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PubMed1998

An integrated approach for a knowledge-based clinical workstation: architecture and experience.

Today, the demand for medical decision support to improve the quality of patient care and to reduce costs in health services is generally recognized. Nevertheless, decision support is not yet established in daily routine within hospital information systems which often show a heterogeneous architecture but offer possibilities of interoperability. Currently, the integration of decision support functions into clinical workstations is the most promising way. Therefore, we first discuss aspects of integrating decision support into clinical workstations including clinical needs, integration of database and knowledge base, knowledge sharing and reuse and the role of standardized terminology. In addition, we draw up functional requirements to support the physician dealing with patient care, medical research and administrative tasks. As a consequence, we propose a general architecture of an integrated knowledge-based clinical workstation. Based on an example application we discuss our experiences concerning clinical applicability and relevance. We show that, although our approach promotes the integration of decision support into hospital information systems, the success of decision support depends above all on an adequate transformation of clinical needs.

Artificial Intelligence↗
PubMed1998

Impact of fibroblast growth factor-2 on tumor microvascular architecture. A tridimensional morphometric study.

Three cell clones originated by transfection of human endometrial adenocarcinoma HEC-1-B cells with fibroblast growth factor-2 (FGF-2) cDNA and characterized by a different capacity to produce and secrete the growth factor were transplanted subcutaneously in nude mice. Corrosion casting of the tumor microvasculature of xenografts produced by injection of 2 x 10(6) or 10 x 10(6) FGF-2-B9 cells (which produce and secrete significant amounts of FGF-2), 10 x 10(6) FGF-2-A8 cells (which produce comparable amounts of FGF-2 but do not secrete it), or 10 x 10(6) control FGF-2-B8 cells (which produce only trace amounts of FGF-2) was performed after 14 days of growth. Interbranching distances, intervascular distances, branching angles, and vessel diameters were then determined using tridimensional stereo pairs of the casted tumor vascularity. When transplanted at the same concentration, FGF-2-B9 cells grew faster in nude mice compared with FGF-2-A8 and FGF-2-B8 clones. The total amount of new vessel formation was far higher in FGF-2-B9 tumors than in FGF-2-B8 or FGF-2-A8 tumors. Also, vessel courses were more irregular and blind-ending vessels and evasates were more frequent in FGF-2-B9 tumors. Moreover, FGF-2-B9 tumor microvasculature was characterized by a wider average vascular diameter and by an extreme variability of the diameter of each individual vessel along its course between two ramifications. No statistical differences were observed when the distribution curves of the values of intervascular distances, interbranching distances, and branching angles of the microvessel network were compared among the different experimental groups. The distinctive features of the microvasculature of FGF-2-B9 tumors were retained, at least in part, in the smaller lesions produced by injection of a limited number of cells. The data indicate that FGF-2 production and release confer to FGF-2-B9 cells the ability to stimulate the formation of new blood vessels with distinctive architectural features. Neovascularization of FGF-2-B9 lesions parallels the faster rate of growth of the neoplastic parenchyma. This does not affect the overall architecture of the microvessel network that appears to be primed by characteristics of the HEC-1-B tumor cell line and/or by the microenvironment of the host. To our knowledge, this work represents the first attempt to define the influence of a single, defined growth factor on the tridimensional tumor vascular pattern.

Adenocarcinoma↗
PubMed1998

Effects of environmental stress on the architecture and permeability of the rat mesenteric microvasculature.

OBJECTIVE: This study was performed to determine the effects of environmental stress on the leakage to albumin and architecture of microvessels in the rat mesentery. METHODS: One group of rats (Group A, n = 6) were examined immediately upon arrival at the animal care facility. Groups B (n = 24) and C (n = 32) were housed in rooms with high and low personnel activity, respectively, for up to 7 weeks. Group D (n = 18) was housed in the high activity room for 2, 3, or 4 weeks followed by the low activity room. RESULTS: Rats in the low activity room for 3-4 weeks showed robust microvascular networks within 25% to 50% of the mesenteric windows (each window consisting of the tissue extending between two adjacent feeding arterioles in the mesentery), whereas rats in Group B only showed fragile vessels at the edges of the mesenteric windows within fat deposits. Groups A and C demonstrated little mesenteric fat and few fragile vessels, in contrast to group B. Group D showed increased mesenteric networks and decreased mesenteric fat as recovery progressed. The microvascular networks of 6 rats, randomly selected from Group C, showed few venular leaks following perfusion with fluorescein isothiocyanate-labeled bovine serum albumin (FITC-BSA). Such leaks were abundant in the mesenteric microvasculature of 3 rats randomly selected from Group B. CONCLUSIONS: This study demonstrates that environmentally induced stress alters the architecture and leakage to albumin of the rat mesenteric microvasculature, and emphasizes the importance of closely monitoring the environment of experimental animals.

