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PubMed1994

On some formulas in a partnership model from the perspective of a semi-Markov process.

Many deterministic models of sexually transmitted diseases, as well as population models in general, contain elements of stochastic or statistical reasoning. An example of such a model is that of Dietz and Hadeler (1988) concerning sexually transmitted diseases in which there is partnership formation and dissolution. Among the interesting formulas in this paper, which enter into the analysis of the model, are those for the expected number of partners a male or female has during a lifetime. To a probabilist such formulas suggest the possibility that some stochastic process may be constructed so as to yield these formulas as well as others that may be of interest. The principal purpose of this paper is to demonstrate that such a stochastic process does indeed exist in the form of a three state semi-Markov process in continuous time with stationary laws of evolution and with a one-step density matrix determined by four parameters which were interpreted as constant latent risk functions in the classical theory of competing risks. This construction of a semi-Markov process not only provides a framework for the systematic derivation of the formulas of Dietz and Hadeler but also suggests pathways for extensions to the age-dependent case.

Female↗
PubMed2000

Long-term interferon beta-1b therapy for MS: is routine thyroid assessment always useful?

BACKGROUND: The authors previously reported on the development of thyroid dysfunction and autoimmunity during 1-year treatment of patients with MS with interferon-beta 1b (IFN beta-1b). OBJECTIVE: To evaluate the evolution of incident thyroid disease and the possible development of more thyroid disease during longer term therapy. PATIENTS: The authors studied 31 patients (aged 34 +/- 7 years; 21 women) with relapsing-remitting MS during 3 years of IFN beta-1b treatment. Systematic thyroid assessment was performed every 3 or 6 months, depending on the development of thyroid disease. RESULTS: After the first year of IFN beta-1b treatment, no further cases of thyroid disease were observed. Among the six patients with early incident subclinical hypothyroidism, thyroid dysfunction persisted only in those with baseline autoimmune thyroiditis (n = 2). The three patients who developed transient hyperthyroidism remained euthyroid throughout the treatment course. A positive autoantibody titer was continually detected in only two out of five patients without baseline autoimmunity. CONCLUSIONS: The risk of thyroid disease seems related to IFN beta-1b treatment during the first year only, particularly in patients with preexisting thyroiditis. Furthermore, incident thyroid dysfunction is generally transient and mild in degree. Indeed, we recommend a routine systematic thyroid assessment only in patients with baseline thyroiditis. During the first year of therapy, serum thyroid-stimulating hormone measurement should suffice as first line test; a systematic thyroid assessment is only useful for those patients with incidental and persistent dysfunction. Further studies with many patients will be necessary to confirm our suggestions as broad clinical guidelines.

Adult↗
PubMed1996

Robotics and the changing face of the clinical laboratory.

Rapid changes in healthcare coupled with parallel advances in technology have stimulated the evolution of new approaches for laboratory automation. In particular, the emergence of commercially available laboratory robotic systems offers promise for streamlining the clinical laboratory. Increasing cost-containment pressures make the application of this technology extremely attractive, and several organizations have begun to systematically integrate robotic devices into their laboratory automation schemes. Integration of these technologies, however, presents many challenges for software developers, instrument manufacturers, and laboratory workers. Differing needs across laboratories require flexibility and intelligence in robots, instruments, and control systems. Standardization of mechanical and electronic interfaces will be key to making these systems easy to integrate. Systems engineering, aided by simulation modeling and artificial intelligence schemes, will be important to assist in the design of optimal configurations. Software for the overall control of integrated automation will be needed that can be tailored by the laboratorian to fit the requirements of the individual laboratory. Thus, laboratory workers will need to be actively involved in implementing this new wave of laboratory automation, becoming well-versed in computers, electronics, and systems engineering.

Autoanalysis↗
PubMed1997

Managed care credentialing of advanced practice nurses.

The enormous and rapid changes taking place in health care delivery are forcing institutions, organizations, and individual providers of care to reexamine their relationships and create new methods of assuring both quality of care and safety for consumers. One result has been the emphasis on systematic methods of credentialing, privileging, and measuring and evaluating an individual's qualifications and actual performance. This article discusses the credentialing and privileging processes that are either in place or evolving for physicians in the managed care health care systems. With the continued evolution of managed care in this country, advanced practice nurses may need to expand their credentialing process. This article provides information on the evolutionary events leading to credentialing and privileging, current and anticipated credentialing measures, sources of measurements, medicolegal issues, and suggestions for expansion of nurse credentialing. A comprehensive credentialing system will provide additional evidence of the nursing profession's capacity to play a major role in the reformed health care system.

