social network structure under laboratory conditions.

We investigated the consistency of association network structure for groups of sticklebacks Gasterosteus aculeatus. Each group was observed twice and we varied the duration between observations and the size of the experimental arena that they were observed in. At the dyad level, we found positive correlations between dyad interaction frequencies across observations. At the group level we found variation in four network metrics between observations, but only in treatments where the duration between observations was short. Specifically, fish formed more and smaller groups in the second observation in this treatment. Fish were also organized into more subunits in the larger arenas. Finally, we saw positive correlations between some group network metrics across observations suggesting relative consistency at the group level. There are several processes that might drive these interaction patterns. Our findings have implications for experimental design and the comparison and integration of findings of experiments from different studies carried out under different conditions.

Standardized grip strength as an outcome measure in early rheumatoid arthritis.

OBJECTIVES: Patients with rheumatoid arthritis (RA) suffer progressive loss of hand function and have weaker hand grip than the healthy population. In this study we aimed to validate hand grip strength standardized by age and gender (z score) against currently accepted clinical measures of disease activity. METHOD: Electronic records of patients with a diagnosis of RA seen between April 2007 and December 2011 were screened for the documentation of tender and swollen joint counts, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP), along with patient global activity score and grip strength. Bilateral grip strengths were converted to z scores on the basis of previously published age- and gender-corrected normative data for grip strength. The z scores were then correlated against components of disease activity scores. RESULTS: Ninety patients diagnosed with RA had been seen 602 times within 2 years of diagnosis. Hand grip data were available for 204 visits. There was a statistically significant inverse correlation between grip strength z scores and the tested variables. The sensitivity and specificity of a hand grip z score of -1.5 for predicting remission were, respectively, 70% and 76% for the right hand and 82% and 69% for the left hand. CONCLUSIONS: Hand grip testing and subsequent conversion to z scores corrected for age and gender correlate with disease activity in early RA. We have shown that the grip strength z scores can discriminate between various disease states, and the strength seems to return to near normative data when the disease is in remission.

The ASAS-OMERACT core domain set for axial spondyloarthritis.

BACKGROUND: The current core outcome set for ankylosing spondylitis (AS) has had only minor adaptations since its development 20 years ago. Considering the significant advances in this field during the preceding decades, an update of this core set is necessary. OBJECTIVE: To update the ASAS-OMERACT core outcome set for AS into the ASAS-OMERACT core outcome set for axial spondyloarthritis (axSpA). METHODS: Following OMERACT and COMET guidelines, an international working group representing key stakeholders (patients, rheumatologists, health professionals, pharmaceutical industry and drug regulatory agency representatives) defined the core domain set for axSpA. The development process consisted of: i) Identifying candidate domains using a systematic literature review and qualitative studies; ii) Selection of the most relevant domains for different stakeholders through a 3-round Delphi survey involving axSpA patients and axSpA experts; iii) Consensus and voting by ASAS; iv) Endorsement by OMERACT. Two scenarios are considered based on the type of therapy investigated in the trial: symptom modifying therapies and disease modifying therapies. RESULTS: The updated core outcome set for axSpA includes 7 mandatory domains for all trials (disease activity, pain, morning stiffness, fatigue, physical function, overall functioning and health, and adverse events including death). There are 3 additional domains (extra-musculoskeletal manifestations, peripheral manifestations and structural damage) that are mandatory for disease modifying therapies and important but optional for symptom modifying therapies. Finally, 3 other domains (spinal mobility, sleep, and work and employment) are defined as important but optional domains for all trials. CONCLUSION: The ASAS-OMERACT core domain set for AS has been updated into the ASAS-OMERACT core domain set for axSpA. The next step is the selection of instruments for each domain.

Photodissociation of aqueous I 3 - observed with liquid-phase ultrafast mega-electron-volt electron diffraction.

Developing femtosecond resolution methods for directly observing structural dynamics is critical to understanding complex photochemical reaction mechanisms in solution. We have used two recent developments, ultrafast mega-electron-volt electron sources and vacuum compatible sub-micron thick liquid sheet jets, to enable liquid-phase ultrafast electron diffraction (LUED). We have demonstrated the viability of LUED by investigating the photodissociation of tri-iodide initiated with a 400 nm laser pulse. This has enabled the average speed of the bond expansion to be measured during the first 750 fs of dissociation and the geminate recombination to be directly captured on the picosecond time scale.

Recognition of inflammatory back pain and ankylosing spondylitis in primary care.

