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PubMed1998

Toward the development of a universal grading system for ovarian epithelial carcinoma. I. Prognostic significance of histopathologic features--problems involved in the architectural grading system.

OBJECTIVE: Because there is no universally accepted grading system for ovarian epithelial carcinoma, we attempted to compare the prognostic utility of the individual components used in some systems--both architectural and cytologic features, as well as mitotic activity and histologic tumor type--to determine which of these components fit best with survival. METHODS: We studied 461 patients with invasive ovarian carcinoma who had uniform treatment, complete clinical data including staging and follow-up, and slides available for review. Each tumor was assigned a histologic subtype, architectural grade (based on whether the predominant pattern was glandular, papillary or solid), nuclear grade, mitotic count, and FIGO grade (based on the system for endometrial carcinoma). These features were compared with each other and with tumor stage and survival. RESULTS: The architectural grade, nuclear grade, and mitotic count were independent variables both in stage I/II and stage III/IV disease. Each of them correlated with survival for most combinations of histologic type and stage. By multivariate analysis, in stage I/II cancer, nuclear grade and architectural grade were significantly correlated with survival, mitotic count showed only a trend, and FIGO grade did not correlate. In stage III/IV disease, nuclear grade, architectural grade 3, and mitotic count were significant, and FIGO grade was not. CONCLUSION: The new architectural grading system proposed worked better than the FIGO system in this study. Furthermore, it could be applied to all histologic subtypes of carcinoma. The nuclear grade and mitotic count were also independent of each other, correlated with survival, and could be utilized for all histologic types. These data support the development of a grading system which combines these architectural, nuclear, and mitotic features and can be applied regardless of the histologic type of carcinoma, modeled after the Nottingham system for grading of breast carcinoma.

Carcinoma↗

PubMed2003

Genetic mapping of QTLs affecting productivity and plant architecture in a full-sib cross from non-inbred parents in Cassava (Manihot esculenta Crantz).

An attempt was made to identify quantitative trait loci (QTLs) for several productivity and plant architecture traits in a full-sib progeny of 144 individuals from two non-inbred parents in cassava. A molecular linkage map of this cross constructed previously with over 250 markers was the source of molecular markers. The progeny were grown under field conditions at two locations (Palmira and Quilichao) in Colombia and evaluated in 2 years (1998 and 1999) for architecture and productivity traits. Architecture traits evaluated were plant height (PH), branching height (BH), branching levels (BL), branching index (BI), stem portion with leaves (SPL) and leaf area index (LAI). Productivity traits were those related to total dry matter production and distribution, namely fresh root yield (FRY), fresh shoot yield (FSY), harvest index (HI) and the number of storage roots (NR). Phenotypic evaluation of the traits in this population revealed continuous variation for all traits. Broad-sense heritability estimates, ranged from 36% (for NR) to 94% (for BH). Several significant phenotypic correlations were observed between architecture and productivity traits. Primary QTLs, using the single-QTL model, and secondary QTLs, by a primary QTL interaction model, were detected by interval mapping. A total of 30 primary QTLs and 84 secondary QTLs were detected. We identified 35% of detected QTLs in two or more trials, the other QTLs were environment-specific. These results underscore the significant genotype x environment interactions found for most of the traits. Several genomic segments affecting multiple traits were identified and were in agreement with correlation among traits. All QTLs identified for FRY were found associated with either component traits of productivity or architecture traits. This study suggests that QTLs for plant architecture can be used to improve productivity. However an exhaustive search and analysis of QTLs controlling architecture is required before marker-assisted selection (MAS) for increasing productivity can be initiated.

Crosses, Genetic↗

PubMed2003

Risedronate preserves bone architecture in early postmenopausal women in 1 year as measured by three-dimensional microcomputed tomography.