Credentialing↗
PubMed2002

Adaptationism--how to carry out an exaptationist program.

Adaptationism is a research strategy that seeks to identify adaptations and the specific selective forces that drove their evolution in past environments. Since the mid-1970s, paleontologist Stephen J. Gould and geneticist Richard Lewontin have been critical of adaptationism, especially as applied toward understanding human behavior and cognition. Perhaps the most prominent criticism they made was that adaptationist explanations were analogous to Rudyard Kipling's Just So Stories (outlandish explanations for questions such as how the elephant got its trunk). Since storytelling (through the generation of hypotheses and the making of inferences) is an inherent part of science, the criticism refers to the acceptance of stories without sufficient empirical evidence. In particular, Gould, Lewontin, and their colleagues argue that adaptationists often use inappropriate evidentiary standards for identifying adaptations and their functions, and that they often fail to consider alternative hypotheses to adaptation. Playing prominently in both of these criticisms are the concepts of constraint, spandrel, and exaptation. In this article we discuss the standards of evidence that could be used to identify adaptations and when and how they may be appropriately used. Moreover, building an empirical case that certain features of a trait are best explained by exaptation, spandrel, or constraint requires demonstrating that the trait's features cannot be better accounted for by adaptationist hypotheses. Thus, we argue that the testing of alternatives requires the consideration, testing, and systematic rejection of adaptationist hypotheses. Where possible, we illustrate our points with examples taken from human behavior and cognition.

Adaptation, Physiological↗
PubMedDate not supplied

The historical evolution of the concept of apoptosis in rheumatic diseases.

Even if the idea of apoptosis may probably be detected for the first time in a Hippocratic treatise, it was Rudolph Virchow, the founder of cellular pathology in the XIX century, who gave the first structured description of the processes underlying the term. In the course of the XX century a body of systematic observations on cell death was elaborated in an organic way. In 1908 Mechnikov won the Nobel Prize for his studies on phagocytosis, while in the '30s and '40s many studies on metamorphosis were carried out, and Fell and Canti identified cell death in chondrocytes in culture. At the end of the '40s Saunders began to observe cell death in chick limbs, and Hamburger and Levi Montalcini began their exploration of nerve growth factors. In mid '50s research on lysosomes began, and in the '60s Kerr defined shrinkage necrosis. The term apoptosis was definitely introduced by Kerr in 1972 to indicate a particular form of death in which cells commit suicide by dissolving themselves into membrane-bounded apoptotic bodies. In the '80s ced-3 was described and at the beginning of the '90s apoptosis genes were identified. In more recent times new instruments have allowed a wide range of cellular deaths to be described, including apoptosis as currently defined. Extremely interesting are its role and function in many different diseases; in particular in rheumatic ones recent evidence indicates that, far from being simple, brief and monomorphic, apoptosis is a complex, long-lasting, and pleiomorphic process.

Apoptosis↗
PubMed2004

The evolution of the Proteocephalidea (Platyhelminthes, Eucestoda) based on an enlarged molecular phylogeny, with comments on their uterine development.

We present a molecular phylogeny of the Proteocephalidea based on 28S rDNA sequence data that is a follow-up to the paper by Zehnder & Mariaux (1999). Twenty-three new sequences, including three outgroups are added in our new data-set. The Gangesiinae Mola, 1929 and the Acanthotaeniinae Freze, 1963 appear to be the most primitive clades. They are followed by a robust clade comprising the Palaearctic Proteocephalinae Mola, 1929 from freshwater fishes. The structure of the more derived clades, comprising most Neotropical and Nearctic species, is less resolved. At the nomenclatural level, we erect a new genus, Glanitaenia n. g. for G. osculata (Goeze, 1782) n. comb., previously Proteocephalus osculatus, and define an aggregate for the Palaearctic Proteocephalus Weinland, 1858. After a re-examination of all of the studied taxa, we identify two types of uterine development and show the importance of this character for the systematics of the order. Our phylogeny does not support the classical view of a Neotropical origin for the Proteocephalidea but rather favours an Old World origin of the group either in saurians or Palaearctic Siluriformes.

Animals↗
PubMed2002

Morphology-based systematics (MBS) and problems with fossil hominoid and hominid systematics.

