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The Drake equation has proven fertile ground for speculation about the abundance, or lack thereof, of communicating extraterrestrial intelligences (CETIs) for decades. It has been augmented by subsequent authors to include random variables in order to understand its probabilistic behaviour. However, in most cases, the emergence and lifetime of CETIs are assumed to be independent of each other. In this paper, we will derive several expressions that can demonstrate how CETIs may relate to each other in technological age as well as how the dynamics of the concurrent CETI population change under basic models of interaction, such as the Allee effect. By defining interaction as the change in the expected communication lifetime with respect to the density of CETI in a region of space, we can use models and simulation to understand how the CETI density can promote or inhibit the longevity and overall population of interstellar technological civilizations.

People living with HIV (PLWH) have rising life expectancy, and robust evidence shows they are also at increased risk of cardiovascular disease. However, sudden cardiac death (SCD) for PLWH on antiretroviral therapy (ART) has received little attention. Our systematic review examines the quantitative adult PLWH SCD risk literature with a sub-focus of PLWH on ART. We conducted systematic searches of PubMed, Embase, CENTRAL, CINAHL, Scopus, and Clinicaltrials.gov for peer-reviewed population studies using search terms \"sudden cardiac death\" AND (\"HIV\" OR \"human immunodeficiency virus\") until 20 June 2025. Two reviewers analysed papers meeting eligibility criteria for their SCD classification methodology including for, but not limited to, comparability, generalizability, and misclassification biases including using the Newcastle-Ottawa Scale. The eight eligible studies included ~98 436 PLWH and demonstrated that males PLWH experience elevated SCD risk compared to the general population. One study with 97% male participants found a hazard ratio (HR) of 1.14 (95% CI: 1.04-1.25) for PLWH compared to non-PLWH. In another, comparing viral load groups of ≥500 vs < 500 found a HR of 1.33 (95% CI: 1.04-1.71) for PLWH with CD4 ≥ 500 compared to HIV-negative HR of 1.03 (95% CI: 0.90-1.18). An autopsy study's male sex arm found a mortality rate ratio for PLWH compared to a reference of 1.34 (95% CI: 0.62-2.87). The limited available research provides evidence that while SCD risk for male PLWH is elevated, maintaining HIV-RNA plasma viral load suppression and ≥200 CD4+ cells/mm3 counts (ideally higher) likely lowers the risk of SCD to a rate that is approaching comparability to the general population. The risk of SCD in women living with HIV is still unknown, due to small sample sizes, as the majority of the participants in the PLWH studies were male.

Post-thrombotic syndrome (PTS) is a common and burdensome complication of deep venous thrombosis (DVT). Previous trials suggesting benefit of elastic compression stockings (ECS) to prevent PTS were small, single-centre studies without placebo control. We aimed to assess the efficacy of ECS, compared with placebo stockings, for the prevention of PTS. We did a multicentre randomised placebo-controlled trial of active versus placebo ECS used for 2 years to prevent PTS after a first proximal DVT in centres in Canada and the USA. Patients were randomly assigned to study groups with a web-based randomisation system. Patients presenting with a first symptomatic, proximal DVT were potentially eligible to participate. They were excluded if the use of compression stockings was contraindicated, they had an expected lifespan of less than 6 months, geographical inaccessibility precluded return for follow-up visits, they were unable to apply stockings, or they received thrombolytic therapy for the initial treatment of acute DVT. The primary outcome was PTS diagnosed at 6 months or later using Ginsberg's criteria (leg pain and swelling of ≥1 month duration). We used a modified intention to treat Cox regression analysis, supplemented by a prespecified per-protocol analysis of patients who reported frequent use of their allocated treatment. This study is registered with ClinicalTrials.gov, number NCT00143598, and Current Controlled Trials, number ISRCTN71334751. From 2004 to 2010, 410 patients were randomly assigned to receive active ECS and 396 placebo ECS. The cumulative incidence of PTS was 14·2% in active ECS versus 12·7% in placebo ECS (hazard ratio adjusted for centre 1·13, 95% CI 0·73–1·76; p=0·58). Results were similar in a prespecified per-protocol analysis of patients who reported frequent use of stockings. ECS did not prevent PTS after a first proximal DVT, hence our findings do not support routine wearing of ECS after DVT. Canadian Institutes of Health Research.

In this paper, new techniques that allow conditional entropy to estimate the combinatorics of symbols are applied to animal communication studies to estimate the communication’s repertoire size. By using the conditional entropy estimates at multiple orders, the paper estimates the total repertoire sizes for animal communication across bottlenose dolphins, humpback whales and several species of birds for an N-gram length of one to three. In addition to discussing the impact of this method on studies of animal communication complexity, the reliability of these estimates is compared to other methods through simulation. While entropy does undercount the total repertoire size due to rare N-grams, it gives a more accurate picture of the most frequently used repertoire than just repertoire size alone.

Hydroxyurea treatment of patients with sickle-cell disease increases fetal hemoglobin (HbF), which reduces hemoglobin S polymerization and clinical complications. Despite its use in the treatment of myeloproliferative diseases for over 30 years, its mechanism of action remains uncertain. Recent studies have demonstrated that hydroxyurea generates the nitric oxide (NO) radical in vivo, and we therefore hypothesized that NO-donor properties might determine the hemoglobin phenotype. We treated both K562 erythroleukemic cells and human erythroid progenitor cells with S-nitrosocysteine (CysNO), an NO donor, and found similar dose- and time-dependent induction of gamma-globin mRNA and HbF protein as we observed with hydroxyurea. Both hydroxyurea and CysNO increased cGMP levels, and the guanylyl cyclase inhibitors ODQ, NS 2028, and LY 83,538 abolished both the hydroxyurea- and CysNO-induced gamma-globin expression. These data provide strong evidence for an NO-derived mechanism for HbF induction by hydroxyurea and suggest possibilities for therapies based on NO-releasing or -potentiating agents.