Risedronate reduces the risk of vertebral fractures by up to 70% within the first year of treatment. Increases in bone mineral density or decreases in bone turnover markers explain only a portion of the anti-fracture effect, suggesting that other factors, such as changes in trabecular bone architecture, also play a role. Our objective was to determine the effects of risedronate on bone architecture by analyzing iliac crest bone biopsy specimens using three-dimensional microcomputed tomography (3-D micro CT). Biopsy specimens were obtained at baseline and after 1 year of treatment from women enrolled in a double-blind, placebo-controlled study of risedronate 5 mg daily for the prevention of early postmenopausal bone loss. Trabecular architecture deteriorated in the placebo group (n = 12), as indicated by a 20.3% decrease in bone volume (25.1% vs. 20.0%, P = 0.034), a 13.5% decrease in trabecular number (1.649 vs. 1.426 mm(-1), P = 0.052), a 13.1% increase in trabecular separation (605 vs. 684 microm, P = 0.056), and an 86.2% increase in marrow star volume (3.251 vs. 6.053 mm(3), P = 0.040) compared with baseline values. These changes in architectural parameters occurred in the presence of a concomitant decrease from baseline in lumbar spine bone mineral density (-3.3%, P = 0.002), as measured by dual energy x-ray absorptiometry. There was no statistically significant ( P < 0.05) deterioration in the risedronate-treated group (n = 14) over the 1-year treatment period. Comparing the actual changes between the two groups, the placebo group experienced decreases in bone volume (placebo, -5.1%; risedronate, +3.5%; P = 0.011), trabecular thickness (placebo, -20 microm; risedronate, +23 microm; P = 0.032), and trabecular number (placebo, -0.223 mm(-1); risedronate, +0.099 mm(-1); P = 0.010), and increases in percent plate (placebo, +2.79%; risedronate, -3.23%; P = 0.018), trabecular separation (placebo, +79 microm; risedronate, -46 microm; P = 0.010) and marrow star volume (placebo, +2.80 mm(3); risedronate, -2.08mm(3); P = 0.036), compared with the risedronate group. These data demonstrate that trabecular architecture deteriorated significantly in this cohort of early postmenopausal women, and that this deterioration was prevented by risedronate. Although there is no direct link in this study between fracture and preservation of architecture, it is reasonable to infer that the preservation of bone architecture may play a role in risedronate's anti-fracture efficacy.

Absorptiometry, Photon↗

PubMed1999

Correlating architectural disorder and cytologic atypia in Clark (dysplastic) melanocytic nevi.

Histological architecture is very important in the pathological diagnosis of Clark (also known as atypical or dysplastic) melanocytic nevi. However, few studies have attempted to quantify architectural features or to correlate them directly with cytology. In 166 consecutive Clark nevi, the presence or absence of the following features in the intraepidermal or junctional component was recorded: (1) Architecture: circumscription, symmetry, cohesiveness of nests, suprabasal melanocytes, confluence, and single-cell proliferation; (2) Cytology of melanocytes: round/euchromatic nuclei, nuclear enlargement, cell enlargement, and prominent nucleoli. Each criterion was given a value of 0 or 1, and a summation score was obtained for both architecture and cytology in each case. The chi-square test was used to determine the significance of relationships among these parameters. The degrees of architectural disorder and of cytologic atypia were positively correlated (P = .026). Scores for both parameters were distributed over a wide range of values and were concentrated toward the low-middle portion of the spectrum. Several particular architectural and cytologic variables showed significant interdependence. Clark nevi exhibit a broad spectrum of architectural disorder and cytologic atypia, which, according to our data, generally are closely related features. Because some cases displayed a relatively high score for one parameter but a low score for the other, quantification of both parameters permits a more complete histopathologic evaluation of these lesions and may provide additional information for their clinical management.

Adolescent↗

PubMed1999

Possible mechanisms through which dietary pectin influences fibrin network architecture in hypercholesterolaemic subjects.

