Treatment Effect and Drug-Resistant Mutations in Chinese AIDS Patients Switching to Second-Line Antiretroviral Therapy

This study aimed to investigate treatment effect, drug resistance changes, and their influencing factors in Chinese AIDS patients after switching to second-line antiretroviral therapy, and thus provide important information for the scale-up of second-line antiretroviral treatment in China. In Weishi county of Henan province, where second-line antiretroviral therapy was introduced early in China, 195 AIDS patients were enrolled, of which 127 patients met the switching criterion and 68 patients volunteered to switch drugs without meeting the switching criterion. CD4 cell count, viral load and in-house PCR genotyping for drug resistance were measured for all 195 subjects before drug switch, as well as 6 and 12 months after drug switch. Extensive secondary mutations to the protease inhibitor were observed, which suggested that long-term drug resistance surveillance is necessary for patients switching to second-line antiretroviral therapy. Multidrug resistance and cross-resistance were extensive in Chinese patients that experienced first-line treatment failure. Patients need timely CD4 count, viral load, and drug resistance monitoring in order to switch to second-line therapy under conditions of relatively good immunity and low viral duplication levels.     

Probability Distribution of Drug-Resistant Mutants in Unselected Populations of Mycobacterium tuberculosis

The fluctuation test shows that Mycobacterium tuberculosis mutates to resistance to isoniazid, streptomycin, ethambutol and rifampin spontaneously and at random. The average mutation rates for the drugs, in the same order, were calculated to be 2.56 × 10⁻⁸, 2.95 × 10⁻⁸, 10⁻⁷, and 2.25 × 10⁻¹⁰ mutation per bacterium per generation. The relatively high mutation rate to ethambutol resistance and the low mutation rate to rifampin resistance were confirmed by analyzing the increase in the proportion of mutants with time in a growing population of the tubercle bacilli. The highest proportions of mutants to be expected in unselected populations of the tubercle bacilli were calculated from the results of fluctuation tests.     

The Effects of Landscape Modifications on the Long-Term Persistence of Animal Populations

Background

The effects of landscape modifications on the long-term persistence of wild animal populations is of crucial importance to wildlife managers and conservation biologists, but obtaining experimental evidence using real landscapes is usually impossible. To circumvent this problem we used individual-based models (IBMs) of interacting animals in experimental modifications of a real Danish landscape. The models incorporate as much as possible of the behaviour and ecology of four species with contrasting life-history characteristics: skylark (Alauda arvensis), vole (Microtus agrestis), a ground beetle (Bembidion lampros) and a linyphiid spider (Erigone atra). This allows us to quantify the population implications of experimental modifications of landscape configuration and composition.

Methodology/Principal Findings

Starting with a real agricultural landscape, we progressively reduced landscape complexity by (i) homogenizing habitat patch shapes, (ii) randomizing the locations of the patches, and (iii) randomizing the size of the patches. The first two steps increased landscape fragmentation. We assessed the effects of these manipulations on the long-term persistence of animal populations by measuring equilibrium population sizes and time to recovery after disturbance. Patch rearrangement and the presence of corridors had a large effect on the population dynamics of species whose local success depends on the surrounding terrain. Landscape modifications that reduced population sizes increased recovery times in the short-dispersing species, making small populations vulnerable to increasing disturbance. The species that were most strongly affected by large disturbances fluctuated little in population sizes in years when no perturbations took place.

Significance

Traditional approaches to the management and conservation of populations use either classical methods of population analysis, which fail to adequately account for the spatial configurations of landscapes, or landscape ecology, which accounts for landscape structure but has difficulty predicting the dynamics of populations living in them. Here we show how realistic and replicable individual-based models can bridge the gap between non-spatial population theory and non-dynamic landscape ecology. A major strength of the approach is its ability to identify population vulnerabilities not detected by standard population viability analyses.     

