An approach for hip joint center calculation for use in seated postures

In seated postures, such as those in office or automotive seats, locating the hip joint center (HJC) using three markers on the pelvis has been difficult if not impossible. A two-target approach by Bell et al. (J. Biomech. 23 (1990) 617) has been used, however, this method was shown to have inaccuracies when compared to the three-target method developed by Seidel et al. (J. Biomech. 28 (1995) 995). A new two-target method that is specific to the seated environment, has better accuracy than the Bell et al. approach, and is based on the Seidel et al. approach was developed and tested on 13 seated subjects. This new method used three targets and an initial reference file to estimate the HJC location. Once the HJC was located, assumptions were made that the magnitudes between the HJC and the respective anterior superior iliac spine, and the HJC and the respective lateral epicondyle remained constant. The primary concern when evaluating this new method was the affect of seated posture movement, in particular leg splay and spinal flexion on the assumptions. The results obtained with the new approach were compared to Seidel et al. and provided HJC locations with average differences of 3.8, 1.2 and 2.8mm for spinal flexion in the anterior/posterior, medial/lateral and superior/inferior directions, respectively, and 2.3, 1.0 and 1.4mm for knee splay. The proposed method provided better HJC estimation than the Bell et al. approach particularly in the superior/inferior dimensions.     

Flow cytometric analysis of European flat oyster, Ostrea edulis, haemocytes using a monoclonal antibody specific for granulocytes

The importance of haemocytes in mollusc defence mechanisms can be inferred from their functions. They participate in pathogen elimination by phagocytosis (Cheng, 1981; Fisher, 1986). Hydrolytic enzymes and cytotoxic molecules produced by haemocytes contribute to the destruction of pathogenic organisms (Cheng, 1983; Leippe & Renwrantz, 1988; Charlet et al., 1996; Hubert et al., 1996; Roch et al., 1996). Haemocytes may also be involved in immunity modulation by the production of cytokines and neuropeptides (Hughes et al., 1990; Stefano et al., 1991; Ottaviani et al., 1996). As a result, the literature dealing with bivalve haemocyte studies has increased during the last two decades. Most of these publications use microscopy for morphological analysis (Seiler & Morse, 1988; Auffret, 1989; Hine & Wesney, 1994; Giamberini et al., 1996; Carballal et al., 1997; Lopez et al., 1997; Nakayama et al., 1997), and functional analysis (e.g. phagocytosis) (Hinsch & Hunte, 1990; Tripp, 1992; Mourton et al., 1992; Fryer & Bayne, 1996; Mortensen & Glette, 1996). Flow cytometry represents a rapid technique applicable to both morphological and functional studies of cells in suspension. While the measurements based on autofluorescence provide information on cell morphology, the analyses with fluorescent markers including labelled antibodies, offer data on phenotyping and cell functions. As a result, its application has greatly contributed to the investigation of immunocyte functions and differentiation in vertebrates (Stewart et al., 1986; Rothe & Valet, 1988; Ashmore et al., 1989; Koumans-van Diepen et al., 1994; Rombout et al., 1996; Caruso et al., 1997). Some authors studied oyster haemocyte populations by flow cytometry based on cellular autofluorescence (Friedl et al., 1988; Fisher & Ford, 1988; Ford et al., 1994). However, no analysis using specific monoclonal antibodies has been reported to date. In this study, a protocol for studying European flat oyster, Ostrea edulis, haemocytes by flow cytometry using a monoclonal antibody specific for granulocytes and an indirect immunofluorescence technique have been developed. European flat oysters, Ostrea edulis, 7-9 cm in shell length were obtained from shellfish farms in Marenne Oléron bay (Charente Maritime, France) on the French Atlantic coast. All individuals were purchased just before each experiment and processed without any previous treatment.     

