Transition probabilities for general birth-death processes with applications in ecology, genetics, and evolution

A birth-death process is a continuous-time Markov chain that counts the number of particles in a system over time. In the general process with $n$ current particles, a new particle is born with instantaneous rate $\lambda_n$ and a particle dies with instantaneous rate $\mu_n$. Currently no robust and efficient method exists to evaluate the finite-time transition probabilities in a general birth-death process with arbitrary birth and death rates. In this paper, we first revisit the theory of continued fractions to obtain expressions for the Laplace transforms of these transition probabilities and make explicit an important derivation connecting transition probabilities and continued fractions. We then develop an efficient algorithm for computing these probabilities that analyzes the error associated with approximations in the method. We demonstrate that this error-controlled method agrees with known solutions and outperforms previous approaches to computing these probabilities. Finally, we apply our novel method to several important problems in ecology, evolution, and genetics

Characteristics, management and attainment of lipid target levels in diabetic and cardiac patients enrolled in Disease Management Program versus those in routine care: LUTZ registry

<p>Abstract</p> <p>Background</p> <p>Since 2002 the sick funds in Germany have widely implemented disease management programs (DMPs) for patients with type 2 diabetes mellitus (DM) and coronary heart disease (CHD). Little is known about the characteristics, treatment and target attainment lipid levels of these patients enrolled in DMPs compared to patients in routine care (non-DMP).</p> <p>Methods</p> <p>In an open, non-interventional registry (LUTZ) in Germany, 6551 physicians documented 15,211 patients with DM (10,110 in DMP, 5101 in routine care) and 14,222 (6259 in DMP, 7963 in routine care) over a follow-up period of 4 months. They received the NCEP ATP III guidelines as a reminder on lipid level targets.</p> <p>Results</p> <p>While demographic characteristics of DMP patients were similar to routine care patients, the former had higher rates of almost all cardiovascular comorbidities. Patients in DMPs received pharmacological treatment (in almost all drug classes) more often than non-DMP patients (e.g. antiplatelets: in DM 27.0% vs 23.8%; in CHD 63.0% vs. 53.6%). The same applied for educational measures (on life style changes and diet etc.). The rate of target level attainment for low density lipoprotein cholesterol (LDL-C) < 100 mg/dl was somewhat higher in DMP patients at inclusion compared to non-DMP patients (DM: 23.9% vs. 21.3%; CHD: 30.6% vs. 23.8%) and increased after 4 months (DM: 38.3% vs. 36.9%; CHD: 49.8% vs. 43.3%). Individual LDL-C target level attainment rates as assessed by the treating physicians were higher (at 4 months in DM: 59.6% vs. 56.5%; CHD: 49.8% vs 43.3%). Mean blood pressure (BP) and HbA_1cvalues were slightly lowered during follow-up, without substantial differences between DMP and non-DMP patients.</p> <p>Conclusion</p> <p>Patients with DM, and (to a greater extent) with CHD in DMPs compared to non-DMP patients in routine care have a higher burden of comorbidities, but also receive more intensive pharmacological treatment and educational measures. The present data support that the substantial additional efforts in DMPs aimed at improving outcomes resulted in quality gains for achieving target LDL-C levels, but not for BP or HbA_1c. Longer-term follow-up is needed to substantiate these results.</p

Engaging in Health Behaviors to Lower Risk for Breast Cancer Recurrence

Purpose While post-treatment breast cancer survivors face up to twice the cancer risk of the general population, modifiable health behaviors may somewhat reduce this risk. We sought to better understand health behaviors that early stage breast cancer survivors engage in to reduce recurrence risk. Methods Data came from a cross-sectional multi-site survey of 186 early-stage breast cancer survivors who received genomic testing for breast cancer recurrence risk (Oncotype DX) during their clinical care. Study outcomes were meeting health behavior recommendations (daily fruit and vegetable intake, regular physical activity, and having a healthy body mass index (BMI)). Results Approximately three-quarters of survivors we surveyed believed the 3 behaviors might reduce their cancer risk but many did not engage in these behaviors for this purpose: 62% for BMI, 36% for fruit and vegetable consumption, and 37% for physical activity. Survivors with higher recurrence risk, as indicated by their genomic test results, were no more likely to meet any of the three health behavior recommendations. Adherence to health behavior recommendations was higher for women who were white, college-educated, and had higher incomes. Conclusions Many nonadherent breast cancer survivors wish to use these behavioral strategies to reduce their risk for recurrence, suggesting an important opportunity for intervention. Improving BMI, which has the largest association with cancer risk, is an especially promising target

