Heat engines and heat pumps in a hydrostatic atmosphere: How surface pressure and temperature constrain wind power output and circulation cell size

The kinetic energy budget of the atmosphere's meridional circulation cells is analytically assessed. In the upper atmosphere kinetic energy generation grows with increasing surface temperature difference \$\Delta T_s\$ between the cold and warm ends of a circulation cell; in the lower atmosphere it declines. A requirement that kinetic energy generation is positive in the lower atmosphere limits the poleward cell extension \$L\$ of Hadley cells via a relationship between \$\Delta T_s\$ and surface pressure difference \$\Delta p_s\$: an upper limit exists when \$\Delta p_s\$ does not grow with increasing \$\Delta T_s\$. This pattern is demonstrated here using monthly data from MERRA re-analysis. Kinetic energy generation along air streamlines in the boundary layer does not exceed \$40\$~J~mol\$^{-1}\$; it declines with growing \$L\$ and reaches zero for the largest observed \$L\$ at 2~km height. The limited meridional cell size necessitates the appearance of heat pumps -- circulation cells with negative work output where the low-level air moves towards colder areas. These cells consume the positive work output of the heat engines -- cells where the low-level air moves towards the warmer areas -- and can in theory drive the global efficiency of atmospheric circulation down to zero. Relative contributions of \$\Delta p_s\$ and \$\Delta T_s\$ to kinetic energy generation are evaluated: \$\Delta T_s\$ dominates in the upper atmosphere, while \$\Delta p_s\$ dominates in the lower. Analysis and empirical evidence indicate that the net kinetic power output on Earth is dominated by surface pressure gradients, with minor net kinetic energy generation in the upper atmosphere. The role of condensation in generating surface pressure gradients is discussed.Comment: 26 pages, 9 figures, 2 tables; re-organized presentation, more discussion and a new figure (Fig. 4) added; in Fig. 3 the previously invisible dots (observations) can now be see

The effect of epidural anaesthesia on peripheral resistance and graft flow following femorodistal reconstruction

Objective:To determine the extent to which epidural anaesthesia influences peripheral resistance and graft blood flow following femorocrural reconstruction.Design:Prospective, controlled study measuring blood flow, arterial pressure and peripheral resistance in femorocrural bypass grafts for 20 min following onset of epidural anaesthesia with 15ml of 0.25% bupivacaine.Patients:Twenty patients undergoing femorocrural reconstruction for critical lower-limb ischaemia with in situ long saphenous vein, under general anaesthesia. Ten patients had epidural cannulae inserted preoperatively and injected with bupivacaine after completion of the graft.Results:Peripheral resistance fell in all 10 patients receiving epidural anaesthesia from a mean (range) of 1.07 PRU (0.32–2.2) to 0.49 PRU (0.19–0.72), compared to control values of 0.95 PRU (0.39–2.0) to 0.91 PRU (0.41–1.51; P < 0.01, Wilcoxon). There was a tendency for blood pressure to fall in the study patients (not significant) but graft blood flow still increased from 98 ml min−1 (41–221) to 160 ml min−1 (101–250), compared to flow in the control patients of 101 ml min−1 (45–176) at baseline to 104 ml min−1 (56–168; p < 0.01) at 20 min.Conclusions:Epidural anaesthesia significantly decreases peripheral resistance and increases graft blood flow in femorocrural grafts and would appear, therefore, to be of benefit for patients undergoing femorodistal reconstruction

HFE genotypes, haemochromatosis diagnosis and clinical outcomes at age 80 years: a prospective cohort study in the UK Biobank

