A generalized Fellner-Schall method for smoothing parameter estimation with application to Tweedie location, scale and shape models

We consider the estimation of smoothing parameters and variance components in models with a regular log likelihood subject to quadratic penalization of the model coefficients, via a generalization of the method of Fellner (1986) and Schall (1991). In particular: (i) we generalize the original method to the case of penalties that are linear in several smoothing parameters, thereby covering the important cases of tensor product and adaptive smoothers; (ii) we show why the method's steps increase the restricted marginal likelihood of the model, that it tends to converge faster than the EM algorithm, or obvious accelerations of this, and investigate its relation to Newton optimization; (iii) we generalize the method to any Fisher regular likelihood. The method represents a considerable simplification over existing methods of estimating smoothing parameters in the context of regular likelihoods, without sacrificing generality: for example, it is only necessary to compute with the same first and second derivatives of the log-likelihood required for coefficient estimation, and not with the third or fourth order derivatives required by alternative approaches. Examples are provided which would have been impossible or impractical with pre-existing Fellner-Schall methods, along with an example of a Tweedie location, scale and shape model which would be a challenge for alternative methods

Analysis of time-to-event for observational studies: Guidance to the use of intensity models

This paper provides guidance for researchers with some mathematical background on the conduct of time-to-event analysis in observational studies based on intensity (hazard) models. Discussions of basic concepts like time axis, event definition and censoring are given. Hazard models are introduced, with special emphasis on the Cox proportional hazards regression model. We provide check lists that may be useful both when fitting the model and assessing its goodness of fit and when interpreting the results. Special attention is paid to how to avoid problems with immortal time bias by introducing time-dependent covariates. We discuss prediction based on hazard models and difficulties when attempting to draw proper causal conclusions from such models. Finally, we present a series of examples where the methods and check lists are exemplified. Computational details and implementation using the freely available R software are documented in Supplementary Material. The paper was prepared as part of the STRATOS initiative.Comment: 28 pages, 12 figures. For associated Supplementary material, see http://publicifsv.sund.ku.dk/~pka/STRATOSTG8

Competitor phenology as a social cue in breeding site selection

Predicting habitat quality is a major challenge for animals selecting a breeding patch, because it affects reproductive success. Breeding site selection may be based on previous experience, or on social information from the density and success of competitors with an earlier phenology. Variation in animal breeding phenology is often correlated with variation in habitat quality. Generally, animals breed earlier in high-quality habitats that allow them to reach a nutritional threshold required for breeding earlier or avoid nest predation. In addition, habitat quality may affect phenological overlap between species and thereby interspecific competition. Therefore, we hypothesized that competitor breeding phenology can be used as social cue by settling migrants to locate high-quality breeding sites. To test this hypothesis, we experimentally advanced and delayed hatching phenology of two resident tit species on the level of study plots and studied male and female settlement patterns of migratory pied flycatchers Ficedula hypoleuca. The manipulations were assigned at random in two consecutive years, and treatments were swapped between years in sites that were used in both years. In both years, males settled in equal numbers across treatments, but later arriving females avoided pairing with males in delayed phenology plots. Moreover, male pairing probability declined strongly with arrival date on the breeding grounds. Our results demonstrate that competitor phenology may be used to assess habitat quality by settling migrants, but we cannot pinpoint the exact mechanism (e.g. resource quality, predation pressure or competition) that has given rise to this pattern. In addition, we show that opposing selection pressures for arrival timing may give rise to different social information availabilities between sexes. We discuss our findings in the context of climate warming, social information use and the evolution of protandry in migratory animals

Baseline serum albumin is a predictive biomarker for patients with advanced pancreatic cancer treated with bevacizumab: A pooled analysis of 7 prospective trials of gemcitabine‐based therapy with or without bevacizumab

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/107373/1/cncr28648.pd

Hepatic retransplantation in cholestatic liver disease: Impact of the interval to retransplantation on survival and resource utilization

The aim of our study was to quantitatively assess the impact of hepatic retransplantation on patient and graft survival and resource utilization. We studied patients undergoing hepatic retransplantation among 447 transplant recipients with primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) at 3 transplantation centers. Cox proportional hazards regression analysis was used for survival analysis. Measures of resource utilization included the duration of hospitalization, length of stay in the intensive care unit, and the duration of transplantation surgery. Forty-six (10.3%) patients received 2 or more grafts during the follow-up period (median, 2.8 years). Patients who underwent retransplantation had a 3.8-fold increase in the risk of death compared with those without retransplantation (P < .01). Retransplantation after an interval of greater than 30 days from the primary graft was associated with a 6.7-fold increase in the risk of death (P < .01). The survival following retransplantations performed 30 days or earlier was similar to primary transplantations. Resource utilization was higher in patients who underwent multiple consecutive transplantations, even after adjustment for the number of grafts during the hospitalization. Among cholestatic liver disease patients, poor survival following hepatic retransplantation is attributed to late retransplantations, namely those performed more than 30 days after the initial transplantation. While efforts must be made to improve the outcome following retransplantation, a more critical evaluation may be warranted for late retransplantation candidates

Relation of vertebral deformities to bone density, structure, and strength.

