Fluctuation Induced Instabilities in Front Propagation up a Co-Moving Reaction Gradient in Two Dimensions

We study 2D fronts propagating up a co-moving reaction rate gradient in finite number reaction-diffusion systems. We show that in a 2D rectangular channel, planar solutions to the deterministic mean-field equation are stable with respect to deviations from planarity. We argue that planar fronts in the corresponding stochastic system, on the other hand, are unstable if the channel width exceeds a critical value. Furthermore, the velocity of the stochastic fronts is shown to depend on the channel width in a simple and interesting way, in contrast to fronts in the deterministic MFE. Thus, fluctuations alter the behavior of these fronts in an essential way. These affects are shown to be partially captured by introducing a density cutoff in the reaction rate. Some of the predictions of the cutoff mean-field approach are shown to be in quantitative accord with the stochastic results

The fixation probability of rare mutators in finite asexual populations

A mutator is an allele that increases the mutation rate throughout the genome by disrupting some aspect of DNA replication or repair. Mutators that increase the mutation rate by the order of 100 fold have been observed to spontaneously emerge and achieve high frequencies in natural populations and in long-term laboratory evolution experiments with \textit{E. coli}. In principle, the fixation of mutator alleles is limited by (i) competition with mutations in wild-type backgrounds, (ii) additional deleterious mutational load, and (iii) random genetic drift. Using a multiple locus model and employing both simulation and analytic methods, we investigate the effects of these three factors on the fixation probability $P_{fix}$ of an initially rare mutator as a function of population size $N$, beneficial and deleterious mutation rates, and the strength of mutations $s$. Our diffusion based approximation for $P_{fix}$ successfully captures effects (ii) and (iii) when selection is fast compared to mutation ($\mu/s \ll 1$). This enables us to predict the conditions under which mutators will be evolutionarily favored. Surprisingly, our simulations show that effect (i) is typically small for strong-effect mutators. Our results agree semi-quantitatively with existing laboratory evolution experiments and suggest future experimental directions.Comment: 46 pages, 8 figure

An empirical approach to modeling ion production rates in Titan's ionosphere II: Ion production rates on the nightside

Ionization of neutrals by precipitating electrons and ions is the main source of Titan's nightside ionosphere. This paper has two goals: (1) characterization of the role of electron impact ionization on the nightside ionosphere for different magnetospheric conditions and (2) presentation of empirical ion production rates determined using densities measured by the Cassini Ion and Neutral Mass Spectrometer on the nightside. The ionosphere between 1000 and 1400 km is emphasized. We adopt electron fluxes measured by the Cassini Plasma Spectrometer-Electron Spectrometer and the Magnetospheric Imaging Instrument as classified by Rymer et al. (2009). The current paper follows an earlier paper (Paper I), in which we investigated sources of Titan's dayside ionosphere and demonstrated that the photoionization process is well understood. The current paper (Paper II) demonstrates that modeled and empirical ionization rates on the nightside are in agreement with an electron precipitation source above 1100 km. Ion production rate profiles appropriate for different Saturnian magnetospheric conditions, as outlined by Rymer et al., are constructed for various magnetic field topologies. Empirical production rate profiles are generated for deep nightside flybys of Titan. The results also suggest that at lower altitudes (below 1100 km) another source, such as ion precipitation, is probably needed

Deep Brain Stimulation of the Subthalamic Nucleus Improves Reward-Based Decision-Learning in Parkinson's Disease

Recently, the subthalamic nucleus (STN) has been shown to be critically involved in decision-making, action selection, and motor control. Here we investigate the effect of deep brain stimulation (DBS) of the STN on reward-based decision-learning in patients diagnosed with Parkinson's disease (PD). We determined computational measures of outcome evaluation and reward prediction from PD patients who performed a probabilistic reward-based decision-learning task. In previous work, these measures covaried with activation in the nucleus caudatus (outcome evaluation during the early phases of learning) and the putamen (reward prediction during later phases of learning). We observed that stimulation of the STN motor regions in PD patients served to improve reward-based decision-learning, probably through its effect on activity in frontostriatal motor loops (prominently involving the putamen and, hence, reward prediction). In a subset of relatively younger patients with relatively shorter disease duration, the effects of DBS appeared to spread to more cognitive regions of the STN, benefiting loops that connect the caudate to various prefrontal areas importantfor outcome evaluation. These results highlight positive effects of STN stimulation on cognitive functions that may benefit PD patients in daily-life association-learning situations