Animals↗
PubMed1998

Linkages of nuclear architecture to biological and pathological control of gene expression.

Functional interrelationships between components of nuclear architecture and control of gene expression are becoming increasingly evident. There is growing appreciation that multiple levels of nuclear organization integrate the regulatory cues that support activation and suppression of genes as well as the processing of gene transcripts. The linear organization of genes and promoter elements provide the potential for responsiveness to physiological regulatory signals. Parameters of chromatin structure and nucleosome organization support synergism between activities at independent regulatory sequences and render promoter elements accessible or refractory to transcription factors. Association of genes, transcription factors, and the machinery for transcript processing with the nuclear matrix facilitates fidelity of gene expression within the three-dimensional context of nuclear architecture. Mechanisms must be defined that couple nuclear morphology with enzymatic parameters of gene expression. The recent characterization of factors that mediate chromatin remodeling and intranuclear targeting signals that direct transcription factors to subnuclear domains where gene expression occurs, reflect linkage of genetic and structural components of transcriptional control. Nuclear reorganization and aberrant intranuclear trafficking of transcription factors for developmental and tissue-specific control that occurs in tumor cells and in neurological disorders provides a basis for high resolution diagnostic and targeted therapy.

Animals↗
PubMed1998

A software architecture to support a large-scale, multi-tier clinical information system.

A robust software architecture is necessary to support a large-scale multi-tier clinical information system. This paper describes our mechanism for enterprise distribution of applications and support files, the consolidation of data-access functions and system utilities stored on the data access tier, and an application framework which implements a coherent clinical computing environment. The software architecture and systems described in this paper have been robust through pilot testing of our applications at Massachusetts General Hospital.

Computer Security↗
PubMed2026

The Spatiotemporal Genetic Architecture of Seed Vigor in Upland Cotton.

Seed vigor underpins uniform crop establishment, but its dynamic genetics are understudied. Combining high-resolution temporal phenotyping and genomics in upland cotton, we used the SeedRanger platform to record 17 image-based traits every 30 min over 120 h, revealing stage-specific heritability and identifying 541 seed-vigor loci. These loci show extensive pleiotropy and temporal coordination, forming a genetic network that preserves developmental continuity; 8.9% overlap regions under domestication selection, indicating concurrent optimization with fiber yield. Functional validation of FLA2, a candidate gene underlying a dynamic QTL, implicates auxin-mediated control of radicle elongation and cotyledon development. This temporal framework exposes dynamic genetic architecture and breeding targets for high-vigor crops.

Gossypium↗
PubMed2026

Shared genetic architecture between DTI-ALPS traits and neurodegenerative diseases.

INTRODUCTION: Diffusion tensor image analysis along the perivascular space (DTI-ALPS) index is associated with neurodegenerative diseases (NDDs), but its shared genetic basis with NDDs remains unclear. METHODS: By integrating genome-wide association datasets for three DTI-ALPS traits and seven NDDs, we quantified polygenic overlap using MiXeR, identified shared loci using conditional and conjunctional false discovery rate analyses, and performed gene mapping, enrichment, temporal expression, and transcriptome-wide association analyses. RESULTS: DTI-ALPS traits showed widespread but heterogeneous polygenic overlap with NDDs. We identified 22 shared loci, including novel associations implicating GAK and SIAH3, with the strongest convergence at 17q21.31. Shared loci mapped to 183 protein-coding genes enriched in the endolysosomal system and microtubule cytoskeleton. These genes showed similar temporal expression patterns, and 45 were associated with both DTI-ALPS traits and NDDs. DISCUSSION: These findings reveal a shared genetic architecture between DTI-ALPS traits and NDDs, highlighting mechanisms that may contribute to their overlap.

Neurodegenerative Diseases↗
PubMed2002

Architectural design of a secure forensic state psychiatric hospital.