Estimation of coalescence probabilities and population divergence times from SNP data

We present a method called the G(A|B) method for estimating coalescence probabilities within population lineages from genome sequences when one individual is sampled from each population. Population divergence times can be estimated from these coalescence probabilities if additional assumptions about the history of population sizes are made. Our method is based on a method presented by Rasmussen et al. (2014) to test whether an archaic genome is from a population directly ancestral to a present-day population. The G(A|B) method does not require distinguishing ancestral from derived alleles or assumptions about demographic history before population divergence. We discuss the relationship of our method to two similar methods, one introduced by Green et al. (2010) and called the F(A|B) method and the other introduced by Schlebusch et al. (2017) and called the TT method. When our method is applied to individuals from three or more populations, it provides a test of whether the population history is treelike because coalescence probabilities are additive on a tree. We illustrate the use of our method by applying it to three high-coverage archaic genomes, two Neanderthals (Vindija and Altai) and a Denisovan.Subject terms: Rare variants, Evolutionary genetics

One of the goals of population genetics is to estimate the divergence time of isolated populations. We will review several methods that have been proposed and present a new method that is closely related to two existing methods. We will emphasize the assumptions made when using different methods. It will be useful to make the distinction between estimating coalescence probabilities within populations and estimating population divergence times. We will also introduce a test for a treelike population history based on our method.For distantly related populations, the numbers of mutational differences between sequences indicate relative times of divergence. Relative times are converted to absolute times by assuming a mutation rate. This method traces to Zuckerkandl and Pauling (1962, 1965) and has been used and refined extensively. This class of methods estimates genomic divergence times. Using it to estimate population or species divergence times assumes that those times are so large that the difference between them can be ignored.For recently diverged populations, the numbers of mutational differences probably do not provide a reliable estimate of population divergence times both because there may be too few mutations that differentiate populations and because the difference between the genomic and population divergence times may be substantial. To overcome this problem, Green et al. (2010) (in Supplement 14) introduced a method that accounts for the difference between genomic and population divergence. This method was used in later papers from the same group (Meyer et al. 2012; Prüfer et al. 2014, 2017).The Green et al. (2010) method is applicable when one genome is sampled from each of two populations. It depends on the statistic F(A|B), which is the fraction of sites in population A that carry the derived allele when that site is heterozygous in population B. Green et al. (2010) showed by simulation that the expectation of F(A|B) decreases roughly exponentially with the separation time of A and B. The rate of decrease depends on the history of population sizes both in B and in the population ancestral to A and B. Green et al. (2010) estimated population divergence times by interpolating their simulation results.More recently, Schlebusch et al. (2017), in Section 9.1 of their supplementary materials, introduced a similar method, called the TT method. Their method is based on analytic expressions for the configuration probabilities of SNPs that are polymorphic in the two populations. The TT method assumes that ancestral and derived alleles can be distinguished and the population before divergence was of constant size. The TT method is developed and elaborated on by Sjödin et al. (2020).In the present paper, we present a new method that is closely related to the F(A|B) and TT methods. We call it the G(A|B) method to emphasize its similarity to F(A|B). Our method is based on a method presented by Rasmussen et al. (2014) to test whether an ancient DNA sequence is from a population directly ancestral to a present-day population. We will show that our method provides a way to test whether the history of three or more populations is accurately represented by a population tree even if the demographic histories of those populations are not known.     

Determining rigid body transformation parameters from ill-conditioned spatial marker co-ordinates

The three-dimensional location of a body-fixed axis system is described by position and orientation parameters that can be calculated knowing local and global coordinates of three or more body-fixed markers. However, marker distribution can become ill-conditioned when marker placement is symmetrical with respect to the mean of the markers. As symmetry and ill-conditioning increases, random errors in marker locations can affect the stability of orientation parameters as a result of the mathematical approach adopted. The present study investigates the methods of Veldpaus et al. [1988; Journal of Biomechanics 21, 45], Challis [1995; Biomechanics 28, 733] and Andriacchi et al. [1998; Journal of Biomedical Engineering 120, 743] for obtaining segment orientation parameters when segment markers ranged from well-defined to highly ill-conditioned depending on the symmetry of segment markers. A novel fourth approach is also presented that enabled comparisons of the root mean square error of reconstructed marker coordinates to verify that an optimal solution was obtained. No single method produced optimal results for all axis orientation parameters when reconstructing movement trials. The best performed was the method of Veldpaus et al. [1988; Journal of Biomechanics 21, 45] based on consistent results and ease of implementation. The fourth approach presented provided a reliable method in all but the highly ill-conditioned markers, however implementation was computationally difficult. The method of Challis [1995; Biomechanics 28, 733] was only suited to well-conditioned marker sets which avoided markers lying in a single plane with symmetries in marker distribution relative to the mean. The method of Andriacchi et al. [1998; Journal of Biomedical Engineering 120, 743] produced, at best, orientation parameters that approximated the results obtained by least squares methods.     