Habitat Fragmentation and the Persistence of Lynx Populations in Washington State

Abstract Lynx (Lynx canadensis) occur in the northern counties of Washington state, USA; however, current distribution and status of lynx in Washington is poorly understood. During winters 2002–2004 we snow-tracked lynx for 155 km within a 211-km² area in northern Washington, to develop a model of lynx-habitat relationships that we could use to assess their potential distribution and status in the state. We recorded movements and behaviors of lynx with a Global Positioning System and overlaid digitized lynx trails on various habitat layers using a Geographic Information System. Based on univariate analyses, lynx preferred Engelmann spruce (Picea engelmannii) and subalpine fir (Abies lasiocarpa) forests, with moderate canopy and understory cover, and elevations ranging from 1,525 m to 1,829 m but avoided Douglas-fir (Pseudotsuga menziesii) and ponderosa pine (Pinus ponderosa) forests, openings, recent burns, open canopy and understory cover, and steep slopes. A map of suitable lynx habitat based on a logistic regression model built using these candidate variables revealed that habitats at elevations >1,400 m where lynx historically occurred in Washington are intersected and fragmented by landscape features and forest conditions that are generally avoided by lynx. Our habitat suitability map predicts 3,800 km² of lynx habitat in Washington that could support 87 lynx, far fewer than previous estimates. Since 1985, natural fires have burned >1,000 km² of forested habitat in Okanogan County, the only region in Washington where lynx occurrence has been documented during that period. Loss of suitable habitat from natural and human-caused disturbances, and the lack of verifiable evidence of lynx occurrence in historic lynx range, suggests that fragmented landscape conditions may have impeded recolonization of these areas by lynx. Consequently, translocations may be necessary to ensure lynx persistence in Washington. We suggest that managers assess the potential for translocation by first identifying the scale and distribution of potential foraging habitats for lynx based on our or similar habitat models, survey various habitat conditions to obtain reliable estimates of snowshoe hare densities, and identify a genetically compatible source population of lynx. If habitat and source populations are adequate, reintroducing lynx to areas of their historic range may be an appropriate conservation strategy.     

GC Fractionation Enhances Microbial Community Diversity Assessment and Detection of Minority Populations of Bacteria by Denaturing Gradient Gel Electrophoresis

Effectively and accurately assessing total microbial community diversity is one of the primary challenges in modern microbial ecology. This is particularly true with regard to the detection and characterization of unculturable populations and those present only in low abundance. We report a novel strategy, GC fractionation combined with denaturing gradient gel electrophoresis (GC-DGGE), which combines mechanistically different community analysis approaches to enhance assessment of microbial community diversity and detection of minority populations of microbes. This approach employs GC fractionation as an initial step to reduce the complexity of the community in each fraction. This reduced complexity facilitates subsequent detection of diversity in individual fractions. DGGE analysis of individual fractions revealed bands that were undetected or only poorly represented when total bacterial community DNA was analyzed. Also, directed cloning and sequencing of individual bands from DGGE lanes corresponding to individual G+C fractions allowed detection of numerous phylotypes that were not recovered using a traditional random cloning and sequencing approach.     

Persistence of Common Alleles in Two Related Populations or Species

Mathematical studies are conducted on three problems that arise in molecular population genetics. (1) The time required for a particular allele to become extinct in a population under the effects of mutation, selection, and random genetic drift is studied. In the absence of selection, the mean extinction time of an allele with an initial frequency close to 1 is of the order of the reciprocal of the mutation rate when 4Nv << 1, where N is the effective population size and v is the mutation rate per generation. Advantageous mutations reduce the extinction time considerably, whereas deleterious mutations increase it tremendously even if the effect on fitness is very slight. (2) Mathematical formulae are derived for the distribution and the moments of extinction time of a particular allele from one or both of two related populations or species under the assumption of no selection. When 4Nv << 1, the mean extinction time is about half that for a single population, if the two populations are descended from a common original stock. (3) The expected number as well as the proportion of common neutral alleles shared by two related species at the tth generation after their separation are studied. It is shown that if 4Nv is small, the two species are expected to share a high proportion of common alleles even 4N generations after separation. In addition to the above mathematical studies, the implications of our results for the common alleles at protein loci in related Drosophila species and for the degeneration of unused characters in cave animals are discussed.     

