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PubMed2006

The first B/G intersubtype recombinant form of human immunodeficiency virus type 1 (HIV-1) identified in Germany was undetected or underquantitated by some commercial viral load assays.

The high level of genetic diversity of human immunodeficiency virus type 1 (HIV-1) and the continual emergence of recombinant forms have important implications not only for the global evolution of HIV but also for diagnosis, monitoring, and treatment strategies. The present study reports the first intersubtype B/G recombinant strain of HIV-1 in Germany. This strain is notable from a clinical perspective, since it was undetectable in the NucliSens HIV-1 QT assay (Organon Tecknika/bioMérieux) and was significantly underquantitated in the Monitor v1.5 test (Roche Molecular Systems) relative to the LCx HIV RNA Quantitative assay (Abbott Laboratories). Gag-encoded p24 (gag p24), pol-encoded integrase (pol IN), and env-encoded gp41 (env gp41) immunodominant region (IDR) sequences were characterized to establish group and subtype designation and to evaluate the degree of genetic diversity at primer and probe binding sites of the viral load assays. Phylogenetic analysis revealed that this virus is an intersubtype B/G recombinant strain. The gag p24 region is subtype G, env gp41 IDR is subtype B, and pol IN is a B/G chimera. Nucleotide mismatches within primer and probe-binding sites provided the molecular basis for differences in quantitation observed between viral load assays. Genetic diversity of HIV-1 continues to challenge the reliability of detection and quantitation by viral load assays.

Adult↗

PubMed2006

Evolution of the human immunodeficiency virus envelope gene is dominated by purifying selection.

The evolution of the human immunodeficiency virus (HIV-1) during chronic infection involves the rapid, continuous turnover of genetic diversity. However, the role of natural selection, relative to random genetic drift, in governing this process is unclear. We tested a stochastic model of genetic drift using partial envelope sequences sampled longitudinally in 28 infected children. In each case the Bayesian posterior (empirical) distribution of coalescent genealogies was estimated using Markov chain Monte Carlo methods. Posterior predictive simulation was then used to generate a null distribution of genealogies assuming neutrality, with the null and empirical distributions compared using four genealogy-based summary statistics sensitive to nonneutral evolution. Because both null and empirical distributions were generated within a coalescent framework, we were able to explicitly account for the confounding influence of demography. From the distribution of corrected P-values across patients, we conclude that empirical genealogies are more asymmetric than expected if evolution is driven by mutation and genetic drift only, with an excess of low-frequency polymorphisms in the population. This indicates that although drift may still play an important role, natural selection has a strong influence on the evolution of HIV-1 envelope. A negative relationship between effective population size and substitution rate indicates that as the efficacy of selection increases, a smaller proportion of mutations approach fixation in the population. This suggests the presence of deleterious mutations. We therefore conclude that intrahost HIV-1 evolution in envelope is dominated by purifying selection against low-frequency deleterious mutations that do not reach fixation.

Base Sequence↗

PubMed1983

[Anatomo-pathological evolution of single-layer end-to-end digestive anastomoses. A study of 210 colonic anastomoses in rats from the 2d to the 180th day].

Two hundred and ten left colonic single-layer end-to-end anastomoses (105 by extramucosal continuous suture, 53 by extramucosal interrupted sutures, 52 by total continuous suture) performed on 105 rats with microsurgical techniques using a slowly resorbed suturing material were examined histologically at nine different times between the 2nd and the 180th days. The histopathological evolution of the inflammatory granuloma, the granulation tissue, the reepithelialization process and the restoration of the smooth muscle layers are described. The rate and the amount of inflammation were found to differ between animals and three different types of evolution could be schematized. The differences could not be due to the suturing techniques since continuous and interrupted sutures gave the same results, but rather to the manner of treating the intestinal cut edges before and during suturing. The amount of inflammation was found to decrease with the operator's training.

Animals↗

PubMed2004

Global dissemination of beta-lactamases mediating resistance to cephalosporins and carbapenems.

