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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↗
PubMed2005

Protein domains and architectural innovation in plant-associated Proteobacteria.

BACKGROUND: Evolution of new complex biological behaviour tends to arise by novel combinations of existing building blocks. The functional and evolutionary building blocks of the proteome are protein domains, the function of a protein being dependent on its constituent domains. We clustered completely-sequenced proteomes of prokaryotes on the basis of their protein domain content, as defined by Pfam (release 16.0). This revealed that, although there was a correlation between phylogeny and domain content, other factors also have an influence. This observation motivated an investigation of the relationship between an organism's lifestyle and the complement of domains and domain architectures found within its proteome. RESULTS: We took a census of all protein domains and domain combinations (architectures) encoded in the completely-sequenced proteobacterial genomes. Nine protein domain families were identified that are found in phylogenetically disparate plant-associated bacteria but are absent from non-plant-associated bacteria. Most of these are known to play a role in the plant-associated lifestyle, but they also included domain of unknown function DUF1427, which is found in plant symbionts and pathogens of the alpha-, beta- and gamma-Proteobacteria, but not known in any other organism. Further, several domains were identified as being restricted to phytobacteria and Eukaryotes. One example is the RolB/RolC glucosidase family, which is found only in Agrobacterium species and in plants. We identified the 0.5% of Pfam protein domain families that were most significantly over-represented in the plant-associated Proteobacteria with respect to the background frequencies in the whole set of available proteobacterial proteomes. These included guanylate cyclase, domains implicated in aromatic catabolism, cellulase and several domains of unknown function. We identified 459 unique domain architectures found in phylogenetically diverse plant pathogens and symbionts that were absent from non-pathogenic and non-symbiotic relatives. The vast majority of these were restricted to a single species or several closely related species and so their distributions could be better explained by phylogeny than by lifestyle. However, several architectures were found in two or more very distantly related phytobacteria but absent from non-plant-associated bacteria. Many of the proteins with these unique architectures are predicted to be secreted. In Pseudomonas syringae pathovar tomato, those genes encoding genes with novel domain architectures tended to have atypical GC contents and were adjacent to insertion sequence elements and phage-like sequences, suggesting acquisition by horizontal transfer. CONCLUSIONS: By identifying domains and architectures unique to plant pathogens and symbionts, we highlighted candidate proteins for involvement in plant-associated bacterial lifestyles. Given that characterisation of novel gene products in vivo and in vitro is time-consuming and expensive, this computational approach may be useful for reducing experimental search space. Furthermore we discuss the biological significance of novel proteins highlighted by this study in the context of plant-associated lifestyles.

Cluster Analysis↗
PubMed2007

Alterations of cortical and trabecular architecture are associated with fractures in postmenopausal women, partially independent of decreased BMD measured by DXA: the OFELY study.

UNLABELLED: We assessed the role of low aBMD and impaired architecture-assessed by an HR-pQCT system-in a case-control study of postmenopausal women with fractures. Vertebral and nonvertebral fractures are associated with low volumetric BMD and architectural alterations of trabecular and cortical bone, independent of aBMD assessed by DXA. INTRODUCTION: Alterations of bone architecture and low BMD both contribute to skeletal fragility, but the contribution of cortical and trabecular architecture, independently of areal BMD (aBMD), to the risk of fracture in postmenopausal women has not been thoroughly evaluated. We assessed the role of impaired architecture and low BMD in postmenopausal women with fractures. MATERIALS AND METHODS: A matched case-control study in women from the OFELY cohort was performed after 13 years of follow-up. One hundred one women (mean, 73.7+/-8 years) who sustained a fragility fracture during the follow-up of the study were age-matched with one control who never had a fracture. Density and architecture at the distal radius and tibia were measured with high-resolution pQCT (HR-pQCT) using an XTreme CT (Scanco Medical AG, Bassersdorf, Switzerland). aBMD at the total hip and ultradistal radius was measured by DXA. RESULTS: There were 80 peripheral fractures in 72 women, 44 vertebral fractures in 34 women, and both types of fractures in 5 women over the 14 years of follow-up. At the distal radius, women with fractures had lower volumetric total (D tot) and trabecular (D trab) BMDs, BV/TV, cortical thickness (Cort Th), trabecular number (TbN), and trabecular thickness (TbTh) and higher trabecular separation (TbSp) and distribution of trabecular separation (TbSpSd) than controls without fractures. In a logistic model, each SD decrease of volumetric total and trabecular densities was associated with a significantly increased risk of fracture at both sites (ORs ranged from 2.00 to 2.47). After adjusting for aBMD measured by DXA at the ultradistal radius, differences between cases and controls remained significant for D trab, and there was a similar trend for TbN, TbSp, and TbSpSd, with adjusted ORs ranging from 1.32 to 1.50. At the distal tibia, before and after adjusting for total hip aBMD, differences between cases and controls remained significant for D tot, D trab, Cort Th, and TbTh, with adjusted ORs ranging from 1.80 to 2.09. CONCLUSIONS: In postmenopausal women, vertebral and nonvertebral fractures are associated with low volumetric BMD and architectural alterations of trabecular and cortical bone that can be assessed noninvasively and that are partially independent of aBMD assessed by DXA.