Costly Inheritance and the Persistence of Insecticide Resistance in Aedes aegypti Populations

Global emergence of arboviruses is a growing public health concern, since most of these diseases have no vaccine or prevention treatment available. In this scenario, vector control through the use of chemical insecticides is one of the most important prevention tools. Nevertheless, their effectiveness has been increasingly compromised by the development of strong resistance observed in field populations, even in spite of fitness costs usually associated to resistance. Using a stage-structured deterministic model parametrised for the Aedes aegypti—the main vector for dengue—we investigated the persistence of resistance by studying the time for a population which displays resistance to insecticide to revert to a susceptible population. By means of a comprehensive series of in-silico experiments, we studied this reversal time as a function of fitness costs and the initial presence of the resistance allele in the population. The resulting map provides both a guiding and a surveillance tool for public health officers to address the resistance situation of field populations. Application to field data from Brazil indicates that reversal can take, in some cases, decades even if fitness costs are not small. As by-products of this investigation, we were able to fit very simple formulas to the reversal times as a function of either cost or initial presence of the resistance allele. In addition, the in-silico experiments also showed that density dependent regulation plays an important role in the dynamics, slowing down the reversal process.     

The Role of Habitat in the Persistence of Fire Ant Populations

The association of the exotic fire ant, Solenopsis invicta with man-modified habitats has been amply demonstrated, but the fate of such populations if ecological succession proceeds has rarely been investigated. Resurvey of a fire ant population in a longleaf pine plantation after 25 years showed that the recovery of the site from habitat disturbance was associated with a large fire ant population decline. Most of the persisting colonies were associated with the disturbance caused by vehicle tracks. In a second study, mature monogyne fire ant colonies that had been planted in experimental plots in native groundcover of the north Florida longleaf pine forest had mostly vanished six years later. These observations and experiments show that S. invicta colonies rarely persist in the native habitat of these pine forests, probably because they are not replaced when they die. A single site harbored a modest population of polygyne fire ants whose persistence was probably facilitated by reproduction through colony fission.     

Precise Estimates of Persistence Time for SIS Infections in Heterogeneous Populations

For a susceptible–infectious–susceptible infection model in a heterogeneous population, we derive simple and precise estimates of mean persistence time, from a quasi-stationary endemic state to extinction of infection. Heterogeneity may be in either individuals’ levels of infectiousness or of susceptibility, as well as in individuals’ infectious period distributions. Infectious periods are allowed to follow arbitrary non-negative distributions. We also obtain a new and accurate approximation to the quasi-stationary distribution of the process, as well as demonstrating the use of our estimates to investigate the effects of different forms of heterogeneity. Our model may alternatively be interpreted as describing an infection spreading through a heterogeneous directed network, under the annealed network approximation.     

Classification of Therapy Resistance Based on Longitudinal Biomarker Profiles

To classify patients either as resistant or non‐resistant to HIV therapy based on longitudinal viral load profiles, we applied longitudinal quadratic discriminant analysis and examined various measures, mainly derived from the Brier Score, to assess the biomarker performance in terms of discrimination and calibration. The analysis of the application data revealed an increase in performance by using longer profiles instead of single biomarker measurements. Simulations showed that the selection of mixed models for the estimation of the group‐specific discriminant rule parameters should be based on BIC, rather than on the best performance measure. An incorrect model selection can lead to spuriously better or worse performance as misclassification and classification certainty regards, especially with increasing length of the profiles and for more complex models with random slopes.     