While the main era of beta-lactam discovery programs is over, these agents continue to be the most widely prescribed antimicrobials in both community and hospital settings. This has led to considerable beta-lactam pressure on pathogens, resulting in a literal explosion of new beta-lactamase variants of existing enzyme classes. Recent advances in the molecular tools used to detect and characterize beta-lactamases and their genes has, in part, fueled the large increase in communications identifying novel beta-lactamases, particularly in Gram-negative bacilli. It now seems clear that the beta-lactams themselves have shaped the field of new enzymes, and the evolution of key amino acid substitutions around the active sites of beta-lactamases continues to drive resistance. Over 130 variants of TEM beta-lactamase now exist, and more are reported in the scientific literature each month. The most disturbing current trend is that many bla structural genes normally limited to the chromosome are now mobilized on plasmids and integrons, broadening the spread of resistance to include carbapenems and cephamycins. Furthermore, in some Enterobacteriaceae, concomitant loss of outer membrane porins act in concert with these transmissible beta-lactamase genes to confer resistance to the most potent beta-lactams and inhibitor combinations available. Continued reviews of the literature are necessary in order to keep abreast of the ingenuity with which bacteria are changing the current genetic landscape to confer resistance to this important class of antimicrobials.

Anti-Bacterial Agents↗

PubMed2003

Kinetics of the ozonation and aerobic biodegradation of wine vinasses in discontinuous and continuous processes.

The oxidation of the organic substrate present in wastewaters generated in wine distilleries ("wine vinasses") is studied by both an ozonation process and by an aerobic activated sludge system. The ozonation process is conducted in a subsequent first discontinuous and a second continuous periods. Values are reported of the organic matter removal, measured as chemical oxygen demand (COD) (5-25.2%) and as total aromatic compounds content (16.8-51.4%). The influences of the inlet ozone partial pressure, the hydraulic retention time in the reactor and the presence of UV radiation and H2O2 in addition to ozone are established. Approximate kinetic studies are conducted for both periods which lead to the evaluation of the apparent rate constants for the substrate decomposition 216l/(mol O3 h) and 232l/(g COD h), respectively. In the aerobic degradation by the activated sludge system, the evolution of the organic substrate and biomass are followed during both the discontinuous and continuous stages of the whole process, and COD removals from 31 to 85% are obtained for a hydraulic retention time between 24 and 72 h. For the first stage, a kinetic study is performed by using the Contois model, which applied to the experimental data provides the specific kinetic parameters: q(max)=0.190 g COD/(g volatile suspended solids (VSS)h) and K(1)=6.48g COD/g VSS. For the continuous period, the kinetic study carried out provides the specific rate constant for the substrate decomposition, q=0.027 g COD/(g VSS h).

Bacteria, Aerobic↗

PubMed1991

Animal asymmetry and human heredity: dextrality, tool use and language in evolution--10 years after Walker (1980).

At the time of the last major review on this subject in the British Journal of Psychology (Walker, 1980) there was, with a few notable exceptions, little evidence of anatomical or behavioural asymmetries in non-human species at all comparable to our own. In the past decade the picture has changed dramatically, and now includes invertebrates from the Cambrian formations of half a billion years ago, many species of birds, rats and mice, antelopes, cats, dogs, whales, and primates. Asymmetries may differ as a function of sex (including hormone status-females of many species including humans appearing more lateralized at a motor level), developmental status and environmental influences. Effects may be manifest anatomically (limb or brain dimensions), or at a sensory, cognitive or motor level (paw preference, turning biases). A recurring observation across species is that the right hemisphere seems to be weakly specialized for spatial and emotional roles, and the left for learning, discriminatory and communicatory functions. Three million years ago our hominid ancestors were more or less fully bipedal, developed the first stone tools and were dextral in manipulating them. However, tool use seems not to have driven the evolution of language, our other strongly lateralized capacity. Evolutionary scenarios for bipedalism, tool use and language are discussed, together with the question of whether human language is continuous, in an evolutionary sense, with earlier primate call systems.

