Tissue-specific silencing of homoeologs in natural populations of the recent allopolyploid Tragopogon mirus

The definitive version is available at www3.interscience.wiley.com http://dx.doi.org/10.1111/j.1469-8137.2010.03205.

Attitudes towards the use and acceptance of eHealth technologies : a case study of older adults living with chronic pain and implications for rural healthcare

Acknowledgements The research described here is supported by the award made by the RCUK Digital Economy programme to the dot.rural Digital Economy Hub; award reference: EP/G066051/1. MC’s time writing the paper is funded by the Scottish Government’s Rural and Environmental Science and Analytical Services Division (RESAS) under Theme 8 ‘Vibrant Rural Communities’ of the Food, Land and People Programme (2011–2016). MC is also an Honorary Research Fellow at the Division of Applied Health Sciences, University of Aberdeen. The input of other members of the TOPS research team, Alastair Mort, Fiona Williams, Sophie Corbett, Phil Wilson and Paul MacNamee who contributed to be wider study and discussed preliminary findings reported here with the authors of the paper is acknowledged. We acknowledge the feedback on earlier versions of this paper provided by members of the Trans-Atlantic Rural Research Network, especially Stefanie Doebler and Carmen Hubbard. We also thank Deb Roberts for her comments.Peer reviewedPublisher PD

Quantitative SPECT/CT parameters of myocardial 99mTechnetium-3,3-diphosphono-1,2-propanodicarboxylic acid (DPD) uptake in suspected cardiac transthyretin amyloidosis

Background: 99mTc-labelled bisphosphonates are used for imaging assessment of patients with transthyretin cardiac amyloidosis (ATTR). Present study evaluates whether quantitative SPECT/CT measurement of absolute myocardial 99mTc-labelled 3,3-diphosphono-1,2-propanodicarboxylic acid (Tc-DPD) uptake can diagnose patients with suspected ATTR. / Methods: Twenty-eight patients (25 male, age 80.03 ± 6.99 years) with suspected ATTR referred for Tc-DPD imaging had planar and SPECT/CT imaging of the chest. Three operators independently obtained Tc-DPD myocardial SUVmax and SUVmean above threshold (SMaT) (20, 40 and 60% of SUVmax), using a semi-automated threshold segmentation method. Results were compared to visual grading (0–3) of cardiac uptake. / Results: Twenty-two patients (78%) had cardiac uptake (2 grade 1, 15 grade 2, 5 grade 3). SUVmax and SMaT segmentation thresholds enabled separating grades 2/3 from 0/1 with excellent inter- and intra-reader correlation. Cut-off values 6.0, 2.5, 3 and 4 for SUVmax, SMaT20,40,60, respectively, separated between grades 2/3 and 0 /1 with PPV and NPV of 100%. SMaT20,40,60(cardiac)/SUVmean (liver) and SMaT20,40,60(cardiac)/SUVmean(liver/lung) separated grades 2 and 3. / Conclusion: Quantitative SPECT/CT parameters of cardiac Tc-DPD uptake are robust, enabling separation of patients with grades 2 and 3 cardiac uptake from grades 0 and 1. Larger patient cohorts will determine the incremental value of SPECT/CT quantification for ATTR management

Anthracycline-Induced Cardiotoxicity: Cardiac Monitoring by Continuous Wave-Doppler Ultrasound Cardiac Output Monitoring and Correlation to Echocardiography

Background: Anthracyclines are agents with a well-known cardiotoxicity. The study sought to evaluate the hemodynamic response to an anthracycline using real-time continuous-wave (CW)-Doppler ultrasound cardiac output monitoring (USCOM) and echocardiography in combination with serum biomarkers. Methods: 50 patients (26 male, 24 female, median age 59 years) suffering from various types of cancer received an anthracycline-based regimen. Patients' responses were measured at different time points (T0 prior to infusion, T1 6 h post infusion, T2 after 1 day, T3 after 7 days, and T4 after 3 months) with CW-Doppler ultrasound (T0-T4) and echocardiography (T1, T4) for hemodynamic parameters such as stroke volume (SV; SVUSCOM ml) and ejection fraction (EF; EFechocardiography%) and with NT-pro-BNP and hs-Troponin T (T0-T4). Results: During the 3-month observation period, the relative decrease in the EF determined by echocardiography was -2.1% (Delta T0-T4, T0 71 +/- 7.8%, T4 69.5 +/- 7%, p = 0.04), whereas the decrease in SV observed using CW-Doppler was -6.5% (Delta T0-T4, T0 54 +/- 19.2 ml, T4 50.5 +/- 20.6 ml, p = 0.14). The kinetics for serum biomarkers were inversely correlated. Conclusions: Combining real-time CW-Doppler USCOM and serum biomarkers is feasible for monitoring the immediate and chronic hemodynamic changes during an anthracycline-based regimen; the results obtained were comparable to those from echocardiography

