A comparison of cardiovascular magnetic resonance and single photon emission computed tomography (SPECT) perfusion imaging in left main stem or equivalent coronary artery disease: a CE-MARC substudy

Background: Assessment of left main stem (LMS) stenosis has prognostic and therapeutic implications. Data on assessment of LMS disease by cardiovascular magnetic resonance (CMR) and single photon emission computed tomography (SPECT) are limited. CE-MARC is the largest prospective comparison of CMR and SPECT against quantitative invasive coronary angiography (QCA) for detection of coronary artery disease (CAD), and provided the framework for this evaluation. The aims of this study were to compare diagnostic accuracy of visual and quantitative perfusion CMR to SPECT in patients with LMS stable CAD. Methods: Fifty-four patients from the CE-MARC study were included: 27 (4%) with significant LMS or LMS-equivalent disease on QCA, and 27 age/sex-matched patients with no flow-limiting CAD. All patients underwent multi-parametric CMR, SPECT and QCA. Performance of visual and quantitative perfusion CMR by Fermi-constrained deconvolution to detect LMS disease was compared with SPECT. Results: Of 27 patients in the LMS group, 22 (81%) had abnormal CMR and 16 (59%) had abnormal SPECT. All patients with abnormal CMR had abnormal perfusion by visual analysis. CMR demonstrated significantly higher area under the curve (AUC) for detection of disease (0.95; 0.85–0.99) over SPECT (0.63; 0.49–0.76) (p = 0.0001). Global mean stress myocardial blood flow (MBF) by CMR in LMS patients was significantly lower than controls (1.77 ± 0.72 ml/g/min vs. 3.28 ± 1.20 ml/g/min, p < 0.001). MBF of <2.08 ml/g/min had sensitivity of 78% and specificity of 85% for diagnosis of LMS disease, with an AUC (0.87; 0.75–0.94) not significantly different to visual CMR analysis (p = 0.18), and more accurate than SPECT (p = 0.003). Conclusion: Visual stress perfusion CMR had higher diagnostic accuracy than SPECT to detect LMS disease. Quantitative perfusion CMR had similar performance to visual CMR perfusion analysis

The effect of exercise training interventions in adult kidney transplant recipients: a systematic review and meta-analysis of randomised control trials

Background: Kidney transplant recipients (KTRs) are characterised by adverse changes in physical fitness and body composition. Post-transplant management involves being physically active, although evidence for the effect of exercise is limited. Objective: To assess the effects of exercise training interventions in KTRs. Methods: NCBI PubMed (MEDLINE) and CENTRAL (EMBASE, WHO ICTRP) databases were searched up to March 2021 to identify eligible randomized controlled trials (RCTs) that studied exercise training in adult KTRs. Outcomes included exercise capacity, strength, blood pressure, body composition, heart rate, markers of dyslipidaemia and renal function, and health-related quality of life (QoL). Results: Sixteen RCTs, containing 827 KTRs, were included. The median intervention length was 14-weeks with participants exercising between 2–7x/week. Most studies used a mixture of aerobic and resistance exercise. Significant improvements were observed in cardiorespiratory function (VO2peak) (3.21 ml/kg/min, p = 0.003), 6MWT (76.3 meters, p = 0.009), physical function (STS-60, 4.8 repetitions, p = 0.04), and high-density lipoprotein (HDL) (0.13 mg/dL, p = 0.03). A moderate increase in maximum heart rate was seen (p = 0.06). A moderate reduction in creatinine was also observed (0.14 mg/dl, p = 0.05). Isolated studies reported improvements in strength, bone health, lean mass, and QoL. Overall, studies had high risk of bias suggestive of publication bias. Conclusions: Exercise training may confer several benefits in adult KTRs, particularly by increasing cardiorespiratory function and exercise capacity, strength, HDL levels, maximum heart rate, and improving QoL. Additional long-term large sampled RCTs, incorporating complex interventions requiring both exercise and dietary behaviour change, are needed to fully understand the effects of exercise in KTRs

