Biomedical subjects

Fred L Bookstein

Publications and source records attributed to Fred L Bookstein.

At least 19 recordsLinked to original sources

PubMed2006

Preserved CD4+ central memory T cells and survival in vaccinated SIV-challenged monkeys.

Vaccine-induced cellular immunity controls virus replication in simian immunodeficiency virus (SIV)-infected monkeys only transiently, leading to the question of whether such vaccines for AIDS will be effective. We immunized monkeys with plasmid DNA and replication-defective adenoviral vectors encoding SIV proteins and then challenged them with pathogenic SIV. Although these monkeys demonstrated a reduction in viremia restricted to the early phase of SIV infection, they showed a prolonged survival. This survival was associated with preserved central memory CD4+ T lymphocytes and could be predicted by the magnitude of the vaccine-induced cellular immune response. These immune correlates of vaccine efficacy should guide the evaluation of AIDS vaccines in humans.

Amino Acid Sequence↗

PubMed2006

Dental arch asymmetry in an isolated Adriatic community.

Developmental stability reflects the ability of a genotype to develop in the same way under varying environmental conditions. Deviations from developmental stability, arising from disruptive effects of environmental and genetic stresses, can be measured in terms of fluctuating asymmetry, a particularly sensitive indicator of the ability to cope with these stresses during ontogeny. In an inbred Adriatic island population, we expected dental arch fluctuating asymmetry 1) to be higher than in an outbred sample from the same island, and 2) within this population, to increase with the level of inbreeding. Due to environmental stress, we also expected to find higher fluctuating asymmetry in the outbred island population than in an urban reference group from the same country. The material consisted of 506 dental casts of 253 children from 1) the island of Hvar, and 2) Zagreb, Croatia. Three-dimensional coordinates of 26 landmarks spanning the arches were digitized. The analysis partitioned the asymmetry of arch forms into components for directional and fluctuating bilateral asymmetry, using the appropriate Procrustes method (geometric morphometrics). The results corroborated the hypotheses. Fluctuating asymmetry was found to be higher on the island than in Zagreb in all groups and in both jaws, and increased significantly with endogamy level in the lower jaw. There was no significant directional asymmetry in the Zagreb sample and likewise none in the upper jaws of the outbred island group, but significant directional asymmetry in both jaws of the inbred population and also in the lower jaws of the outbred island group. These results suggest an environmental as well as a genetic influence on dental arch asymmetry. Although the lower jaws expressed these two stresses almost additively, the upper jaws appeared to be better buffered. The role of directional asymmetry as a potential indicator of craniofacial developmental instability clearly merits further attention.

Adolescent↗

PubMed2006

Functional morphology of the first cervical vertebra in humans and nonhuman primates.

The cervical vertebral column bears or balances the weight of the head supported by the nuchal muscles that partly originate from the cervical vertebrae. The position of the head relative to the vertebral column, and consequently locomotion and posture behavior, could thus be associated with the form of the cervical vertebrae. In spite of this assumption and some empirical indications along these lines, primate vertebral morphologies have been reported to be very similar and not clearly related to locomotion. We therefore study the relationship between the morphology of the first cervical vertebra, the atlas, and the locomotion pattern within primates using a geometric morphometric approach. Our analysis is based on a total of 116 vertebrae of adult Homo sapiens, Gorilla gorilla, Pan troglodytes, Pongo pygmaeus, Hylobates lar, Macaca mulatta, Papio hamadryas, Ateles geoffroyi, and Alouatta palliata. On each atlas, 56 landmarks were digitized and superimposed by Procrustes registration. The resulting shape variables were analyzed by principal component analysis, multivariate regression, and partial least-squares analysis. We found that the nine primate species differ clearly in their atlas morphology and that allometric shape change is distinct between the nonhuman primates and Homo sapiens. We could further identify morphological features that relate to the species' locomotion pattern. Human atlas shape, however, cannot be predicted by an extrapolation of the nonhuman primate model. This implies that either the primate atlas is generalized enough to allow bipedal locomotion or else the human atlas morphology is a unique adaptation different from that in the more orthograde nonhuman primates.

Alouatta↗

PubMed2006

Damage to the human cerebellum from prenatal alcohol exposure: the anatomy of a simple biometrical explanation.

