• C-H arylation of arenes at room temperature using visible light ruthenium C-H activation.

      Sagadevan, Arunachalam; orcid: 0000-0001-9486-1706; Charitou, Anastasios; orcid: 0000-0002-9100-8950; Wang, Fen; Ivanova, Maria; Vuagnat, Martin; Greaney, Michael F; orcid: 0000-0001-9633-1135 (2020-04-07)
      A ruthenium-catalyzed C-H arylation process is described using visible light. Using the readily available catalyst [RuCl ( -cymene)] , visible light irradiation was found to enable arylation of 2-aryl-pyridines at room temperature for a range of aryl bromides and iodides. [Abstract copyright: This journal is © The Royal Society of Chemistry.]
    • Ca

      Lim, Dmitry; email: dmitry.lim@uniupo.it; Dematteis, Giulia; Tapella, Laura; Genazzani, Armando A; Calì, Tito; Brini, Marisa; Verkhratsky, Alexei; email: alexej.verkhratsky@manchester.ac.uk (2021-08-05)
      Mitochondria-endoplasmic reticulum (ER) contact sites (MERCS) are morpho-functional units, formed at the loci of close apposition of the ER-forming endomembrane and outer mitochondrial membrane (OMM). These sites contribute to fundamental cellular processes including lipid biosynthesis, autophagy, apoptosis, ER-stress and calcium (Ca ) signalling. At MERCS, Ca ions are transferred from the ER directly to mitochondria through a core protein complex composed of inositol-1,4,5 trisphosphate receptor (InsP R), voltage-gated anion channel 1 (VDAC1), mitochondrial calcium uniporter (MCU) and adaptor protein glucose-regulated protein 75 (Grp75); this complex is regulated by several associated proteins. Deregulation of ER-mitochondria Ca transfer contributes to pathogenesis of neurodegenerative and other diseases. The efficacy of Ca transfer between ER and mitochondria depends on the protein composition of MERCS, which controls ER-mitochondria interaction regulating, for example, the transversal distance between ER membrane and OMM and the extension of the longitudinal interface between ER and mitochondria. These parameters are altered in neurodegeneration. Here we overview the ER and mitochondrial Ca homeostasis, the composition of ER-mitochondrial Ca transfer machinery and alterations of the ER-mitochondria Ca transfer in three major neurodegenerative diseases: motor neurone diseases, Parkinson disease and Alzheimer's disease. [Abstract copyright: Copyright © 2021 Elsevier Ltd. All rights reserved.]
    • Cage and maternal effects on the bacterial communities of the murine gut.

      Singh, Gurdeep; Brass, Andrew; Cruickshank, Sheena M; email: sheena.cruickshank@manchester.ac.uk; Knight, Christopher G (2021-05-10)
      Findings from gut microbiome studies are strongly influenced by both experimental and analytical factors that can unintentionally bias their interpretation. Environment is also critical. Both co-housing and maternal effects are expected to affect microbiomes and have the potential to confound other manipulated factors, such as genetics. We therefore analysed microbiome data from a mouse experiment using littermate controls and tested differences among genotypes (wildtype versus colitis prone-mdr1a ), gut niches (stool versus mucus), host ages (6 versus 18 weeks), social groups (co-housed siblings of different genotypes) and maternal influence. We constructed a 16S phylogenetic tree from bacterial communities, fitting random forest models using all 428,234 clades identified. Models discriminated all criteria except host genotype, where no community differences were found. Host social groups differed in abundant, low-level, taxa whereas intermediate phylogenetic and abundance scales distinguished ages and niches. Thus, a carefully controlled experiment treating evolutionary clades of microbes equivalently without reference to taxonomy, clearly identifies whether and how gut microbial communities are distinct across ecologically important factors (niche and host age) and other experimental factors, notably cage effects and maternal influence. These findings highlight the importance of considering such environmental factors in future microbiome studies.
    • Calcium signaling in neuroglia.