Mycobacterium tuberculosis cords within lymphatic endothelial cells to evade host immunity

The ability of Mycobacterium tuberculosis to form serpentine cords is intrinsically related to its virulence, but specifically how M. tuberculosis cording contributes to pathogenesis remains obscure. Here, we show that several M. tuberculosis clinical isolates form intracellular cords in primary human lymphatic endothelial cells (hLECs) in vitro and in the lymph nodes of patients with tuberculosis. We identified via RNA-Seq a transcriptional program that activated, in infected-hLECs, cell survival and cytosolic surveillance of pathogens pathways. Consistent with this, cytosolic access was required for intracellular M. tuberculosis cording. Mycobacteria lacking ESX-1 type VII secretion system or phthiocerol dimycocerosates expression, which failed to access the cytosol, were indeed unable to form cords within hLECs. Finally, we show that M. tuberculosis cording is a size-dependent mechanism used by the pathogen to avoid its recognition by cytosolic sensors and evade either resting or IFN-γ–induced hLEC immunity. These results explain the long-standing association between M. tuberculosis cording and virulence and how virulent mycobacteria use intracellular cording as strategy to successfully adapt and persist in the lymphatic tracts

Fast Directional Changes during Geomagnetic Transitions: Global Reversals or Local Fluctuations?

Paleomagnetic investigations from sediments in Central and Southern Italy found directional changes of the order of 10∘ per year during the last geomagnetic field reversal (which took place about 780,000 years ago). These values are orders of magnitudes larger than what is expected from the estimated millennial timescales for geomagnetic field reversals. It is yet unclear whether these extreme changes define the timescale of global dipolar change or whether they indicate a rapid, but spatially localised feature that is not indicative of global variations. Here, we address this issue by calculating the minimum amount of kinetic energy that flows at the top of the core required to instantaneously reproduce these two scenarios. We found that optimised flow structures compatible with the global-scale interpretation of directional change require about one order of magnitude more energy than those that reproduce local change. In particular, we found that the most recently reported directional variations from the Sulmona Basin, in Central Italy, can be reproduced by a core-surface flow with rms values comparable to, or significantly lower than, present-day estimates of about 8 to 22 km/y. Conversely, interpreting the observations as global changes requires rms flow values in excess of 77 km/y, with pointwise maximal velocities of 127 km/y, which we deem improbable. We therefore concluded that the extreme variations reported for the Sulmona Basin were likely caused by a local, transient feature during a longer transition

Health Centre Surveys as a Potential Tool for Monitoring Malaria Epidemiology by Area and over Time

BACKGROUND: Presently, many malaria control programmes use health facility data to evaluate the impact of their interventions. Facility-based malaria data, although useful, have problems with completeness, validity and representativeness and reliance on routinely collected health facility data might undermine demonstration of the magnitude of the impact of the recent scaleups of malaria interventions. To determine whether carefully conducted health centre surveys can be reliable means of monitoring area specific malaria epidemiology, we have compared malaria specific indices obtained from surveys in health centres with indices obtained from cross-sectional surveys conducted in their catchment communities. METHODS: A series of age stratified, seasonal, cross-sectional surveys were conducted during the peak malaria transmission season in 2008 and during the following dry season in 2009 in six ecologically diverse areas in The Gambia. Participants were patients who attended the health centres plus a representative sample from the catchment villages of these health facilities. Parasitaemia, anaemia, attributable proportion of fever and anti-MSP1-(19) antibody seroprevalence were compared in the health facility attendees and community participants. RESULTS: A total of 16,230 subjects completed the study; approximately half participated in the health centre surveys and half in the wet season surveys. Data from both the health centre and community surveys showed that malaria endemicity in The Gambia is now low, heterogeneous and seasonal. In the wet season, parasitaemia, seroprevalence and fever prevalence were higher in subjects seen in the health centres than in the community surveys. Age patterns of parasitaemia, attributable proportions of fever and seroprevalence rates were similar in subjects who participated in the community and health centre surveys. CONCLUSION: Health centre surveys have potential as a surveillance tool for evaluating area specific malaria control activities and for monitoring changes in local malaria epidemiology over time