On the time dependent diffusion of macromolecules through transient open junctions and their subendothelial spread. 2. Long time model for interaction between leakage sites

In Part 1 of this study (Weinbaum et al., 1988) a short time model has been proposed to describe the initial time dependent leakage of macromolecules at short distances (5 microns or less) from the exit of a transient open junction which the authors have hypothesized as a characteristic feature of endothelial cells in the process of turnover (Weinbaum et al., 1985). This open junction pathway has also been proposed (Weinbaum et al., 1988) to be the primary ultrastructural correlate of the 20 nm diameter large pore suggested by Renkin et al. (1977) using the predictions of cylindrical pore theory. The short time model in (Weinbaum et al., 1988), however, has major limitations in that it neglects the interaction between leakage sites, macromolecular entry through other pathways, the finite thickness of the vessel wall and the curvature of the cell perimeter. The longer time model developed herein will attempt to describe each of these features and also present an improved model and analytic solution for the steady state flux and uptake. In the previous steady state model developed by Weinbaum et al. (1985) the effect of the resistance of the transient open junctions and the non-isotropic diffusion in the underlying tissue due to the internal elastic lamina (IEL) were both neglected. New solutions are first presented which describe the effect of these important model refinements on the steady state macromolecular permeability of the major arteries. Time dependent solutions are then presented to predict the transient longer time labeling following the introduction of tracer macromolecules of varying size. These solutions and the corresponding short time solutions in Weinbaum et al. (1988) are the first solutions to our knowledge to describe the difficult time-dependent boundary value problem to determine how the channel exit concentration and flux at a leaky junction vary with time. This is accomplished by casting the boundary value problem in the form of an integral equation for the unknown flux at the cleft exit and then solving this problem using a specially designed numerical technique. The theoretical predictions are used to interpret the behavior of the localized leaks to HRP and albumin that have been reported in Stemerman et al. (1986) and our own recent experiments (Lin et al., 1988).     

Capture-recapture when time and behavioral response affect capture probabilities

We consider a capture-recapture model in which capture probabilities vary with time and with behavioral response. Two inference procedures are developed under the assumption that recapture probabilities bear a constant relationship to initial capture probabilities. These two procedures are the maximum likelihood method (both unconditional and conditional types are discussed) and an approach based on optimal estimating functions. The population size estimators derived from the two procedures are shown to be asymptotically equivalent when population size is large enough. The performance and relative merits of various population size estimators for finite cases are discussed. The bootstrap method is suggested for constructing a variance estimator and confidence interval. An example of the deer mouse analyzed in Otis et al. (1978, Wildlife Monographs 62, 93) is given for illustration.     

Description of a new computer wire coding method and its application to evaluate potential control selection bias in the Savitz et al. childhood cancer study

We developed a new computer wire coding method and then applied it to investigate the suggestion that control selection bias might explain the observed association between wire codes and childhood cancer made in the study conducted by Savitz et al. in the Denver area. The computer wire coding method used a geographic information system approach with data on the local distribution electric system and from tax assessor records. Individual residences were represented as a circle scaled to the ground floor area of the residence and centered on the lot centroid. The wire code of the residence was determined from the distance between the circle and the relevant power line, and from the current carrying capacity of that line. Using this method, wire codes were generated for 238 290 residences built before 1986, the time of the Savitz et al. study, in the Denver metropolitan area. We then attempted to reconstruct the 1985 population of hypothetically eligible control children in the Denver metropolitan area by using 1980 census data. Since data were not available to locate the children in each residence within a census block, uniform, Poisson, and negative binomial distributions were used to randomly assign children to residences. To evaluate the likelihood of the wire code distribution of the controls selected by Savitz et al., 100 random trials were conducted for each distribution, matching two controls to each case. The odds ratios between childhood cancer and very high current configuration (VHCC) wire codes were reduced when the assigned controls were used, suggesting control selection bias may have been present. However, control selection bias is unlikely to account for all the reported association between childhood cancer and wire codes in the Savitz et al. study.     