This article describes the architectural design of a secure forensic state psychiatric hospital. The project combined input from staff at all levels of the client organization, outside consultants, and a team of experienced architects. The design team was able to create a design that maximized patient dignity and privacy on one hand, and the ability of staff to observe all patient activity on the other. The design centers around 24-bed units, broken into smaller living wings of eight beds each. Each eight-bed living wing has its own private bathrooms (two) and showers (two), as well as a small living area solely reserved for these eight patients and their guests. An indoor-outdoor dayroom allows patients to go outside whenever they choose, while allowing staff to continue observing them. The heart of the facility is a large treatment mall, designed to foster the acquisition of social, emotional, cognitive, and behavioral skills that will help patients to safely return to their communities.

Architecture↗
PubMed2026

Evolutionary Reorganization of Transcriptomic Architecture Across a UVB Tolerance Gradient in Fish.

Environmental stressors such as ultraviolet radiation impose strong selective pressures on organisms, yet how adaptation to such stressors shapes transcriptomic responses at the network level remains poorly understood. Although stratospheric ozone is recovering globally, substantial regional variation in UV exposure persists, particularly in high-altitude environments where extreme UV levels can occur. Here, we compared three fish models representing distinct biological responses to UVB exposure: wild-type zebrafish (Danio rerio), a melanin-deficient zebrafish mutant (nacre) lacking a major protective mechanism against UVB damage, and the high-altitude Andean killifish Orestias ascotanensis, a species naturally exposed to extreme UVB radiation. Together, these models define a gradient spanning physiological protection, impaired protection, and evolutionary adaptation to UVB stress. Using RNA-seq and protein-protein interaction networks, we show that transcriptomic responses differ markedly across this gradient. Wild-type and nacre zebrafish exhibited relatively limited transcriptomic changes (∼2%-2.4% of genes changing), whereas O. ascotanensis displayed a large-scale and highly coordinated response (∼21.6% of genes changing) characterized by functionally specialized networks enriched in DNA repair pathways. These differences involved not only transcriptomic magnitude but also marked reorganization of transcriptomic architecture. Integration with positive selection analyses revealed that positively selected genes were concentrated within highly interconnected regions of transcriptomic networks, consistent with adaptation involving network reorganization. Furthermore, ortholog-based analyses suggest that adaptive responses involve differential reorganization of a conserved functional background. Together, our results support a model in which adaptation to environmental stress is associated with the reorganization of conserved transcriptomic networks across physiological and evolutionary contexts, providing a systems-level perspective on the molecular basis of adaptation.

UVB radiation↗
PubMed2026

Shared genetic architecture and cellular convergence between female reproductive disorders and pulmonary function: a genome-wide cross-trait analysis.

Female reproductive disorders (FRDs), including polycystic ovary syndrome, endometriosis, uterine leiomyomata, and infertility, have been epidemiologically associated with impaired pulmonary function. However, it remains unclear whether this cross-organ link reflects shared genetic etiology and, if so, which cellular mechanisms mediate it. We performed a systematic genome-wide cross-trait analysis of three FRDs and lung function traits (FEV₁, FVC, FEV₁/FVC) using GWAS summary statistics from individuals of European ancestry, integrating genetic correlation, bidirectional causal inference, pleiotropy mapping, and single-cell enrichment analyses. We identified significant negative genetic correlations between FRDs and lung volume traits, most prominently for FVC (rg range: - 0.077 to - 0.178). Bidirectional causal analyses indicated that FRDs have a detrimental effect on lung volume, with higher FRD genetic liability associated with reduced lung volume. Cross-trait meta-analysis identified 17 pleiotropic variants across 11 loci, with the 19q13.2 (LTBP4) and 12q13.13 (HOXC6/HOXC9) loci showing strong evidence of shared causal variants. Critically, single-cell analyses revealed that shared genetic risk converged on mesenchymal lineages across organs, specifically alveolar adventitial fibroblasts in the lung and stromal/smooth muscle cells in the endometrium. Transcriptome-wide analyses further nominated the estrogen-responsive gene RERG as a convergent gene linking these conditions with lung function. Our study revealed a shared genetic architecture between female reproductive disorders and lung function traits, providing a basis for further mechanistic investigations and potential clinical evaluation. Furthermore, our findings suggest that shared fibroproliferative and hormone-responsive pathways may offer insights into the biological mechanisms underlying these conditions.