Early risk and protective factors for problem gambling: a systematic review and meta-analysis of longitudinal studies

This systematic review aimed to identify early risk and protective factors (in childhood, adolescence or young adulthood) longitudinally associated with the subsequent development of gambling problems. A systematic search of peer-reviewed and grey literature from 1990 to 2015 identified 15 studies published in 23 articles. Meta-analyses quantified the effect size of 13 individual risk factors (alcohol use frequency, antisocial behaviours, depression, male gender, cannabis use, illicit drug use, impulsivity, number of gambling activities, problem gambling severity, sensation seeking, tobacco use, violence, undercontrolled temperament), one relationship risk factor (peer antisocial behaviours), one community risk factor (poor academic performance), one individual protective factor (socio-economic status) and two relationship protective factors (parent supervision, social problems). Effect sizes were on average small to medium and sensitivity analyses revealed that the results were generally robust to the quality of methodological approaches of the included articles. These findings highlight the need for global prevention efforts that reduce risk factors and screen young people with high-risk profiles. There is insufficient investigation of protective factors to adequately guide prevention initiatives. Future longitudinal research is required to identify additional risk and protective factors associated with problem gambling, particularly within the relationship, community, and societal levels of the socio-ecological model

Dynamo constraints on the long-term evolution of Earth's magnetic field strength

Elucidating the processes in the liquid core that have produced observed palaeointensity changes over the last 3.5 Gyr is crucial for understanding the dynamics and long-term evolution of Earth’s deep interior. We combine numerical geodynamo simulations with theoretical scaling laws to investigate the variation of Earth’s magnetic field strength over geological time. Our approach follows the study of Aubert et al., adapted to include recent advances in numerical simulations, mineral physics and palaeomagnetism. We first compare the field strength within the dynamo region and on the core–mantle boundary (CMB) between a suite of 314 dynamo simulations and two power-based theoretical scaling laws. The scaling laws are both based on a Quasi-Geostropic (QG) force balance at leading order and a Magnetic, Archimedian, and Coriolis (MAC) balance at first order and differ in treating the characteristic length scale of the convection as fixed (QG-MAC-fixed) or determined as part of the solution (QG-MAC-free). When the data set is filtered to retain only simulations with magnetic to kinetic energy ratios greater than at least two we find that the internal field together with the root-mean-square and dipole CMB fields exhibit power-law behaviour that is compatible with both scalings within uncertainties arising from different heating modes and boundary conditions. However, while the extrapolated intensity based on the QG-MAC-free scaling matches Earth’s modern CMB field, the QG-MAC-fixed prediction shoots too high and also significantly overestimates palaeointensities over the last 3.5 Gyr. We combine the QG-MAC-free scaling with outputs from 275 realizations of core–mantle thermal evolution to construct synthetic true dipole moment (TDM) curves spanning the last 3.5 Gyr. Best-fitting TDMs reproduce binned PINT data during the Bruhnes and before inner core nucleation (ICN) within observational uncertainties, but PINT does not contain the predicted strong increase and subsequent high TDMs during the early stages of inner core growth. The best-fitting models are obtained for a present-day CMB heat flow of 11–16 TW, increasing to 17–22 TW at 4 Ga, and predict a minimum TDM at ICN