前瞻研究中多因素人群归因危险度的Poisson回归模型估计

本文提出多因素前瞻研究中利用Poisson回归发病率预测模型和相对危险度估计调整和综合人群归因危险度的方法,与Bruzzi等和Deubner等提出的多因素人群归因危险度估计方法进行了比较,强调在前瞻资料的人群归因危险度的估计中利用poisson回归模型考虑失访病例和随访时间效应,并能直接估计相对危险度的优势.应用所建立的方法对启东县肝病人群14年前瞻观察资料进行肝癌危险因素的人群归因危险度的估计。     

Does frequency-dependent selection optimize fitness?

In evolutionary biology, the axiom that natural selection tends ideally to maximize inclusive fitness of the individual or some other suitable quantity is often advanced (Cody, 1974; Maynard Smith, 1978; Krebs & McCleery, 1984; Houston et al., 1988). Moreover, the evolutionists generally distinguish two situations (Dawkins, 1980; Maynard Smith, 1982): one in which fitness is independent of the frequency of the phenotypes present in the population (frequency-independent selection), and one in which it does depend on this frequency (frequency-dependent selection). This led some authors such as Parker (1984), and more recently Parker & Maynard Smith (1990), to consider "a 2-speed optimization": frequency-independent selection should lead to a "simple optimum" at the end of the selective process, since all the individuals should have the same strategy and the mean fitness of the population should be maximized; frequency-dependent selection, formulated in terms of the theory of games, should lead to a "competitive optimum" even though the "evolutionary stable strategy" (or "ESS"; Maynard Smith & Price, 1973) characterizing the equilibrium "is not the strategy that maximizes fitness in a population sense" (Parker & Maynard Smith, 1990: 30). Our aim in this short communication is to criticize the concept of "competitive optimum" by Parker & Maynard Smith, as well as the general ability of natural selection to "maximize fitness", even in "phenotypic models" (Lloyd, 1977). These models, devoid of genetic constraints since each strategist is assumed to reproduce its own kind, are especially suitable for examining the ideal effect of natural selection.     

On analyzing circadian rhythms data using nonlinear mixed models with harmonic terms

Wang, Ke, and Brown (2003, Biometrics59, 804-812) developed a smoothing-based approach for modeling circadian rhythms with random effects. Their approach is flexible in that fixed and random covariates can affect both the amplitude and phase shift of a nonparametrically smoothed periodic function. In motivating their approach, Wang et al. stated that a simple sinusoidal function is too restrictive. In addition, they stated that "although adding harmonics can improve the fit, it is difficult to decide how many harmonics to include in the model, and the results are difficult to interpret." We disagree with the notion that harmonic models cannot be a useful tool in modeling longitudinal circadian rhythm data. In this note, we show how nonlinear mixed models with harmonic terms allow for a simple and flexible alternative to Wang et al.'s approach. We show how to choose the number of harmonics using penalized likelihood to flexibly model circadian rhythms and to estimate the effect of covariates on the rhythms. We fit harmonic models to the cortisol circadian rhythm data presented by Wang et al. to illustrate our approach. Furthermore, we evaluate the properties of our procedure with a small simulation study. The proposed parametric approach provides an alternative to Wang et al.'s semiparametric approach and has the added advantage of being easy to implement in most statistical software packages.     