An empirical approach to modeling ion production rates in Titan’s ionosphere I: Ion production rates on the dayside and globally

Titan's ionosphere is created when solar photons, energetic magnetospheric electrons or ions, and cosmic rays ionize the neutral atmosphere. Electron densities generated by current theoretical models are much larger than densities measured by instruments on board the Cassini orbiter. This model density overabundance must result either from overproduction or from insufficient loss of ions. This is the first of two papers that examines ion production rates in Titan's ionosphere, for the dayside and nightside ionosphere, respectively. The first (current) paper focuses on dayside ion production rates which are computed using solar ionization sources (photoionization and electron impact ionization by photoelectrons) between 1000 and 1400 km. In addition to theoretical ion production rates, empirical ion production rates are derived from CH4, CH3+, and CH4+ densities measured by the INMS (Ion Neutral Mass Spectrometer) for many Titan passes. The modeled and empirical production rate profiles from measured densities of N2+ and CH4+ are found to be in good agreement (to within 20%) for solar zenith angles between 15 and 90°. This suggests that the overabundance of electrons in theoretical models of Titan's dayside ionosphere is not due to overproduction but to insufficient ion losses

A Tribute to Charlie Chaplin: Induced Positive Affect Improves Reward-Based Decision-Learning in Parkinson’s Disease

Reward-based decision-learning refers to the process of learning to select those actions that lead to rewards while avoiding actions that lead to punishments. This process, known to rely on dopaminergic activity in striatal brain regions, is compromised in Parkinson’s disease (PD). We hypothesized that such decision-learning deficits are alleviated by induced positive affect, which is thought to incur transient boosts in midbrain and striatal dopaminergic activity. Computational measures of probabilistic reward-based decision-learning were determined for 51 patients diagnosed with PD. Previous work has shown these measures to rely on the nucleus caudatus (outcome evaluation during the early phases of learning) and the putamen (reward prediction during later phases of learning). We observed that induced positive affect facilitated learning, through its effects on reward prediction rather than outcome evaluation. Viewing a few minutes of comedy clips served to remedy dopamine-related problems associated with frontostriatal circuitry and, consequently, learning to predict which actions will yield reward

Exposing an “Intangible” Cognitive Skill Among Collegiate Football Players: II. Enhanced Response Impulse Control

American football is played in a dynamic environment that places considerable demands on a player’s ability to make fast, precise reactions while controlling premature, impulsive reactions to spatial misinformation. We investigated the hypothesis that collegiate football players are more proficient than their non-athlete counterparts at controlling impulsive motor actions. National Collegiate Athletic Association (NCAA) Division I football players (n = 280) and non-athlete controls (n = 32) completed a variant of the Simon conflict task, which quantifies choice reaction speed and the proficiency of controlling spatially driven response impulses. Overall, the choice reaction times (RTs) and accuracy rates of football players and controls were equivalent. Similarly, football players and controls were equally susceptible to producing incorrect impulsive motor responses. However, the slowing of RT attributed to the activation and successful inhibition of these impulses (i.e., the Simon effect) was reduced significantly among football players compared to controls. Moreover, differences in impulse control varied by position among the players, with the reduction being greater for offensive than for defensive players. Among offensive players, running backs, wide receivers, and offensive linemen had greater impulse control than did controls, whereas among defensive players only linebackers had greater control. Notably, the Simon effect was reduced by 60% in running backs compared to controls. These results contribute to emerging evidence that elite football players possess more proficient executive control over their motor systems than their age counterparts and suggest that the speed of controlling impulsive motor reactions may represent an enhanced cognitive “intangible” among football players

General Practitioners involvement in enteral tube feeding at home: a qualitative study