Living with frailty and haemodialysis: a qualitative study

Background: Frailty is highly prevalent in people receiving haemodialysis (HD) and is associated with poor outcomes. Understanding the lived experiences of this group is essential to inform holistic care delivery. / Methods: Semi-structured interviews with N = 25 prevalent adults receiving HD from 3 HD units in the UK. Eligibility criteria included a Clinical Frailty Scale (CFS) score of 4–7 and a history of at least one fall in the last 6 months. Sampling began guided by maximum variation sampling to ensure diversity in frailty status; subsequently theoretical sampling enabled exploration of preliminary themes. Analysis was informed by constructivist grounded theory; later we drew upon the socioecological model. / Results: Participants had a mean age of 69 ± 10 years, 13 were female, and 13 were White British. 14 participants were vulnerable or mildly frail (CFS 4–5), and 11 moderately or severely frail (CFS 6–7). Participants characterised frailty as weight loss, weakness, exhaustion, pain and sleep disturbance arising from multiple long-term conditions. Participants’ accounts revealed: the consequences of frailty (variable function and psychological ill-health at the individual level; increasing reliance upon family at the interpersonal level; burdensome health and social care interactions at the organisational level; reduced participation at the community level; challenges with financial support at the societal level); coping strategies (avoidance, vigilance, and resignation); and unmet needs (overprotection from family and healthcare professionals, transactional health and social care exchanges). / Conclusions: The implementation of a holistic needs assessment, person-centred health and social care systems, greater family support and enhancing opportunities for community participation may all improve outcomes and experience. An approach which encompasses all these strategies, together with wider public health interventions, may have a greater sustained impact. Trial registration: ISRCTN12840463

Acute Reverse Remodelling After Transcatheter Aortic Valve Implantation: A Link Between Myocardial Fibrosis and Left Ventricular Mass Regression

Background: Despite the wealth of data showing the positive effects on cardiac reverse remodelling in the long-term, the immediate effects of transcatheter aortic valve implantation (TAVI) on the left ventricle are yet to be comprehensively described using cardiovascular magnetic resonance imaging. Also, the link between myocardial fibrosis and acute left ventricular (LV) mass regression is unknown. Methods: Fifty-seven patients with severe aortic stenosis awaiting TAVI underwent paired cardiovascular magnetic resonance scans before and early after the procedure (4 [interquartile range, 3-5] days). LV mass, volume, and function were measured. Late gadolinium enhancement (LGE) imaging was performed to assess for the presence of and pattern of myocardial fibrosis. Results: After the procedure, 53 (95%) patients experienced an immediate (10.1 ± 7.1%) reduction in indexed LV mass (LVMi) from 76 ± 15.5 to 68.4 ± 14.7 g/m2 (P < 0.001). Those with no LGE experienced the greatest LVMi regression (13.9 ± 7.1%) compared with those with a midwall/focal fibrosis pattern LGE (7.4 ± 5.8%) and infarct pattern LGE (7.2 ± 7.0%; P = 0.005). There was no overall change in LV ejection fraction (LVEF; 55.1 ± 12.1% to 55.5 ± 10.9%; P = 0.867), however a significant improvement in LVEF was seen in those with abnormal (< 55%; n = 24; 42%) baseline LVEF (43.2 ± 8.9 to 46.7 ± 10.5%; P = 0.027). Baseline LVMi (P = 0.005) and myocardial fibrosis (P < 0.001) were strong independent predictors of early LVMi regression. Conclusions: LV reverse remodelling occurs immediately after TAVI, with significant LV mass regression in the total population and an improvement in LVEF in those with preexisting LV impairment. Those without myocardial fibrosis at baseline experience greater LV mass regression than those with fibrosis

Powering Earth's Ancient Dynamo With Silicon Precipitation

Earth's core has produced a global magnetic field for at least the last 3.5 Gyrs, presently sustained by inner core (IC) growth. Models of the core with high thermal conductivity suggest potentially insufficient power available for the geodynamo prior to IC formation ∼1 Ga. Precipitation of silicon from the liquid core might offer an alternative power source for the ancient magnetic field, although few estimates of the silicon partition coefficient exist for conditions of the early core. We present the first ab initio determination of the silicon partition coefficient at core-mantle boundary conditions and use these results to confirm a thermodynamic description of partitioning that is integrated into a model of coupled core-mantle thermal evolution. We show that models including precipitation of silicon can satisfy constraints of IC size, mantle convective heat flux, mantle temperature and a persistent ancient geodynamo, and favor an oxygen poor initial core composition