Evaluation of the maximum likelihood estimate of the evolutionary tree topologies from DNA sequence data,and the branching order in hominoidea

Summary A maximum likelihood method for inferring evolutionary trees from DNA sequence data was developed by Felsenstein (1981). In evaluating the extent to which the maximum likelihood tree is a significantly better representation of the true tree, it is important to estimate the variance of the difference between log likelihood of different tree topologies. Bootstrap resampling can be used for this purpose (Hasegawa et al. 1988; Hasegawa and Kishino 1989), but it imposes a great computation burden. To overcome this difficulty, we developed a new method for estimating the variance by expressing it explicitly.The method was applied to DNA sequence data from primates in order to evaluate the maximum likelihood branching order among Hominoidea. It was shown that, although the orangutan is convincingly placed as an outgroup of a human and African apes clade, the branching order among human, chimpanzee, and gorilla cannot be determined confidently from the DNA sequence data presently available when the evolutionary rate constancy is not assumed.     

Long-range walking techniques in positional cloning strategies

Conclusion The past several years have seen an explosive growth in our understanding of the organization and structure of mammalian genomes, and refinements of existing techniques for genetic analysis, physical mapping, and large-fragment cloning techniques may well be enough to continue the momentum of that explosion for some time to come. Although refinement of existing techniques will certainly be necessary, the development of new and better cloning techniques may, perhaps, no longer be our most urgent need. The most important challenge that we face at present may in fact be that of finding efficient ways to share existing resources and information rapidly and equitably throughout the scientific community so that progress can continue unimpeded, and to catalog, correlate, and interpret the wealth of new data that is so rapidly accumulating.New strategies aimed at whole-genome mapping (Coulson et al. 1986, 1988; Michiels et al. 1987; Brenner and Livak 1989; Carrano et al. 1989; Lehrach et al. 1991) and sequencing (Church and Keifer-Higgins 1988; Bains and Smith 1988; Drmanac et al. 1989; Strzoska et al. 1991) may someday make the current method of long-range walking and physical mapping nearly passe. For example, since most of the relatively small nematode genome is now stored as ordered sets of cosmid and YAC clones (Coulson et al. 1986, 1988), a walk between a mapped marker and an uncloned gene can be accomplished rapidly, through a request for the appropriate series of clones from the ordered library. Vigorous drives by many laboratories to produce ordered clone libraries for murine and human chromosomes (Lehrach et al. 1991) may transform the process of cloning mammalian genes into a relatively trivial matter within the foreseeable future. The remarkable number of positional-cloning successes that have been reported in recent years may indicate that most of the best-defined, simply inherited mouse mutations and human hereditary disorders will have already been cloned by that time. When that is accomplished, the true challenging task will just begin: we must learn to decipher the complex biological programs encoded by our large and ever-growing storehouse of cloned, mapped and sequenced genes, before we can begin to understand what might be held in the vast silent mass of mammalian genomes. Offprint requests to: L. Stubbs     

Formulas predicting survival in patients with heart transplantation

Kirklin et al. (J Heart Transpl, 7 (1988) 331–336) reported survival data in 132 patients who underwent heart transplantation. Survival was evaluated by using the product-limit method of Kaplan-Meier and maximum likelihood method. In addition, the effect of pulmonary vascular resistance on survival was estimated by using multivariate analysis. A microcomputer program in BASIC for predicting the survival probability after transplantation in patients with heart transplantation is designed. The formula used in this program is derived from the survival data reported by Kirklin et al. (J Heart Transpl, 7 (1988) 331–336). A mathematical model of the ‘probacent’-probability equation and a computer program previously published by the author are employed in this study. Analysis of the computer-assisted predicted values and the data reported by Kirklin et al. (J Heart Transpl, 7 (1988) 331–336) indicates that the program is accurate and reliable with a complete agreement in expressing survival probability as a function of time after heart transplantation. The computer-assisted predictive formula can determine the relationship between the time and the survival probability and may be of value for prognostic evaluation of patients. The computer-assisted mathematical model of the ‘probacent’-probability equation may be proposed as a general approximation method to make useful predictions of probable outcomes in various biomedical phenomena.     

