A Bayesian method to estimate the optimal threshold of a longitudinal biomarker

The objective of this study was to develop methods to estimate the optimal threshold of a longitudinal biomarker and its credible interval when the diagnostic test is based on a criterion that reflects a dynamic progression of that biomarker. Two methods are proposed: one parametric and one non‐parametric. In both the cases, the Bayesian inference was used to derive the posterior distribution of the optimal threshold from which an estimate and a credible interval could be obtained. A numerical study shows that the bias of the parametric method is low and the coverage probability of the credible interval close to the nominal value, with a small coverage asymmetry in some cases. This is also true for the non‐parametric method in case of large sample sizes. Both the methods were applied to estimate the optimal prostate‐specific antigen nadir value to diagnose prostate cancer recurrence after a high‐intensity focused ultrasound treatment. The parametric method can also be applied to non‐longitudinal biomarkers.     

Optimization of the Transcranial Magnetic Stimulation Protocol by Defining a Reliable Estimate for Corticospinal Excitability

The goal of this study was to optimize the transcranial magnetic stimulation (TMS) protocol for acquiring a reliable estimate of corticospinal excitability (CSE) using single-pulse TMS. Moreover, the minimal number of stimuli required to obtain a reliable estimate of CSE was investigated. In addition, the effect of two frequently used stimulation intensities [110% relative to the resting motor threshold (rMT) and 120% rMT] and gender was evaluated. Thirty-six healthy young subjects (18 males and 18 females) participated in a double-blind crossover procedure. They received 2 blocks of 40 consecutive TMS stimuli at either 110% rMT or 120% rMT in a randomized order. Based upon our data, we advise that at least 30 consecutive stimuli are required to obtain the most reliable estimate for CSE. Stimulation intensity and gender had no significant influence on CSE estimation. In addition, our results revealed that for subjects with a higher rMT, fewer consecutive stimuli were required to reach a stable estimate of CSE. The current findings can be used to optimize the design of similar TMS experiments.     

A systematic review of the frequency of neurocyticercosis with a focus on people with epilepsy

Background

The objective of this study is to conduct a systematic review of studies reporting the frequency of neurocysticercosis (NCC) worldwide.

Methods/Principal Findings

PubMed, Commonwealth Agricultural Bureau (CAB) abstracts and 23 international databases were systematically searched for articles published from January 1, 1990 to June 1, 2008. Articles were evaluated for inclusion by at least two researchers focusing on study design and methods. Data were extracted independently using standardized forms. A random-effects binomial model was used to estimate the proportion of NCC among people with epilepsy (PWE). Overall, 565 articles were retrieved and 290 (51%) selected for further analysis. After a second analytic phase, only 4.5% of articles, all of which used neuroimaging for the diagnosis of NCC, were reviewed. Only two studies, both from the US, estimated an incidence rate of NCC using hospital discharge data. The prevalence of NCC in a random sample of village residents was reported from one study where 9.1% of the population harboured brain lesions of NCC. The proportion of NCC among different study populations varied widely. However, the proportion of NCC in PWE was a lot more consistent. The pooled estimate for this population was 29.0% (95%CI: 22.9%–35.5%). These results were not sensitive to the inclusion or exclusion of any particular study.

Conclusion/Significance

Only one study has estimated the prevalence of NCC in a random sample of all residents. Hence, the prevalence of NCC worldwide remains unknown. However, the pooled estimate for the proportion of NCC among PWE was very robust and could be used, in conjunction with estimates of the prevalence and incidence of epilepsy, to estimate this component of the burden of NCC in endemic areas. The previously recommended guidelines for the diagnostic process and for declaring NCC an international reportable disease would improve the knowledge on the global frequency of NCC.     

Measuring dose from radiotherapy treatments in the vicinity of a cardiac pacemaker

This study investigated the dose absorbed by tissues surrounding artificial cardiac pacemakers during external beam radiotherapy procedures. The usefulness of out-of-field reference data, treatment planning systems, and skin dose measurements to estimate the dose in the vicinity of a pacemaker was also examined. Measurements were performed by installing a pacemaker onto an anthropomorphic phantom, and using radiochromic film and optically stimulated luminescence dosimeters to measure the dose in the vicinity of the device during the delivery of square fields and clinical treatment plans. It was found that the dose delivered in the vicinity of the cardiac device was unevenly distributed both laterally and anteroposteriorly. As the device was moved distally from the square field, the dose dropped exponentially, in line with out-of-field reference data in the literature. Treatment planning systems were found to substantially underestimate the dose for volumetric modulated arc therapy, helical tomotherapy, and 3D conformal treatments. The skin dose was observed to be either greater or lesser than the dose received at the depth of the device, depending on the treatment site, and so care should be if skin dose measurements are to be used to estimate the dose to a pacemaker. Square field reference data may be used as an upper estimate of absorbed dose per monitor unit in the vicinity of a cardiac device for complex treatments involving multiple gantry angles.     