<p>Abstract</p> <p>Background</p> <p>Complex medical treatment is moving from hospital to primary care and General Practitioners (GPs) are increasingly asked to undertake new roles. There are now an estimated 19,500 patients being fed in the UK in the community on enteral tube feeding using a variety of different feeding tubes (Percutaneous endoscopic gastrostomy (PEG), Jejunostomy, or nasogastric (NG). The majority of patients are over the age of 65 years when they had artificial feeding initiated and mainly because of dysphagia. The aim of this study was to explore GPs knowledge, attitudes and skills relating to enteral feeding in the community.</p> <p>Methods</p> <p>Semi-structured one-to-one interviews with a convenience sample of GPs in Northern Ireland.</p> <p>Results</p> <p>Twenty-three GPs in three health boards in Northern Ireland participated in the study. Most found dealing with enteral feeding to be a predominantly negative experience. They had little involvement in patient selection for the procedure and poor or no discharge information. GPs felt inadequately trained, there was poor communication between primary and secondary care and little support. There was anger and frustration among GPs about lack of resources (funding and training), and the perception that primary care was used as a dumping ground.</p> <p>Conclusion</p> <p>Moving complex medical treatment from secondary to primary care has major implications for GPs who should be included in the patient selection process, have adequate discharge information about their patients, be adequately resourced and have appropriate support and training.</p

Actionable, Pathogenic Incidental Findings in 1,000 Participants’ Exomes

The incorporation of genomics into medicine is stimulating interest on the return of incidental findings (IFs) from exome and genome sequencing. However, no large-scale study has yet estimated the number of expected actionable findings per individual; therefore, we classified actionable pathogenic single-nucleotide variants in 500 European- and 500 African-descent participants randomly selected from the National Heart, Lung, and Blood Institute Exome Sequencing Project. The 1,000 individuals were screened for variants in 114 genes selected by an expert panel for their association with medically actionable genetic conditions possibly undiagnosed in adults. Among the 1,000 participants, 585 instances of 239 unique variants were identified as disease causing in the Human Gene Mutation Database (HGMD). The primary literature supporting the variants’ pathogenicity was reviewed. Of the identified IFs, only 16 unique autosomal-dominant variants in 17 individuals were assessed to be pathogenic or likely pathogenic, and one participant had two pathogenic variants for an autosomal-recessive disease. Furthermore, one pathogenic and four likely pathogenic variants not listed as disease causing in HGMD were identified. These data can provide an estimate of the frequency (∼3.4% for European descent and ∼1.2% for African descent) of the high-penetrance actionable pathogenic or likely pathogenic variants in adults. The 23 participants with pathogenic or likely pathogenic variants were disproportionately of European (17) versus African (6) descent. The process of classifying these variants underscores the need for a more comprehensive and diverse centralized resource to provide curated information on pathogenicity for clinical use to minimize health disparities in genomic medicine

Understanding how education/support groups help lone mothers

<p>Abstract</p> <p>Background</p> <p>Lone-mother led families are at increased risk of psychosocial disadvantage, social isolation and mental health morbidity. Community-based programs are more accessible for families seeking assistance. We examine the experiences of eight lone mothers participating in a larger randomized controlled trial (RCT) of a community-based education/support group program using mixed methods.</p> <p>Methods</p> <p>A purposeful sample of eight mothers participating in the intervention arm of an RCT of community-based support/education groups was selected for the qualitative study. Individual interviews asked mothers about themselves and their relationships with their children before and after the group. Interviews were taped, transcribed and content analysis was used to code and interpret the data. Quantitative data collected in the RCT were used to describe these mothers.</p> <p>Results</p> <p>Mothers participating in the RCT and qualitative study experienced multiple difficulties, including financial and mood problems. These mothers reported that before participating in the group, they had shared experiences of social isolation, stigma, a sense of failure, poor relationships with their children and difficulties with financial management. After the group, mothers identified improved self-esteem, support from other mothers, improved parenting skills and improved communication with their children as outcomes of group participation.</p> <p>Conclusions</p> <p>The qualitative data revealed mothers' perceptions of specific areas that improved by participating in the group. The utility of complementary information provided by qualitative and quantitative methods in understanding program impact, as well as the need for broader assistance is noted.</p