It is suspected that not only fibrinogen concentration but also the quality of fibrin networks may contribute to cardiovascular risk. Evidence is accumulating that a "prudent" diet may protect against diseases associated with raised clotting factors. The effect of diet on fibrinogen is, however, still controversial. In a previous study performed in our laboratory, it was shown that dietary pectin influences fibrin network architecture in hypercholesterolaemic men without causing any changes in fibrinogen concentration. To elucidate the possible mechanisms, it was necessary to study the possibility that pectin may itself have indirect effects on fibrin network architecture. Pectin is fermented in the gastrointestinal tract to acetate, propionate, and butyrate. In humans, only acetate reaches the circulation beyond the liver. This investigation primarily examined the possibility that pectin may, through acetate, influence fibrin network architecture in vivo. The effects of pectin and acetate supplementation in hypercholesterolaemic subjects were compared. Furthermore, this study also aimed at describing the possible in vitro effects of acetate on fibrin network architecture. Two groups of 10 male hyperlipidaemic volunteers each received a pectin (15 g/day) or acetate (6.8 g/day) supplement for 4 weeks. Acetate supplementation did not cause a significant change in plasma fibrinogen levels. As in the pectin group, significant differences were found in the characteristics of fibrin networks developed in plasma after 4 weeks of acetate supplementation. Fibrin networks were more permeable (from 213+/-76 to 307+/-81 x 10(11) cm2), had lower tensile strength (from 23+/-3 to 32+/-9% compaction), and were more lyseable (from 252+/-11 to 130+/-15 minutes). These results strongly suggest that the effect of pectin on network architecture could partially be mediated by acetate. Progressive amounts of acetate were used in vitro to investigate the possibility that acetate may be directly responsible for changes that occurred in fibrin network architecture in the plasma medium. Results indicated that acetate influenced fibrin network architecture directly. From the results, it seems highly possible that acetate may be responsible in part for the beneficial effects of pectin supplementation in vivo. It is evident that pectin or acetate supplementation can be useful during the treatment or prevention of some clinical manifestations, especially those associated with raised total cholesterol and possibly also plasma fibrinogen.

Adult↗

PubMed1996

Comparison of cytomorphological and architectural heterogeneity in mammographically-detected ductal carcinoma in situ.

Many classification schemes have been proposed for ductal carcinoma in situ. Architectural heterogeneity is widely recognized. Cytonuclear grade appears to have greater prognostic significance than architectural pattern. This study assesses heterogeneity using a classification based on cytological grade and compares this to architectural heterogeneity in mammographically detected ductal carcinoma in situ. One hundred and twelve cases were classified according to architectural subtypes and the carcinoma nuclei were graded. Necrosis and microcalcification were assessed. Eighty-four percent of ductal carcinomas in situ had a single nuclear grade, whereas only 39% showed a single architectural pattern. High grade nuclei were present in 87% of cases. Necrosis was associated with high nuclear grade. In contrast to architectural heterogeneity, this study shows little ductal carcinoma in situ heterogeneity when classification is based on nuclear grade. Thus, a cytomorphological classification should have the advantage of consistency and reproducibility in comparison to architecture-based classification systems.

Aged↗

PubMed1992

An evolutionary Wolff's law for trabecular architecture.

A continuum model is proposed to describe the temporal evolution of both the density changes and the reorientation of the trabecular architecture given the applied stress state in the bone and certain material parameters of the bone. The data upon which the proposed model is to be based consist of experimentally determined remodeling rate coefficients and quantitative stereological and anisotropic elastic constant measurements of cancellous bone. The model shows that the system of differential equations governing the temporal changes in architecture is necessarily nonlinear. This nonlinearity is fundamental in that it stems from the fact that, during remodeling, the relationship between stress and strain is changing as the stress and strain variables themselves are changing. In order to preserve the remodeling property of the model, terms that are of the order strain times the changes in density and/or microstructural properties must be retained. If these terms were dropped, there would be no feedback mechanism for architectural adaptation and no adaptation of the trabecular architecture. There is, therefore, no linearized version of the model of the temporal evolution of trabecular architecture. An application of the model is illustrated by an example problem in which the temporal evolution of homogeneous trabecular architecture is predicted. A limitation of the proposed continuum model is the length scale below which it cannot be applied. The model cannot be applied in regions of cancellous bone where the trabecular bone architecture is relatively inhomogeneous or at a bone-implant interface.