European Permanent Grasslands: A Systematic Review of Economic Drivers of Change, Including a Detailed Analysis of the Czech Republic, Spain, Sweden, and UK

\ua9 2024 by the authors. Permanent grasslands (PG) feature in the European rural landscape and represent a major agricultural production resource. They support multiple non-provisioning ecosystem services (ES), including climate regulation, flood control, biodiversity, and pollination. PG are at risk of loss or degradation due to agricultural land use and land management changes. The objective of this systematic review is to identify the main economic influences shaping management and maintenance of PG, and the risks and opportunities for delivery of a range of ES. A total of 51 papers were included. Relevant policy interventions and economic drivers are identified in relation to how they shape the management of EU grasslands over time and across farming systems, countries, or biogeographic zones. A high reliance on public payments from the EU Common Agricultural Policy (CAP), with uneven impact on mitigating PG losses and associated ES provisions, was identified, which needs to be considered in relation to ongoing CAP reform. There is a gap in the literature regarding economic tipping points for change. Future research needs to identify and map ES provisions by PG along with trade-offs and synergies, and link this to policy. There are substantive challenges to maintaining Europe’s PG area and management, which must be addressed through EU-wide instruments

Gene conversion in human rearranged immunoglobulin genes

Over the past 20 years, many DNA sequences have been published suggesting that all or part of the V<sub>H</sub> segment of a rearranged immunoglobulin gene may be replaced in vivo. Two different mechanisms appear to be operating. One of these is very similar to primary V(D)J recombination, involving the RAG proteins acting upon recombination signal sequences, and this has recently been proven to occur. Other sequences, many of which show partial V<sub>H</sub> replacements with no addition of untemplated nucleotides at the V<sub>H</sub>–V<sub>H</sub> joint, have been proposed to occur by an unusual RAG-mediated recombination with the formation of hybrid (coding-to-signal) joints. These appear to occur in cells already undergoing somatic hypermutation in which, some authors are convinced, RAG genes are silenced. We recently proposed that the latter type of V<sub>H</sub> replacement might occur by homologous recombination initiated by the activity of AID (activation-induced cytidine deaminase), which is essential for somatic hypermutation and gene conversion. The latter has been observed in other species, but not in human Ig genes, so far. In this paper, we present a new analysis of sequences published as examples of the second type of rearrangement. This not only shows that AID recognition motifs occur in recombination regions but also that some sequences show replacement of central sections by a sequence from another gene, similar to gene conversion in the immunoglobulin genes of other species. These observations support the proposal that this type of rearrangement is likely to be AID-mediated rather than RAG-mediated and is consistent with gene conversion

