Binding Potassium to Improve Treatment With Renin-Angiotensin-Aldosterone System Inhibitors: Results From Multiple One-Stage Pairwise and Network Meta-Analyses of Clinical Trials.

This manuscript presents findings from the first dichotomous data pooling analysis on clinical trials (CT) regarding the effectiveness of binding potassium. The results emanated from pairwise and network meta-analyses aiming evaluation of response to commercial potassium-binding polymers, that is, to achieve and maintain normal serum potassium (n = 1,722), and the association between this response and an optimal dosing of renin-angiotensin-aldosterone system inhibitors (RAASi) needing individuals affected by heart failure (HF) or resistant hypertension, who may be consuming other hyperkalemia-inducing drugs (HKID) (e.g., β-blockers, heparin, etc.), and frequently are affected by chronic kidney disease (CKD) (n = 1,044): According to the surface under the cumulative ranking area (SUCRA), sodium zirconium cyclosilicate (SZC) (SUCRA >0.78), patiromer (SUCRA >0.58) and sodium polystyrene sulfonate (SPS) (SUCRA <0.39) were different concerning their capacity to achieve normokalemia (serum potassium level (sK+) 3.5-5.0 mEq/L) or acceptable kalemia (sK+ ≤ 5.1 mEq/L) in individuals with hyperkalemia (sK+ >5.1 mEq/L), and, when normokalemia is achieved, patiromer 16.8-25.2 g/day (SUCRA = 0.94) and patiromer 8.4-16.8 g/day (SUCRA = 0.41) can allow to increase the dose of spironolactone up to 50 mg/day in subjects affected by heart failure (HF) or with resistant hypertension needing treatment with other RAASi. The potential of zirconium cyclosilicate should be explored further, as no data exists to assess properly its capacity to optimize dosing of RAASi, contrarily as it occurs with patiromer. More research is also necessary to discern between benefits of binding potassium among all type of hyperkalemic patients, for example, patients with DM who may need treatment for proteinuria, patients with early hypertension, etc. Systematic Review Registration:https://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42020185614, CRD42020185558, CRD42020191430

The Equifinality of Archaeological Networks: an Agent-Based Exploratory Lab Approach

When we find an archaeological network, how can we explore the necessary versus contingent processes at play in the formation of that archaeological network? Given a set of circumstances or processes, what other possible network shapes could have emerged? This is the problem of equifinality, where many different means could potentially arrive at the same end result: the networks that we observe. This paper outlines how agent-based modelling can be used as a laboratory for exploring different processes of archaeological network formation. We begin by describing our best guess about how the (ancient) world worked, given our target materials (here, the networks of production and patronage surrounding the Roman brick industry in the hinterland of Rome). We then develop an agent-based model of the Roman extractive economy which generates different kinds of networks under various assumptions about how that economy works. The rules of the simulation are built upon the work of Bang (2006; 2008) who describes a model of the Roman economy which he calls the ‘imperial Bazaar’. The agents are allowed to interact, and the investigators compare the kinds of networks this description generates over an entire landscape of economic possibilities. By rigorously exploring this landscape, and comparing the resultant networks with those observed in the archaeological materials, the investigators will be able to employ the principle of equifinality to work out the representativeness of the archaeological network and thus the underlying processes

Sport, War and Democracy in Classical Athens

This article concerns the paradox of athletics in classical Athens. Democracy may have opened up politics to every class of Athenian but it had little impact on sporting participation. The city’s athletes continued to drawn predominantly from the upper class. It comes as a surprise then that lower-class Athenians actually esteemed athletes above every other group in the public eye, honoured them very generously when they won, and directed a great deal of public and private money to sporting competitions and facilities. In addition athletics escaped the otherwise persistent criticism of upper-class activities in the popular culture of the democracy. The research of social scientists on sport and aggression suggests this paradox may have been due to the cultural overlap between athletics and war under the Athenian democracy. The article concludes that the practical and ideological democratization of war by classical Athens legitimized and supported upper-class sport

Pastoralism and Emergent Complex Settlement in the Middle Bronze Age, Azerbaijan: Isotopic analyses of mobility strategies in transformation

Objectives. This article explores the scale and seasonal patterns of mobility at the complex settlement site of Qızqala during the Middle Bronze Age (2400–1,500 BCE). By integrating human bone, teeth, and environmental samples this research tests the hypothesis of the persistent importance of community-wide seasonal pastoral transhumance during the early formation of complex settlement systems of the South Caucasus. Methods. This research applies stable oxygen and radiogenic strontium isotope analyses on incremental samples of human tooth enamel, bulk tooth enamel, and bone to resolve mobility patterns. Sequential and bulk sampling techniques elucidate seasonal and residential mobility behaviors. Extensive environmental isotope samples of plant and water were collected through regional survey and establish local and regional isotopic baselines, which are compared to human isotope analysis results. Results. Qızqala individuals exhibit low isotopic variability compared to regional contemporaries. 87Sr/86Sr ratios from human remains indicate seasonal and residential isotopic variability within the baseline ranges of local landscapes. δ18O values display erratic patterns, but correspond to seasonal variability with fluctuations between highland and lowland altitudinal zone baseline values. Conclusions. Results suggest that isotopic analysis of multiple elements and sequential enamel samples offers finer resolution on the complexities of human mobility strategies and elucidate the daily lives of often overlooked mobile populations. Higher resolution of individual mobility reveals shared routine behaviors that underscore the importance of diverse social collaborations in forming complex polities in the South Caucasus

The number of FoxP3 regulatory T cells in the circulation may be a predictive biomarker for kidney transplant recipients: A multistage systematic review.