There exist reaction products of nitric oxide (NO) with blood that conserve its bioactivity and transduce an endocrine vasomotor function under certain conditions. Although S-nitrosated albumin has been considered the major species subserving this activity, recent data suggest that additional NO species, such as nitrite, nitrated lipids, N-nitrosamine, and iron-nitrosyl complexes, may contribute. We therefore examined the end products of NO reactions in plasma and blood in vitro and in vivo by using reductive chemiluminescent assays and electron paramagnetic resonance spectroscopy. We found that NO complexes in plasma previously considered to be S-nitrosated albumin were <10 nM after elimination of nitrite and were mercury-stable, consistent with iron-nitrosyl or N-nitrosamine complex. During clinical NO gas inhalation protocols or in vitro NO donor treatment of human plasma, S-nitroso-albumin did not form with NO exposure <2 μM, but plasma methemoglobin was detectable by paramagnetic resonance spectroscopy. Consistent with this formation of methemoglobin, human plasma was found to consume ≈2 μM NO at a rate equivalent to that of hemoglobin. This NO consumption was mediated by the reaction of NO with plasma haptoglobin-hemoglobin complexes and limited slower reaction pathways required for S-nitrosation. These data suggest that high-affinity, metal-based reactions in plasma with the haptoglobin-hemoglobin complex modulate plasmatic NO reaction products and limit S-nitrosation at low NO flux. The studies further suggest that alternative NO reaction end products in plasma, such as nitrite, N-nitrosamines, iron-nitrosyls, and nitrated lipids, should be evaluated in blood NO transport along the vasculature.

Background The guanine nucleotide binding protein (G protein)-coupled receptors (GPCRs) regulate cell growth, proliferation and differentiation. G proteins are also implicated in erythroid differentiation, and some of them are expressed principally in hematopoietic cells. GPCRs-linked NO/cGMP and p38 MAPK signaling pathways already demonstrated potency for globin gene stimulation. By analyzing erythroid progenitors, derived from hematopoietic cells through in vitro ontogeny, our study intends to determine early markers and signaling pathways of globin gene regulation and their relation to GPCR expression. Results Human hematopoietic CD34 + progenitors are isolated from fetal liver (FL), cord blood (CB), adult bone marrow (BM), peripheral blood (PB) and G-CSF stimulated mobilized PB (mPB), and then differentiated in vitro into erythroid progenitors. We find that growth capacity is most abundant in FL- and CB-derived erythroid cells. The erythroid progenitor cells are sorted as 100% CD71 + , but we did not find statistical significance in the variations of CD34, CD36 and GlyA antigens and that confirms similarity in maturation of studied ontogenic periods. During ontogeny, beta-globin gene expression reaches maximum levels in cells of adult blood origin (176 fmol/μg), while gamma-globin gene expression is consistently up-regulated in CB-derived cells (60 fmol/μg). During gamma-globin induction by hydroxycarbamide, we identify stimulated GPCRs ( PTGDR, PTGER1 ) and GPCRs-coupled genes known to be activated via the cAMP/PKA ( ADIPOQ ), MAPK pathway ( JUN ) and NO/cGMP ( PRPF18 ) signaling pathways. During ontogeny, GPR45 and ARRDC1 genes have the most prominent expression in FL-derived erythroid progenitor cells, GNL3 and GRP65 genes in CB-derived cells (high gamma-globin gene expression), GPR110 and GNG10 in BM-derived cells, GPR89C and GPR172A in PB-derived cells, and GPR44 and GNAQ genes in mPB-derived cells (high beta-globin gene expression). Conclusions These results demonstrate the concomitant activity of GPCR-coupled genes and related signaling pathways during erythropoietic stimulation of globin genes. In accordance with previous reports, the stimulation of GPCRs supports the postulated connection between cAMP/PKA and NO/cGMP pathways in activation of γ-globin expression, via JUN and p38 MAPK signaling.

This paper develops a detailed quantitative model which uses the Drake equation and an assumption of an average maximum radio broadcasting distance by an communicative civilization. Using this basis, it estimates the minimum civilization density for contact between two civilizations to be probable in a given volume of space under certain conditions, the amount of time it would take for a first contact, and the question of whether reciprocal contact is possible.

Codon usage bias is a well recognized phenomenon but the relative influence of its major causes: G+C content, mutational biases, and selection, are often difficult to disentangle. This paper presents methods to calculate modified effective codon numbers that allow the investigation of the relative strength of each of these forces and how genes or organisms have their codon biases shaped. In particular, it demonstrates that variation in codon usage bias across organisms is likely driven more by mutational forces while the variation in codon usage bias within genomes is likely driven by selectional forces.

The mathematical theory of quantitative traits is over one hundred years old but it is still a fertile area for research and analysis. However, the effects of selection on a quantitative trait, while well understood for the effects on the mean and variance, have traditionally been difficult to attack from the perspective of analyzing the probability density of the breeding values and deriving higher (third and fourth) moments as well as analyzing the impact of recombination. In this paper, the exact formula for the breeding value distribution after selection is derived and, using new integral tables, the first four moments are given exact expressions for the first time. In addition, the effects of recombination on the full distribution of breeding values are demonstrated. Finally, the changes of GXE covariance in the selected parent population caused by factors similar to the Bulmer Effect are also investigated in detail. Competing Interest Statement The authors have declared no competing interest.