Poor nutritional condition as a consequence of high dominance status in the Coal Tit Parus ater

The costs and benefits of dominance status have been investigated in the past and it has generally been reported that subdominant birds are at a nutritional disadvantage owing to their low dominance status. The nutritional condition of birds during winter can be important in determining their likelihood of survival. This is particularly so in small passerines that are sensitive to severe weather conditions. Ptilochronology is an accurate method used to produce a long-term estimate of body condition spanning the number of days that it takes to grow a new feather. Ptilochronology was used during this study to estimate the nutritional condition of Coal Tits Parus ater during one winter and how condition was affected by dominance status. Dominant Coal Tits produced poorer quality feathers, which they grew at a slower rate, than did subdominant conspecifics. This study highlights a nutritional cost to high dominance status that could have long-term consequences because the induced tail feathers will not be replaced for at least 5 months.     

Evolution of consanguinity in a French alpine valley: the Vallouise in the Brianfon region (17th-19th Centuries)

The present study considers the evolution of consanguinity in the Vallouise, a high glacial valley in the French Alps. The genealogical method was used to estimate consanguinity in this Alpine population from the 17th to the 19th centuries. This method was then compared with three other methods used to measure consanguinity. The results indicate that while consanguinity increased through time (marriage dispensations and genealogies), the structural consanguinity (isonymy) was very stable throughout the entire period.     

Assessment of mark–recapture models to estimate the abundance of a humpback whale feeding aggregation in Southeast Alaska

Aim The aim of this study was to use photographs of the unique pattern on the ventral surface of the flukes to estimate the abundance of humpback whales (Megaptera novaeangliae) in a discrete feeding aggregation in northern Southeast Alaska. Location The study was located in northern Southeast Alaska, USA, in the eastern North Pacific Ocean. Methods This study evaluated mark–recapture models, ranging from the simpler models (pooled and stratified, closed Petersen estimators) to more complex multi‐strata models (closed Darroch and open Hilborn). The Akaike Information Criterion, corrected (AICc) was used as a model comparison statistic. Results Our best estimate of whale abundance in northern Southeast Alaska in 2000 is 961 whales [95% confidence interval (657, 1076)]. This estimate comes from the Hilborn open, multi‐strata approach with constant migration over time, time‐dependent capture probabilities by area, and a fixed survival rate of 0.98. The simpler models were problematic owing to several aspects of whale behaviour, including that (1) the whales did not mix randomly throughout the study area, (2) some whales emigrated temporarily outside the study area and were not available for capture, and (3) whales were not equally identifiable because they did not behave in the same way when they showed their flukes upon diving. This led to heterogeneity in capture probability and a bias in the estimates. The more complex models stratified by area, and using migration movements among areas, compensated for some of these issues when estimating population size. Main conclusions We believe that the Hilborn open, multi‐strata model produced the best estimate because: (1) it incorporated the best information about survival, (2) it used detailed information about the various release groups, (3) the analysis provided an integrated environment in which parameters such as migration and capture probabilities are shared, (4) the three strata encompassed a large portion of the areas used by whales, and (5) the Hilborn model selected was superior in terms of model selection criteria and biological realism. These data provide valuable insights into the numbers and movements of humpback whales in three areas of Southeast Alaska.     