      Lim, Dmitry; email: dmitry.lim@uniupo.it; Semyanov, Alexey; Genazzani, Armando; Verkhratsky, Alexei; email: alexej.verkhratsky@manchester.ac.uk (2021-04-10)
      Glial cells exploit calcium (Ca ) signals to perceive the information about the activity of the nervous tissue and the tissue environment to translate this information into an array of homeostatic, signaling and defensive reactions. Astrocytes, the best studied glial cells, use several Ca signaling generation pathways that include Ca entry through plasma membrane, release from endoplasmic reticulum (ER) and from mitochondria. Activation of metabotropic receptors on the plasma membrane of glial cells is coupled to an enzymatic cascade in which a second messenger, InsP is generated thus activating intracellular Ca release channels in the ER endomembrane. Astrocytes also possess store-operated Ca entry and express several ligand-gated Ca channels. In vivo astrocytes generate heterogeneous Ca signals, which are short and frequent in distal processes, but large and relatively rare in soma. In response to neuronal activity intracellular and inter-cellular astrocytic Ca waves can be produced. Astrocytic Ca signals are involved in secretion, they regulate ion transport across cell membranes, and are contributing to cell morphological plasticity. Therefore, astrocytic Ca signals are linked to fundamental functions of the central nervous system ranging from synaptic transmission to behavior. In oligodendrocytes, Ca signals are generated by plasmalemmal Ca influx, or by release from intracellular stores, or by combination of both. Microglial cells exploit Ca permeable ionotropic purinergic receptors and transient receptor potential channels as well as ER Ca release. In this contribution, basic morphology of glial cells, glial Ca signaling toolkit, intracellular Ca signals and Ca -regulated functions are discussed with focus on astrocytes. [Abstract copyright: Copyright © 2021 Elsevier Inc. All rights reserved.]
    • Can common mycorrhizal fungal networks be managed to enhance ecosystem functionality?

      Alaux, Pierre‐Louis; orcid: 0000-0002-2518-7911; email: pierre-louis.alaux@manchester.ac.uk; Zhang, Yaqian; orcid: 0000-0002-7172-4503; Gilbert, Lucy; orcid: 0000-0002-9139-8450; Johnson, David; orcid: 0000-0003-2299-2525 (2021-02-02)
      Societal Impact Statement: Mycorrhizal fungi are key components of soil biodiversity that offer potential to provide sustainable solutions for land management, notably in agriculture and forestry. Several studies conducted in controlled environments show that key functional attributes of common mycorrhizal networks (CMNs), which inter‐link different plants, are influenced by management practices. Here, we highlight the need to consider how land management affects the ubiquity and function of CMNs in nature to maximize the role of mycorrhizal fungi in enhancing ecosystem services. We emphasize that CMNs can sometimes negatively affect aspects of plant performance, but there remain major gaps in understanding before explicit consideration of CMN management can be delivered. Summary: Most mycorrhizal fungi have the capacity to develop extensive extraradical mycelium, and thus have the potential to connect multiple plants and form a ‘common mycorrhizal network’. Several studies have shown that these networks can influence plant establishment, nutrition, productivity and defense, nutrient distribution and storage, and multitrophic interactions. However, many of these studies have focused on the importance of common mycorrhizal networks in ecological contexts and there has been less emphasis in managed systems, including croplands, grassland, agroforestry and forestry, on which humankind relies. Here we review the evidence of the potential importance of common mycorrhizal networks in managed systems, and provide insight into how these networks could be managed effectively to maximize the functions and outputs from managed systems. We also emphasize possible negative effects of common mycorrhizal networks on plant performance and question popular views that mycorrhizal networks may offer a panacea for enhancing ecosystem services. We highlight the need to gain greater insight into the ubiquity, functioning, and response to management interventions of common mycorrhizal networks and, critically, the need to determine the extent to which these networks can add value to the promotion of mycorrhizal colonization.
    • Can molecular flexibility control crystallization? The case of

