Can a renal nurse assess fluid status using ultrasound on the inferior vena cava? A cross-sectional interrater study: Ultrasound on the inferior vena cava

Introduction: Ultrasound of the inferior vena cava (IVC-US) has been used to estimate intravascular volume status and fluid removal during a hemodialysis session. Usually, renal nurses rely on other, imprecise methods to determine ultrafiltration. To date, no study has examined whether renal nurses can reliably perform ultrasound for volume assessment and for potential prevention of intradialytic hypotension. This pilot study aimed to determine if a renal nurse could master the skill of performing and correctly interpreting Point of Care Ultrasound on patients receiving hemodialysis. Methods: After receiving theoretical training and performing 100 training scans, a renal nurse performed 60 ultrasound scans on 10 patients. These were categorized by the nurse into hypovolemic, euvolemic, or hypervolemic through measurement of the maximal diameter and degree of collapse of the IVC. Scans were subsequently assessed for adequacy and quality by two sonologists, who were blinded to each other\u27s and the nurse\u27s results. Findings: The interrater reliability of 60 scans was good, with intraclass correlation 0.79 (95% confidence interval (CI) =0.63–0.87) and with a good interrater agreement for the following estimation of intravascular volume (Cohen\u27s weighted Kappa κw = 0.62), when comparing the nurse to an expert sonographer. Discussion: A renal nurse can reliably perform ultrasound of the IVC in hemodialysis patients, obtaining high quality scans for volume assessment of hemodialysis patients. This novel approach could be more routinely applied by other renal nurses to obtain objective measures of patient volume status in the dialysis setting

Transit time simulation

This r script simulates the number of generations until a successfully invading allele reaches polymorphic equilibrium under balancing selection. Output applies to figure 1 of the manuscript

DFE sim n = 10 dimensions

DFE sim n = 10 dimension

Hitchhiking of a neutral allele

This r script simulates the hitchhiking effect caused by a successfully invading allele that evolves toward a polymorphic equilibrium. Output applies to figure 2 of the manuscript

Sex-Differential Selection and the Evolution of X Inactivation Strategies

<div><p>X inactivation—the transcriptional silencing of one X chromosome copy per female somatic cell—is universal among therian mammals, yet the choice of which X to silence exhibits considerable variation among species. X inactivation strategies can range from strict paternally inherited X inactivation (PXI), which renders females haploid for all maternally inherited alleles, to unbiased random X inactivation (RXI), which equalizes expression of maternally and paternally inherited alleles in each female tissue. However, the underlying evolutionary processes that might account for this observed diversity of X inactivation strategies remain unclear. We present a theoretical population genetic analysis of X inactivation evolution and specifically consider how conditions of dominance, linkage, recombination, and sex-differential selection each influence evolutionary trajectories of X inactivation. The results indicate that a single, critical interaction between allelic dominance and sex-differential selection can select for a broad and continuous range of X inactivation strategies, including unequal rates of inactivation between maternally and paternally inherited X chromosomes. RXI is favored over complete PXI as long as alleles deleterious to female fitness are sufficiently recessive, and the criteria for RXI evolution is considerably more restrictive when fitness variation is sexually antagonistic (<i>i.e.</i>, alleles deleterious to females are beneficial to males) relative to variation that is deleterious to both sexes. Evolutionary transitions from PXI to RXI also generally increase mean relative female fitness at the expense of decreased male fitness. These results provide a theoretical framework for predicting and interpreting the evolution of chromosome-wide expression of X-linked genes and lead to several useful predictions that could motivate future studies of allele-specific gene expression variation.</p></div

Sexually antagonistic fitness variation and the change in mean fitness following the evolution of RXI.

<p>In an ancestral population with PXI, and segregating for a sexually antagonistic balanced polymorphism, unbiased RXI is favored and may evolve when <i>h</i><<i>h_crit</i> = (1−<i>t_m</i>)/(2−<i>t_m</i>). Following such an evolutionary transition, the male-beneficial/female-detrimental allele approaches a new equilibrium frequency, and mean fitness per sex evolves to a new equilibrium.</p

Relationship between X inactivation rule and parent-of-origin dominance coefficients (<b><i>h_mat</i></b><b>, </b><b><i>h_pat</i></b><b>; see </b><b>Table 1</b><b>).</b>

<p>Results are based on the power function for female fitness, <i>w</i>(<i>x</i>) = 1−<i>x^ks_f</i>, where <i>x</i> represents the proportion of female cells expressing the <i>A</i>₁ allele, <i>s_f</i> is the haploid or homozygous selection coefficient, <i>h</i> is the degree of masking (equivalent to a dominance coefficient of <i>A</i>₁) in individuals practicing unbiased RXI (<i>ξ</i>₁₁ = ½), and <i>k</i> = −ln(2)/ln(<i>h</i>). For additional details, see the main text. The figure is modified from, and inspired by, <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003440#pgen-1003440-g001" target="_blank">Figure 1a</a> of <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003440#pgen.1003440-Guillaume1" target="_blank">[50]</a>.</p

Criteria for the evolution of RXI.

<p>Black curves are based on <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003440#pgen.1003440.e005" target="_blank">eq. (3)</a> for the mutation-selection balance model of genetic variation (in which case, the <i>x</i>-axis refers to the female selection coefficient, <i>s_f</i>). The gray curve is based on <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003440#pgen.1003440.e006" target="_blank">eq. (4)</a> for sexually antagonistic alleles maintained by balancing selection (here, the <i>x</i>-axis refers to the male selection coefficient: <i>t_m</i>). The area above each curve represents parameter space where unbiased RXI is not favored over PXI. RXI is favored under the complementary parameter space below each curve.</p

Fitnesses and frequencies of genotypes at the <i>A</i> locus.¹

1<p>The maternally inherited allele is listed first and the paternally inherited allele is listed second; frequencies in gametes are <i>q_f</i> = [<i>A</i>₁] in eggs and <i>q_m</i> = [<i>A</i>₁] in sperm; 0<<i>s_f</i>, <i>s_m</i>, <i>t_m</i>, <i>h_mat</i>, <i>h_pat</i><1.</p

Sex-differential selection favors the evolution of biased RXI.

<p>Black curves are based on <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003440#pgen.1003440.e017" target="_blank">eq. (8)</a> for the mutation-selection balance model of genetic variation; diamonds are based on numerical evaluation of the more exact <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003440#pgen.1003440.e011" target="_blank">eq. (7)</a>. Gray curves are based on <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003440#pgen.1003440.e018" target="_blank">eq. (9)</a> for sexually antagonistic alleles maintained by balancing selection. Results for the mutation-selection balance case assume equal male and female selection coefficients (<i>s_m</i> = <i>s_f</i>). Biases are further accentuated when <i>s_m</i>><i>s_f</i>; biases may be dampened or reversed when <i>s_m</i><<i>s_f</i>.</p