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↗
PubMed2004

Migration aspects of telemedical software architectures.

Many existing medical systems are good candidates for improvement via incremental migration. Incremental software improvement is, however, much more difficult if the system consists of independent functional modules built with different technologies. The goal of this paper is to present architecture migration aspects of contemporary telemedical systems. The paper discusses two approaches: the Software Architecture Analysis Method, and the Architecture Tradeoff Analysis Method in the context of migration of the medical teleconsultation system Konsul. The system, designed and implemented under KCT activity, is being successfully employed in day-to-day activities at the John Paul II Hospital in Krakow despite many existing drawbacks in its internal architecture. The paper presents the SAAM method of analysis of legacy systems. Two architectures are proposed as a result of this analysis - one based on the migration of the existing architecture, the other built according to the state-of-the-art Service Oriented Architecture. Konsul II, implementing the migration approach, has already been developed whereas Konsul III is in the design phase. The paper concludes with remarks about migration of telemedical systems.

Computer Systems↗
PubMed2002

Architecture and trabecular bone - toward an improved understanding of the biomechanical effects of age, sex and osteoporosis.

From an engineering perspective, trabecular bone is a highly complex material, being anisotropic with different strengths in tension, compression, and shear and with mechanical properties that vary widely across anatomic sites, and with aging and disease. While mechanical properties depend very much on volume fraction, the role of architecture and tissue material properties remain uncertain. In the context of osteoporosis, there is wide interest in the biomechanical role of architecture since this should lead to improved understanding of the disease and ultimately better diagnosis and drug treatment assessment. This study reviews what is known about architectural changes in trabecular bone associated with age, gender and osteoporosis and the role of these changes in the mechanical properties of bone. Recent development of three-dimensional high-resolution imaging technologies has provided more accurate measures of quantitative metrics of architecture, thereby providing new data and raising questions about earlier conclusions. Focusing on the hip and spine, this literature is synthesized and outstanding issues are identified. In addition, the changing paradigm of biomechanical research on trabecular architecture is addressed. Because of the complexity of the trabecular micromechanics, the prevailing approach to date can be classified as an inverse one, whereby candidate metrics of architecture are developed and tested for efficacy in an empirical trial-and-error fashion. In this approach, the biomechanics is treated only as an assay since it is not used to guide development of the candidate metrics. By contrast, a more forward approach is to study the associated micromechanics using engineering analysis and from that identify the metrics that in theory most affect mechanical properties. The latter approach, facilitated by the new high-resolution imaging techniques and increased computational power, is discussed in an attempt to direct attention to new types of architectural metrics that are independent of bone density and that should improve the ability to explain how age, gender and osteoporosis affect the mechanical properties of trabecular bone.

Journal Article↗
PubMed2005

PICNIC Architecture.

The PICNIC architecture aims at supporting inter-enterprise integration and the facilitation of collaboration between healthcare organisations. The concept of a Regional Health Economy (RHE) is introduced to illustrate the varying nature of inter-enterprise collaboration between healthcare organisations collaborating in providing health services to citizens and patients in a regional setting. The PICNIC architecture comprises a number of PICNIC IT Services, the interfaces between them and presents a way to assemble these into a functioning Regional Health Care Network meeting the needs and concerns of its stakeholders. The PICNIC architecture is presented through a number of views relevant to different stakeholder groups. The stakeholders of the first view are national and regional health authorities and policy makers. The view describes how the architecture enables the implementation of national and regional health policies, strategies and organisational structures. The stakeholders of the second view, the service viewpoint, are the care providers, health professionals, patients and citizens. The view describes how the architecture supports and enables regional care delivery and process management including continuity of care (shared care) and citizen-centred health services. The stakeholders of the third view, the engineering view, are those that design, build and implement the RHCN. The view comprises four sub views: software engineering, IT services engineering, security and data. The proposed architecture is founded into the main stream of how distributed computing environments are evolving. The architecture is realised using the web services approach. A number of well established technology platforms and generic standards exist that can be used to implement the software components. The software components that are specified in PICNIC are implemented in Open Source.