Bone Density↗

PubMed1997

Cytological and architectural heterogeneity in ductal carcinoma in situ of the breast.

AIM: The traditional architecture based classification system of ductal carcinoma in situ (DCIS) has been criticised on the grounds that individual lesions often show more than one pattern resulting in a large mixed category. New DCIS classification systems have emphasised the importance of cytological grade, which is reputed to be more uniformly expressed throughout a lesion. This study investigates the hypothesis that cytological heterogeneity is less common than architectural heterogeneity within DCIS lesions. METHODS: 121 cases of DCIS were graded as poorly, intermediately, or well differentiated according to a recently developed classification system that employs cytonuclear morphology as the major diagnostic criterion. Cases were categorised as pure when only one grade was present and as mixed if more than one grade was observed. Architecturally the cases were classified as solid, cribriform, micropapillary, or papillary and were described as pure if only one architectural pattern was present and as mixed if more than one pattern was seen. The incidence of cytological heterogeneity was compared with that of architectural heterogeneity. The presence of necrosis was assessed as an independent parameter and the relation to DCIS grade evaluated. RESULTS: Using the cytology based classification system 102 cases (84%) were classified as pure (65 poorly differentiated, 25 intermediately differentiated, and 12 well differentiated) and 19 cases (16%) as mixed. Extensive necrosis was observed in 61 (50%) cases and was closely correlated to DCIS grade. Architecturally 46 cases (38%) were classified as pure (38 solid, 5 cribriform, 2 micropapillary, and 1 papillary) and 75 (62%) as mixed. CONCLUSIONS: Cytological heterogeneity is much less common than architectural heterogeneity in DCIS lesions. The assessment of cytonuclear morphology is therefore likely to provide more consistent information about DCIS, particularly in small biopsy specimens where only part of the lesion may be available for examination.

Adult↗

PubMed2003

Computer-aided detection (CAD) in screening mammography: sensitivity of commercial CAD systems for detecting architectural distortion.

OBJECTIVE: Computer-aided detection (CAD) algorithms have successfully revealed breast masses and microcalcifications on screening mammography. The purpose of our study was to evaluate the sensitivity of commercially available CAD systems for revealing architectural distortion, the third most common appearance of breast cancer. MATERIALS AND METHODS: Two commercially available CAD systems were used to evaluate screening mammograms obtained in 43 patients with 45 mammographically detected regions of architectural distortion. For each CAD system, we determined the sensitivity for revealing architectural distortion on at least one image of the two-view mammographic examination (case sensitivity) and for each individual mammogram (image sensitivity). Surgical biopsy results were available for each case of architectural distortion. RESULTS: Architectural distortion was deemed present and actionable by a panel of expert breast imagers in 80 views of the 45 cases. One CAD system detected distortion in 22 of 45 cases of distortion (case sensitivity, 49%) and in 30 of 80 mammograms (image sensitivity, 38%); it displayed 0.7 false-positive marks per image. Another CAD system identified distortion in 15 of 45 cases (case sensitivity, 33%) and 17 of 80 mammograms (image sensitivity, 21%); it displayed 1.27 false-positive marks per image. Sensitivity for malignancy-caused distortion was similar to or lower than sensitivity for all causes of distortion. CONCLUSION: Fewer than one half of the cases of architectural distortion were detected by the two most widely available CAD systems used for interpretations of screening mammograms. Considerable improvement in the sensitivity of CAD systems is needed for detecting this type of lesion. Practicing breast imagers who use CAD systems should remain vigilant for architectural distortion.

Adult↗

PubMed2000

Chromosome territories, interchromatin domain compartment, and nuclear matrix: an integrated view of the functional nuclear architecture.