Animals↗

PubMed1994

Social evolution of hospitals. How is it relevant for health policy?

There are different kinds of hospitals. Doctors and nurses are the most prominent and visible components of a hospital. Development of nursing profession and medical technology have been two very significant factors in making hospitals a viable proposition. The hospitals were to start with very much as social institutions. The social basis of hospitals continues to be valid today. In this way, it is tried in this paper to highlight the evolution of different types of hospitals as social and technological institutions with the help of existing literature on history of hospitals and professions associated with it.

Health Policy↗

PubMed1999

Ethical, social and economic issues in familial breast cancer: a compilation of views from the E.C. Biomed II Demonstration Project.

Demand for clinical services for familial breast cancer is continuing to rise across Europe. Service provision is far from uniform and, in most centres, its evolution has been determined by local conditions, specifically by local research interests, rather than by central planning. However, in a number of countries there is evidence of progress towards co-ordinated development and audit of clinics providing risk assessment, counselling, screening and, in some cases, prophylactic intervention. Much important information should emerge from continued observation and comparative assessment of these developments. In most countries for which relevant data are available, there is a distinct bias towards higher social class among those who avail themselves of clinic facilities (in line with findings from many other health-promotion initiatives). This should be addressed when considering future organisation of clinical services. Molecular genetic studies designed to identify the underlying mutations responsible for familial breast cancer are not generally regarded as part of the clinical service and are funded through research grants (if at all). Economic considerations suggest that there is a case for keeping this policy under review. Familial cancers throw into sharp relief certain ethical and legal issues that have received much recent attention from government advisory bodies, patients' representatives, professional commentators and the popular media. Two are of particular importance; first, the right to gain access to medical records of relatives, in order to provide accurate risk assessment for a given family member, versus the right to privacy in respect of personal medical information and, second, the obligation (or otherwise) to inform family members of their risk status if they have not actively sought that knowledge. The legal position seems to vary from country to country and, in many cases, is unclear. In view of pressures to establish uniform approaches to medical confidentiality across the EC, it is important to evaluate the experience of participants in this Demonstration Programme and to apply the principle of "non-malfeasance" in formulating regulations that should govern future practice in this field. Data on economic aspects of familial breast cancer are remarkably sparse and outdated. As evidence accrues on the influence of screening and intervention programmes on morbidity and mortality, there is a strong case for evaluating the cost-effectiveness of different models of service provision.

Breast Neoplasms↗

PubMed2003

An integrated approach to taphonomy and faunal change in the Shungura formation (Ethiopia) and its implication for hominid evolution.

Environmental and faunal changes through time have been recorded for many African Plio-Pleistocene sites. Fossil evidence suggests that there is a continuous, if not uniform, transformation of the fauna and flora from the Pliocene through the end of Pleistocene. However, discerning major biotic turnovers and linking them to global and regional climatic changes have been complicated by many factors, notably taphonomy and discontinuity of the fossil evidence, notwithstanding the considerable work of some researchers (e.g., Vrba, E.S., 1988. Late Pliocene climatic events and hominid evolution, in: Grine, F. (Ed.), Evolutionary History of the "Robust" Australopithecines. De Gruyter, New York, pp. 405-426, Vrba, E.S., 1995. The fossil record of African (Mammalia, Bovidae) in relation to human evolution and paleoclimate, in: Vrba, E.S., Denton, G.H., Partridge, T.C., Burkle, L.H. (Eds.), Paleoclimate and Evolution, with Emphasis on Human Origins. Yale University Press, New Haven, pp. 385-424). A sample of over 22,000 fossils collected by the French Omo Expedition, from the Shungura Formation of Ethiopia, was analyzed using an integrated approach to investigate taphonomic and faunal change patterns. The following results are obtained: (1) Univariate and multivariate studies support continuous faunal change from Member A through Member G of the Shungura sequence; (2) Correspondence analysis (CA) on extant bovids in African game parks shows that bovid tribes and genera are generally characterized by habitat specificity; (3) Taphonomic studies demonstrate that the relative abundance of different skeletal elements varies according to depositional environment; (4) CA on 73 localities of the Shungura Formation and 19 mammalian taxa points to a major faunal change around the base of Member G dated to ca. 2.3 Ma. This transformation is characterized by a change to open and edaphic grassland as a dominant type of environment; (5) This major faunal change correlates in time with the appearance of A. boisei. It is tentatively suggested that this major biome change is associated with an anagenetic speciation from A. aethiopicus to A. boisei.