      Tang, Sin Kim; Davey, Roger J; orcid: 0000-0002-4690-1774; Sacchi, Pietro; orcid: 0000-0001-5066-4508; Cruz-Cabeza, Aurora J; orcid: 0000-0002-0957-4823 (2020-11-16)
      Despite the technological importance of crystallization from solutions almost nothing is known about the relationship between the kinetic process of nucleation and the molecular and crystal structures of a crystallizing solute. Nowhere is this more apparent than in our attempts to understand the behavior of increasingly large, flexible molecules developed as active components in the pharmaceutical arena. In our current contribution we develop a general protocol involving a combination of computation (conformation analysis, lattice energy), and experiment (measurement of nucleation rates), and show how significant advances can be made. We present the first systematic study aimed at quantifying the impact of molecular flexibility on nucleation kinetics. The nucleation rates of 4 substituted benzoic acids are compared, two of which have substituents with flexible chains. In making this comparison, the importance of normalizing data to account for differing solubilities is highlighted. These data have allowed us to go beyond popular qualitative descriptors such 'crystallizability' or 'crystallization propensity' in favour of more precise nucleation rate data. Overall, this leads to definite conclusions as to the relative importance of solution chemistry, solid-state interactions and conformational flexibility in the crystallization of these molecules and confirms the key role of intermolecular stacking interactions in determining relative nucleation rates. In a more general sense, conclusions are drawn as to conditions under which conformational change may become rate determining during a crystallization process. [Abstract copyright: This journal is © The Royal Society of Chemistry.]
    • Can molecular flexibility control crystallization? The case of <i>para</i> substituted benzoic acids.

      Tang, Sin Kim; Davey, Roger J; orcid: 0000-0002-4690-1774; Sacchi, Pietro; orcid: 0000-0001-5066-4508; Cruz-Cabeza, Aurora J; orcid: 0000-0002-0957-4823 (2020-11-16)
      Despite the technological importance of crystallization from solutions almost nothing is known about the relationship between the kinetic process of nucleation and the molecular and crystal structures of a crystallizing solute. Nowhere is this more apparent than in our attempts to understand the behavior of increasingly large, flexible molecules developed as active components in the pharmaceutical arena. In our current contribution we develop a general protocol involving a combination of computation (conformation analysis, lattice energy), and experiment (measurement of nucleation rates), and show how significant advances can be made. We present the first systematic study aimed at quantifying the impact of molecular flexibility on nucleation kinetics. The nucleation rates of 4 <i>para</i> substituted benzoic acids are compared, two of which have substituents with flexible chains. In making this comparison, the importance of normalizing data to account for differing solubilities is highlighted. These data have allowed us to go beyond popular qualitative descriptors such 'crystallizability' or 'crystallization propensity' in favour of more precise nucleation rate data. Overall, this leads to definite conclusions as to the relative importance of solution chemistry, solid-state interactions and conformational flexibility in the crystallization of these molecules and confirms the key role of intermolecular stacking interactions in determining relative nucleation rates. In a more general sense, conclusions are drawn as to conditions under which conformational change may become rate determining during a crystallization process.
    • Can Skin Aging Contribute to Systemic Inflammaging?

      Pilkington, Suzanne M; email: suzanne.pilkington@manchester.ac.uk; Bulfone-Paus, Silvia; Griffiths, Christopher E M; Watson, Rachel E B (2021-10-28)
    • Can we achieve better recruitment by providing better information? Meta-analysis of 'studies within a trial' (SWATs) of optimised participant information sheets.

