Diffusion Approximations for Demographic Inference: DaDi

Models of demographic history (population sizes, migration rates, and divergence times) inferred from genetic data complement archeology and serve as null models in genome scans for selection. Most current inference methods are computationally limited to considering simple models or non-recombining data. We introduce a method based on a diffusion approximation to the joint frequency spectrum of genetic variation between populations. Our implementation, DaDi, can model up to three interacting populations and scales well to genome-wide data. We have applied DaDi to human data from Africa, Europe, and East Asia, building the most complex statistically well-characterized model of human migration out of Africa to date

Why taking moderate positions may help the Democrats to retake the House this fall

Partisan polarization has steadily increased in recent decades, culminating in record highs in recent years. In new research, Jamie Carson and Ryan Williamson compare the ideology of winning and losing candidates in US House elections between 1992 and 2012. They find that winning candidates are much less ideologically extreme than those who lose elections. Though some districts prefer more extreme representatives, these are a minority. Together, these findings show that if challengers were more skilled at winning elections, polarization in Congress might be even greater than it is now

The story of the midterms is the triumph of the moderates – on both sides

Following this week’s midterm elections, in 2019 the Democratic Party will be in the majority in the US House of Representatives. Ryan Williamson and Jamie Carson have previously argued that more moderate Democratic candidates were more likely to win House seats. Analyzing the midterm results, they find that this year Democratic candidates who were more moderate were indeed able to win back seats from incumbent conservative candidates, and were also more likely to outperform Clinton’s vote from 2016

Inferring the Joint Demographic History of Multiple Populations from Multidimensional SNP Frequency Data

Demographic models built from genetic data play important roles in illuminating prehistorical events and serving as null models in genome scans for selection. We introduce an inference method based on the joint frequency spectrum of genetic variants within and between populations. For candidate models we numerically compute the expected spectrum using a diffusion approximation to the one-locus, two-allele Wright-Fisher process, involving up to three simultaneous populations. Our approach is a composite likelihood scheme, since linkage between neutral loci alters the variance but not the expectation of the frequency spectrum. We thus use bootstraps incorporating linkage to estimate uncertainties for parameters and significance values for hypothesis tests. Our method can also incorporate selection on single sites, predicting the joint distribution of selected alleles among populations experiencing a bevy of evolutionary forces, including expansions, contractions, migrations, and admixture. We model human expansion out of Africa and the settlement of the New World, using 5 Mb of noncoding DNA resequenced in 68 individuals from 4 populations (YRI, CHB, CEU, and MXL) by the Environmental Genome Project. We infer divergence between West African and Eurasian populations 140 thousand years ago (95% confidence interval: 40–270 kya). This is earlier than other genetic studies, in part because we incorporate migration. We estimate the European (CEU) and East Asian (CHB) divergence time to be 23 kya (95% c.i.: 17–43 kya), long after archeological evidence places modern humans in Europe. Finally, we estimate divergence between East Asians (CHB) and Mexican-Americans (MXL) of 22 kya (95% c.i.: 16.3–26.9 kya), and our analysis yields no evidence for subsequent migration. Furthermore, combining our demographic model with a previously estimated distribution of selective effects among newly arising amino acid mutations accurately predicts the frequency spectrum of nonsynonymous variants across three continental populations (YRI, CHB, CEU).</p

Michelle Nunn’s midterm result shows that Georgia’s demographics may be shifting to favor the Democrats

In Georgia’s Senate race Republican David Purdue defeated Democrat Michelle Nunn by nearly eight points, despite polling that had shown a much closer contest. Jamie L. Carson, Joel Sievert, and Ryan D. Williamson reflect on Georgia’s midterm election results, writing that in gaining more than 40 percent of the vote, Nunn outperformed many previous Democratic candidates in the state. They argue that if the Democratic Party continues to field good candidates in Georgia, shifting demographics may mean that they will be able to take statewide races within a few election cycles

In order to increase competition in U.S. House races, states should look to extra-legislative bodies to redraw congressional boundaries

Politicians and pundits alike regularly bemoan the lack of electoral competition in congressional races as incumbent reelection rates frequently soar to over 90 percent. Redistricting and gerrymandering are often blamed as a way to lock members into their seats for at least a decade. Jamie L. Carson, Michael H. Crespin and Ryan D. Williamson ask if there are ways to inject more competition into elections during the mandated redistricting cycles. Based on an analysis of redistricting cycles from 1972 to 2012, they show that commission and court-drawn districts experience marginally more competition than those drawn by state legislatures. These results provide additional support for the argument that one way to increase the competitiveness of congressional elections is to allow extra-legislative bodies to draw congressional district boundaries

Empathy Gaps Between Helpers and Help-Seekers: Implications for Cooperation

Help-seekers and potential helpers often experience an “empathy gap” – an inability to understand each other’s unique perspectives. Both parties are concerned about their reputation, self-esteem, and relationships, but these concerns differ in ways that lead to misinterpretation of the other party’s actions, and, in turn, missed opportunities for cooperation. In this article, we review research that describes the role-specific concerns of helpers and help-seekers. We then review studies of emotional perspective-taking, which can help explain why help-seekers and helpers often experience empathy gaps. We go on to discuss recent work that illustrates the consequences of empathy gaps between helpers and help-seekers—social prediction errors that prevent helping and misguided intentions that can lead to unhelpful help. Finally, we discuss some promising directions for future research