木材上的微生物类群对木材的分解及其演替规律

论述了木材上的微生物类群以及各类群在木材生物分解过程中的演替规律 ,并解释了活立木心材能够发生腐朽的原因。结果表明 :能够生长在木材上的微生物类群有木材腐朽菌、木材软腐菌、木材变色菌、污染性霉菌、细菌、放线菌等多种。这些微生物类群共同合作完成对复杂的木质有机物质的生物分解。它们按一定次序进行作用 ,在木材生物分解的不同时期显示出明显的菌种协调与演替规律。一般情况是细菌、一些半知菌、接合菌和子囊菌等先驱微生物首先侵入 ,然后草本对策的木材腐朽菌开始出现 ,最后由竞争对策或忍耐对策的木腐菌取代草本对策的木腐菌 ,这时木材的分解过程就进入稳定的发展阶段 ,最后使木材分解或腐朽。木材腐朽最终是腐殖化阶段 ,这时微生物群落被土壤习居菌如毛霉、青霉、木霉、镰刀菌及细菌与放线菌等所取代。     

Primate Populations and Their Interactions with Changing Habitats

Given that 90% of nonhuman primates depend on tropical forests, the most effective way to conserve them must emphasize the conservation of tropical forest habitats. To achieve this effectively, we need to address root causes of forest disturbance in developing nations: poverty, high population growth rates, crippling foreign debts, and the overdependence on tree and land resources. Moreover, it is now generally accepted that most primate populations will in future live in modified forest habitats. Studies of how primate populations respond to forest habitat modifications are therefore critical to future primate conservation. Currently most studies of primate responses to forest habitat alterations are difficult to interpret owing to differences in research methods and lack of information on the past histories of the modified forests. We review potential factors that may have to be considered while evaluating primate responses to forest habitat changes such as degradation and fragmentation.     

Diversity and Persistence of Ectomycorrhizal Fungi and Their Effect on Nursery-Inoculated Pinus pinaster in a Post-fire Plantation in Northern Portugal

Ectomycorrhizal fungi (ECMF) play an important role in forest ecosystems, often mitigating stress factors and increasing seedling performance. The aim of this study was to investigate the effects of a nursery inoculation on Pinus pinaster growth and on the fungal communities established when reforesting burned areas. Inoculated P. pinaster saplings showed 1.5-fold higher stem height than the non-inoculated controls after a 5 year growth period, suggesting that fungal inoculation could potentiate tree growth in the field. Ordination analysis revealed the presence of different ECMF communities on both plots. Among the nursery-inoculated fungi, Laccaria sp., Rhizopogon sp., Suillus bovinus and Pisolithus sp. were detected on inoculated Pinus saplings on both sampling periods, indicating that they persisted after field establishment. Other fungi were also detected in the inoculated plants. Phialocephala sp. was found on the first assessment, while Terfezia sp. was detected on both sampling periods. Laccaria sp. and Rhizopogon sp. were identified in the control saplings, belonging however to different species than those found in the inoculated plot. Inocybe sp., Thelephora sp. and Paxillus involutus were present on both sampling periods in the non-inoculated plots. The results suggest that ECMF inoculation at nursery stage can benefit plant growth after transplantation to a post-fire site and that the inoculated fungi can persist in the field. This approach has great potential as a biotechnological tool to aid in the reforestation of burned areas.     

Extended Survival and Persistence of Campylobacter spp. in Water and Aquatic Biofilms and Their Detection by Immunofluorescent-Antibody and -rRNA Staining

In water microcosm experiments, the survival times of Campylobacter isolates differed by up to twofold, as determined by culturing; this difference increased to fourfold when particular combinations of temperature and oxygenation were used. The mean survival times were much longer at 4 and 10°C (202 and 176 h, respectively) than at 22 and 37°C (43 and 22 h, respectively). The influence of anaerobiosis on survival time was less dramatic and differed considerably between isolates. In a two-stage water distribution model preparation containing a biofilm consisting of standardized autochthonous water microflora, Campylobacter isolates continued to differ in survival time. However, the survival times of cultures were considerably longer in the presence of the autochthonous water microflora (strains CH1 and 9752 survived 700 and 360 h, respectively, at 4°C) than in the sterile microcosms (strains CH1 and 9752 survived 230 and 157 h, respectively). Although increased temperature and oxygenation were generally detrimental to culturability, the interaction of these two factors influenced the two strains examined differently. When the organisms were grown aerobically at 30°C, the survival of the two strains was reversed; aerobiosis decreased the survival time of strain CH1 by 30%, but unexpectedly improved the persistence time of strain 9752 by more than threefold. Persistence times within biofilms were much longer when they were determined by detection methods not involving culturing. Immunofluorescent-antibody staining demonstrated that the pathogen persisted up to the termination of the experiments after 28 and 42 days of incubation at 30 and 4°C, respectively. The specificity of detection within intact biofilms was reduced because of high background fluorescence. However, preliminary studies with a Campylobacter-specific rRNA probe revealed the same extended persistence of the pathogen within the biofilms.     

