The clinical use of Cogmed Working Memory Training (CWMT): a clinician survey

This is the author accepted manuscript. The final version is available from the British Psychological SocietyDespite controversy surrounding the effectiveness of working memory training, Cogmed Working Memory Training (CWMT, Pearson) remains a popular choice of intervention. We surveyed 100 CWMT practitioners from Australia, U.S.A., the Netherlands, and the U.K. to find out how CWMT is used, who with, and what outcomes are measured. Practitioners reported that CWMT was easy-to-use and a valuable use of clinical resources. Findings are discussed in relation to current research and recommendations for practice are made.This project was supported by generous grants from the Henry Smith Charity and Action Medical Research

Formulation and antibacterial properties of clay mineral-tetracycline and -doxycycline composites

Clay minerals have been used as adsorbents for decades but research into their use within healthcare as drug-carriers and modified drug release materials is an increasingly common area of interest. In current clinical practice the management of acute bacterial skin and skin-structure infections (ABSSSIs) requires patients to take systemic antibacterial treatment due to a lack of appropriate topical options. In this research tetracycline (TC) and doxycycline (DC) were adsorbed onto a range of clay minerals (kaolinite, montmorillonite, acid-activated montmorillonite, Laponite® RD and Laponite® XL21) to evaluate their potential as materials for the delivery of these antibiotics to infected wounds. A dispersion pH that favoured the zwitterionic form of the antibiotic molecules was shown to favour adsorption onto the clay minerals. FTIR and pXRD showed that positively charged groups on the antibiotic molecules interacted with the negatively charged clay mineral surface, whilst negatively charged groups on the antibiotic molecules could interact with the positively charged edge-sites of the clay minerals. Swelling clays such as the two Laponites® were able to adsorb much more TC and DC due to their structure and chemistry. The clay minerals alone did not have any antibacterial effects against Staphylococcus epidermidis, Cutibacterium acnes, and Pseudomonas aeruginosa. Antibiotic containing composites successfully released TC and DC, exhibiting activity against the three bacterial strains proportional to the antibiotic-loading on the composites. This research demonstrates the ability of these clay minerals to deliver TC and DC against common skin pathogens and their potential for future development towards clinical applications

The impact of the COVID-19 pandemic on mental health and well-being of people living with a long-term physical health condition: a qualitative study

BACKGROUND: The COVID-19 pandemic and associated restrictions caused major global disruption. Individuals with long-term physical health conditions (LTCs) are at higher risk of severe illness and often subject to the strictest pandemic guidance, so may be disproportionally affected. The aim of this study was to qualitatively explore how living with a LTC during the COVID-19 pandemic affected people's mental health and wellbeing. METHODS: Participants were people living with LTCs who participated in telephone/video call interviews based on a semi-structured topic guide. Key themes and subthemes were determined using deductive and inductive thematic analysis. RESULTS: The sample included 32 participants with LTCs (most commonly cancer, respiratory conditions or cardiovascular diseases), mean age 57 (SD 13) years, 66% female and 72% white British. There were four overarching themes specific to living with a LTC. These were 1) high levels of fear and anxiety related to perceived consequences of catching COVID-19, 2) impact of shielding/isolation on mental health and wellbeing, 3) experience of healthcare during the pandemic and 4) anxiety created by uncertainty about the future. Fourteen subthemes were identified, including concerns about accessing essential supplies and the importance of social support. Individuals who lived alone and were advised to shield could be profoundly negatively affected. CONCLUSIONS: This study found that there were a number of aspects of living with a LTC during the pandemic that had a significant impact on mental health and well-being. There should be focus on how best to provide practical and social support to people with LTCs during a pandemic, particularly if they have to shield or isolate

The effect of inhibition of leukotriene synthesis on the activity of interleukin-8 and granulocyte-macrophage colony-stimulating factor

The cytokines interleukin-8 (IL-8) and granulocyte-macrophage colony-stimulating factor (GM-CSF) enhanced the extracellular release of arachidonate metabolites from ionophore-stimulated neutrophils by 145 +/- 10% (mean +/- S.E.M., n = 13) and 182 +/- 11% (n = 16), respectively. To determine whether enhanced leukotriene production mediates the effects of these cytokines on neutrophil activity, two different specific arachidonate 5-lipoxygenase (5-LO) inhibitors, piriprost and MK-886, were used to inhibit leukotriene synthesis. Neither inhibitor affected the upregulation of CD11b beta2-integrin expression or priming of superoxide generation stimulated by IL-8 and GM-CSF. It is concluded that leukotrienes do not mediate either the direct or priming effects of these cytokines and that these classes of anti-inflammatory drugs are therefore unlikely to inhibit the effects of IL-8 and GM-CSF on neutrophil activation

Signatures of Reductive Magnetic Mineral Diagenesis From Unmixing of First-Order Reversal Curves

