The Influence of Gene Flow on Species Tree Estimation: A Simulation Study

Gene flow among populations or species and incomplete lineage sorting (ILS) are two evolutionary processes responsible for generating gene tree discordance and therefore hindering species tree estimation. Numerous studies have evaluated the impacts of ILS on species tree inference, yet the ramifications of gene flow on species trees remain less studied. Here, we simulate and analyse multilocus sequence data generated with ILS and gene flow to quantify their impacts on species tree inference. We characterize species tree estimation errors under various models of gene flow, such as the isolation-migration model, the n-island model, and gene flow between non-sister species or involving ancestral species, and species boundaries crossed by a single gene copy (allelic introgression) or by a single migrant individual. These patterns of gene flow are explored on species trees of different sizes (4 vs. 10 species), at different time scales (shallow vs. deep), and with different migration rates. Species trees are estimated with the multispecies coalescent model using Bayesian methods (BEST and *BEAST) and with a summary statistic approach (MPEST) that facilitates phylogenomic-scale analysis. Even in cases where the topology of the species tree is estimated with high accuracy, we find that gene flow can result in overestimates of population sizes (species tree dilation) and underestimates of species divergence times (species tree compression). Signatures of migration events remain present in the distribution of coalescent times for gene trees, and with sufficient data it is possible to identify those loci that have crossed species boundaries. These results highlight the need for careful sampling design in phylogeographic and species delimitation studies as gene flow, introgression, or incorrect sample assignments can bias the estimation of the species tree topology and of parameter estimates such as population sizes and divergence times

A Case-Control Study to Identify Community Venues Associated with Genetically-clustered, Multidrug-resistant Tuberculosis Disease in Lima, Peru

Background: The majority of tuberculosis transmission occurs in community settings. Our primary aim in this study was to assess the association between exposure to community venues and multidrug-resistant (MDR) tuberculosis. Our secondary aim was to describe the social networks of MDR tuberculosis cases and controls. / Methods: We recruited laboratory-confirmed MDR tuberculosis cases and community controls that were matched on age and sex. Whole-genome sequencing was used to identify genetically clustered cases. Venue tracing interviews (nonblinded) were conducted to enumerate community venues frequented by participants. Logistic regression was used to assess the association between MDR tuberculosis and person-time spent in community venues. A location-based social network was constructed, with respondents connected if they reported frequenting the same venue, and an exponential random graph model (ERGM) was fitted to model the network. / Results: We enrolled 59 cases and 65 controls. Participants reported 729 unique venues. The mean number of venues reported was similar in both groups (P = .92). Person-time in healthcare venues (adjusted odds ratio [aOR] = 1.67, P = .01), schools (aOR = 1.53, P < .01), and transportation venues (aOR = 1.25, P = .03) was associated with MDR tuberculosis. Healthcare venues, markets, cinemas, and transportation venues were commonly shared among clustered cases. The ERGM indicated significant community segregation between cases and controls. Case networks were more densely connected. / Conclusions: Exposure to healthcare venues, schools, and transportation venues was associated with MDR tuberculosis. Intervention across the segregated network of case venues may be necessary to effectively stem transmission

Dihydropyrimidine dehydrogenase deficiency and fluorouracil-related toxicity

Dihydropyrimidine dehydrogenase (DPD) is the initial and rate-limiting enzyme of 5-fluorouracil (5-FU) catabolism. We report lymphocytic DPD data concerning a group of 53 patients (23 men, 30 women, mean age 58, range 36–73), treated by 5-FU-based chemotherapy in different French institutions and who developed unanticipated 5-FU-related toxicity. Lymphocyte samples (standard collection procedure) were sent to us for DPD determination (biochemical method). Among the whole group of 53 patients, 19 had a significant DPD deficiency (DD; below 150 fmol min−1 mg−1 protein, i.e. less than 70% of the mean value observed from previous population study). There was a greater majority of women in the DD group (15 out of 19, 79%) compared with the remaining 34 patients (15 out of 34, 44%, P<0.014). Toxicity was often severe, leading to patient death in two cases (both women). The toxicity score (sum of WHO grading, theoritical range 0–20) was twice as high in patients with marked DD (below 100 pmol min−1 mg−1 protein, n = 11, mean score = 13.2) compared with patients with moderate DD (between 150 and 100 pmol min−1 mg−1 protein, n = 8, mean score = 6.8), P = 0.008. In the DD group, there was a high frequency of neurotoxic syndromes (7 out of 19, 37%). The two deceased patients both had severe neurotoxicity. The occurrence of cardiac toxicity was relatively rare (1 out of 19, 5%). These data suggest that women are particularly prone to DPD deficiency and allow a more precise definition of the DD toxicity profile. © 1999 Cancer Research Campaig

Interaction of perceptual grouping and crossmodal temporal capture in tactile apparent-motion

