Homeomorphic Embedding for Online Termination of Symbolic Methods

Well-quasi orders in general, and homeomorphic embedding in particular, have gained popularity to ensure the termination of techniques for program analysis, specialisation, transformation, and verification. In this paper we survey and discuss this use of homeomorphic embedding and clarify the advantages of such an approach over one using well-founded orders. We also discuss various extensions of the homeomorphic embedding relation. We conclude with a study of homeomorphic embedding in the context of metaprogramming, presenting some new (positive and negative) results and open problems

Cardiorespiratory and perceptual responses to self-regulated and imposed submaximal arm-leg ergometry

Purpose: This study compared cardiorespiratory and perceptual responses to exercise using self-regulated and imposed power outputs distributed between the arms and legs. Methods Ten males (age 21.7 ± 3.4 years) initially undertook incremental arm-crank ergometry (ACE) and cycle ergometry (CYC) tests to volitional exhaustion to determine peak power output (Wpeak). Two subsequent tests involved 20-min combined arm–leg ergometry (ALE) trials, using imposed and self-regulated protocols, both of which aimed to elicit an exercising heart rate of 160 beats min−1. During the imposed trial, arm and leg intensity were set at 40% of each ergometer-specific Wpeak. During the self-regulated trial, participants were asked to self-regulate cadence and resistance to achieve the target heart rate. Heart rate (HR), oxygen uptake (V˙O2 ), pulmonary ventilation (V˙E ), and ratings of perceived exertion (RPE) were recorded continuously. Results As expected, there were no differences between imposed and self-regulated trials for HR, V˙O2 , and V˙E (all P ≥ 0.05). However, central RPE and local RPE for the arms were lower during self-regulated compared imposed trials (P ≤ 0.05). Lower RPE during the self-regulated trial was related to preferential adjustments in how the arms (33 ± 5% Wpeak) and legs (46 ± 5% Wpeak) contributed to the exercise intensity. Conclusions: This study demonstrates that despite similar metabolic and cardiovascular strain elicited by imposed and self-regulated ALE, the latter was perceived to be less strenuous, which is related to participants doing more work with the legs and less work with the arms to achieve the target intensity

Pulmonary artery perfusion versus no pulmonary perfusion during cardiopulmonary bypass in patients with COPD:a randomised clinical trial

INTRODUCTION: Absence of pulmonary perfusion during cardiopulmonary bypass (CPB) may be associated with reduced postoperative oxygenation. Effects of active pulmonary artery perfusion were explored in patients with chronic obstructive pulmonary disease (COPD) undergoing cardiac surgery. METHODS: 90 patients were randomised to receive pulmonary artery perfusion during CPB with either oxygenated blood (n=30) or histidine-tryptophan-ketoglutarate (HTK) solution (n=29) compared with no pulmonary perfusion (n=31). The coprimary outcomes were the inverse oxygenation index compared at 21 hours after starting CPB and longitudinally in a mixed-effects model (MEM). Secondary outcomes were tracheal intubation time, serious adverse events, mortality, days alive outside the intensive care unit (ICU) and outside the hospital. RESULTS: 21 hours after starting CPB patients receiving pulmonary artery perfusion with normothermic oxygenated blood had a higher oxygenation index compared with no pulmonary perfusion (mean difference (MD) 0.94; 95% CI 0.05 to 1.83; p=0.04). The blood group had also a higher oxygenation index both longitudinally (MEM, p=0.009) and at 21 hours (MD 0.99; CI 0.29 to 1.69; p=0.007) compared with the HTK group. The latest result corresponds to a difference in the arterial partial pressure of oxygen of 23 mm Hg with a median fraction of inspired oxygen of 0.32. Yet the blood or HTK groups did not demonstrate a longitudinally higher oxygenation index compared with no pulmonary perfusion (MEM, p=0.57 and 0.17). Similarly, at 21 hours there was no difference in the oxygenation index between the HTK group and those no pulmonary perfusion (MD 0.06; 95% CI −0.73 to 0.86; p=0.87). There were no statistical significant differences between the groups for the secondary outcomes. DISCUSSION: Pulmonary artery perfusion with normothermic oxygenated blood during cardiopulmonary bypass appears to improve postoperative oxygenation in patients with COPD undergoing cardiac surgery. Pulmonary artery perfusion with hypothermic HTK solution does not seem to improve postoperative oxygenation. TRIAL REGISTRATION NUMBER: NCT01614951; Pre-results

Parasite-Derived Plasma Microparticles Contribute Significantly to Malaria Infection-Induced Inflammation through Potent Macrophage Stimulation