Diagenetic alteration of magnetic minerals occurs in all sedimentary environments and tends to be severe in reducing environments. Magnetic minerals provide useful information about sedimentary diagenetic processes, which makes it valuable to use magnetic properties to identify the diagenetic environment in which the magnetic minerals occur and to inform interpretations of paleomagnetic recording or environmental processes. We use a newly developed first-order reversal curve (FORC) unmixing method on well-studied samples to illustrate how magnetic properties can be used to assess diagenetic processes in reducing sedimentary environments. From our analysis of multiple data sets, consistent magnetic components are identified for each stage of reductive diagenesis. Relatively unaltered detrital and biogenic magnetic mineral assemblages in surficial oxic to manganous diagenetic environments undergo progressive dissolution with burial into ferruginous and sulfidic environments, and largely disappear at the sulfate-methane transition (SMT). Below the SMT, a weak superparamagnetic to largely non-interacting stable single domain (SD) greigite component is observed in all studied data sets. Moderately interacting stable SD authigenic pyrrhotite and strongly interacting stable SD greigite are observed commonly in methanic environments. Recognition of these characteristic magnetic components enables identification of key diagenetic processes and should help to constrain interpretation of magnetic mineral assemblages in future studies. A key question for future studies concerns whether stable SD greigite forms in the sulfidic or methanic zones, where formation in deeper methanic sediments will cause greater delays in paleomagnetic signal recording. Authigenic pyrrhotite forms in methanic environments, so it will usually record a delayed paleomagnetic signal.European Research Council (320750) Australian Research Council (DP160100805

Dynamic contrast-enhanced MRI of synovitis in knee osteoarthritis: repeatability, discrimination and sensitivity to change in a prospective experimental study

OBJECTIVES: Evaluate test-retest repeatability, ability to discriminate between osteoarthritic and healthy participants, and sensitivity to change over 6 months, of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) biomarkers in knee OA. METHODS: Fourteen individuals aged 40-60 with mild-moderate knee OA and 6 age-matched healthy volunteers (HV) underwent DCE-MRI at 3 T at baseline, 1 month and 6 months. Voxelwise pharmacokinetic modelling of dynamic data was used to calculate DCE-MRI biomarkers including Ktrans and IAUC60. Median DCE-MRI biomarker values were extracted for each participant at each study visit. Synovial segmentation was performed using both manual and semiautomatic methods with calculation of an additional biomarker, the volume of enhancing pannus (VEP). Test-retest repeatability was assessed using intraclass correlation coefficients (ICC). Smallest detectable differences (SDDs) were calculated from test-retest data. Discrimination between OA and HV was assessed via calculation of between-group standardised mean differences (SMD). Responsiveness was assessed via the number of OA participants with changes greater than the SDD at 6 months. RESULTS: Ktrans demonstrated the best test-retest repeatability (Ktrans/IAUC60/VEP ICCs 0.90/0.84/0.40, SDDs as % of OA mean 33/71/76%), discrimination between OA and HV (SMDs 0.94/0.54/0.50) and responsiveness (5/1/1 out of 12 OA participants with 6-month change > SDD) when compared to IAUC60 and VEP. Biomarkers derived from semiautomatic segmentation outperformed those derived from manual segmentation across all domains. CONCLUSIONS: Ktrans demonstrated the best repeatability, discrimination and sensitivity to change suggesting that it is the optimal DCE-MRI biomarker for use in experimental medicine studies. KEY POINTS: • Dynamic contrast-enhanced MRI (DCE-MRI) provides quantitative measures of synovitis in knee osteoarthritis which may permit early assessment of efficacy in experimental medicine studies. • This prospective observational study compared DCE-MRI biomarkers across domains relevant to experimental medicine: test-retest repeatability, discriminative validity and sensitivity to change. • The DCE-MRI biomarker Ktrans demonstrated the best performance across all three domains, suggesting that it is the optimal biomarker for use in future interventional studies

Domain State Diagnosis in Rock Magnetism: Evaluation of Potential Alternatives to the Day Diagram

The Day diagram is used extensively in rock magnetism for domain state diagnosis. It has been shown recently to be fundamentally ambiguous for ten sets of reasons. This ambiguity highlights the urgency for adopting suitable alternative approaches to identify the domain state of magnetic mineral components in rock magnetic studies. We evaluate ten potential alternative approaches here and conclude that four have value for identifying data trends, but, like the Day diagram, they are affected by use of bulk parameters that compromise domain state diagnosis in complex samples. Three approaches based on remanence curve and hysteresis loop unmixing, when “supervised” by independent data to avoid non-uniqueness of solutions provide valuable component-specific information that can be linked by inference to domain state. Three further approaches based on first-order reversal curve (FORC) diagrams provide direct domain state diagnosis with varying effectiveness. Environmentally important high coercivity hematite and goethite are represented with variable effectiveness in the evaluated candidate approaches. These minerals occur predominantly in non-interacting single domain particle assemblages in paleomagnetic contexts, so domain state diagnosis is more critical for ferrimagnetic minerals. Treating the high-coercivity component separately following normal rock magnetic procedures allows focus on the more vexing problem of diagnosing domain state in ferrimagnetic mineral assemblages. We suggest a move away from non-diagnostic methods based on bulk parameters and adoption of approaches that provide unambiguous component-specific domain state identification, among which various FORC-based approaches provide diagnostic information.European Research Council (ERC) Australian Research Council (ARC