Advances in the specific fluorescent labeling of chromatin in fixed and living human cells in combination with three-dimensional (3D) and 4D (space plus time) fluorescence microscopy and image analysis have opened the way for detailed studies of the dynamic, higher-order architecture of chromatin in the human cell nucleus and its potential role in gene regulation. Several features of this architecture are now well established: 1. Chromosomes occupy distinct territories in the cell nucleus with preferred nuclear locations, although there is no evidence of a rigid suprachromosomal order. 2. Chromosome territories (CTs) in turn contain distinct chromosome arm domains and smaller chromatin foci or domains with diameters of some 300 to 800 nm and a DNA content in the order of 1 Mbp. 3. Gene-dense, early-replicating and gene-poor, middle-to-late-replicating chromatin domains exhibit different higher-order nuclear patterns that persist through all stages of interphase. In mitotic chromosomes early replicating chromatin domains give rise to Giemsa light bands, whereas middle-to-late-replicating domains form Giemsa dark bands and C-bands. In an attempt to integrate these experimental data into a unified view of the functional nuclear architecture, we present a model of a modular and dynamic chromosome territory (CT) organization. We propose that basically three nuclear compartments exist, an "open" higher-order chromatin compartment with chromatin domains containing active genes, a "closed" chromatin compartment comprising inactive genes, and an interchromatin domain (ICD) compartment (Cremer et al., 1993; Zirbel et al., 1993) that contains macromolecular complexes for transcription, splicing, DNA replication, and repair. Genes in "open," but not in "closed" higher-order chromatin compartments have access to transcription and splicing complexes located in the ICD compartment. Chromatin domains that build the "open" chromatin compartment are organized in a way that allows the direct contact of genes and nascent RNA to transcription and splicing complexes, respectively, preformed in the ICD compartment. In contrast, chromatin domains that belong to the "closed" compartment are topologically arranged and compacted in a way that precludes the accessibility of genes to transcription complexes. We argue that the content of the ICD compartment is highly enriched in DNA depleted biochemical matrix preparations. The ICD compartment may be considered as the structural and functional equivalent of the in vivo nuclear matrix. A matrix in this functional sense is compatible with but does not necessitate the concept of a 3D nuclear skeleton existing of long, extensively arborized filaments. In the absence of unequivocal evidence for such a structural matrix in the nucleus of living cells we keep an agnostic attitude about its existence and possible properties in maintaining the higher-order nuclear architecture. Quantitative modeling of the 3D and 4D human genome architecture in situ shows that such an assumption is not necessary to explain presently known aspects of the higher-order nuclear architecture. We expect that the interplay of quantitative modeling and experimental tests will result in a better understanding of the compartmentalized nuclear architecture and its functional consequences.

Animals↗

PubMed2001

Intervertebral disc disorganisation and its relationship to age adjusted vertebral body morphometry and vertebral bone architecture.

Vertebral deformity, intervertebral disc disorganisation, and change to vertebral bone architecture are morphological features that are associated with low back pain. The purpose of this study was to examine the influence of the morphological disorganisation of the intervertebral disc on vertebral body shape indices and vertebral cancellous bone architecture. Lumbar spines, T12-S1, were collected from 27 cadavers. The motion segments T12-L1, L2-L3 and L4-L5 were selected for the study. There were 8 females aged 35-94 years and 19 males aged 20-90 years. An intervertebral disc grade signifying the severity of disc disorganisation was assigned to each disc using the macroscopic disc grading criteria of Hansson and Roos (Spine, 1981; 6:147-153.). Vertebral shape indices and vertebral body bone histomorphometric analyses were performed on the vertebral bodies. Where appropriate, data were age adjusted and the influence of morphological disc disorganisation on vertebral body deformity and cancellous bone architecture analysed. Increased vertebral body axial area and the ratio of vertebral body axial area to sagittal area were associated with an increase in vertebral deformity and disc disorganisation. This suggests that vertebral deformity that remains clinically silent in the general population is influenced by intervertebral disc disorganisation. Vertebral cancellous bone architecture undergoes change associated with increased disc disorganisation, consistent with increased vertebral deformity. Vertebral bodies adjacent to degenerate discs (Grade 4) showed increased BV/TV and Tb.Th and decreased BS/BV. This shows that disc disorganisation may modulate vertebral cancellous bone architecture such that it protects against age-related bone changes. In addition, vertebral body wedging and concavity are associated with smaller vertebral body size and vertebral body compression is associated with larger vertebral body size and compromised cancellous bone architecture.