Since 1973, it has become clear that exposure of otherwise normal human fetuses to high levels of alcohol damages a substantial number of the exposed brains in a wide variety of ways nowadays referred to collectively as the fetal alcohol spectrum disorders (FASDs). Averages of images and measurements of brains with these disorders are quantitatively different from normal, and the cerebellum is one of the structures at which differences are typically noted. The present article extends these techniques to a simple, practical, and enlightening detection rule for fetal alcohol damage in adolescents and adults known to have been heavily exposed. The data arise from 180 clinical MR brain images (half of adolescents, half of adults; half male, half female; one-third each fetal alcohol syndrome, fetal alcohol effects, and unexposed). The 180 cerebellums were represented by 328-semilandmark triangulations covering most of the cerebellar surface. Statistical analysis exploited the now-conventional methods of Procrustes analysis in three dimensions, along with a recent extension to incorporate size information explicitly. If we reduce the data complexity even further, to just 23 points along the silhouette of the cerebellum as viewed from above along the aqueductal axis, the analysis becomes more precise. Now a single multivariate summary score, very strongly correlated with size, supports a discrimination (diagnosed vs. unexposed) with about 75% accuracy. About one-quarter of our FASD sample overlaps with the central range of the unexposed in the distribution of this size-based score, with the other three-quarters distinctly showing cerebellar damage. The finding, which corresponds quite closely to the fundamental finding of cerebellar hypoplasia in animal experiments, bears implications for fetal alcohol epidemiology, for geometric morphometrics, and for the geometric complexity of useful data structures derived from clinical brain imaging.

Adolescent↗

PubMed2006

Binge drinking during pregnancy as a predictor of psychiatric disorders on the Structured Clinical Interview for DSM-IV in young adult offspring.

OBJECTIVE: This study explored the extent to which the high frequency of psychiatric problems reported in clinical groups with fetal alcohol spectrum disorders might also be observed in a nonclinical group of young adults and the psychiatric conditions that are related to prenatal alcohol exposure in this group. METHOD: From a longitudinal prospective study beginning with interviews of 1,529 pregnant women, a birth cohort of about 500 newborns was chosen to include all of the most heavily alcohol exposed plus a sampling of the continuum of alcohol exposures from total abstinence through heavy drinking. At an average age of 25.7 years, 400 members of this birth cohort were administered valid Structured Clinical Interviews for DSM-IV (SCID), including both the SCID for axis I disorders and the SCID for axis II personality disorders. RESULTS: The odds of the appearance of six psychiatric disorders and traits were more than double in adults exposed to one or more binge alcohol episodes in utero. Three of these six odds ratios were uniformly stable against confounding: axis I substance dependence or abuse disorders and axis II passive-aggressive and antisocial personality disorders or traits. CONCLUSIONS: Prenatal exposure to alcohol may be a risk factor for specific psychiatric disorders and traits in early adulthood, even in a nonclinical group.

Adolescent↗

PubMed2005

Second to fourth digit ratio and face shape.

The average human male face differs from the average female face in size and shape of the jaws, cheek-bones, lips, eyes and nose. It is possible that this dimorphism is determined by sex steroids such as testosterone (T) and oestrogen (E), and several studies on the perception of such characteristics have been based on this assumption, but those studies focussed mainly on the relationship of male faces with circulating hormone levels; the corresponding biology of the female face remains mainly speculative. This paper is concerned with the relative importance of prenatal T and E levels (assessed via the 2D : 4D finger length ratio, a proxy for the ratio of T/E) and sex in the determination of facial form as characterized by 64 landmark points on facial photographs of 106 Austrians of college age. We found that (i) prenatal sex steroid ratios (in terms of 2D : 4D) and actual chromosomal sex dimorphism operate differently on faces, (ii) 2D : 4D affects male and female face shape by similar patterns, but (iii) is three times more intense in men than in women. There was no evidence that these effects were confounded by allometry or facial asymmetry. Our results suggest that studies on the perception of facial characteristics need to consider differential effects of prenatal hormone exposure and actual chromosomal gender in order to understand how characteristics have come to be rated 'masculine' or 'feminine' and the consequences of these perceptions in terms of mate preferences.

Adult↗

PubMed2005

Effects of prenatal alcohol exposure on fine motor coordination and balance: A study of two adult samples.