Animals↗

PubMed1996

[School at the end of life. What objectives what hope?].

BACKGROUND: School intervention programs for children and adolescents with cancer have been developed in France during the last years. Their primary objective is to improve the pschychosocial adaptation of these children to normal life through school integration. These programs are however inadequate for these children who will ultimately die from their disease and may require a specific school intervention. MATERIAL AND METHODS: School data from 30 children requiring palliative care were prospectively collected. School interest, its evolution and specific adaptations according to the child's status were analysed. RESULTS: Sixty per cent of the children showed a continuous desire for school education throughout their life's end. Reading, mathematics and computer work were the most favorite topics. Physical disability and fatigue may change their request during the evolution of the disease. School refusal occurred in 40% of the children and is mainly due to other extra-academic topics, or related to uncontrolled pain. CONCLUSION: Objectives of life's end school are different from educational programs proposed for children with cancer. They must be part of palliative care and have to be defined as a specific entity.

Adolescent↗

PubMed1999

Variable investment, the Continuous Prisoner's Dilemma, and the origin of cooperation.

Cooperation is fundamental to many biological systems. A common metaphor for studying the evolution of cooperation is the Prisoner's Dilemma, a game with two strategies: cooperate or defect. However, cooperation is rare all or nothing, and its evolution probably involves the gradual extension of initially modest degrees of assistance. The inability of the Prisoner's Dilemma to capture this basic aspect limits its use for understanding the evolutionary origins of cooperation. Here we consider a framework for cooperation based on the concept of investment: an act which is costly, but which benefits other individuals, where the cost and benefit depend on the level of investment made. In the resulting Continuous Prisoner's Dilemma the essential problem of cooperation remains: in the absence of any additional structure non-zero levels of investment cannot evolve. However, if investments are considered in a spatially structured context, selfish individuals who make arbitrarily low investments can be invaded by higher-investing mutants. This results in the mean level of investment evolving to significant levels, where it is maintained indefinitely. This approach provides a natural solution to the fundamental problem of how cooperation gradually increases from a non-cooperative state.

Biological Evolution↗

PubMed2005

Evolution driven by differential dispersal within a wild bird population.

Evolutionary theory predicts that local population divergence will depend on the balance between the diversifying effect of selection and the homogenizing effect of gene flow. However, spatial variation in the expression of genetic variation will also generate differential evolutionary responses. Furthermore, if dispersal is non-random it may actually reinforce, rather than counteract, evolutionary differentiation. Here we document the evolution of differences in body mass within a population of great tits, Parus major, inhabiting a single continuous woodland, over a 36-year period. We show that genetic variance for nestling body mass is spatially variable, that this generates different potential responses to selection, and that this diversifying effect is reinforced by non-random dispersal. Matching the patterns of variation, selection and evolution with population ecological data, we argue that the small-scale differentiation is driven by density-related differences in habitat quality affecting settlement decisions. Our data show that when gene flow is not homogeneous, evolutionary differentiation can be rapid and can occur over surprisingly small spatial scales. Our findings have important implications for questions of the scale of adaptation and speciation, and challenge the usual treatment of dispersal as a force opposing evolutionary differentiation.

Aging↗

PubMed2006

From embryo to adult--beyond the conventional periodization of arthropod development.