Aerial survey as a tool to estimate whale shark abundance trends

Aerial surveys have been used to estimate population abundance of both terrestrial and marine species; in the marine environment this has largely been used for air-breathing species that spend time regularly at the surface. Whale sharks spend a large proportion of their time close to the surface and so are amenable to aerial survey techniques. This study presents the results of six years of synoptic aerial belt-surveys done nearly daily during the peak whale shark season around the island of Mahe, Seychelles. A total of 580 survey flights were flown providing 699.7 hours of survey record. A seasonal peak of shark sightings per hour was recorded in September or October in most years with the maximum on a single survey of 28.4 h^- 1 in October 2006. The aerial survey data were used to generate an estimate of relative population abundance indicating that highest mean annual relative population estimate was also in 2006, with an estimate of 38, while the lowest mean estimate was 11 in 2004. These estimates were then compared to weekly capture-mark-recapture estimates of abundance based on unique individual identification data. The results indicate that the use of aerial survey data alone may give an acceptable indication of instantaneous relative population abundance but further refinement is necessary to estimate absolute regional abundance.     

Estimating the fraction of invariable codons with a capture-recapture method

Summary A codon-based approach to estimating the number of variable sites in a protein is presented. When first and second positions of codons are assumed to be replacement positions, a capture-recapture model can be used to estimate the number of variable codons from every pair of homologous and aligned sequences. The capture-recapture estimate is compared to a maximum likelihood estimate of the number of variable codons and to previous approaches that estimate the number of variable sites (not codons) in a sequence. Computer simulations are presented that show under which circumstances the capture-recapture estimate can be used to correct biases in distance matrices. Analysis of published sequences of two genes, calmodulin and serum albumin, shows that distance corrections that employ a capture-recapture estimate of the number of variable sites may be considerably different from corrections that assume that the number of variable sites is equal to the total number of positions in the sequence. Offprint requests to: A. Sidow     

Non-parametric estimation of the age-at-onset distribution from a cross-sectional sample

We propose and study a simple and innovative non-parametric approach to estimate the age-of-onset distribution for a disease from a cross-sectional sample of the population that includes individuals with prevalent disease. First, we estimate the joint distribution of two event times, the age of disease onset and the survival time after disease onset. We accommodate that individuals had to be alive at the time of the study by conditioning on their survival until the age at sampling. We propose a computationally efficient expectation–maximization (EM) algorithm and derive the asymptotic properties of the resulting estimates. From these joint probabilities we then obtain non-parametric estimates of the age-at-onset distribution by marginalizing over the survival time after disease onset to death. The method accommodates categorical covariates and can be used to obtain unbiased estimates of the covariate distribution in the source population. We show in simulations that our method performs well in finite samples even under large amounts of truncation for prevalent cases. We apply the proposed method to data from female participants in the Washington Ashkenazi Study to estimate the age-at-onset distribution of breast cancer associated with carrying BRCA1 or BRCA2 mutations.     

On the Bayesian estimation of a closed population size in the presence of heterogeneity and model uncertainty

Summary .   We consider the estimation of the size of a closed population, often of interest for wild animal populations, using a capture–recapture study. The estimate of the total population size can be very sensitive to the choice of model used to fit to the data. We consider a Bayesian approach, in which we consider all eight plausible models initially described by Otis et al. (1978, Wildlife Monographs 62, 1–135) within a single framework, including models containing an individual heterogeneity component. We show how we are able to obtain a model-averaged estimate of the total population, incorporating both parameter and model uncertainty. To illustrate the methodology we initially perform a simulation study and analyze two datasets where the population size is known, before considering a real example relating to a population of dolphins off northeast Scotland.     

Systematic comparison of the empirical and factorial methods used to estimate the nutrient requirements of growing pigs

Empirical and factorial methods are currently used to estimate nutrient requirements for domestic animals. The purpose of this study was to estimate the nutrient requirements of a given pig population using the empirical and factorial methods; to establish the relationship between the requirements estimated with these two methods; and to study the limitations of the methods when used to determine the level of a nutrient needed to optimize individual and population responses of growing pigs. A systematic analysis was carried out on optimal lysine-to-net-energy (Lys : NE) ratios estimated by the empirical and factorial methods using a modified InraPorc® growth model. Sixty-eight pigs were individually simulated based on detailed experimental data. In the empirical method, population responses were estimated by feeding pigs with 11 diets of different Lys : NE ratios. Average daily gain and feed conversion ratio were the chosen performance criteria. These variables were combined with economic information to estimate the economic responses. In the factorial method, the Lys : NE ratio for each animal was estimated by model inversion. Optimal Lys : NE ratios estimated for growing pigs (25 to 105 kg) differed between the empirical and the factorial method. When the average pig is taken to represent a population, the factorial method does not permit estimation of the Lys : NE ratio that maximizes the response of heterogeneous populations in a given time or weight interval. Although optimal population responses are obtained by the empirical method, the estimated requirements are fixed and cannot be used for other growth periods or populations. This study demonstrates that the two methods commonly used to estimate nutrient requirements provide different nutrient recommendations and have important limitations that should be considered when the goal is to optimize the response of individuals or pig populations.     