OBJECTIVE: The diagnosis of AS is often delayed in primary care. This may partly be due to inability to differentiate inflammatory back pain (IBP) from mechanical. The aim of this study was to assess current practice of general practitioners (GPs) in using clinical, radiological and laboratory investigations to assess patients with IBP. METHODS: A postal questionnaire was sent to all GPs in Norfolk. It was designed to test GPs ability to identify symptoms suggestive of IBP in patients with back pain. It also enquired whether GPs considered other features of SpA. Their perceptions of usefulness of various investigations when considering a diagnosis of AS, management and their unmet needs were recorded. RESULTS: A total of 62% of completed questionnaires were returned. Only 5% of GPs could identify all eight features known to be indicative of IBP, 78% between four and eight and 17% identified less than four features. GPs had a range of views regarding the utility of a positive family history, HLA-B27, use of X-ray and physiotherapy in patients with suspected IBP. GPs awareness of the associated features of SpA was low. There were inconsistencies in the use of diagnostic tests and management of AS. Improving musculoskeletal education in primary care was identified as one of the unmet needs by the majority of GPs. CONCLUSIONS: In a survey of GPs, we identified inconsistencies in their perceptions and approach to the diagnosis and management of AS. Education in primary care and the wider use of diagnostic algorithms may improve early detection and hence outcome of AS.

Influence of biologic therapy on return to work in people with work disability due to ankylosing spondylitis.

OBJECTIVE: To answer the question 'does TNF blockade therapy enable people with severe AS to return to work or work more productively?'. METHODS: All patients with AS currently receiving anti-TNF therapy at two UK Hospitals were asked to complete a questionnaire. This asked about occupational history, type of work, degree of job-related physical activity, working hours and sickness absence from work both currently (on anti-TNF treatment) and pre-treatment. RESULTS: Sixty-five patients (72.3% male), aged 29-64 (mean 46.1) yrs, whose duration of anti-TNF treatment ranged from 3 to 56 (mean 19.1) months were studied. Twenty-four (36.9%) patients were receiving infliximab, 21 (32.3%) etanercept and 20 (30.8%) adalimumab. Pre-treatment, 46 (70.8%) were in employment (1 was a student); 38 (58.5%) were working full-time and 8 (12.3%) part-time; 19 (29.2%) were not working. On treatment, 50 (76.9%) patients were working, 44 (67.7%) full-time and 6 (9.2%) part-time. Two individuals who worked part-time pre-treatment had returned to work full-time. Thus, on treatment, 4 of the 19 patients who were previously unable to work returned to employment, and 2 others increased their work from part-time to full-time. Patients rated the effect of AS on work capacity as 7.05/10 pre-treatment and 2.92/10 post-treatment. Those who were working lost, on average, 15 days from work due to sick leave in the 12 months pre-treatment and 0.91 days in the first 12 months on treatment. CONCLUSIONS: Treatment of active AS with TNF blockade appears to be associated with improved capacity for work.

Probing ultrafast ππ*/nπ* internal conversion in organic chromophores via K-edge resonant absorption.

Many photoinduced processes including photosynthesis and human vision happen in organic molecules and involve coupled femtosecond dynamics of nuclei and electrons. Organic molecules with heteroatoms often possess an important excited-state relaxation channel from an optically allowed ππ* to a dark nπ* state. The ππ*/nπ* internal conversion is difficult to investigate, as most spectroscopic methods are not exclusively sensitive to changes in the excited-state electronic structure. Here, we report achieving the required sensitivity by exploiting the element and site specificity of near-edge soft X-ray absorption spectroscopy. As a hole forms in the n orbital during ππ*/nπ* internal conversion, the absorption spectrum at the heteroatom K-edge exhibits an additional resonance. We demonstrate the concept using the nucleobase thymine at the oxygen K-edge, and unambiguously show that ππ*/nπ* internal conversion takes place within (60 ± 30) fs. High-level-coupled cluster calculations confirm the method's impressive electronic structure sensitivity for excited-state investigations.Many photo-induced processes such as photosynthesis occur in organic molecules, but their femtosecond excited-state dynamics are difficult to track. Here, the authors exploit the element and site selectivity of soft X-ray absorption to sensitively follow the ultrafast ππ*/nπ* electronic relaxation of hetero-organic molecules.

Identification of the dominant photochemical pathways and mechanistic insights to the ultrafast ligand exchange of Fe(CO)5 to Fe(CO)4EtOH.