      Madurasinghe, Vichithranie W; Bower, Peter; orcid: 0000-0001-9558-3349; email: peter.bower@manchester.ac.uk; Eldridge, Sandra; Collier, David; Graffy, Jonathan; Treweek, Shaun; Knapp, Peter; Parker, Adwoa; Rick, Jo; Salisbury, Chris; et al. (2021-09-23)
      <h4>Background</h4>The information given to people considering taking part in a trial needs to be easy to understand if those people are to become, and then remain, trial participants. However, there is a tension between providing comprehensive information and providing information that is comprehensible. User-testing is one method of developing better participant information, and there is evidence that user-tested information is better at informing participants about key issues relating to trials. However, it is not clear if user-testing also leads to changes in the rates of recruitment in trials, compared to standard trial information. As part of a programme of research, we embedded 'studies within a trial' (SWATs) across multiple ongoing trials to see if user-tested materials led to better rates of recruitment.<h4>Methods</h4>Seven 'host' trials included a SWAT evaluation and randomised their participants to receive routine information sheets generated by the research teams, or information sheets optimised through user-testing. We collected data on trial recruitment and analysed the results across these trials using random effects meta-analysis, with the primary outcome defined as the proportion of participants randomised in a host trial following an invitation to take part.<h4>Results</h4>Six SWATs (n=27,805) provided data on recruitment. Optimised participant information sheets likely result in little or no difference in recruitment rates (7.2% versus 6.8%, pooled odds ratio = 1.03, 95% CI 0.90 to 1.19, p-value = 0.63, I<sup>2</sup> = 0%).<h4>Conclusions</h4>Participant information sheets developed through user testing did not improve recruitment rates. The programme of work showed that co-ordinated testing of recruitment strategies using SWATs is feasible and can provide both definitive and timely evidence on the effectiveness of recruitment strategies.<h4>Trial registration</h4>Healthlines Depression (ISRCTN14172341) Healthlines CVD (ISRCTN27508731) CASPER (ISRCTN02202951) ISDR (ISRCTN87561257) ECLS (NCT01925625) REFORM (ISRCTN68240461) HeLP Diabetes (ISRCTN02123133).
    • Can we achieve better recruitment by providing better information? Meta-analysis of ‘studies within a trial’ (SWATs) of optimised participant information sheets

      Madurasinghe, Vichithranie W.; Bower, Peter; orcid: 0000-0001-9558-3349; email: peter.bower@manchester.ac.uk; Eldridge, Sandra; Collier, David; Graffy, Jonathan; Treweek, Shaun; Knapp, Peter; Parker, Adwoa; Rick, Jo; Salisbury, Chris; et al. (BioMed Central, 2021-09-23)
      Abstract: Background: The information given to people considering taking part in a trial needs to be easy to understand if those people are to become, and then remain, trial participants. However, there is a tension between providing comprehensive information and providing information that is comprehensible. User-testing is one method of developing better participant information, and there is evidence that user-tested information is better at informing participants about key issues relating to trials. However, it is not clear if user-testing also leads to changes in the rates of recruitment in trials, compared to standard trial information. As part of a programme of research, we embedded ‘studies within a trial’ (SWATs) across multiple ongoing trials to see if user-tested materials led to better rates of recruitment. Methods: Seven ‘host’ trials included a SWAT evaluation and randomised their participants to receive routine information sheets generated by the research teams, or information sheets optimised through user-testing. We collected data on trial recruitment and analysed the results across these trials using random effects meta-analysis, with the primary outcome defined as the proportion of participants randomised in a host trial following an invitation to take part. Results: Six SWATs (n=27,805) provided data on recruitment. Optimised participant information sheets likely result in little or no difference in recruitment rates (7.2% versus 6.8%, pooled odds ratio = 1.03, 95% CI 0.90 to 1.19, p-value = 0.63, I2 = 0%). Conclusions: Participant information sheets developed through user testing did not improve recruitment rates. The programme of work showed that co-ordinated testing of recruitment strategies using SWATs is feasible and can provide both definitive and timely evidence on the effectiveness of recruitment strategies. Trial registration: Healthlines Depression (ISRCTN14172341) Healthlines CVD (ISRCTN27508731) CASPER (ISRCTN02202951) ISDR (ISRCTN87561257) ECLS (NCT01925625) REFORM (ISRCTN68240461) HeLP Diabetes (ISRCTN02123133)
    • Can Weight Watchers (WW) Help Address Maternal Obesity? An Audit of Weight Change in Women of Childbearing Age and Mothers-To-Be, Referred into a Commercial Slimming Programme.