The generalized/primitive nature of the hominoid dentition and often fragmentary nature of fossils, coupled with enthusiastic optimism for making revolutionary finds, has wreaked havoc with recognition of early human ancestors and reconstruction of fossil hominoid phylogeny. As such, the history of paleoanthropology is one of repeated misidentification of fossil ancestors and of occasional fraud. Although this history has led many workers to lose confidence in morphology based systematics (MBS), past and present misidentifications are actually due to a disregard of systematic methodology. Systematics depends on the continuity of life and gains its objectivity largely from the order alpha taxonomy imposes on morphologic discontinuities in closely related taxa (i.e., species and genera). Transformation of characters fixed in species into character complexes, as manifested in taxa nested at different levels of relationship, form the foundation for higher-level taxonomy and for phylogeny. Because in most cases, hominoid fossils are unable to provide the data needed to resolve alpha taxonomy, classification and phylogeny of fossil taxa must be guided by analogies to living taxa. Hominid and hominoid fossil taxonomy and phylogeny, however, has been based largely on preevolutionary notions and on misinterpretations of the polarity of assumed diagnostic characters. More often than not, fossils lack resolution for the taxonomic level or rank they are assigned to and taxa are erected without appropriate analogies to living forms. As such, phylogenies based on these classifications are unlikely to be correct. More in-depth anatomical studies that are in accordance with systematic methodology are likely to hold the key to correctly classifying fossils and unraveling hominoid and hominid phylogeny.

Animals↗
PubMed2000

Sequence analysis of transposable elements in the sea squirt, Ciona intestinalis.

A systematic search of 1 Mb of genomic sequences from the sea squirt, Ciona intestinalis, revealed the presence of six families of transposable elements. The Cigr-1 retrotransposon contains identical 245-bp long terminal repeats (LTRs) and a 3,630-bp open reading frame (ORF) encoding translation products in the same order as the domains characteristic of gypsy/Ty3-type LTR retrotransposons. The closest homologs of the reverse transcriptase domain were in gypsy elements from Drosophila and the sushi element from the pufferfish. However, the capsid-nucleocapsid region shows the clearest homology to an echinoderm element, Tgr1. Database searches also indicated two classes of non-LTR retrotransposon, named Cili-1 and Cili-2. The Cili-1 sequences show matches to regions of the ORF2 product of mammalian L1 elements. The Cili-2 sequences possess similarity to the RNaseH domain of Lian-Aa1, a mosquito non-LTR retrotransposon. The most abundant element was a short interspersed nucleotide element named Cics-1 with a copy number estimated at 40,000. Cics-1 consists of two conserved domains separated by an A-rich stretch. The 172-bp 5' domain is related to tRNA sequences, whereas the 110-bp 3' domain is unique. Cics-1 is unusual, not just in its modular structure, but also in its lack of a 3' poly(A) tail or direct flanking repeats. A second abundant element, Cimi-1, has an A+T-rich 193-bp consensus sequence and 30-bp terminal inverted repeats (TIRs) and is usually flanked by A+T-rich 2-4-bp putative target site duplications-characteristics of miniature inverted-repeat transposable elements found in plants and insects. A single 2,444-bp foldback element was found, possessing long TIRs containing an A+T-rich internal domain, an array of subrepeats, and a flanking domain at the TIR ends; this is the first example of a chordate foldback element. This study provides the first systematic characterization of the families of transposable elements in a lower chordate.

Amino Acid Sequence↗
PubMedDate not supplied

Social cognition and psychopathology in an evolutionary perspective. Current status and proposals for research.

The phylogenetic and ontogenetic developments of social cognition have been a major research focus of evolutionary and developmental psychology. Theory of mind or so-called Machiavellian intelligence, that is the capacity to infer mental states of other individuals and to manipulate them in order to maximise social success, probably emerged due to the need to cope with an increasingly complex social environment. Studies on social reasoning suggest disturbances of mental state attribution in psychiatric disorders. However, apart from autism spectrum disorders, the systematic evaluation of social cognition is still in its infancy, and the present data are ambiguous due to methodological difficulties. Based on the concept of the modular organisation of the mind, a stepwise investigation of social cognition in psychiatric disorders is proposed, including clinical description and available standardised methods. The specific characteristics of psychiatric disorders in respect of social cognition, therefore, may vary according to the hierarchical organisation of the social module. Systematic studies on social reasoning processes in psychiatric disorders may provide new insights also useful for the development of coping strategies in cognitive-behavioural therapy.