The traditional framework for the description of arthropod development takes the molt-to-molt interval as the fundamental unit of periodization, which is similar to the morphological picture of the main body axis as a series of segments. Developmental time is described as the subdivision into a few major stages of one or more instars each, which is similar to the subdivision of the main body axis into regions of one to many segments each. Parallel to recent criticisms to the segment as the fundamental building block of arthropod anatomy, we argue that, while a firm subdivision of development in stages is useful for describing arthropod ontogeny, this is limiting as a starting point for studying its evolution. Evolutionary change affects the association between different developmental processes, some of which are continuous in time whereas others are linked to the molting cycle. Events occurring but once in life (hatching; first achieving sexual maturity) are traditionally used to establish boundaries between major units of arthropod developmental time, but these boundaries are quite labile. The presence of embryonic molts, the 'gray zone' of development accompanying hatching (with the frequent delivery of an immature whose qualification as 'free-embryo' or ordinary postembryonic stage is arbitrary), and the frequent decoupling of growth and molting suggest a different view. Beyond the simple comparison of developmental schedules in terms of heterochrony, the flexible canvas we suggest for the analysis of arthropod development opens new vistas into its evolution. Examples are provided as to the origin of holometaboly and hypermetaboly within the insects.

Animals↗

PubMed1983

Response of preleukemic syndromes to continuous infusion of low-dose cytarabine.

Preleukemic syndromes are a group of acquired bone-marrow disorders characterized by dysplastic maturation of hematopoietic cells and peripheral-blood cytopenias. Although the clinical course is variable, most patients succumb to hemorrhage, infection, or acute leukemia. These syndromes are generally considered untreatable. We administered low doses of cytarabine by continuous intravenous infusion for 7 to 21 days in eight patients with preleukemia or with preleukemia in evolution to acute leukemia. Eight of 13 courses were associated with marked increases in peripheral-blood granulocyte, platelet, and red-cell counts, with the result that six of the eight patients needed no transfusions for 2 to over 14 months. These preliminary results demonstrate that continuous infusion of low-dose cytarabine can offer patients with preleukemic syndromes hematologic improvement with limited toxicity.

Adult↗

PubMed2004

Allelic variation of HERV-K(HML-2) endogenous retroviral elements in human populations.

Human endogenous retroviruses (HERVs) are the remnants of ancient germ cell infection by exogenous retroviruses and occupy up to 8% of the human genome. It has been suggested that HERV sequences have contributed to primate evolution by regulating the expression of cellular genes and mediating chromosome rearrangements. After integration approximately 28 million years ago, members of the HERV-K (HML-2) family have continued to amplify and recombine. To investigate the utility of HML-2 polymorphisms as markers for the study of more recent human evolution, we compiled a list of the structure and integration sites of sequences that are unique to humans and screened each insertion for polymorphism within the human genome databases. Of the total of 74 HML-2 sequences, 18 corresponded to complete or near-complete proviruses, 49 were solitary long terminal repeats (LTRs), 6 were incomplete LTRs, and 1 was a SVA retrotransposon. A number of different allelic configurations were identified including the alternation of a provirus and solitary LTR. We developed polymerase chain reaction-based assays for seven HML-2 loci and screened 109 human DNA samples from Africa, Europe, Asia, and Southeast Asia. Our results indicate that the diversity of HML-2 elements is higher in African than non-African populations, with population differentiation values ranging from 0.6 to 9.8%. These findings denote a recent expansion from Africa. We compare the phylogenetic relationships of HML-2 sequences that are unique to humans and consider whether these elements have played a role in the remodeling of the hominid genome.

Alleles↗

PubMed2005

[The role of the primary care physician in the care of the psychotic patient].