Motor coordination was assessed in two samples of adult subjects: one sample (n = 90) included adults previously diagnosed with one of a number of Fetal Alcohol Spectrum Disorders (FASD) and comparison peers, the second was a prospective longitudinal study of adults who were exposed to varying levels of alcohol as fetuses (n = 402). This comparative analysis sought to determine whether motor effects seen in both clinical and nonclinical children persist into adulthood, whether any individual motor tasks show significant effects of prenatal alcohol exposure across the age range, and whether motor assessments of adults have any role in diagnostic strategies for adults suspected of FASD. Motor tests included balance and unilateral, bilateral, finger, hand and foot coordination. Three-quarters of the subjects with FASD demonstrated deficits in motor function outside the range of comparison subjects. Adults with FASD performed more poorly, on average, on all individual tests including balance and fine motor control. In the prospective longitudinal sample, only subjects who had been previously identified in childhood as having a possible diagnosis on the Fetal Alcohol Spectrum were still in deficit as adults on motor tasks, relative to comparison subjects. Thus, the dose-dependent motor coordination effects of alcohol previously found in children do not appear to persist into adulthood, except in those most highly exposed children who also have other accompanying neuropsychological effects in childhood.

Adult↗

PubMed2005

Preliminary evidence that prenatal alcohol damage may be visible in averaged ultrasound images of the neonatal human corpus callosum.

Brain damage consequent to prenatal alcohol exposure can be detected by measurements of the corpus callosum in the midline magnetic resonance (MR) brain image in adolescents and adults. The present article extends this finding into the neonatal period, when the power of detection to ameliorate the quality of the child's future life is greatest. The midline corpus callosum of the very young infant can be located reliably in multiple frames of clinical transfontanelle ultrasound. We studied a sample of 18 children aged 17 weeks or less, 7 of whom were exposed to high levels of alcohol prenatally and 11 of whom were not exposed or only minimally exposed. The midline callosum of each child was imaged up to 50 times by a standard clinical device, and coplanar subsets of these series were averaged with reference to fiducial image structures. On each average image four semilandmark points were set and their configuration quantified by standard landmark methods. The angle between the terminal bulb of splenium and the long axis of the callosal outline classifies four of the seven exposed infants as different from all 11 of the unexposed infants. This simple angle measurement upon averaged ultrasound images of the human neonatal midline corpus callosum, perhaps a version of the long-sought "biomarker of prenatal alcohol damage," may be able to discriminate baby brains affected by prenatal alcohol exposure from those that were unaffected.

Adult↗

PubMed2005

A three-dimensional morphometric study of craniofacial shape in schizophrenia.

BACKGROUND: Subtle dysmorphogenesis of the craniofacial region constitutes important corroborating evidence of the neurodevelopmental origins of schizophrenia. Advances in facial visualization now allow for three-dimensional anthropometric evaluations of potentially greater discriminatory power in examining the complex geometric relationships of facial topography. METHOD: Sixty-five anthropometrically derived landmarks were identified from three-dimensional facial images collected from 14 patients with schizophrenia and 11 comparison subjects, imaged with a high-resolution, portable laser scanner. RESULTS: Using the Procrustes morphometric approach for shape analysis, the difference in mean shapes was highly significant, with patients exhibiting superoinferior elongation of the face. CONCLUSIONS: The topography of craniofacial anomalies in schizophrenia is not random and points to midline deformation.

Adult↗

PubMed2005

Visualizing facial shape regression upon 2nd to 4th digit ratio and testosterone.

Sex steroids are supposed to moderate the differences between male and female facial characteristics. Studies on women's preferences for male faces reported increased preferences for facial architecture developed under the influence of testosterone as this may indicate masculinity, dominance and social status. Recent research demonstrates that facial sexual dimorphism does not only develop at puberty but may be organized much earlier in ontogeny. However, the actual cause and timing of variation in facial shape due to sex-steroids remains speculative. This study uses data from Neave and colleagues who measured digit ratio (2D:4D) as a proxy to prenatal testosterone and also salivary testosterone samples in order to study differential effects of androgens on perceived male facial shape. Male facial shape was regressed upon 2D:4D ratio and circulating levels of testosterone by means of geometric morphometric methods. We found some evidence for opposite effects of early androgen action (via 2D:4D ratio) on the upper and the lower face respectively (i.e. low 2D:4D ratio results in a relatively robust and prominent lower face), whereas circulating testosterone seems to cause a rather uniform elongation of the face. Local deformations primarily show pronounced and medially tailed eyebrows for the shapes associated with increasing salivary testosterone. These preliminary results suggest that prenatal and pubertal testosterone have differential effects on male facial shape that should be considered in future studies on women's preferences towards male facial appearance.