Previous studies have shown that in tasks requiring participants to report the direction of apparent motion, task-irrelevant mono-beeps can &quot;capture'' visual motion perception when the beeps occur temporally close to the visual stimuli. However, the contributions of the relative timing of multimodal events and the event structure, modulating uni- and/or crossmodal perceptual grouping, remain unclear. To examine this question and extend the investigation to the tactile modality, the current experiments presented tactile two-tap apparent-motion streams, with an SOA of 400 ms between successive, left-/right-hand middle-finger taps, accompanied by task-irrelevant, non-spatial auditory stimuli. The streams were shown for 90 seconds, and participants' task was to continuously report the perceived (left-or rightward) direction of tactile motion. In Experiment 1, each tactile stimulus was paired with an auditory beep, though odd-numbered taps were paired with an asynchronous beep, with audiotactile SOAs ranging from -75 ms to 75 ms. Perceived direction of tactile motion varied systematically with audiotactile SOA, indicative of a temporal-capture effect. In Experiment 2, two audiotactile SOAs-one short (75 ms), one long (325 ms)-were compared. The long-SOA condition preserved the crossmodal event structure (so the temporal-capture dynamics should have been similar to that in Experiment 1), but both beeps now occurred temporally close to the taps on one side (even-numbered taps). The two SOAs were found to produce opposite modulations of apparent motion, indicative of an influence of crossmodal grouping. In Experiment 3, only odd-numbered, but not even-numbered, taps were paired with auditory beeps. This abolished the temporal-capture effect and, instead, a dominant percept of apparent motion from the audiotactile side to the tactile-only side was observed independently of the SOA variation. These findings suggest that asymmetric crossmodal grouping leads to an attentional modulation of apparent motion, which inhibits crossmodal temporal-capture effects

Conservative management of a grade V injury to an ectopic pelvic kidney following blunt trauma to the lower abdomen: a case report

<p>Abstract</p> <p>Introduction</p> <p>Ectopic pelvic kidneys represent an anatomic variant that remains clinically asymptomatic in most patients. While there is some literature to suggest that ectopic kidneys may be more predisposed to blunt trauma injuries, there are few examples to guide the management of these injuries. To our knowledge, we present the first case of a grade V renal injury to an ectopic pelvic kidney managed successfully with conservative measures.</p> <p>Case Presentation</p> <p>We present a case of grade V renal injury to an ectopic pelvic kidney in a 21 year-old African-American male. The clinical and radiographic findings are presented, along with the patient's conservative hospital course.</p> <p>Conclusion</p> <p>We suggest that management of grade V renal injuries to ectopic pelvic kidneys can be treated similarly to that of kidneys in normal anatomic position. Conservative measures may be considered in properly selected patients.</p

Analysis of the efficacy, safety, and regulatory status of novel forms of creatine

Creatine has become one of the most popular dietary supplements in the sports nutrition market. The form of creatine that has been most extensively studied and commonly used in dietary supplements is creatine monohydrate (CM). Studies have consistently indicated that CM supplementation increases muscle creatine and phosphocreatine concentrations by approximately 15–40%, enhances anaerobic exercise capacity, and increases training volume leading to greater gains in strength, power, and muscle mass. A number of potential therapeutic benefits have also been suggested in various clinical populations. Studies have indicated that CM is not degraded during normal digestion and that nearly 99% of orally ingested CM is either taken up by muscle or excreted in urine. Further, no medically significant side effects have been reported in literature. Nevertheless, supplement manufacturers have continually introduced newer forms of creatine into the marketplace. These newer forms have been purported to have better physical and chemical properties, bioavailability, efficacy, and/or safety profiles than CM. However, there is little to no evidence that any of the newer forms of creatine are more effective and/or safer than CM whether ingested alone and/or in combination with other nutrients. In addition, whereas the safety, efficacy, and regulatory status of CM is clearly defined in almost all global markets; the safety, efficacy, and regulatory status of other forms of creatine present in today’s marketplace as a dietary or food supplement is less clear

Superficial simplicity of the 2010 El Mayor–Cucapah earthquake of Baja California in Mexico

The geometry of faults is usually thought to be more complicated at the surface than at depth and to control the initiation, propagation and arrest of seismic ruptures. The fault system that runs from southern California into Mexico is a simple strike-slip boundary: the west side of California and Mexico moves northwards with respect to the east. However, the M_w 7.2 2010 El Mayor–Cucapah earthquake on this fault system produced a pattern of seismic waves that indicates a far more complex source than slip on a planar strike-slip fault. Here we use geodetic, remote-sensing and seismological data to reconstruct the fault geometry and history of slip during this earthquake. We find that the earthquake produced a straight 120-km-long fault trace that cut through the Cucapah mountain range and across the Colorado River delta. However, at depth, the fault is made up of two different segments connected by a small extensional fault. Both segments strike N130° E, but dip in opposite directions. The earthquake was initiated on the connecting extensional fault and 15 s later ruptured the two main segments with dominantly strike-slip motion. We show that complexities in the fault geometry at depth explain well the complex pattern of radiated seismic waves. We conclude that the location and detailed characteristics of the earthquake could not have been anticipated on the basis of observations of surface geology alone

One-sided versus two-sided stochastic descriptions

It is well-known that discrete-time finite-state Markov Chains, which are described by one-sided conditional probabilities which describe a dependence on the past as only dependent on the present, can also be described as one-dimensional Markov Fields, that is, nearest-neighbour Gibbs measures for finite-spin models, which are described by two-sided conditional probabilities. In such Markov Fields the time interpretation of past and future is being replaced by the space interpretation of an interior volume, surrounded by an exterior to the left and to the right. If we relax the Markov requirement to weak dependence, that is, continuous dependence, either on the past (generalising the Markov-Chain description) or on the external configuration (generalising the Markov-Field description), it turns out this equivalence breaks down, and neither class contains the other. In one direction this result has been known for a few years, in the opposite direction a counterexample was found recently. Our counterexample is based on the phenomenon of entropic repulsion in long-range Ising (or "Dyson") models.Comment: 13 pages, Contribution for "Statistical Mechanics of Classical and Disordered Systems