Female↗
PubMed2006

Setting the space for sex: architecture, desire and health issues in gay bathhouses.

This aim of this study was to describe and compare the physical design, as well as the atmosphere of urban gay bathhouses, and reflect on how desire operates within these premises when it intersects with the bathhouse environment and health imperatives. Three bathhouses were studied for a total of 147 h of observation. Men's desire for other men has created a landscape of spaces (real and virtual) where sex takes place in parks, alleys, restrooms, rest stops, adult theatres, video arcades, bookstores, bars, gay bathhouses and finally, the Internet. Although the Internet is perceived as an easy way for encountering sexual partners, gay bathhouses remain the most popular and convenient way, for men having sex with men to meet for regular or casual sex. This paper presents the descriptive results of an ethnographic nursing study that took place in three gay bathhouses located in two Canadian metropolitan areas. Gay bathhouses offer patrons a space within which a wide range of interactions, sensations and pleasure can be experienced. This paper highlights the specific features of three gay bathhouses, compares settings according to their specific architectural features and related sexual activities, and finally, proposes some changes in light of certain health issues.

Anthropology, Cultural↗
PubMed2006

Life cycle assessment of wood wastes: A case study of ephemeral architecture.

One of the most commonly used elements in ephemeral architecture is a particleboard panel. These types of wood products are produced from wood wastes and they are used in temporary constructions such as trade fairs. Once the event is over, they are usually disposed into landfills. This paper intends to assess the environmental effects related to the use of these wood wastes in the end-of-life stage. The Life Cycle Assessment (LCA) of two scenarios was performed, considering the recycling of wood waste for particleboard manufacture and energy generation from non-renewable resources (Scenario 1) versus the production of energy from the combustion of wood waste and particleboard manufacture with conventional wooden resources (Scenario 2). A sensitive analysis was carried out taking into account the influence of the percentage of recycled material and the emissions data from wood combustion. According to Ecoindicator 99 methodology, Damage to Human Health and Ecosystem Quality are more significant in Scenario 2 whereas Scenario 1 presents the largest contribution to Damage to Resources. Between the two proposed alternatives, the recycling of wood waste for particleboard manufacture seems to be more favorable under an environmental perspective.

Architecture↗
PubMed2025

Deconvoluting clonal and cellular architecture in IDH-mutant acute myeloid leukemia.

Isocitrate dehydrogenase 1/2 (IDH) mutations are early initiating events in acute myeloid leukemia (AML). The complex clonal architecture and cellular heterogeneity in IDH-mutant AML underlies the heterogeneous clinical presentation and outcomes. Integrating single-cell genotyping and transcriptomics, we demonstrate a stem-like and inflammatory phenotype of IDH-mutant AML and identify clone-specific programs associated with NPM1, NRAS, and SRSF2 co-mutations. Furthermore, these clones had distinct responses to treatment with combination IDH inhibitors and chemotherapy, including elimination, reconstitution of myeloid differentiation, or retention within progenitor populations. At relapse after IDH inhibitor monotherapy, we identify upregulated stemness, inflammation, mitochondrial metabolism, and anti-apoptotic factors, as well as downregulated major histocompatibility complex (MHC) class II antigen presentation. At the pre-leukemic stage, we observe upregulation of IDH2-associated pathways, including inflammation. We deliver a detailed phenotyping of IDH-mutant AML and a framework for dissecting contributions of recurrently mutated genes in AML at diagnosis and following therapy, with implications for precision medicine.

Leukemia, Myeloid, Acute↗
PubMed2000

Architecture signifying social control: the restoration of asylumdom in mental health care?

Prior to the era of community care, the asylum has been an architectural manifestation of the power of psychiatry and the State. Asylumdom was a period in which custodial warehouses were used by the State to store sections of the population considered to be 'unreasonable'. There are signs, however, of a re-birth of asylumdom in both the UK and Australia. For example, there is a projected growth in the number of 'secure units' in the community, and a growing concern with issues of security and risk management in mental health care. Furthermore, new technologies for containment and surveillance are being installed in acute inpatient psychiatric units. Once again the asylum will symbolize emphatically the authority of the State (and its agencies of social control), and re-emphasize the exclusion of 'unreason' from the 'reasonable' society.