This is the final version. Available on open access from BMJ Publishing Group via the DOI in this recordData availability statement Data may be obtained from a third party and are not publicly available. Data are available on application to the UK Biobank (www.ukbiobank.ac.uk/register-apply).OBJECTIVES: HFE haemochromatosis genetic variants have an uncertain clinical penetrance, especially to older ages and in undiagnosed groups. We estimated p.C282Y and p.H63D variant cumulative incidence of multiple clinical outcomes in a large community cohort. DESIGN: Prospective cohort study. SETTING: 22 assessment centres across England, Scotland, and Wales in the UK Biobank (2006-2010). PARTICIPANTS: 451 270 participants genetically similar to the 1000 Genomes European reference population, with a mean of 13.3-year follow-up through hospital inpatient, cancer registries and death certificate data. MAIN OUTCOME MEASURES: Cox proportional HRs of incident clinical outcomes and mortality in those with HFE p.C282Y/p.H63D mutations compared with those with no variants, stratified by sex and adjusted for age, assessment centre and genetic stratification. Cumulative incidences were estimated from age 40 years to 80 years. RESULTS: 12.1% of p.C282Y+/+ males had baseline (mean age 57 years) haemochromatosis diagnoses, with a cumulative incidence of 56.4% at age 80 years. 33.1% died vs 25.4% without HFE variants (HR 1.29, 95% CI: 1.12 to 1.48, p=4.7×10-4); 27.9% vs 17.1% had joint replacements, 20.3% vs 8.3% had liver disease, and there were excess delirium, dementia, and Parkinson's disease but not depression. Associations, including excess mortality, were similar in the group undiagnosed with haemochromatosis. 3.4% of women with p.C282Y+/+ had baseline haemochromatosis diagnoses, with a cumulative incidence of 40.5% at age 80 years. There were excess incident liver disease (8.9% vs 6.8%; HR 1.62, 95% CI: 1.27 to 2.05, p=7.8×10-5), joint replacements and delirium, with similar results in the undiagnosed. p.C282Y/p.H63D and p.H63D+/+ men or women had no statistically significant excess fatigue or depression at baseline and no excess incident outcomes. CONCLUSIONS: Male and female p.C282Y homozygotes experienced greater excess morbidity than previously documented, including those undiagnosed with haemochromatosis in the community. As haemochromatosis diagnosis rates were low at baseline despite treatment being considered effective, trials of screening to identify people with p.C282Y homozygosity early appear justified.National Institute for Health and Care Research (NIHR

Approximate probabilistic verification of hybrid systems

Hybrid systems whose mode dynamics are governed by non-linear ordinary differential equations (ODEs) are often a natural model for biological processes. However such models are difficult to analyze. To address this, we develop a probabilistic analysis method by approximating the mode transitions as stochastic events. We assume that the probability of making a mode transition is proportional to the measure of the set of pairs of time points and value states at which the mode transition is enabled. To ensure a sound mathematical basis, we impose a natural continuity property on the non-linear ODEs. We also assume that the states of the system are observed at discrete time points but that the mode transitions may take place at any time between two successive discrete time points. This leads to a discrete time Markov chain as a probabilistic approximation of the hybrid system. We then show that for BLTL (bounded linear time temporal logic) specifications the hybrid system meets a specification iff its Markov chain approximation meets the same specification with probability $1$. Based on this, we formulate a sequential hypothesis testing procedure for verifying -approximately- that the Markov chain meets a BLTL specification with high probability. Our case studies on cardiac cell dynamics and the circadian rhythm indicate that our scheme can be applied in a number of realistic settings

High intensity interval training in a real world setting: A randomized controlled feasibility study in overweight inactive adults, measuring change in maximal oxygen uptake

Background In research clinic settings, overweight adults undertaking HIIT (high intensity interval training) improve their fitness as effectively as those undertaking conventional walking programs but can do so within a shorter time spent exercising. We undertook a randomized controlled feasibility (pilot) study aimed at extending HIIT into a real world setting by recruiting overweight/obese, inactive adults into a group based activity program, held in a community park. Methods Participants were allocated into one of three groups. The two interventions, aerobic interval training and maximal volitional interval training, were compared with an active control group undertaking walking based exercise. Supervised group sessions (36 per intervention) were held outdoors. Cardiorespiratory fitness was measured using VO2max (maximal oxygen uptake, results expressed in ml/min/kg), before and after the 12 week interventions. Results On ITT (intention to treat) analyses, baseline (N = 49) and exit (N = 39) O2 was 25.3±4.5 and 25.3±3.9, respectively. Participant allocation and baseline/exit VO2max by group was as follows: Aerobic interval training N =  16, 24.2±4.8/25.6±4.8; maximal volitional interval training N = 16, 25.0±2.8/25.2±3.4; walking N = 17, 26.5±5.3/25.2±3.6. The post intervention change in VO2max was +1.01 in the aerobic interval training, −0.06 in the maximal volitional interval training and −1.03 in the walking subgroups. The aerobic interval training subgroup increased VO2max compared to walking (p = 0.03). The actual (observed, rather than prescribed) time spent exercising (minutes per week, ITT analysis) was 74 for aerobic interval training, 45 for maximal volitional interval training and 116 for walking (p =  0.001). On descriptive analysis, the walking subgroup had the fewest adverse events. Conclusions In contrast to earlier studies, the improvement in cardiorespiratory fitness in a cohort of overweight/obese participants undertaking aerobic interval training in a real world setting was modest. The most likely reason for this finding relates to reduced adherence to the exercise program, when moving beyond the research clinic setting