Biological Evolution↗
PubMed1991

Community oriented primary care: origins, evolution, applications.

Community oriented primary care is a commonly used term applied to a variety of situations and programs. Its use frequently extends beyond an understanding of its specific elements or an appreciation of its history and development. This article discusses the origins and evolution of the ideas, theory and practice of community oriented primary care. In South Africa in the 1940s a team headed by Sidney Kark embarked on work in the Pholela region of Natal that became the forerunner of ideas that were later formalized and systematized under the rubric of community oriented primary care. Widespread implementation took place in South Africa but was prematurely curtailed following the accession to power of the National Party. By the early 1960s many in the team had moved to Jerusalem where the theoretical basis of the concept was strengthened and came to describe a form of practice in which aspects of primary medical care and community health are integrated and systematically applied to a defined community. Experience with community oriented primary care in the United States and elsewhere is growing. This experience is reviewed and an assessment and critique offered.

Community Health Services↗
PubMed2004

Phase diagrams of Wyoming Na-montmorillonite clay. Influence of particle anisotropy.

Natural Na-Wyoming montmorillonite was size fractionated by successive centrifugation. Polydisperse particles with average sizes of 400, 290, and 75 nm were then obtained. As the structural charge of the particles belonging to three fractions (determined by cationic exchange capacity measurements) is the same, such a procedure allows studying the effect of particle anisotropy on the colloidal phase behavior of swelling clay particles. Osmotic stress experiments were carried out at different ionic strengths. The osmotic pressure curves display a plateau whose beginning systematically coincides with the sol/gel transition determined by oscillatory stress measurements. The concentration corresponding to the sol/gel transition increases linearly with particle anisotropy, which shows that the sol/gel transition is not directly related to an isotropic/nematic transition of individual clay particles. Indeed, a reverse evolution should be observed for an I/N transition involving the individual clay particles. Still, when observed between crossed polarizer and analyzer, the gel samples exhibit permanent birefringent textures, whereas in the "sol" region, transient birefringence is observed when the samples are sheared. This suggests that interacting clay particles are amenable to generate, at rest and/or under shear, large anisotropic particle associations.

Aluminum Silicates↗
PubMed2002

Discovering regulatory and signalling circuits in molecular interaction networks.

MOTIVATION: In model organisms such as yeast, large databases of protein-protein and protein-DNA interactions have become an extremely important resource for the study of protein function, evolution, and gene regulatory dynamics. In this paper we demonstrate that by integrating these interactions with widely-available mRNA expression data, it is possible to generate concrete hypotheses for the underlying mechanisms governing the observed changes in gene expression. To perform this integration systematically and at large scale, we introduce an approach for screening a molecular interaction network to identify active subnetworks, i.e., connected regions of the network that show significant changes in expression over particular subsets of conditions. The method we present here combines a rigorous statistical measure for scoring subnetworks with a search algorithm for identifying subnetworks with high score. RESULTS: We evaluated our procedure on a small network of 332 genes and 362 interactions and a large network of 4160 genes containing all 7462 protein-protein and protein-DNA interactions in the yeast public databases. In the case of the small network, we identified five significant subnetworks that covered 41 out of 77 (53%) of all significant changes in expression. Both network analyses returned several top-scoring subnetworks with good correspondence to known regulatory mechanisms in the literature. These results demonstrate how large-scale genomic approaches may be used to uncover signalling and regulatory pathways in a systematic, integrative fashion.

Algorithms↗
PubMed2025

Enhanced RNA replication and pathogenesis in recent SARS-CoV-2 variants harboring the L260F mutation in NSP6.

The COVID-19 pandemic has been driven by SARS-CoV-2 variants with enhanced transmission and immune escape. Apart from extensive evolution in the Spike protein, non-Spike mutations are accumulating across the entire viral genome and their functional impact is not well understood. To address the contribution of these mutations, we reconstructed genomes of recent Omicron variants with disabled Spike expression (replicons) to systematically compare their RNA replication capabilities independently from Spike. We also used a single reference replicon and complemented it with various Omicron variant Spike proteins to quantify viral entry capabilities in single-round infection assays. Viral entry and RNA replication were negatively correlated, suggesting that as variants evolve reduced entry functions under growing immune pressure on Spike, RNA replication increases as a compensatory mechanism. We identified multiple mutations across the viral genome that enhanced viral RNA replication. NSP6 emerged as a hotspot with a distinct L260F mutation independently arising in the BQ.1.1 and XBB.1.16 variants. Using mutant and revertant NSP6 viral clones, the L260F mutation was validated to enhance viral replication in cells and increase pathogenesis in mice. Notably, this mutation reduced host lipid droplet content by NSP6. Collectively, a systematic analysis of RNA replication of recent Omicron variants defined NSP6's key role in viral RNA replication that provides insight into evolutionary trajectories of recent variants with possible therapeutic implications.