Adult↗

PubMed2000

Synthetic nano-fibrillar extracellular matrices with predesigned macroporous architectures.

Scaffolding plays a pivotal role in tissue engineering. To mimic the architecture of a natural extracellular matrix component-collagen, nona-fibrous matrices have been created with synthetic biodegradable polymers in our laboratory using a phase-separation technique. To improve the cell seeding, distribution, mass transport, and new tissue organization, three-dimensional macroporous architectures are built in the nano-fibrous matrices. Water-soluble porogen materials are first fabricated into three-dimensional negative replicas of the desired macroporous architectures. Polymer solutions are then cast over the porogen assemblies in a mold, and are thermally phase-separated to form nano-fibrous matrices. The porogen materials are leached out with water to finally form the synthetic nano-fibrous extracellular matrices with predesigned macroporous architectures. In this way, synthetic polymer matrices are created with architectural features at several levels, including the anatomical shape of the matrix, macroporous elements (100 microm to millimeters), interfiber distance (microns), and the diameter of the fibers (50-500 nm). These scaffolding materials circumvent the concerns of pathogen transmission and immuno-rejection associated with natural collagen. With the flexibility in the design of chemical structure, molecular weight, architecture, degradation rate, and mechanical properties, these novel synthetic matrices may serve as superior scaffolding for tissue engineering.

Artificial Organs↗

PubMed2001

Three-dimensional microimaging (MRmicroI and microCT), finite element modeling, and rapid prototyping provide unique insights into bone architecture in osteoporosis.

With the proportion of elderly people increasing in many countries, osteoporosis has become a growing public health problem, with rising medical, social, and economic consequences. It is well recognized that a combination of low bone mass and the deterioration of the trabecular architecture underlies osteoporotic fractures. A comprehensive understanding of the relationships between bone mass, the three-dimensional (3D) architecture of bone and bone function is fundamental to the study of new and existing therapies for osteoporosis. Detailed analysis of 3D trabecular architecture, using high-resolution digital imaging techniques such as magnetic resonance microimaging (MRmicroI), micro-computed tomography (microCT), and direct image analysis, has become feasible only recently. Rapid prototyping technology is used to replicate the complex trabecular architecture on a macroscopic scale for visual or biomechanical analysis. Further, a complete set of 3D image data provides a basis for finite element modeling (FEM) to predict mechanical properties. The goal of this paper is to describe how we can integrate three-dimensional microimaging and image analysis techniques for quantitation of trabecular bone architecture, FEM for virtual biomechanics, and rapid prototyping for enhanced visualization. The integration of these techniques provide us with an unique ability to investigate the role of bone architecture in osteoporotic fractures and to support the development of new therapies.

Aged↗

PubMed2002

The geometric architecture of the subtalar and midtarsal joints in rheumatoid arthritis based on magnetic resonance imaging.