There is considerable debate as to the nature of the primary parasite-derived moieties that activate innate pro-inflammatory responses during malaria infection. Microparticles (MPs), which are produced by numerous cell types following vesiculation of the cellular membrane as a consequence of cell death or immune-activation, exert strong pro-inflammatory activity in other disease states. Here we demonstrate that MPs, derived from the plasma of malaria infected mice, but not naive mice, induce potent activation of macrophages in vitro as measured by CD40 up-regulation and TNF production. In vitro, these MPs induced significantly higher levels of macrophage activation than intact infected red blood cells. Immunofluorescence staining revealed that MPs contained significant amounts of parasite material indicating that they are derived primarily from infected red blood cells rather than platelets or endothelial cells. MP driven macrophage activation was completely abolished in the absence of MyD88 and TLR-4 signalling. Similar levels of immunogenic MPs were produced in WT and in TNF−/−, IFN-γ−/−, IL-12−/− and RAG-1−/− malaria-infected mice, but were not produced in mice injected with LPS, showing that inflammation is not required for the production of MPs during malaria infection. This study therefore establishes parasitized red blood cell-derived MPs as a major inducer of systemic inflammation during malaria infection, raising important questions about their role in severe disease and in the generation of adaptive immune responses

Integrative omics reveals subtle molecular perturbations following ischemic conditioning in a porcine kidney transplant model

BACKGROUND: Remote Ischemic Conditioning (RIC) has been proposed as a therapeutic intervention to circumvent the ischemia/reperfusion injury (IRI) that is inherent to organ transplantation. Using a porcine kidney transplant model, we aimed to decipher the subclinical molecular effects of a RIC regime, compared to non-RIC controls. METHODS: Kidney pairs (n = 8 + 8) were extracted from brain dead donor pigs and transplanted in juvenile recipient pigs following a period of cold ischemia. One of the two kidney recipients in each pair was subjected to RIC prior to kidney graft reperfusion, while the other served as non-RIC control. We designed an integrative Omics strategy combining transcriptomics, proteomics, and phosphoproteomics to deduce molecular signatures in kidney tissue that could be attributed to RIC. RESULTS: In kidney grafts taken out 10 h after transplantation we detected minimal molecular perturbations following RIC compared to non-RIC at the transcriptome level, which was mirrored at the proteome level. In particular, we noted that RIC resulted in suppression of tissue inflammatory profiles. Furthermore, an accumulation of muscle extracellular matrix assembly proteins in kidney tissues was detected at the protein level, which may be in response to muscle tissue damage and/or fibrosis. However, the majority of these protein changes did not reach significance (p < 0.05). CONCLUSIONS: Our data identifies subtle molecular phenotypes in porcine kidneys following RIC, and this knowledge could potentially aid optimization of remote ischemic conditioning protocols in renal transplantation. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12014-022-09343-3

Translating HbA1c measurements into estimated average glucose values in pregnant women with diabetes

Aims/hypothesis This study aimed to examine the relationship between average glucose levels, assessed by continuous glucose monitoring (CGM), and HbA1c levels in pregnant women with diabetes to determine whether calculations of standard estimated average glucose (eAG) levels from HbA1c measurements are applicable to pregnant women with diabetes. Methods CGM data from 117 pregnant women (89 women with type 1 diabetes; 28 women with type 2 diabetes) were analysed. Average glucose levels were calculated from 5–7 day CGM profiles (mean 1275 glucose values per profile) and paired with a corresponding (±1 week) HbA1c measure. In total, 688 average glucose–HbA1c pairs were obtained across pregnancy (mean six pairs per participant). Average glucose level was used as the dependent variable in a regression model. Covariates were gestational week, study centre and HbA1c. Results There was a strong association between HbA1c and average glucose values in pregnancy (coefficient 0.67 [95% CI 0.57, 0.78]), i.e. a 1% (11 mmol/mol) difference in HbA1c corresponded to a 0.67 mmol/l difference in average glucose. The random effects model that included gestational week as a curvilinear (quadratic) covariate fitted best, allowing calculation of a pregnancy-specific eAG (PeAG). This showed that an HbA1c of 8.0% (64 mmol/mol) gave a PeAG of 7.4–7.7 mmol/l (depending on gestational week), compared with a standard eAG of 10.2 mmol/l. The PeAG associated with maintaining an HbA1c level of 6.0% (42 mmol/mol) during pregnancy was between 6.4 and 6.7 mmol/l, depending on gestational week. Conclusions/interpretation The HbA1c–average glucose relationship is altered by pregnancy. Routinely generated standard eAG values do not account for this difference between pregnant and non-pregnant individuals and, thus, should not be used during pregnancy. Instead, the PeAG values deduced in the current study are recommended for antenatal clinical care