SARS-CoV-2↗
PubMed2002

[Idiopathic cardiomyopathies].

These heart muscle diseases, associated with systolic or diastolic dysfunction, are associated with a high prevalence and morbidity, because of the frequent evolution towards congestive heart failure or sudden death. Dilated cardiomyopathy is the first cause of heart transplantation and Hypertrophic cardiomyopathy is the first cause of sudden death in athletes. Familial and monogenic forms of these diseases are frequent and this should lead to a systematic cardiological familial inquest in first degree relatives of a patient. Although they were previously called as "idiopathic", the pathophysiology of the disease is actually under investigation thanks to molecular genetics. This completely new knowledge should lead to the development of new therapeutic strategies.

Cardiomyopathy, Dilated↗
PubMedDate not supplied

Quality assurance in radiotherapy of prostatic cancer.

External beam radiotherapy is a widely experimented treatment modality in prostatic cancer. Recently published studies have documented a close dependence of clinical results, in terms of local control and toxicity in particular, on radiation therapy quality. Efforts to improve results of conventional radiotherapy were directed towards the identification of new therapeutic modalities (conformal therapy, fast neutron radiotherapy, neoadjuvant hormonotherapy) as well as towards the optimization of treatment accuracy. In this respect, the following procedures have been particularly effective: 1. the systematic use of CT and retrograde urethrography in PTV definition; 2. immobilization systems which allow a significant reduction in positioning errors; 3. checks before and during treatment by "portal imaging" which allow the identification and correction of a relevant percentage of inaccuracies. The general evolution in treatment planning occurred in recent years has introduced into prostatic cancer radiotherapy new methods and calculation algorithms. While at present the use of new and at the same time complex techniques makes the need for quality assurance of radiation treatments increasingly critical, it is in any case a daily requirement even in most conventional routine treatments.

Humans↗
PubMed2004

Dracula ant phylogeny as inferred by nuclear 28S rDNA sequences and implications for ant systematics (Hymenoptera: Formicidae: Amblyoponinae).

Ants are one of the most ecologically and numerically dominant families of organisms in almost every terrestrial habitat throughout the world, though they include only about 1% of all described insect species. The development of eusociality is thought to have been a driving force in the striking diversification and dominance of this group, yet we know little about the evolution of the major lineages of ants and have been unable to clearly determine their primitive characteristics. Ants within the subfamily Amblyoponinae are specialized arthropod predators, possess many anatomically and behaviorally primitive characters and have been proposed as a possible basal lineage within the ants. We investigate the phylogenetic relationships among the members of the subfamily, using nuclear 28S rDNA sequence data. Outgroups for the analysis include members of the poneromorph and leptanillomorph (Apomyrma, Leptanilla) ant subfamilies, as well as three wasp families. Parsimony, maximum likelihood, and Bayesian analyses provide strong support for the monophyly of a clade containing the two genera Apomyrma+Mystrium (100% bpp; 97% ML bs; and 97% MP bs), and moderate support for the monophyly of the Amblyoponinae as long as Apomyrma (Apomyrminae) is included (87% bpp; 57% ML bs; and 76% MP bs). Analyses did not recover evidence of monophyly of the Amblyopone genus, while the monophyly of the other genera in the subfamily is supported. Based on these results we provide a morphological diagnosis of the Amblyoponinae that includes Apomyrma. Among the outgroup taxa, Typhlomyrmex grouped consistently with Ectatomma, supporting the recent placement of Typhlomyrmex in the Ectatomminae. The results of this present study place the included ant subfamilies into roughly two clades with the basal placement of Leptanilla unclear. One clade contains all the Amblyoponinae (including Apomyrma), Ponerinae, and Proceratiinae (Poneroid clade). The other clade contains members from subfamilies Cerapachyinae, Dolichoderinae, Ectatomminae, Formicinae, Myrmeciinae, and Myrmicinae (Formicoid clade).

Animals↗