Because they are not reliably discriminated by areal bone mineral density (aBMD) measurements, it is unclear whether minimal vertebral deformities represent early osteoporotic fractures. To address this, we compared 90 postmenopausal women with no deformity (controls) with 142 women with one or more semiquantitative grade 1 (mild) deformities and 51 women with any grade 2-3 (moderate/severe) deformities. aBMD was measured by dual-energy X-ray absorptiometry (DXA), lumbar spine volumetric bone mineral density (vBMD) and geometry by quantitative computed tomography (QCT), bone microstructure by high-resolution peripheral QCT at the radius (HRpQCT), and vertebral compressive strength and load-to-strength ratio by finite-element analysis (FEA) of lumbar spine QCT images. Compared with controls, women with grade 1 deformities had significantly worse values for many bone density, structure, and strength parameters, although deficits all were much worse for the women with grade 2-3 deformities. Likewise, these skeletal parameters were more strongly associated with moderate to severe than with mild deformities by age-adjusted logistic regression. Nonetheless, grade 1 vertebral deformities were significantly associated with four of the five main variable categories assessed: bone density (lumbar spine vBMD), bone geometry (vertebral apparent cortical thickness), bone strength (overall vertebral compressive strength by FEA), and load-to-strength ratio (45-degree forward bending ÷ vertebral compressive strength). Thus significantly impaired bone density, structure, and strength compared with controls indicate that many grade 1 deformities do represent early osteoporotic fractures, with corresponding implications for clinical decision making

Modeling trajectories of perceived leg exertion during maximal cycle ergometer exercise in children and adolescents

BACKGROUND: Borg developed scales for rating pain and perceived exertion in adults that have also been used in pediatric populations. Models describing functional relationships between perceived exertion and work capacity have not been studied in children. We compared different models and their fits to individual trajectories and assessed the variability in these trajectories. METHODS: Ratings of perceived exertion (RPE) were collected from 79 children. Progressive cycle ergonometric testing was performed to maximal work capacity with test duration ranging from 6‐ 12 minutes. Ratings were obtained during each 1‐minute increment. Work was normalized to individual maximal work capacity (Wmax). A delay was defined as the fraction of Wmax at which point an increase in ratings of leg fatigue occurred. Such a delay term allows the characterization of trajectories for children whose ratings were initially constant with increasing work. Two models were considered, a delay model and a power model that is commonly used to analyze Borg ratings. Individual model fit was assessed with root mean squared error (RMSE). Functional clustering algorithms were used to identify patterns. RESULTS: Leg tiredness developed quickly for some children while for others there was a delay before an in‐ creased ratings of leg exertion occurred with increasing work. Models for individual trajectories with the smallest RMSE included a delay and a quadratic term (quadratic‐delay model), or a power function and a delay term (power‐delay model) compared to a simple power function. The median delay was 40% Wmax (interquartile range (IQR): 26‐49%) in a quadratic‐delay model, while the median exponent was 1.03 (IQR: 0.83‐1.78) in a power‐delay model. Nine clusters were identified showing linear or quadratic patterns with or without a delay. Cluster membership did not depend on age, gender or diagnosis. CONCLUSION: Children and adolescents vary widely in their capacity to rate their perceptions and exhibit different functional relationships between ratings of perceived exertion and work capacity normalized across individuals. Models including a delay term, a linear component, or a power function can describe these individual trajectories of perceived leg exertion during incremental exercise to voluntary exhaustion

Parasite infections in a social carnivore: Evidence of their fitness consequences and factors modulating infection load

There are substantial individual differences in parasite composition and infection load in wildlife populations. Few studies have investigated the factors shaping this heterogeneity in large wild mammals or the impact of parasite infections on Darwinian fitness, particularly in juveniles. A host's parasite composition and infection load can be shaped by factors that determine contact with infective parasite stages and those that determine the host's resistance to infection, such as abiotic and social environmental factors, and age. Host–parasite interactions and synergies between coinfecting parasites may also be important. We test predictions derived from these different processes to investigate factors shaping infection loads (fecal egg/oocyte load) of two energetically costly gastrointestinal parasites: the hookworm Ancylostoma and the intracellular Cystoisospora, in juvenile spotted hyenas (Crocuta crocuta) in the Serengeti National Park, in Tanzania. We also assess whether parasite infections curtail survival to adulthood and longevity. Ancylostoma and Cystoisospora infection loads declined as the number of adult clan members increased, a result consistent with an encounter‐reduction effect whereby adults reduced encounters between juveniles and infective larvae, but were not affected by the number of juveniles in a clan. Infection loads decreased with age, possibly because active immune responses to infection improved with age. Differences in parasite load between clans possibly indicate variation in abiotic environmental factors between clan den sites. The survival of juveniles (<365 days old) to adulthood decreased with Ancylostoma load, increased with age, and was modulated by maternal social status. High‐ranking individuals with low Ancylostoma loads had a higher survivorship during the first 4 years of life than high‐ranking individuals with high Ancylostoma loads. These findings suggest that high infection loads with energetically costly parasites such as hookworms during early life can have negative fitness consequences