Adolescent↗

PubMed2004

Comparison of cranial ontogenetic trajectories among great apes and humans.

Molecular data suggest that humans are more closely related to chimpanzees than either is to the gorillas, yet one finds the closest similarity in craniofacial morphology to be among the great apes to the exclusion of humans. To clarify how and when these differences arise in ontogeny, we studied ontogenetic trajectories for Homo sapiens, Pan paniscus, Pan troglodytes, Gorilla gorilla and Pongo pygmaeus. A total of 96 traditional three-dimensional landmarks and semilandmarks on the face and cranial base were collected on 268 adult and sub-adult crania for a geometric morphometric analysis. The ontogenetic trajectories are compared by various techniques, including a new method, relative warps in size-shape space. We find that adult Homo sapiens specimens are clearly separated from the great apes in shape space and size-shape space. Around birth, Homo sapiens infants are already markedly different from the great apes, which overlap at this age but diverge among themselves postnatally. The results suggest that the small genetic differences between Homo and Pan affect early human ontogeny to induce the distinct adult human craniofacial morphology. Pure heterochrony does not sufficiently explain the human craniofacial morphology nor the differences among the African apes.

Adult↗

PubMed2004

Craniofacial sexual dimorphism patterns and allometry among extant hominids.

Craniofacial sexual dimorphism in primates varies in both magnitude and pattern among species. In the past two decades, there has been an increasing emphasis in exploring the correlations of these patterns with taxonomy and the variation in patterns within and among the craniofacial regions. Scrutinising these relationships for hominids, we decompose the craniofacial morphology in five taxa: Homo sapiens, Pan paniscus, Pan troglodytes, Gorilla gorilla and Pongo pygmaeus. 3D coordinates of 35 traditional landmarks and 61 semilandmarks, covering five ridge curves, are measured for each of 268 adult and sub-adult specimens and analysed using geometric morphometric methods. A multivariate analysis in size-shape space shows that ontogenetic scaling contributes to the development of sexual dimorphism in all five taxa, but to a varying extent. In absolute as well as in relative terms P. pygmaeus shows the greatest allometric component, followed by G. gorilla. Homo is intermediate, while in Pan the non-allometric constituent part contributes a large fraction to the actual sexual dimorphism, most markedly in the pygmy chimpanzee. An eigendecomposition of the five vectors of sexual dimorphism reveals two dimensions independent of allometry. One separates orang-utan sexual dimorphism from the African apes and Homo, and the other differentiates between the great apes and Homo with Pan mediating. We discuss these patterns and speculate on their use as characters for taxonomic analysis in the fossil record.

Animals↗

PubMed2004

Risk factors for adverse life outcomes in fetal alcohol syndrome and fetal alcohol effects.

Clinical descriptions of patients with Fetal Alcohol Syndrome (FAS) and Fetal Alcohol Effects (FAE) suggest major problems with adaptive behavior. Five operationally defined adverse outcomes and 18 associated risk/protective factors were examined using a Life History Interview with knowledgeable informants of 415 patients with FAS or FAE (median age 14 years, range 6-51; median IQ 86, range 29-126). Eighty percent of these patients were not raised by their biological mothers. For adolescents and adults, the life span prevalence was 61% for Disrupted School Experiences, 60% for Trouble with the Law, 50% for Confinement (in detention, jail, prison, or a psychiatric or alcohol/drug inpatient setting), 49% for Inappropriate Sexual Behaviors on repeated occasions, and 35% for Alcohol/Drug Problems. The odds of escaping these adverse life outcomes are increased 2- to 4-fold by receiving the diagnosis of FAS or FAE at an earlier age and by being reared in good stable environments.

Adolescent↗

PubMed2004

Anthropology takes control of morphometrics.

There has been a startling change over the last decade in the intellectual context of morphometrics. In the 1990's, this field, which has not altered its focus upon the quantitative analysis of biomedical shape variation and shape change, was principally centered around concerns of medical image analysis; but now it is driven mainly by the demands of researchers in human variability, physical anthropology, primatology, and paleoanthropology instead. This essay celebrates that change and tries to account for it by reference to cognitive and intellectual aspects of the new home.

Animals↗

PubMed2003

Cranial allometry, phylogeography, and systematics of large-bodied papionins (primates: Cercopithecinae) inferred from geometric morphometric analysis of landmark data.