Using a television programme as a tool to increase perceived awareness of mental health and well-being - Findings from ' Our Mental Health ' survey

Background: International research shows that media can increase knowledge, raise public awareness and reduce stigma relating to mental health.Methods: Following the broadcast of a documentary on national television featuring interviews with young people who had experienced mental health difficulties and suicidal behaviour, an anonymous online survey, aimed at examining public perceptions of the impact of a television documentary, was conducted, using a mixed methods approach.Results: 2311 people completed the survey. Of those who watched the documentary and answered the closed questions (n = 854), 94% stated that the documentary will positively impact young people's mental health and well-being. The majority (91%) stated that the documentary will encourage young people to talk to someone if experiencing difficulties and 87% indicated it will help to reduce stigma associated with mental health. Viewers had a 5% higher level of intention to seek help than non-viewers. Participants indicated that the identifiable personal stories and discourse around stigma and shame, and the increased understanding and awareness gained, had the most profound impact on them.Conclusions: These findings indicate that a documentary addressing mental health and suicidal behaviour, which incorporates real life identifiable stories of resilience and recovery, has the potential to impact positively on emotional well-being and general mood, to reduce stigma related to mental health and to encourage help-seeking behaviour. Documentaries including these concepts, with a public mental health focus and a consistent message, incorporating pre- and post-evaluations, and customisation for target audiences in compliance with current media recommendations, should be considered

Blood flow restriction exercise attenuates the exercise-induced endothelial progenitor cells in healthy, young men.

Endothelial progenitor cells (EPCs) are a vasculogenic subset of progenitors, which play a key role in maintenance of endothelial integrity. These cells are exercise-responsive, and thus exercise may play a key role in vascular repair and maintenance via mobilization of such cells. Blood flow restriction exercise, due to the augmentation of local tissue hypoxia, may promote exercise-induced EPC mobilization. Nine, healthy, young (18-30yrs) males participated in the study. Participants undertook 2 trials of single leg knee extensor (KE) exercise, at 60% of thigh occlusion pressure (4 sets at 30% maximal torque) (BFR) or non- blood flow restricted (non-BFR), in a fasted state. Blood was taken prior, immediately after, and 30 minutes after exercise. Blood was used for the quantification of haematopoietic progenitor cells (HPCs: CD34+CD45dim), EPCs (CD34+VEGFR2+/CD34+CD45dimVEGFR2+) by flow cytometry. Our results show that unilateral KE exercise did not affect circulating HPC levels (p = 0.856), but did result in increases in both CD34+VEGFR2+ and CD34+CD45dimVEGFR2+ EPCs, but only in the non-BFR trial (CD34+VEGFR2+: 269 ± 42 cells·mL-1 to 573 ± 90 cells·mL-1, pre- to immediately post-exercise, p = 0.008; CD34+CD45dimVEGFR2+: 129 ± 21 cells·mL-1 to 313 ± 103 cells·mL-1, pre- to 30 min post-exercise, p = 0.010). In conclusion, low intensity BFR exercise did not result in significant circulating changes in EPCs in the post-exercise recovery period and may impair exercise-induced EPC mobilization compared to non-BFR exercise

Assessing the Evolutionary Impact of Amino Acid Mutations in the Human Genome

Quantifying the distribution of fitness effects among newly arising mutations in the human genome is key to resolving important debates in medical and evolutionary genetics. Here, we present a method for inferring this distribution using Single Nucleotide Polymorphism (SNP) data from a population with non-stationary demographic history (such as that of modern humans). Application of our method to 47,576 coding SNPs found by direct resequencing of 11,404 protein coding-genes in 35 individuals (20 European Americans and 15 African Americans) allows us to assess the relative contribution of demographic and selective effects to patterning amino acid variation in the human genome. We find evidence of an ancient population expansion in the sample with African ancestry and a relatively recent bottleneck in the sample with European ancestry. After accounting for these demographic effects, we find strong evidence for great variability in the selective effects of new amino acid replacing mutations. In both populations, the patterns of variation are consistent with a leptokurtic distribution of selection coefficients (e.g., gamma or log-normal) peaked near neutrality. Specifically, we predict 27–29% of amino acid changing (nonsynonymous) mutations are neutral or nearly neutral (|s|<0.01%), 30–42% are moderately deleterious (0.01%<|s|<1%), and nearly all the remainder are highly deleterious or lethal (|s|>1%). Our results are consistent with 10–20% of amino acid differences between humans and chimpanzees having been fixed by positive selection with the remainder of differences being neutral or nearly neutral. Our analysis also predicts that many of the alleles identified via whole-genome association mapping may be selectively neutral or (formerly) positively selected, implying that deleterious genetic variation affecting disease phenotype may be missed by this widely used approach for mapping genes underlying complex traits