The Evolution of Gene Expression QTL in Saccharomyces cerevisiae

Understanding the evolutionary forces that influence patterns of gene expression variation will provide insights into the mechanisms of evolutionary change and the molecular basis of phenotypic diversity. To date, studies of gene expression evolution have primarily been made by analyzing how gene expression levels vary within and between species. However, the fundamental unit of heritable variation in transcript abundance is the underlying regulatory allele, and as a result it is necessary to understand gene expression evolution at the level of DNA sequence variation. Here we describe the evolutionary forces shaping patterns of genetic variation for 1206 cis-regulatory QTL identified in a cross between two divergent strains of Saccharomyces cerevisiae. We demonstrate that purifying selection against mildly deleterious alleles is the dominant force governing cis-regulatory evolution in S. cerevisiae and estimate the strength of selection. We also find that essential genes and genes with larger codon bias are subject to slightly stronger cis-regulatory constraint and that positive selection has played a role in the evolution of major trans-acting QTL

Modelling the impact of toxic and disturbance stress on white-tailed eagle (Haliaeetus albicilla) populations

Several studies have related breeding success and survival of sea eagles to toxic or non-toxic stress separately. In the present investigation, we analysed single and combined impacts of both toxic and disturbance stress on populations of white-tailed eagle (Haliaeetus albicilla), using an analytical single-species model. Chemical and eco(toxico)logical data reported from laboratory and field studies were used to parameterise and validate the model. The model was applied to assess the impact of ∑PCB, DDE and disturbance stress on the white-tailed eagle population in The Netherlands. Disturbance stress was incorporated through a 1.6% reduction in survival and a 10–50% reduction in reproduction. ∑PCB contamination from 1950 up to 1987 was found to be too high to allow the return of white-tailed eagle as a breeding species in that period. ∑PCB and population trends simulated for 2006–2050 suggest that future population growth is still reduced. Disturbance stress resulted in a reduced population development. The combination of both toxic and disturbance stress varied from a slower population development to a catastrophical reduction in population size, where the main cause was attributed to the reduction in reproduction of 50%. Application of the model was restricted by the current lack of quantitative dose–response relationships between non-toxic stress and survival and reproduction. Nevertheless, the model provides a first step towards integrating and quantifying the impacts of multiple stressors on white-tailed eagle populations

Blood Parasites in Owls with Conservation Implications for the Spotted Owl (Strix occidentalis)

The three subspecies of Spotted Owl (Northern, Strix occidentalis caurina; California, S. o. occidentalis; and Mexican, S. o. lucida) are all threatened by habitat loss and range expansion of the Barred Owl (S. varia). An unaddressed threat is whether Barred Owls could be a source of novel strains of disease such as avian malaria (Plasmodium spp.) or other blood parasites potentially harmful for Spotted Owls. Although Barred Owls commonly harbor Plasmodium infections, these parasites have not been documented in the Spotted Owl. We screened 111 Spotted Owls, 44 Barred Owls, and 387 owls of nine other species for haemosporidian parasites (Leucocytozoon, Plasmodium, and Haemoproteus spp.). California Spotted Owls had the greatest number of simultaneous multi-species infections (44%). Additionally, sequencing results revealed that the Northern and California Spotted Owl subspecies together had the highest number of Leucocytozoon parasite lineages (n = 17) and unique lineages (n = 12). This high level of sequence diversity is significant because only one Leucocytozoon species (L. danilewskyi) has been accepted as valid among all owls, suggesting that L. danilewskyi is a cryptic species. Furthermore, a Plasmodium parasite was documented in a Northern Spotted Owl for the first time. West Coast Barred Owls had a lower prevalence of infection (15%) when compared to sympatric Spotted Owls (S. o. caurina 52%, S. o. occidentalis 79%) and Barred Owls from the historic range (61%). Consequently, Barred Owls on the West Coast may have a competitive advantage over the potentially immune compromised Spotted Owls

Joint sequencing of human and pathogen genomes reveals the genetics of pneumococcal meningitis.

Streptococcus pneumoniae is a common nasopharyngeal colonizer, but can also cause life-threatening invasive diseases such as empyema, bacteremia and meningitis. Genetic variation of host and pathogen is known to play a role in invasive pneumococcal disease, though to what extent is unknown. In a genome-wide association study of human and pathogen we show that human variation explains almost half of variation in susceptibility to pneumococcal meningitis and one-third of variation in severity, identifying variants in CCDC33 associated with susceptibility. Pneumococcal genetic variation explains a large amount of invasive potential (70%), but has no effect on severity. Serotype alone is insufficient to explain invasiveness, suggesting other pneumococcal factors are involved in progression to invasive disease. We identify pneumococcal genes involved in invasiveness including pspC and zmpD, and perform a human-bacteria interaction analysis. These genes are potential candidates for the development of more broadly-acting pneumococcal vaccines