OBJECTIVE: To compare in vivo the 3-dimensional (3-D) geometric architecture of the subtalar and midtarsal joints in normal and rheumatoid arthritic (RA) feet, using magnetic resonance imaging (MRI) analysis. METHODS: MRI was performed on 23 patients with RA, all of whom had disease activity in the subtalar and/or midtarsal joints. Image processing techniques were used to create 3-D reconstructions of the calcaneus (C), cuboid (c), navicular (N), and talus (T) bones. Twenty-four standard architectural parameters were measured from the reconstructions and were compared with data from 10 normal subjects. These parameters defined both 3-D distance and angular relationships among the 4 bones studied. Pattern classification techniques were used to establish a geometric architecture foot profile for the RA patients. The degree of individual patient fit to the new RA foot profile and to profiles for normal, pes planus, and pes cavus foot types was derived. Logistic regression was used to examine the relationship of foot architecture to inflammatory disease characteristics and physical examination variables. RESULTS: Subtalar or midtarsal pain was reported by all 23 patients, and 22 of the 23 patients presented with >/=1 clinical feature of pes planovalgus deformity. In 21 patients, ultrasonography revealed synovitis at >/=1 tarsal joint or surrounding tendon. In the RA group, the normalized distances between the geometric centroids were significantly closer for bone pairs Cc and cT and significantly distracted for bone pair CN compared with the distances in normal subjects. In RA patients (versus normal subjects), the angles subtended at the bone centroids were significantly decreased in 3 bone groups (CNc, TCN, and TNc) and significantly increased in 3 bone groups (CcN, CcT, NTc). The angles formed between the major principal axes of bone pairs CT and cT were significantly increased in RA patients compared with those in normal subjects. Pattern classification defined 11 RA feet as having normal structure and 12 as having abnormal structure. However, the abnormal feet did not fit consistently with structures defined for RA, pes planus, or pes cavus foot types. Logistic regression demonstrated that subtalar joint synovitis was the only predictive factor for abnormal subtalar and midtarsal architecture (odds ratio 19.2, 95% confidence interval 1.77-200.0). CONCLUSION: This unique 3-D MRI-based technique successfully quantified the effects of RA on the geometric architecture of the foot and the patient-specific nature of these changes. This technique can be used to provide logical therapy for correction.

Adult↗

PubMed1999

[Age and aging as incomplete architecture of human ontogenesis].

The focus is on the basic biological-genetic and social-cultural architecture of human development across the life span. The starting point is the frame provided by past evolutionary forces. A first conclusion is that for modern times and the relative brevity of the time windows involved in modernity, further change in human functioning is primarily dependent on the evolution of new cultural forms of knowledge rather than evolution-based changes in the human genome. A second conclusion concerns the general architecture of the life course. Three governing lifespan developmental principles coexist. First, because long-term evolutionary selection evince a negative age correlation, genome-based plasticity and biological potential decrease with age. Second, for growth aspects of human development to extend further into the life span, culture-based resources are required at ever increasing levels. Third, because of age-related losses in biological plasticity and negative effects associated with some principles of learning (e.g., negative transfer), the efficiency of culture is reduced as lifespan development unfolds. Joint application of these principles suggests that the lifespan architecture becomes more and more incomplete with age. Three examples are given to illustrate the implications of the lifespan architecture outlined. The first is a general theory of development involving the orchestration of three component processes and their age-related dynamics: Selection, optimization, and compensation. The second example is theory and research on lifespan intelligence that distinguishes between the biology-based mechanics and culture-based pragmatics of intelligence and specifies distinct age gradients for the two categories of intellectual functioning. The third example considers the goal of evolving a positive biological and cultural scenario for the last phase of life (fourth age). Because of the general lifespan architecture outlined, this objective becomes increasingly difficult to achieve. In fact, for other reasons (such as the obsolescence created by rapid technological change) the 21st century can be considered as the century of the permanently incomplete mind. The advent of intervention genetics creates a new scenario with promise and despair. Promise because of the possibility to complete the biological-genetic architecture of the life course through a priori and a posteriori genetic engineering, despair because of a new schism created by the risk of dissociation of the time course of genetic intervention and cultural evolution. For the first time in history, humankind is truly in charge of it's biocultural "natural" destiny.

Age Factors↗

PubMed1996

Dynamic relationships of trabecular bone density, architecture, and strength in a computational model of osteopenia.