We utilized femtosecond time-resolved resonant inelastic X-ray scattering and ab initio theory to study the transient electronic structure and the photoinduced molecular dynamics of a model metal carbonyl photocatalyst Fe(CO)5 in ethanol solution. We propose mechanistic explanation for the parallel ultrafast intra-molecular spin crossover and ligation of the Fe(CO)4 which are observed following a charge transfer photoexcitation of Fe(CO)5 as reported in our previous study [Wernet et al., Nature 520, 78 (2015)]. We find that branching of the reaction pathway likely happens in the (1)A1 state of Fe(CO)4. A sub-picosecond time constant of the spin crossover from (1)B2 to (3)B2 is rationalized by the proposed (1)B2 → (1)A1 → (3)B2 mechanism. Ultrafast ligation of the (1)B2 Fe(CO)4 state is significantly faster than the spin-forbidden and diffusion limited ligation process occurring from the (3)B2 Fe(CO)4 ground state that has been observed in the previous studies. We propose that the ultrafast ligation occurs via (1)B2 → (1)A1 → (1)A' Fe(CO)4EtOH pathway and the time scale of the (1)A1 Fe(CO)4 state ligation is governed by the solute-solvent collision frequency. Our study emphasizes the importance of understanding the interaction of molecular excited states with the surrounding environment to explain the relaxation pathways of photoexcited metal carbonyls in solution.

Osteopontin gene is expressed in the dermal papilla of pelage follicles in a hair-cycle-dependent manner.

Hair follicle formation and maintenance involve intimate interactions between follicular epithelial cells and a group of specialized mesenchymal cells known as the dermal papilla. Using the random primer polymerase chain reaction, we have identified an approximately 1.4 kb osteopontin mRNA that is present in large quantities in cultured rat vibrissa dermal papilla cells but undetectable in cultured rat skin fibroblasts. In situ hybridization showed that the osteopontin gene is expressed in dermal papilla cells of pelage follicles during catagen but not in anagen or telogen. As an acidic glycosylated RGD-containing extracellular matrix protein, osteopontin can function both as a cell attachment protein and as a soluble cytokine playing roles in signaling, cell migration, tissue survival, anti-inflammation, and T-cell-mediated cellular immunity. Our results indicate that the comparison of the mRNA of cultured dermal papilla cells and fibroblasts can lead to the identification of not only anagen-specific genes (e.g., nexin 1), but also a catagen-specific gene. We have thus provided evidence that specific genes are turned on during catagen, which is therefore not simply a passive "degenerative" phase. The functional role of osteopontin in catagen is unclear but it may promote the formation of a tightly aggregated dermal papilla, and/or protect the dermal papilla cells from apoptosis induced by cytokines or hypoxia during catagen.

Detection and investigation of the molecular nature of low-molecular-mass copper ions in isolated rheumatoid knee-joint synovial fluid.

Low-molecular-mass copper(II) species have been detected and quantified in ultrafiltrates (n = 7) of rheumatoid synovial fluid (SF) by a highly-sensitive HPLC-based assay system with the ability to determine Cu(II) concentrations of < 10(-7) mol.dm-3. High field 1H NMR spectroscopy demonstrated that addition of Cu(II)(aq.) to isolated samples of RA SF ultrafiltrates resulted in complexation by histidine > alanine > formate > threonine > lactate > tyrosine > phenylalanine, their effectiveness in this context being in the given order. CD spectra of Cu(II)-treated samples of intact SF exhibited absorption bands typical of copper(II)-albumin complexes, in addition to a band attributable to a low-molecular-mass histidinate complex (lambda min 610 nm). Since both albumin and histidine are potent radical scavengers, these results indicate that any .OH radical generated from bound copper ions will be 'site-specifically' scavenged. Hence, low-molecular-mass copper complexes with the ability to promote the generation of .OH radical which can then escape from the metal ion co-ordination sphere (and in turn, cause damage to critical biomolecules) appear to be absent from inflammatory SF.

A modified form of low-density lipoprotein with increased electronegative charge is present in rheumatoid arthritis synovial fluid.

Reactive oxygen species (ROS) are pro-inflammatory factors in the pathogenesis of rheumatoid arthritis. During inflammation, the amount of low-density lipoprotein (LDL) in the inflamed joint is increased. LDL is known to be susceptible to oxidation by ROS. Oxidized LDL may serve as a mediator for joint damage, further exacerbating the inflammatory process. LDL isolated from synovial fluid and plasma from individual patients (paired samples) with rheumatoid arthritis or osteoarthritis was characterized by crossed immunoelectrophoresis. On analysis by this technique, synovial fluid LDL from most patients with rheumatoid arthritis contained two peaks: one corresponding to normal plasma native LDL, and the other having an increased electrophoretic mobility associated with oxidized LDL. Paired plasma LDL samples contained native LDL alone, as did paired synovial fluid and plasma LDL from patients with osteoarthritis. Thus, in addition to native LDL, a second form of LDL was shown to be present in rheumatoid synovial fluid, which had properties consistent with those of oxidized LDL.