DPD Quantification in Cardiac Amyloidosis A Novel Imaging Biomarker

OBJECTIVES: To assess whether single-photon emission computed tomography (SPECT/CT) quantification of bone scintigraphy would improve diagnostic accuracy and offer a means of quantifying amyloid burden. BACKGROUND: Transthyretin-related cardiac amyloidosis is common and can be diagnosed noninvasively using bone scintigraphy; interpretation, however, relies on planar images. SPECT/CT imaging offers 3-dimensional visualization. METHODS: This was a single-center, retrospective analysis of 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid (DPD) scans reported using the Perugini grading system (0 = negative; 1 to 3 = increasingly positive). Conventional planar quantification techniques (heart/contralateral lung, and heart/whole-body retention ratios) were performed. Heart, adjacent vertebra, paraspinal muscle and liver peak standardized uptake values (SUVpeak) were recorded from SPECT/CT acquisitions. An SUV retention index was also calculated: (cardiac SUVpeak/vertebral SUVpeak) × paraspinal muscle SUVpeak. In a subgroup of patients, SPECT/CT quantification was compared with myocardial extracellular volume quantification by CT imaging (ECVCT). RESULTS: A total of 100 DPD scans were analyzed (patient age 84 ± 9 years; 52% male): 40 were Perugini grade 0, 12 were grade 1, 41 were grade 2, and 7 were grade 3. Cardiac SUVpeak increased from grade 0 to grade 2; however, it plateaued between grades 2 and 3 (p < 0.001). Paraspinal muscle SUVpeak increased with grade (p < 0.001), whereas vertebral SUVpeak decreased (p < 0.001). The composite parameter of SUV retention index overcame the plateauing of the cardiac SUVpeak and increased across all grades (p < 0.001). Cardiac SUVpeak correlated well (r2 = 0.73; p < 0.001) with ECVCT. Both the cardiac SUVpeak and SUV retention index had excellent diagnostic accuracy (area under the curve [AUC]: 0.999). The heart to contralateral lung ratio performed the best of the planar quantification techniques (AUC: 0.987). CONCLUSIONS: SPECT/CT quantification in DPD scintigraphy is possible and outperforms planar quantification techniques. Differentiation of Perugini grade 2 or 3 is confounded by soft tissue uptake, which can be overcome by a composite SUV retention index. This index can help in the diagnosis of cardiac amyloidosis and may offer a means of monitoring response to therapy

Susceptibility of hamsters to clostridium difficile isolates of differing toxinotype

Clostridium difficile is the most commonly associated cause of antibiotic associated disease (AAD), which caused ~21,000 cases of AAD in 2011 in the U.K. alone. The golden Syrian hamster model of CDI is an acute model displaying many of the clinical features of C. difficile disease. Using this model we characterised three clinical strains of C. difficile, all differing in toxinotype; CD1342 (PaLoc negative), M68 (toxinotype VIII) and BI-7 (toxinotype III). The naturally occurring non-toxic strain colonised all hamsters within 1-day post challenge (d.p.c.) with high-levels of spores being shed in the faeces of animals that appeared well throughout the entire experiment. However, some changes including increased neutrophil influx and unclotted red blood cells were observed at early time points despite the fact that the known C. difficile toxins (TcdA, TcdB and CDT) are absent from the genome. In contrast, hamsters challenged with strain M68 resulted in a 45% mortality rate, with those that survived challenge remaining highly colonised. It is currently unclear why some hamsters survive infection, as bacterial and toxin levels and histology scores were similar to those culled at a similar time-point. Hamsters challenged with strain BI-7 resulted in a rapid fatal infection in 100% of the hamsters approximately 26 hr post challenge. Severe caecal pathology, including transmural neutrophil infiltrates and extensive submucosal damage correlated with high levels of toxin measured in gut filtrates ex vivo. These data describes the infection kinetics and disease outcomes of 3 clinical C. difficile isolates differing in toxin carriage and provides additional insights to the role of each toxin in disease progression

Validation of the Oxford WebQ online 24-hour dietary questionnaire using biomarkers

Oxford WebQ is an online dietary questionnaire covering 24 hours, appropriate for repeated administration in large-scale prospective studies including UK Biobank and the Million Women Study. We compared performance of the Oxford WebQ and a traditional interviewer-administered multi-pass 24-hour recall against biomarkers for protein, potassium and total sugar intake, and total energy expenditure estimated by accelerometry. 160 participants were recruited between 2014 and 2016 in London, UK, and measured at 3 non-consecutive time-points. The measurement error model simultaneously compared all 3 methods. Attenuation factors for protein, potassium, sugars and total energy intake estimated by the mean of 2 Oxford WebQs were 0.37, 0.42, 0.45, and 0.31 respectively, with performance improving incrementally for the mean of more measures. Correlation between the mean of 2 Oxford WebQs and estimated true intakes, reflecting attenuation when intake is categorised or ranked, was 0.47, 0.39, 0.40, and 0.38 respectively, also improving with repeated administration. These were similar to the more administratively burdensome interviewer-based recall. Using objective biomarkers as the standard, Oxford WebQ performs well across key nutrients in comparison with more administratively burdensome interviewer-based 24-hour recalls. Attenuation improves when the average is taken over repeated administration, reducing measurement error bias in assessment of diet-disease associations