Cooperative Behavior↗
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↗
PubMed2004

Angio-architecture of spinal cord arteriovenous shunts at presentation. Clinical correlations in adults and children. The Bicêtre experience on 155 consecutive patients seen between 1981-1999.

OBJECTIVE: To analyse possible relationships between the symptoms and signs created by intradural spinal cord arteriovenous shunts (SCAVSs) and their angio-architecture. METHODS: The clinical and radiological files of 155 patients, both adults and children, seen between 1981 and 1999 with a SCAVS were retrospectively reviewed. SCAVSs were divided into nidus type (small superficial or large intramedullary), and fistulas (micro (mAVFs)- or macrofistulas (MAVFs)). The angio-architectural points studied were arterial stenosis, proximal arterial aneurysm, distal arterial aneurysm, arteriovenous fistulas, pial venous drainage and/or reflux, venous ectasias, venous stenosis, venous thrombosis, false aneurysms. Correlations between architecture, location, age groups and symptoms and signs were made. FINDINGS: A male predominance was noted in both adults and children. Most of the lesions were located at the thoracic level, but hemorrhage occurred as the presenting event predominantly in cervical localizations. 30 patients (20 AVMs; 4 mAVFs, 6 MAVFs) were children. 5 of the 6 MAVFs found in children were associated with Hereditary Hemorrhagic Telengiectasia (HHT1). Twenty one children (70%) had bled. Spontaneous total or subtotal recovery was the rule in 15 of those who had bled (72%) but early recurrent hemorrhages occurred in 2. Among 125 adults 56 presented with hemorrhage (45%). The proportions of those who recovered spontaneously (71%) or rebled (3,6%) in the same year after the initial episode were very similar to children. All other adults presented with acute or progressive non-hemorrhagic episodes. There was no significant difference in the angio-architecture between hemorrhagic and non hemorrhagic SCAVS, except for that occurrence of pseudo-aneurysms. Hemorrhage in SCAVSs may not be exclusively due to haemodynamic factors. Venous congestion was responsible for progressive symptoms. Acute deficits unrelated to bleeds were due to intralesional thrombosis or hemodynamic changes. INTERPRETATION: The short term prognosis of hemorrhagic SCAVSs is good, and there is no need for emergency treatment. MRI delineates the cord and makes the diagnosis of the lesion but angiography remains the gold standard for analysis of the vasculature. The angio-architecture reflects the ageing of the lesion but there is not a precise correlation between angio-architecture and clinical symptoms, except for pseudoaneurysms which relate to the hemorrhagic portion of the lesion.

Adolescent↗
PubMed2006

Chromatin architectural proteins.

The accessibility of eukaryotic DNA is dependent upon the hierarchical level of chromatin organization. These include (1) intra-nucleosome interactions, (2) inter-nucleosome interactions and (3) the influence of non-histone chromatin architectural proteins. There appears to be interplay between all these levels, in that one level can override another or that two or more can act in concert. In the first level, the stability of the nucleosome itself is dependent on the number and type of contacts between the core histones and the surrounding DNA, as well as protein-protein interactions within the core histone octamer. Core histone variants, post-translational modifications of the histones, and linker histones binding to the DNA all influence the organization and stability of the nucleosome. When nucleosomes are placed end-to-end in linear chromatin arrays, the second level of organization is revealed. The amino terminal tails of the histone proteins make contacts with adjacent and distant nucleosomes, both within the fiber and between different fibers. The third level of organization is imposed upon these 'intrinsic' constraints, and is due to the influence of chromatin binding proteins that alter the architecture of the underlying fiber. These chromatin architectural proteins can, in some cases, bypass intrinsic constraints and impart their own topological affects, resulting in truly unique, supra-molecular assemblages that undoubtedly influence the accessibility of the underlying DNA. In this review we will provide a brief summary of what has been learned about the intrinsic dynamics of chromatin fibers, and survey the biology and architectural affects of the handful of chromatin architectural proteins that have been identified and characterized. These proteins are likely only a small subset of the architectural proteins encoded within the eukaryotic genome. We hope that an increased understanding and appreciation of the contribution of these proteins to genome accessibility will hasten the identification and characterization of more of these important regulatory factors.

Animals↗
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↗