The cranial morphology of the African Old World monkeys Mandrillus, Papio, and Theropithecus (i.e., baboons) has been the subject of a number of studies investigating their systematic relationships, patterns of scaling, and growth. In this study, we use landmark-based geometric morphometrics and multivariate analysis to assess the effects of size, sex, taxonomy, and geographic location on cranial shape. Forty-five landmarks were digitized in three dimensions on 452 baboon crania and subjected to generalized Procrustes analysis (GPA), which standardizes geometric size but leaves scaling-based shape differences in the data. The resulting shape coordinates were submitted to regression analysis, principal components analysis (PCA), partial least-squares (PLS) analysis, and various clustering techniques. Scaling (shape differences correlated with size) was the largest single factor explaining cranial shape variation. For instance, most (but not all) of the shape differences between the sexes were explained by size dimorphism. However, central tendencies of shape clearly varied by taxon (both specific and subspecific) even after variations in size and sex were adjusted out. Within Papio, about 60% of the size- and sex-adjusted shape variations were explained by the geographic coordinates of the specimen's provenance, revealing a stepped cline in cranial morphology, with the greatest separation between northern and southern populations. Based on evidence from genetic studies, and the presence of at least two major hybrid/interbreeding zones, we interpret the phylogeographic pattern of cranial variation as indicating that these populations are best ranked as subspecies of a single species, rather than as two or more distinct biological species. This objective approach can be applied to other vertebrate species or species groups to help determine the taxonomic rank of problematic taxa.

Africa↗

PubMed2003

Statistical estimators of frontal sinus cross section ontogeny from very noisy data.

Cross-sectional areas of human frontal sinuses in the occipitofrontal projection are a good surrogate for frontal sinus volumes. This study looks at these areas in a dataset of some 200 children and 100 adults of both sexes. As measured by planimetry of roentgenograms, the areas are extremely variable ("noisy" in a statistical sense). In fact, they appear to be distributed log-normally with quite high variance. The mean of the distribution is evidently a function of age and the variances differ by sex. After logarithmic transformation, the data are adequately fitted by one sigmoid curve for each sex. Our discussion highlights implications of this finding for the biological aspects of frontal sinuses and methodological issues in ontogenetic analysis of data so noisy.

Adult↗

PubMed2003

Cranial integration in Homo: singular warps analysis of the midsagittal plane in ontogeny and evolution.

This study addresses some enduring issues of ontogenetic and evolutionary integration in the form of the hominid cranium. Our sample consists of 38 crania: 20 modern adult Homo sapiens, 14 sub-adult H. sapiens, and four archaic Homo. All specimens were CT-scanned except for two infant H. sapiens, who were imaged by MR instead. For each specimen 84 landmarks and semi-landmarks were located on the midsagittal plane and converted to Procrustes shape coordinates. Integration was quantified by the method of singular warps, a new geometric-statistical approach to visualizing correlations among regions. The two classic patterns of integration, evolutionary and ontogenetic, were jointly explored by comparing analyses of overlapping subsamples that span ranges of different hypothetical factors. Evolutionary integration is expressed in the subsample of 24 adult Homo, and ontogenetic integration in the subsample of 34 H. sapiens. In this data set, vault, cranial base, and face show striking and localized patterns of covariation over ontogeny, similar but not identical to the patterns seen over evolution. The principal differences between ontogeny and phylogeny pertain to the cranial base. There is also a component of cranial length to height ratio not reducible to either process. Our methodology allows a separation of these independent processes (and their impact on cranial shape) that conventional methods have not found.

Adult↗

PubMed2003

Computing the uniform component of shape variation.

Any change in shape of a configuration of landmark points in two or three dimensions includes a uniform component, a component that is a wholly linear (affine) transformation. The formulas for estimating this component have been standardized for two-dimensional data but not for three-dimensional data. We suggest estimating the component by way of the complementarity between the uniform component and the space of partial warps. The component can be estimated by regression in either one space or the other: regression on the partial warps, followed by their removal, or regression on a basis for the uniform component itself. Either of the new methods can be used for both two- and three-dimensional landmark data and thus generalize Bookstein's (1996, pages 153-168 in Advances in morphometrics [L. F. Marcus et al., eds.], Plenum, New York) linearized Procrustes formula for estimating the uniform component in two dimensions.

Algorithms↗