The Self Model and the Conception of Biological Identity in Immunology

The self/non-self model, first proposed by F.M. Burnet, has dominated immunology for sixty years now. According to this model, any foreign element will trigger an immune reaction in an organism, whereas endogenous elements will not, in normal circumstances, induce an immune reaction. In this paper we show that the self/non-self model is no longer an appropriate explanation of experimental data in immunology, and that this inadequacy may be rooted in an excessively strong metaphysical conception of biological identity. We suggest that another hypothesis, one based on the notion of continuity, gives a better account of immune phenomena. Finally, we underscore the mapping between this metaphysical deflation from self to continuity in immunology and the philosophical debate between substantialism and empiricism about identity

Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure

Heart failure (HF) is a leading cause of morbidity and mortality worldwide. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained. We report results from a GWAS meta-analysis of HF comprising 47,309 cases and 930,014 controls. Twelve independent variants at 11 genomic loci are associated with HF, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function, suggesting shared genetic aetiology. Functional analysis of non-CAD-associated loci implicate genes involved in cardiac development (MYOZ1, SYNPO2L), protein homoeostasis (BAG3), and cellular senescence (CDKN1A). Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension. These findings extend our knowledge of the pathways underlying HF and may inform new therapeutic strategies

Chromatographic cation exchange separation of decigram quantities of californium and other transplutonium elements

Decigram quantities of highly radioactive transplutonium elements are routinely partitioned at TRU by chromatographic elution from cation resin using AHIB eluent. By using two high-pressure ion exchange columns, a small one for the initial loading of the feed and a large one for the elution, batch runs containing up to 200 mg of /sup 252/Cf can be made in about 5 hours (2 hours to load the feed and 3 hours for the elution). The number of effluent product fractions and the amount of actinides that must be collected in intermediate fractions are minimized by monitoring response from a flow-through alpha-detector. This process has been reliable and relatively easy to operate, and will continue to be used for partitioning transplutonium elements at TRU

Boreal forest fire CO and CH4emission factors derived from tower observations in Alaska during the extreme fire season of 2015

© Author(s) 2021.Recent increases in boreal forest burned area, which have been linked with climate warming, highlight the need to better understand the composition of wildfire emissions and their atmospheric impacts. Here we quantified emission factors for CO and CH4 from a massive regional fire complex in interior Alaska during the summer of 2015 using continuous high-resolution trace gas observations from the Carbon in Arctic Reservoirs Vulnerability Experiment (CRV) tower in Fox, Alaska. Averaged over the 2015 fire season, the mean CO=CO2 emission ratio was 0.142-0.051, and the mean CO emission factor was 127-40 g kg-1 dry biomass burned. The CO=CO2 emission ratio was about 39% higher than the mean of previous estimates derived from aircraft sampling of wildfires from boreal North America. The mean CH4 =CO2 emission ratio was 0.010-0.004, and the CH4 emission factor was 5.3-1.8 g kg-1 dry biomass burned, which are consistent with the mean of previous reports. CO and CH4 emission ratios varied in synchrony, with higher CH4 emission factors observed during periods with lower modified combustion efficiency (MCE). By coupling a fire emissions inventory with an atmospheric model, we identified at least 34 individual fires that contributed to trace gas variations measured at the CRV tower, representing a sample size that is nearly the same as the total number of boreal fires measured in all previous field campaigns. The model also indicated that typical mean transit times between trace gas emission within a fire perimeter and tower measurement were 1-3 d, indicating that the time series sampled combustion across day and night burning phases. The high CO emission ratio estimates reported here provide evidence for a prominent role of smoldering combustion and illustrate the importance of continuously sampling fires across timevarying environmental conditions that are representative of a fire season

A Randomized Controlled Trial of Fludrocortisone for the Treatment of Hyperkalemia in Hemodialysis Patients

Background Previous small uncontrolled studies suggested that fludrocortisone may significantly decrease serum potassium concentrations in hemodialysis patients, possibly through enhancement of colonic potassium secretion. The aim of this study is to evaluate the effect of oral fludrocortisone on serum potassium concentrations in hyperkalemic hemodialysis patients in an open-label randomized controlled trial. Methods: Thirty-seven hemodialysis patients with predialysis hyperkalemia were randomly allocated to administration of either oral fludrocortisone (0.1 mg/d; n = 18) or no treatment (control; n = 19) for 3 months. The primary outcome measure was midweek predialysis serum potassium concentration, which was measured monthly during the trial. Prospective power calculations indicated that the study had an 80% probability of detecting a decrease in serum potassium levels of 0.7 mEq/L (0.7 mmol/L). Results: Baseline patient characteristics were similar, except for slightly longer total weekly dialysis hours in the fludrocortisone group (13.0 +/- 1.3 versus 12.1 +/- 1.0; P = 0.02). At the end of the study period, no significant changes in serum potassium concentrations were observed between the fludrocortisone and control groups (4.8 +/- 0.5 versus 5.2 +/- 0.7 mEq/L [mmol/L], respectively; P = 0.10). Similar results were obtained when changes in serum potassium levels over time were examined between the 2 arms by using repeated-measures analysis of variance, with or without adjustment for total weekly dialysis hours. Secondary outcomes, including predialysis mean arterial pressure, interdialytic weight gain, serum sodium level, and hospitalization for hyperkalemia, were not significantly different between groups. There were no observed adverse events. Conclusion: Administering fludrocortisone to hyperkalemic hemodialysis patients is safe and well tolerated, but does not achieve clinically important decreases in serum potassium levels