      Tocque, Karen; Kennedy, Lynne; orcid: 0000-0002-4699-2602; email: l.kennedy@chester.ac.uk (2021-11-05)
      The scale of overweight and obesity amongst women of childbearing age or mothers to be, living in Wales, places a considerable burden on the NHS and public health. High BMI (over 30) during pregnancy increases the health risks for mother and baby. Policy advice recommends weight management services are available to help women lose weight before and whilst planning pregnancy. In parts of Wales, NHS partnerships with commercial companies provide weight management services for women considering or planning pregnancy. This study evaluates whether an established referral Weight Watchers (WW) programme, known to be effective in adults in England, can help mothers-to-be living in North Wales lose weight. Analysis used routine data from 82 referrals to WW between June 2013 and January 2015. Participants received a referral letter inviting them to attend face-to-face group workshops combined with a digital experience. The programme encompassed healthy eating, physical activity and positive mind-set. Trained WW staff measured bodyweight before, during and at 12 weeks. On entry to the course, participants had a median age of 31.4 years (interquartile range (IQR) 28-34) with a median BMI of 36.8 kg/m (IQR 33.3-43.7). Women completing the course (n = 34) had a median weight loss of 5.65 kg (IQR 0.45-10.85), equating to 5.7% (SD 3.46) of initial body weight. Intention-to-treat analysis (last observation carried forward), which included lapsed courses n = 66, showed a median weight loss of 3.6 kg (IQR - 2.53 to 9.73), equating to 3.7% (SD 3.62) of initial body weight. Overall, there was significant weight loss during the WW programme (Wilcoxon signed rank test Z = - 6.16; p < 0.001). Weight loss was significantly correlated with the number of workshops attended (Spearman correlation coefficient 0.61 p < 0.001). The proportion of all 82 participants (intention to treat, baseline observation carried forward) that achieved a weight loss of ≥ 5% initial weight was 30.5%. Referral of obese mothers-to-be into WW can successfully achieve short-term weight loss, at or above 5%, in approximately one third of participants. The dose-response effect supports a causal inference. Successful weight loss at this critical life stage may provide women with the necessary motivation to initiate weight loss for healthy pregnancy, however further research is required. [Abstract copyright: © 2021. The Author(s).]
    • Cancellation of Tollmien–Schlichting waves with surface heating

      Brennan, Georgia S.; orcid: 0000-0002-4914-5716; Gajjar, Jitesh S. B.; orcid: 0000-0001-8744-0102; email: jitesh.gajjar@manchester.ac.uk; Hewitt, Richard E.; orcid: 0000-0003-3056-1346 (Springer Netherlands, 2021-04-22)
      Abstract: Two-dimensional boundary layer flows in quiet disturbance environments are known to become unstable to Tollmien–Schlichting waves. The experimental work of Liepmann et al. (J Fluid Mech 118:187–200, 1982), Liepmann and Nosenchuck (J Fluid Mech 118:201–204, 1982) showed how it is possible to control and reduce unstable Tollmien–Schlichting wave amplitudes using unsteady surface heating. We consider the problem of an oncoming planar compressible subsonic boundary layer flow with a three-dimensional vibrator mounted on a flat plate, and with surface heating present. It is shown using asymptotic methods based on triple-deck theory that it is possible to choose an unsteady surface heating distribution to cancel out the response due to the vibrator. An approximation based on the exact formula is used successfully in numerical computations to confirm the findings. The results presented here are a generalisation of the analogous results for the two-dimensional problem in Brennan et al. (J Fluid Mech 909:A16-1, 2020).
    • Canine Genetics and Epidemiology is now Canine Medicine and Genetics

      Ollier, William; email: Bill.Ollier@manchester.ac.uk; Gaschen, Frédéric; email: fgaschen@lsu.edu; Kennedy, Lorna (BioMed Central, 2020-07-27)
    • Capital requirements, risk-taking and welfare in a growing economy