A computational model was developed to study the effects of short- and long-term periods of disuse osteopenia and repair to elucidate the interrelationships between bone mass, architecture, and strength. The model is one in which the sequence of structural change events is followed in time. This temporal feature contrasts with studies of real trabecular tissue which are necessarily cross-sectional in nature and do not lend themselves to insights into the dynamic nature of the structural changes with time. In the model it was assumed that the stimulus for bone adaptation to mechanical load is the local mechanical strain rate, according to which the trabecular surfaces are differentially formed and resorbed. The effects of mechanical loading and unloading (disuse) on the cancelous bone properties were studied. The bone mass, architecture, and elastic stiffness were shown to be strongly dependent upon the period of the unloading phase, as well as the period of the reloading phase. Mechanical stiffness is demonstrated computationally to be a multivalued function of bone mass, if architecture is not accounted for. The model shows how the same value of trabecular bone mass can be associated with two or more distinct values of biomechanical stiffness. This result is the first explicit demonstration of how bone mass, architecture, and strength are related under dynamical load-bearing conditions. The results explain the empirical observation that bone mass can account for about 65% of the observed variation in bone strength, but that by incorporating measures of bony architecture into the analysis, the predictability is increased to 94%. The computational model may be used to explore the effects of different loading regimes on mass, architecture, and strength, and potentially for assistance in designing both animal and clinical bone loss studies.

Adaptation, Physiological↗

PubMed1997

A Bayesian Approach to Model Selection in Hierarchical Mixtures-of-Experts Architectures.

There does not exist a statistical model that shows good performance on all tasks. Consequently, the model selection problem is unavoidable; investigators must decide which model is best at summarizing the data for each task of interest. This article presents an approach to the model selection problem in hierarchical mixtures-of-experts architectures. These architectures combine aspects of generalized linear models with those of finite mixture models in order to perform tasks via a recursive "divide-and-conquer" strategy. Markov chain Monte Carlo methodology is used to estimate the distribution of the architectures' parameters. One part of our approach to model selection attempts to estimate the worth of each component of an architecture so that relatively unused components can be pruned from the architecture's structure. A second part of this approach uses a Bayesian hypothesis testing procedure in order to differentiate inputs that carry useful information from nuisance inputs. Simulation results suggest that the approach presented here adheres to the dictum of Occam's razor; simple architectures that are adequate for summarizing the data are favored over more complex structures. Copyright 1997 Elsevier Science Ltd. All Rights Reserved.

Journal Article↗

PubMed1997

Three-dimensional methods for quantification of cancellous bone architecture.

Recent development in three-dimensional (3-D) imaging of cancellous bone has made possible true 3-D quantification of trabecular architecture. This provides a significant improvement of the tools available for studying and understanding the mechanical functions of cancellous bone. This article reviews the different techniques for 3-D imaging, which include serial sectioning, X-ray tomographic methods, and NMR scanning. Basic architectural features of cancellous bone are discussed, and it is argued that connectivity and architectural anisotropy (fabric) are of special interest in mechanics-architecture relations. A full characterization of elastic mechanical properties is, with traditional mechanical testing, virtually impossible, but 3-D reconstruction in combination with newly developed methods for large-scale finite element analysis allow calculations of all elastic properties at the cancellous bone continuum level. Connectivity has traditionally been approached by various 2-D methods, but none of these methods have any known relation to 3-D connectivity. A topological approach allows unbiased quantification of connectivity, and this further allows expressions of the mean size of individual trabeculae, which has previously also been approached by a number of uncertain 2-D methods. Anisotropy may be quantified by fundamentally different methods. The well-known mean intercept length method is an interface-based method, whereas the volume orientation method is representative of volume-based methods. Recent studies indicate that volume-based methods are at least as good as interface-based methods in predicting mechanical anisotropy. Any other architectural property may be quantified from 3-D reconstructions of cancellous bone specimens as long as an explicit definition of the property can be given. This challenges intuitive and vaguely defined architectural properties and forces bone scientists toward 3-D thinking.

Anisotropy↗