Multi-analyte interrogation using the fiber optic biosensor.

The capabilities of the portable, automated fiber optic biosensor, RAPTOR, have recently been evaluated. Developed to perform rapid fluoroimmunoassays in the field, the RAPTOR was designed to test samples for up to four different target analytes simultaneously. Assay time could be varied from a 3-min rapid screen to a standard 10-min test. A trial of 203 blind samples tested for Staphylococcal enterotoxin B, ricin, Francisella tularensis, and Bacillus globigii has been conducted. Sensitivities obtained were 10, 50 ng/ml, 5 x 10(5), and 5 x 10(4) cfu/ml, respectively.

The impact of HIV disease on an Irish prison population.

Between January 1987 and January 1991, 168 known HIV-infected prisoners have been incarcerated in Dublin's Mountjoy prison. This figure constitutes 16.6% of the total HIV-infected population in the Republic of Ireland over the same period. One hundred and forty-one (84%) of these prisoners have attended the Department of Genitourinary Medicine, St James's Hospital, Dublin. This group displayed considerable morbidity from HIV-related disease. Respiratory tract infection was the most frequent complication seen. Much additional morbidity was directly attributable to intravenous drug use. A survey of a representative group of inmates revealed that 64.7% were diagnosed HIV-positive in prison. The mean length of time spent incarcerated since the diagnosis of HIV infection was 38.9 months. Twenty-nine of 34 individuals who answered a questionnaire were imprisoned for drug-related crimes and 32 of 34 prisoners admitted to parenteral drug use within the prison. As the HIV epidemic unfolds in Dublin, increasing numbers of prisoners with symptomatic HIV disease will spend time incarcerated in Mountjoy prison. This will pose a considerable burden on prison and hospital medical services alike.

Stressful events among pregnant Salvadoran women: a cross-cultural comparison.

OBJECTIVE: To compare stressful events, including violent episodes, experienced by pregnant Salvadoran women with those experienced by two other groups of low-income, pregnant women living in the United States (non-Salvadoran Hispanics and non-Hispanics) and to examine the association between episodes of violence and drug or alcohol use among the three groups. DESIGN: Comparative, descriptive study. SETTING: Public health prenatal clinics. PARTICIPANTS: One hundred four Salvadoran, 69 non-Salvadoran Hispanic, and 187 non-Hispanic pregnant women. MAIN OUTCOME MEASURES: Difficult Life Circumstances (DLC) scale and psychosocial history assessment. RESULTS: Statistically significant differences were found among the three groups in total DLC scores, F(2, 357) = 14.98, p < .001; reported episodes of violence, F(2, 357 = 17.82, p < .001; and drug or alcohol use, F(2, 357) = 6.33, p < .001. A significant difference was found to the extent that alcohol or drug use accounted for the variance in violence among the three groups, F(3, 360) = 6.28, p < .001. CONCLUSIONS: Cross-cultural comparisons revealed group differences in the number of stressful events, including episodes of violence and alcohol or drug use.

PIP: A comparative, descriptive study was conducted among 104 Salvadoran, 69 non-Salvadoran Hispanic, and 187 non-Hispanic pregnant women concerning the stressful events including episodes of violence experienced. Furthermore, it also compared the relationship between episodes of violence and drug or alcohol use among the three groups. The measures used are the Difficult Life Circumstances scale and psychosocial history assessment. Results showed that stressful events were found to occur more frequently among the non-Hispanic mothers than among either Hispanic subgroups. However, cultural distinctions between Salvadoran and non-Salvadoran Hispanic mothers did not emerge. Alcohol and drug use differed significantly among the groups in this study. In conclusion, cross-cultural comparisons revealed group differences in the number of stressful events, including episodes of violence and alcohol or drug use.

Assessing infant health promotion: a cross-cultural comparison.

The purpose of this cross-cultural, correlational study was to evaluate two popular clinical/research assessment tools, the NCAST Teaching Scale and the Home Observation Measurement of the Environment (HOME) Inventory, as measures of infant health promotion behaviors for low-income, foreign-born Hispanic mothers in the United States. Based on the assumption that both measures tap universal attributes of the mother-infant relationship, it was hypothesized that maternal performance for the study group and a comparison group of U.S.-born, low-income mothers would be similar. Comparable performance on the NCAST Teaching Scale included a full range of scores, including the capacity to identify mothers most in need of clinical intervention. Study fundings supported the clinical use of this assessment scale with mothers represented by the study sample. Consistently lower scores by the foreign-born Hispanic mothers on the HOME Inventory led to the conclusion that the instrument may not tap cultural universals in the mother-infant relationship.