      Agénor, Pierre-Richard; orcid: 0000-0001-5720-3544; email: pierre-richard.agenor@manchester.ac.uk; Silva, Luiz A. Pereira da (Springer US, 2021-08-27)
      Abstract: The effects of capital requirements on risk-taking and welfare are studied in an overlapping generations model of endogenous growth with banking, limited liability, and government guarantees. Capital producers face a choice between a safe technology and a risky, more productive but socially inefficient, technology. Bank risk-taking is endogenous. As a result of a skin in the game effect—motivated either as an aggregate externality, or as the outcome of the optimal choice of monitoring effort by individual banks—default risk is inversely related to the capital adequacy ratio. Numerical simulations show that in an equilibrium where banks extend both safe and risky loans, the skin in the game effect must be sufficiently strong for a welfare-maximizing regulatory policy to exist. These results remain qualitatively similar with endogenous monitoring costs and a strong effect of monitoring on entrepreneurial moral hazard. However, numerical experiments also suggest that the optimal capital adequacy ratio may be too high in practice and may require concomitantly a broadening of the perimeter of regulation and a strengthening of financial supervision to prevent disintermediation and distortions in financial markets.
    • Capturing convection essential for projections of climate change in African dust emission

      Garcia-Carreras, Luis; orcid: 0000-0002-9844-3170; email: luis.garcia-carreras@manchester.ac.uk; Marsham, John H.; orcid: 0000-0003-3219-8472; Stratton, Rachel A.; Tucker, Simon (Nature Publishing Group UK, 2021-09-24)
      Abstract: The summertime Sahara and Sahel are the world’s largest source of airborne mineral dust. Cold-pool outflows from moist convection (‘haboobs’) are a dominant source of summertime uplift but are essentially missing in global models, raising major questions on the reliability of climate projections of dust and dust impacts. Here we use convection-permitting simulations of pan-African climate change, which explicitly capture haboobs, to investigate whether this key limitation of global models affects projections. We show that explicit convection is key to capturing the observed summertime maximum of dust-generating winds, which is missed with parameterised convection. Despite this, future climate changes in dust-generating winds are more sensitive to the effects of explicit convection on the wider meteorology than they are to the haboobs themselves, with model differences in the change in dust-generating winds reaching 60% of current values. The results therefore show the importance of improving convection in climate models for dust projections.
    • Carbon nanotubes and their polymeric composites: the applications in tissue engineering

      Huang, Boyang; orcid: 0000-0001-5669-349X; email: boyang.huang@manchester.ac.uk (Springer International Publishing, 2020-10-10)
      Abstract: Carbon nanotubes (CNTs), with unique graphitic structure, superior mechanical, electrical, optical and biological properties, has attracted more and more interests in biomedical applications, including gene/drug delivery, bioimaging, biosensor and tissue engineering. In this review, we focus on the role of CNTs and their polymeric composites in tissue engineering applications, with emphasis on their usages in the nerve, cardiac and bone tissue regenerations. The intrinsic natures of CNTs including their physical and chemical properties are first introduced, explaining the structure effects on CNTs electrical conductivity and various functionalization of CNTs to improve their hydrophobic characteristics. Biosafety issues of CNTs are also discussed in detail including the potential reasons to induce the toxicity and their potential strategies to minimise the toxicity effects. Several processing strategies including solution-based processing, polymerization, melt-based processing and grafting methods are presented to show the 2D/3D construct formations using the polymeric composite containing CNTs. For the sake of improving mechanical, electrical and biological properties and minimising the potential toxicity effects, recent advances using polymer/CNT composite the tissue engineering applications are displayed and they are mainly used in the neural tissue (to improve electrical conductivity and biological properties), cardiac tissue (to improve electrical, elastic properties and biological properties) and bone tissue (to improve mechanical properties and biological properties). Current limitations of CNTs in the tissue engineering are discussed and the corresponded future prospective are also provided. Overall, this review indicates that CNTs are promising “next-generation” materials for future biomedical applications.
    • Cardiac rehabilitation patients experiences and understanding of group metacognitive therapy: a qualitative study.