Serum CYR61 as a potential biomarker for the diagnosis of esophagogastric junction tumor

Background: Esophagogastric junction tumor (EGJ) is a rare but fatal disease with a rapid rising incidence worldwide in the late 20 years, and it lacks a convenient and safe method for diagnosis. The present study aimed to evaluate the potential of serum CYR61 as a biomarker for the diagnosis of EGJ tumor.Methods: Enzyme-linked immunosorbent assay (ELISA) was used to estimate CYR61 levels in sera of 152 EGJ tumor patients and 137 normal controls. Receiver operating characteristics (ROC) was carried out to evaluate the diagnostic accuracy. The Mann–Whitney’s U test was used to compare the difference of serum levels of CYR61 between groups. And chi-square tests were employed to estimate the correlation of the positive rate of serum CYR61 between/among subgroups.Results: Serum CYR61 levels were statistically lower in EGJ tumor and early-stage EGJ tumor patients than those in normal controls (P<0.0001). The sensitivity, specificity and the area under the curve (AUC) of this biomarker in EGJ tumor were 88.2%, 43.8% and 0.691, respectively, and those for early stage of EGJ tumor were 80.0%, 66.4% and 0.722, respectively. Analyses showed that there was no correlation between the clinical data and the levels of CYR61 (P>0.05).Conclusion: The present study showed that CYR61 might be a potential biomarker to assist the diagnosis of EGJ tumor.     

On the mechanical stability of porous coated press fit titanium implants: a finite element study of a pushout test

Pushout tests can be used to estimate the shear strength of the bone implant interface. Numerous such experimental studies have been published in the literature. Despite this researchers are still some way off with respect to the development of accurate numerical models to simulate implant stability. In the present work a specific experimental pushout study from the literature was simulated using two different bones implant interface models. The implant was a porous coated Ti-6Al-4V retrieved 4 weeks postoperatively from a dog model. The purpose was to find out which of the interface models could replicate the experimental results using physically meaningful input parameters. The results showed that a model based on partial bone ingrowth (ingrowth stability) is superior to an interface model based on friction and prestressing due to press fit (initial stability). Even though the present study is limited to a single experimental setup, the authors suggest that the presented methodology can be used to investigate implant stability from other experimental pushout models. This would eventually enhance the much needed understanding of the mechanical response of the bone implant interface and help to quantify how implant stability evolves with time.     

The contribution of nitrification in the water column and profundal sediments to the total oxygen deficit of the hypolimnion of a mesotrophic lake (Grasmere,English Lake District)

Estimates ofin situ nitrifying activity have been made in the hypolimnetic water column and surface 1.0 cm of profundal sediments at 2 sites in Grasmere, a mesotrophic lake in the English Lake District. Increases of nitrate concentrations were used to estimate nitrification in the water column whereas a mini-core technique, involving the use of a nitrification inhibitor (allylthiourea), was used to estimate the rate in surface sediments. The pattern of oxygen depletion in the water column was used to estimate the maximum depth to which sediments affect the overlying water. Nitrification in the sediment and in the water column made approximately equal contributions to the total areal oxygen deficit and, as a whole, nitrification accounted for 15–20% of the total oxygen depletion. There was no significant difference in oxygen depletion due to nitrification between the 2 sites. Attempts were made, using the nitrification potential technique, to determine the depth distribution of nitrifying activity in the surface 1.0 cm of sediment.     

Home range size and distribution in a wild population of Cape pangolins, Manis temminckii, in north‐west Zimbabwe

The aim of this study was to estimate the size of the home range used by individual Cape pangolins ( Manis temminckii ). The study was conducted in 1991–95 at Sengwa Wildlife Research Institute, Gokwe, Zimbabwe. Radio‐telemetry was used to repeatedly locate study pangolins. Home range area was estimated from the location of the burrows used by each pangolin. It was established that pangolins must be tracked for 85+ days to generate a reliable estimate of home range. The size of home ranges, determined from 1141 tracking days of data for 10 pangolins (3·0–15·8 kg body mass) that were each tracked for at least 85 days, was from 0·17 to 11·07 km². Larger (older) pangolins used more burrows and had larger home ranges than smaller (younger) pangolins. The data indicate that large adult males had larger home ranges than large adult females. Within each sex, the home ranges were adjacent to each other with only slight overlap at the boundaries. There was clear overlap of home ranges between males and females.     