Omadacycline gut microbiome exposure does not induce Clostridium difficile proliferation or toxin production in a model that simulates the proximal, medial and distal human colon

A clinically reflective model of the human colon was used to investigate the effects of the broad-spectrum antibiotic omadacycline on the gut microbiome, and subsequent potential to induce simulated Clostridium difficile infection (CDI). Triple stage chemostat gut models were inoculated with pooled human faecal slurry from healthy volunteers (age ≥60 years). Models were challenged twice with 107 cfu C. difficile spores (PCR ribotype 027). Omadacycline effects were assessed in a single gut model. Observations were confirmed in a parallel study with omadacycline and moxifloxacin. Antibiotic instillation was performed once daily for 7 days. The models were observed for 3 weeks post-antibiotic challenge. Gut microbiota populations and C. difficile total viable and spore counts were enumerated daily by culture. Cytotoxin titres and antibiotic concentrations were also measured. Gut microbiota populations were stable before antibiotic challenge. Moxifloxacin instillation caused a ∼4 log10 cfu/mL decline in enterococci and Bacteroides fragilis group populations, and a ∼3 log10 cfu/mL decline in bifidobacteria and lactobacilli, followed by simulated CDI (vegetative cell proliferation and detectable toxin). In both models, omadacycline instillation decreased populations of bifidobacteria (∼8 log10 cfu/mL), B. fragilis group populations (7-8 log10 cfu/mL), lactobacilli (2-6 log10 cfu/mL), and enterococci (4-6 log10 cfu/mL). Despite these microbial shifts, there was no evidence of C. difficile germination or toxin production. In contrast to moxifloxacin, omadacycline exposure did not facilitate simulated CDI, suggesting this antibiotic may have a low propensity to induce CDI in the clinical setting

Patient-relevant outcomes following elective, aseptic revision knee arthroplasty: a systematic review

Background The aim of this systematic review was to summarise the evidence for the clinical effectiveness of revision knee arthroplasty (rKA) compared to non-operative treatment for the management of patients with elective, aseptic causes for a failed knee arthroplasty. Methods MEDLINE, Embase, AMED and PsychINFO were searched from inception to 1st December 2020 for studies on patients considering elective, aseptic rKA. Patient-relevant outcomes (PROs) were defined as implant survivorship, joint function, quality of life (QoL), complications and hospital admission impact. Results No studies compared elective, aseptic rKA to non-operative management. Forty uncontrolled studies reported on PROs following elective, aseptic rKA (434434 rKA). Pooled estimates for implant survivorship were: 95.5% (95% CI 93.2–97.7%) at 1 year [seven studies (5524 rKA)], 90.8% (95% CI 87.6–94.0%) at 5 years [13 studies (5754 rKA)], 87.4% (95% CI 81.7–93.1%) at 10 years [nine studies (2188 rKA)], and 83.2% (95% CI 76.7–89.7%) at 15 years [two studies (452 rKA)]. Twelve studies (2382 rKA) reported joint function and/or QoL: all found large improvements from baseline to follow-up. Mortality rates were low (0.16% to 2% within 1 year) [four studies (353064 rKA)]. Post-operative complications were common (9.1 to 37.2% at 90 days). Conclusion Higher-quality evidence is needed to support patients with decision-making in elective, aseptic rKA. This should include studies comparing operative and non-operative management. Implant survivorship following elective, aseptic rKA was ~ 96% at 1 year, ~ 91% at 5 years and ~ 87% at 10 years. Early complications were common after elective, aseptic rKA and the rates summarised here can be shared with patients during informed consent. Systematic review registration PROSPERO CRD4202019692