Architecture↗
PubMed2004

Does the architecture of hospital facilities influence nosocomial infection rates? A systematic review.

OBJECTIVE: To review the evidence regarding the effects of interventions to improve hospital design and construction on the occurrence of nosocomial infections. METHODS: Systematic review of experimental and non-experimental, architectural intervention studies in intensive care units (ICUs), surgical departments, isolation units, and hospitals in general. The studies dated from 1975, and were in English, French, German, Italian, and Spanish. Regardless of format, the studies were identified through seven medical databases, reference lists, and expert consultation. RESULTS: One hundred seventy-eight scientific articles were identified; however, none of these described a meta-analysis, systematic review, or randomized, controlled trial. Most of the articles were categorized at the lowest level of evidence (expert judgment or consensus statements). Only 17 described completed concurrent or historical cohort studies matching the inclusion criteria (ICUs, 9; surgical departments, 4; isolation units, 2; hospitals in general, 2). The interventions generally included a move to other premises or renovation. However, in many studies, the staff-to-patient ratio was also improved. Some studies showed lower infection rates after intervention, but this finding cannot be generalized because of confounding and frequently small study populations. CONCLUSIONS: The lack of stringent evidence linking hospital design and construction with the prevention of nosocomial infection is partly attributable to the multifactorial nature of these infections, and some improvement will be seen if basic conditions such as the availability of sufficient space, isolation capacity, and facilities for handwashing are met. However, to our knowledge, other factors, especially the improper hand hygiene of medical staff, have greater impact.

Architecture↗
PubMed2026

Using deep learning models as a genetic architecture for the simulation of breeding schemes.

In several simulation studies, long-term selection led to the rapid depletion of genetic variance. These outcomes differ from real-life observations that we aim to replicate, thereby highlighting a fundamental limitation of current classical quantitative genetic simulation models. Deep learning (DL) models have demonstrated promising results in capturing complex interactions essential for maintaining genetic variance; thus, we hypothesize that DL-based genetic simulation models may preserve more genetic variance than classical models, because the biological pathways underlying complex traits exhibit interactions that classical models ignore. The primary objective of this study was to introduce alternative DL-based genetic simulation models and compare them with classical genetic simulation models in terms of their retention of additive genetic variance under truncation selection in a simulated full-sib pig breeding scheme using real haplotypes as founders. After 20 generations of directional truncation selection, the classical models (A, ADAA, and ADAAADDD) retained between 55% and 64% of their initial additive genetic variance. In contrast, while the DL_simple model lost all its additive variance, the DL medium retained 92% to 98% of its additive variance, and the DL_complex model's initial additive variance increased by 296% to 314%. This paper introduces DL-based genetic simulation models and concludes that their ability to retain additive genetic variance depends on the models' architectural complexity. When sufficiently complex, DL-based models exhibit greater retention of additive genetic variance because they intrinsically capture epistatic interactions that are converted into additive variance, as selection progresses, thus, affirming the role of non-additive genetic effects in maintaining long-term genetic variation.

Deep Learning↗
PubMed1980

Assessing the physical and architectural features of sheltered care settings.

The Physical and Architectural Features Checklist (PaF) measures the physical resources of sheltered care settings in terms of nine conceptually unified and empirically derived dimensions. The development of the PAF is described, and psychometric characteristics, based on data from 93 representative facilities, are presented. These data show that facilities which have more physical resources are seen as attractive by outside observers and pleasant by residents. Larger facilities are more likely to provide barrier-free environments, more flexible physical settings, and more staff facilities. Cost is not related to any PAF dimension; however, nonprofit facilities score higher on several dimensions than do proprietary facilities. Richer physical settings tend to offer residents more policy resources. They are more selective, provide more privacy, allow residents a higher degree of influence and choice, and have clearer policies. Sample profiles illustrate the usefulness of this instrument for describing and comparing facilities; additional uses are discussed.

Aged↗
PubMed1995

Combining aesthetics and practicality in health care architecture.

Architecture, like health care, is a service profession. It serves not only a functional purpose by providing designs for shelter, but also incorporates social purpose. It allows people to conduct business, congregate for amusement, express their faith, and educate themselves. It is also a collaborative art, creating an environment that influences its users by their interactions with it and how they use it.

Ambulatory Care Facilities↗