An assessment of a simple method for estimating the relative contributions of point and diffuse source phosphorus to in-river phosphorus loads

Implementation of the Urban Wastewater Treatment (UWWT) Directive requires a relatively simple methodology to partition in-river phosphorus (P) loads between diffuse and point sources in a catchment. In this study, standard monitoring data from the River Avon in Warwickshire, U.K. were used to estimate in-river loads. A novel aspect was the application of uncalibrated P run-off coefficients from the literature to areas of different land-use to estimate the diffuse P load. Point source P-loads were estimated either from monitoring data or from published export coefficient values. Analysis of the data showed that the main source of variability in the estimate of in-river loads was from the flow data, which, at many sites, did not cover a sufficient range of natural flow rates to allow reliable estimates of the annual load to be made. Analysis of data from 20 sites where this condition was fulfilled showed that, in the large, urbanised (15% land cover) River Avon catchment the use of uncalibrated run-off coefficients gave reliable estimates of diffuse loads.     

Estimation of the efficacy of screened natural hypolipidemic compounds in a model of rabbit hypercholesterolemia]

Thirteen strains producing hydrophobic compounds with high hypolipidemic activity were screened among 657 tested strains of fungi, actinomycetes and bacteria with the use of 2 models. The further aim of the study was to estimate the efficacy of the compounds with respect to their ability to inhibit cholesterol synthesis in vivo. For that purpose a model of hyperlipidemia in rabbits was used. The model provided screening of 9 new compounds that showed satisfactory hypolipidemic effect evident from a significant decrease of the lipid levels in the rabbit serum. The study of the serum lipid profile revealed that the inhibitory effect of compounds No. 16 and No. 281 was similar to that of lovastatin whereas the serum level of general cholesterol remained decreased for a longer period. Compound No. 25 was of interest because of its possible use in low doses and significant effect on the serum triglyceride fraction.     

A survey of the apes in the Dzanga-Ndoki National Park, Central African Republic: a comparison between the census and survey methods of estimating the gorilla (Gorilla gorilla gorilla) and chimpanzee (Pan troglodytes) nest group density

A survey of apes was carried out between October 1996 and May 1997 in the Dzanga sector of the Dzanga‐Ndoki National Park, Central African Republic (CAR), to estimate gorilla (Gorilla gorilla gorilla) and chimpanzee (Pan troglodytes) densities. The density estimates were based on nest counts. The strip transect census and the line transect survey method (Standing Crop Nest Count) were used to estimate the gorilla nest group density. The strip transect has been most commonly used to date. It assumes that all nest groups within the width of the strip are detected, but as this assumption is easily violated in the dense tropical rain forest, the line transect survey was also used. In this method, only the nest groups on the transect line itself should be detected. This method proved to be an adequate and easy technique for estimating animal densities in dense vegetation. The gorilla density of 1.6 individuals km^?2 (line transect survey method) found for the Dzanga sector is one of the highest densities ever reported in the literature for the Western lowland gorilla. The density estimate for chimpanzees was 0.16 individuals km^?2 (census method). The results of this study confirm the importance of the Dzanga‐Ndoki National Park for primate conservation.     

Larval densities and a life-table for the gypsy moth, Lymantria dispar, estimated using the head-capsule collection method

ABSTRACT. 1. In order to estimate the absolute larval density in each stage of a larval population of the gypsy moth, Lymantria dispar L., in a deciduous forest in northern Japan, the head-capsule collection method was used. An estimate by this method was compared with estimates based on two kinds of frass collection methods.
2. Twenty-one traps made of cloth were put in a study plot. Each trap was of 24.5 cm diameter. Larval head-capsules falling into the traps were collected and sorted by hand. On the first sampling occasion, the population was also estimated using the frass-collection method.
3. Larval numbers estimated by the head-capsule collection method were almost identical to estimates by the two frass methods. Larval numbers entering the four larval instar were successfully estimated by the head-capsule collection method, and an age-specific life table was established using the resultant estimates.