      McPhillips, Rebecca; orcid: 0000-0003-4296-5970; email: rebecca.mcphillips@manchester.ac.uk; Capobianco, Lora; Cooper, Bethany Grace; Husain, Zara; Wells, Adrian (2021-07-01)
      <h4>Objective</h4>Depression and anxiety are up to three times more prevalent in cardiac patients than the general population and are linked to increased risks of future cardiac events and mortality. Psychological interventions for cardiac patients vary in content and are often associated with weak outcomes. A recent treatment, metacognitive therapy (MCT) has been shown to be highly effective at treating psychological distress in mental health settings. This is the first study to explore qualitatively, cardiac rehabilitation (CR) patients' experiences and understanding of group MCT with the aim of examining aspects of treatment that patients experienced as helpful.<h4>Methods</h4>In-depth qualitative interviews were conducted with 24 purposively sampled CR patients following group MCT. Data were analysed using thematic analysis.<h4>Results</h4>Two main themes were identified: (1) general therapy factors that were seen largely as beneficial, where patients highlighted interaction with other CR patients and CR staff delivery of treatment and their knowledge of cardiology; (2) group MCT-specific factors that were seen as beneficial encompassed patients' understanding of the intervention and use of particular group MCT techniques. Most patients viewed MCT in a manner consistent with the metacognitive model. All the patients who completed group MCT were positive about it and described self-perceived changes in their thinking and well-being. A minority of patients gave specific reasons for not finding the treatment helpful.<h4>Conclusion</h4>CR patients with anxiety and depression symptoms valued specific group MCT techniques, the opportunity to learn about other patients, and the knowledge of CR staff. The data supports the transferability of treatment to a CR context and advantages that this might bring.
    • Cardiac rehabilitation patients experiences and understanding of group metacognitive therapy: a qualitative study.

      McPhillips, Rebecca; orcid: 0000-0003-4296-5970; email: rebecca.mcphillips@manchester.ac.uk; Capobianco, Lora; Cooper, Bethany Grace; Husain, Zara; Wells, Adrian (2021-07)
      Depression and anxiety are up to three times more prevalent in cardiac patients than the general population and are linked to increased risks of future cardiac events and mortality. Psychological interventions for cardiac patients vary in content and are often associated with weak outcomes. A recent treatment, metacognitive therapy (MCT) has been shown to be highly effective at treating psychological distress in mental health settings. This is the first study to explore qualitatively, cardiac rehabilitation (CR) patients' experiences and understanding of group MCT with the aim of examining aspects of treatment that patients experienced as helpful. In-depth qualitative interviews were conducted with 24 purposively sampled CR patients following group MCT. Data were analysed using thematic analysis. Two main themes were identified: (1) general therapy factors that were seen largely as beneficial, where patients highlighted interaction with other CR patients and CR staff delivery of treatment and their knowledge of cardiology; (2) group MCT-specific factors that were seen as beneficial encompassed patients' understanding of the intervention and use of particular group MCT techniques. Most patients viewed MCT in a manner consistent with the metacognitive model. All the patients who completed group MCT were positive about it and described self-perceived changes in their thinking and well-being. A minority of patients gave specific reasons for not finding the treatment helpful. CR patients with anxiety and depression symptoms valued specific group MCT techniques, the opportunity to learn about other patients, and the knowledge of CR staff. The data supports the transferability of treatment to a CR context and advantages that this might bring. [Abstract copyright: © Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.]
    • Cardiac Transverse Tubules in Physiology and Heart Failure.

      Dibb, Katharine M; Louch, William E; Trafford, Andrew W (2021-11-15)
      In mammalian cardiac myocytes, the plasma membrane includes the surface sarcolemma but also a network of membrane invaginations called transverse (t-) tubules. These structures carry the action potential deep into the cell interior, allowing efficient triggering of Ca release and initiation of contraction. Once thought to serve as rather static enablers of excitation-contraction coupling, recent work has provided a newfound appreciation of the plasticity of the t-tubule network's structure and function. Indeed, t-tubules are now understood to support dynamic regulation of the heartbeat across a range of timescales, during all stages of life, in both health and disease. This review article aims to summarize these concepts, with consideration given to emerging t-tubule regulators and their targeting in future therapies. Expected final online publication date for the , Volume 84 is February 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.