Home cage presentation of complex discrimination tasks to marmosets and rhesus monkeys

The study reported here demonstrates the feasibility of presenting cognitive tests from the Cambridge Neuropsychological Test Automated Battery (CANTAB) to either marmosets or rhesus monkeys in their home cages. This location of testing offers opportunities for the measurement of additional indices, for example spontaneous behaviour (Prowse et al. 1995) and electrophysiology (Pearce et al. 1998) as well as facilitating repeated test presentation. Results from 12 marmosets and 4 rhesus monkeys which have completed several sequences of an eight-stage discrimination task involving simple discriminations, compound discriminations and reversals are reported. The paradigm developed has application in long-term studies. Tests from CANTAB have been used extensively in normal humans (Robbins et al. 1994) as well as a range of patient groups (Owen et al. 1992, Elliott et al. 1995) and to assess drug effects (Coull et al. 1996). Additionally some of these tests have been presented to marmosets (Roberts et al. 1988) to examine neuropsychological functioning. This comparative approach facilitates meaningful cross species comparison, particularly in the study of the effects of pharmacological intervention.     

A comparative review of statistical methods for discovering differentially expressed genes in replicated microarray experiments

MOTIVATION: A common task in analyzing microarray data is to determine which genes are differentially expressed across two kinds of tissue samples or samples obtained under two experimental conditions. Recently several statistical methods have been proposed to accomplish this goal when there are replicated samples under each condition. However, it may not be clear how these methods compare with each other. Our main goal here is to compare three methods, the t-test, a regression modeling approach (Thomas et al., Genome Res., 11, 1227-1236, 2001) and a mixture model approach (Pan et al., http://www.biostat.umn.edu/cgi-bin/rrs?print+2001,2001a,b) with particular attention to their different modeling assumptions. RESULTS: It is pointed out that all the three methods are based on using the two-sample t-statistic or its minor variation, but they differ in how to associate a statistical significance level to the corresponding statistic, leading to possibly large difference in the resulting significance levels and the numbers of genes detected. In particular, we give an explicit formula for the test statistic used in the regression approach. Using the leukemia data of Golub et al. (Science, 285, 531-537, 1999), we illustrate these points. We also briefly compare the results with those of several other methods, including the empirical Bayesian method of Efron et al. (J. Am. Stat. Assoc., to appear, 2001) and the Significance Analysis of Microarray (SAM) method of Tusher et al. (PROC: Natl Acad. Sci. USA, 98, 5116-5121, 2001).     

Oocyte maturation and cell cycle control: a farewell symposium for Pr Marcel Dorée

Oocyte maturation and early development have been intensively studied for well over 100 years. The earliest theory proposed that after fertilisation and during cell division determinants were unequally distributed to control cell fate; experimental proof came from using frog eggs (Roux, 1888). After understanding the contribution of the nucleus and the chromosomes into cell cycle progression using sea urchin eggs (Boveri, 1902), it was the discovery of the cytoplasm contribution to the G2/M transition that led the cell cycle community in search of the "mitosis-inducing factor", MPF. Yoshio Masui was the first to experimentally demonstrate that few nanoliters of cytoplasm taken from a metaphase-arrested oocyte and microinjected in a G2-arrested oocyte was able to trigger the G2 to metaphase transition (Masui and Markert, 1971). Although the way to identify the mitotic factor seemed obvious, it proved very hard and was not purified until 1988 (Lohka et al, 1988), then work from a variety of organisms including Xenopus, starfish, clams, sea urchins and yeast converged on the identification of MPF as a complex of cdc2 and cyclin B (Dunphy et al, 1988; Gautier et al., 1988; Draetta et al., 1889; Meijer et al., 1989; Labbé et al., 1989; Gautier et al., 1990). Since then, the oocyte and egg extracts developed by Lohka and Masui have often been used to study cell cycle events such as nuclear envelop formation, chromatin condensation, DNA replication, repair, and recombination, Golgi formation, microtubule dynamics, spindle assembly, chromosome segregation as well as cell cycle controls.     

Properties of structured association approaches to detecting population stratification

OBJECTIVE: To examine the properties of the structured association approach for the detection and correction of population stratification. METHOD: A method is developed, within a latent class analysis framework, similar to the methods proposed by Satten et al. (2001) and Pritchard et al. (2000). A series of simulations illustrate the relative impact of number and type of loci, sample size and population structure. RESULTS: The ability to detect stratification and assign individuals to population strata is determined for a number of different scenarios. CONCLUSION: The results underline the importance of careful marker selection.