The primary care physician (PCP) plays an important role in the outpatient care of psychotic patients, particularly in the early detection of these disorders. Through the PCP's status as a trusted individual who knows the patient and his/her family, his/her opinion and attitude influence treatment acceptance and, consequently, the prognosis. By ensuring the continuity of care, in collaboration with a psychiatrist, the PCP helps prevent relapse and the evolution towards chronicity and long-term handicaps. A high incidence of cardiopulmonary disease and concomitant substance abuse in the population of chronic psychotic patients, as well as the monitoring of potential somatic side effects of psychotropic medication, require regular somatic follow-up by the PCP.

Continuity of Patient Care↗

PubMed2004

The modern theory of biological evolution: an expanded synthesis.

In 1858, two naturalists, Charles Darwin and Alfred Russel Wallace, independently proposed natural selection as the basic mechanism responsible for the origin of new phenotypic variants and, ultimately, new species. A large body of evidence for this hypothesis was published in Darwin's Origin of Species one year later, the appearance of which provoked other leading scientists like August Weismann to adopt and amplify Darwin's perspective. Weismann's neo-Darwinian theory of evolution was further elaborated, most notably in a series of books by Theodosius Dobzhansky, Ernst Mayr, Julian Huxley and others. In this article we first summarize the history of life on Earth and provide recent evidence demonstrating that Darwin's dilemma (the apparent missing Precambrian record of life) has been resolved. Next, the historical development and structure of the "modern synthesis" is described within the context of the following topics: paleobiology and rates of evolution, mass extinctions and species selection, macroevolution and punctuated equilibrium, sexual reproduction and recombination, sexual selection and altruism, endosymbiosis and eukaryotic cell evolution, evolutionary developmental biology, phenotypic plasticity, epigenetic inheritance and molecular evolution, experimental bacterial evolution, and computer simulations (in silico evolution of digital organisms). In addition, we discuss the expansion of the modern synthesis, embracing all branches of scientific disciplines. It is concluded that the basic tenets of the synthetic theory have survived, but in modified form. These sub-theories require continued elaboration, particularly in light of molecular biology, to answer open-ended questions concerning the mechanisms of evolution in all five kingdoms of life.

Animals↗

PubMed1999

The evolution of retirement: results of the 1999 Retirement Confidence Survey.

The ninth annual Retirement Confidence Survey (RCS) shows continued evidence of progress in the drive for retirement income security for American workers. However, there are still hurdles to overcome. The RCS tracks Americans' retirement planning and saving behavior and their confidence regarding various aspects of their retirement. It also categorizes workers and retirees into distinct groups based on their individual views on retirement, retirement planning, and saving. The retirement envisioned by today's workers looks different in many respects from that now experienced by current retirees. Today's workers expect to work longer than current retirees actually worked before retiring--and many say they plan to work for pay after they retire. Twenty-four percent of workers reported that they are very confident they will have enough money to live comfortably in retirement, and 45 percent reported that they are somewhat confident. However, there are indications that many may be falsely confident. The good news is that 70 percent of Americans are saving for retirement, and a growing percentage (49 percent) are going further and determining how much they need to save to fund their retirement. The bad news is that 30 percent of Americans have not begun to save for their retirement, and 51 percent have never tried to determine how much they need to save. Employers play a major role in ensuring adequate retirement preparation. Forty percent of all workers said they expect that money provided by their employer will be a major source of retirement income. Forty-six percent expect the money they put into a retirement plan at work to be a major source of income. The availability of a retirement plan at work is credited by 48 percent of savers as motivation to save. While worker education is a point of emphasis among both employers and policymakers, more remains to be done. For example, 59 percent of workers expect to be eligible for full Social Security benefits sooner than they actually will be, and an additional 19 percent admit they do not know when they will be eligible. There is evidence that education can have an impact on individual behavior. Forty percent of workers receiving educational material at work in the last year said that information caused them to begin saving (19 percent) or resume saving (21 percent) for retirement, while 40 percent said they changed the amount they were contributing to a retirement savings plan and 41 percent changed the allocation of their money in a retirement savings plan.

Attitude↗