The kinetics of the FoxP3 regulatory T-cell (Treg) population in kidney transplant recipients (KTR) are related to the clinical effect of immunosuppression based on mammalian Target Of Rapamycin inhibitors (mTORi) with/without belatacept (predictive biomarker). A multistage systematic review of published and unpublished literature is presented [registration IDs in the International Prospective Register of Systematic Reviews (PROSPERO): CRD42017057570, CRD42018085019, CRD42018084941, CRD42018085186]. A multidisciplinary supervision mechanism for contextualizing of search findings was required. The peripheral blood immune cell phenotypes encompassing all regulatory cells in KTRs were assessed in order to suggest new markers of acute rejection-associated acute allograft dysfunction (AR/AAD) events in KTRs treated with mTORi alone or combined to belatacept. Quantitative estimates and evaluation of the body of evidence are provided. An increase in Tregs and other regulatory cell types in the circulation in KTRs under mTORi with/without belatacept were observed. Patients with increased Tregs presented a low frequency of AR/AAD events compared to those in which the number of Tregs remained unchanged or even diminished [Odds Ratio (OR)/95% confidence interval (95% CI)/I <sup>2</sup> /number of studies (n): 0.31/0.10-0.93/0%/6]. Nevertheless, there are too few trials to consider Tregs in the circulation as a predictive biomarker. Inadequate reporting prevents appreciating clinical relevance in such studies. Despite advances, clinical qualification of potential predictive biomarkers continues to be difficult. Clinical evidence on Tregs in KTRs needs to be enlarged. Biomarkers should be able to evaluate the effect of medicines targeted to specific patient populations

Antioxidant effect of Kimchi supplemented with Jeju citrus concentrate and its antiobesity effect on 3T3‐L1 adipocytes

Citrus is cultivated throughout Jeju Island and is thought to possess some medicinal properties. Citrus concentrate is the most extensively utilized form of citrus in the food industry. In this study, antioxidant and antiobesity effects of Kimchi supplemented with citrus concentrate were investigated. Prepared Kimchi was infused with 7% citrus concentrate (CK) and freeze‐dried for analysis. Normal Kimchi (NK) without citrus concentrate was utilized as a control. Total phenol content (TPC), total flavonoid content (TFC), and antioxidant activities were examined. Cytotoxicity, intracellular triglycerides (TG), and total cholesterol (TC) levels in 3T3‐L1 adipocytes were also measured. Additionally, the inhibitory effects on lipid accumulation were trialed by measuring the oil‐red O (ORO)‐stained cells. TPC, TFC, and antioxidant activities of CK were significantly higher than those of NK (p < .05). CK showed less cytotoxicity and attenuated the lipid accumulation at all concentrations by reducing TG and TC levels compared to NK. The inhibitory effect of CK on lipid accumulation was observed via reducing ORO‐stained lipid droplets. Consequently, the antioxidant and antiobesity effects of CK were revealed in vitro. Furthermore, the addition of citrus may provide competitive price due to low production costs as well as health functionality

Evidence for long-term averaging of strontium in bovine enamel using TIMS and LA-MC-ICP-MS strontium isotope intra-molar profiles

High spatial resolution micro-sampling of tooth enamel offers the possibility of high temporal resolution isotope data to reconstruct climate, environment, diet and mobility. Questions remain about the duration and pattern of the maturation phase of enamel and the existence and direction of chronological 'time-lines'. LA-MC-ICP-MS measurements of c. 400 μm craters and TIMS analyses of transverse enamel sections of an archaeological bovine third molar were undertaken to investigate the long-term averaging of incorporated strontium. The same gradually increasing isotope profile was obtained from both approaches, indicating that the large increase in spatial resolution did not change the response profile obtained. The results suggest that even at the microscopic scale, strontium is incorporated over a period in excess of 12 months. Averaging of the input signal may result from both long-term retention of strontium in the skeleton and recirculation in the body pool, or long-term maturation of enamel on a microscopic scale. Whichever mechanism is responsible, it may not be possible to recover strontium isotope ratios with a high time resolution from cattle molar enamel unless there is a large imbalance in the amount of strontium supplied by different sources. Consequently, strontium isotope profiles may not be synchronous with those of lighter isotope systems