Seasonal Fluctuations and Long-Term Persistence of Pathogenic Populations of Agrobacterium spp. in Soils

Short- and long-term persistence of pathogenic (i.e., tumor forming) agrobacteria in soil was investigated in six nursery plots with a history of high crown gall incidence. No pathogenic Agrobacterium strains were isolated in soil samples taken in fall and winter in any plots, but such strains were isolated from both bulk soils and weed rhizospheres (over 0.5 × 10⁵ pathogenic CFU/g of bulk soil or rhizosphere) in three out of six plots in spring and summer. PCR amplifications of a vir sequence from DNA extracted from soil confirmed the presence of Ti plasmids in summer and their absence in fall and winter. The results indicate that strains that harbor a Ti plasmid had an unforeseen positive fitness versus Ti plasmid-free strains in soil and rhizosphere in spring and summer in spite of the apparent absence of tumor, and hence of opines. The gain of fitness occurred during a bloom of all cultivable agrobacteria observed only in conducive soils. An evolution of the pathogenic population was recorded during a 4-year period in one particularly conducive soil. In 1990, the pathogenic population in this soil consisted of only biovar 1 strains harboring both octopine- and nopaline-type Ti plasmids. In 1994, it consisted of only nopaline-type Ti plasmids equally distributed among biovar 1 and 2 strains. These results suggest that nopaline-type Ti plasmids conferred a better survival ability than octopine-type Ti plasmids to biovar 2 agrobacteria under the present field conditions.     

Consequences of Environmental Fluctuations on Taylor’s Power Law and Implications for the Dynamics and Persistence of Populations

Conservation Biologists have found that demographic stochasticity causes the mean time to extinction to increase exponentially with population size. This has proved helpful in analyses determining extinction times and characterizing the pathway to extinction. The aim of this investigation is to explore the possible interactions between environmental/demographic noises and the scaling effect of the mean population size with its variance, which is expected to follow Taylor’s power law relationship. We showed that the combined effects of environmental/demographic noises and the scaling of population size variability interact with the population dynamics and affect the mean time to extinction.     

Compliance and Persistence in Pediatric and Adult Patients Receiving Growth Hormone Therapy

ObjectiveTo identify key factors that influence compliance and persistence in patients receiving growth hormone (GH) therapy and to promote the development of interventions to support continuous GH use.MethodsA 134-question survey was conducted involving 158 adult patients, 326 adolescents or teens, and 398 parents of children currently receiving or previously treated with GH. Questions explored perceptions about GH deficiency and treatment outcomes, quality of training received for administration of injections, and disruptions affecting compliance and persistence with therapy. Compliance was defined by a categorical assessment of frequency of missed GH doses for specific reasons. Persistence was defined as continuing GH therapy with no interruption.ResultsOn the basis of their responses to questions about potential reasons for missing GH doses, patients were categorized by level of compliance into 3 segments—highly compliant, occasionally noncompliant, or noncompliant and skeptical. Noncompliance with GH therapy (that is, classification in one of the last 2 segments) ranged from 64% to 77% among the 3 age-groups evaluated, with teens having the highest rate of noncompliance. Misperceptions about the consequences of missed GH doses, discomfort with injections, dissatisfaction with treatment results, and inadequate contact with health-care providers (along with other factors) were strongly associated with noncompliance. Survey questions related to these factors were considered useful for identifying patients requiring additional support or intervention to improve compliance.ConclusionRoutine education should emphasize therapeutic end points and their relationship to compliance with GH therapy in an effort to convince and empower patients with GH deficiency to use self-care strategies to achieve their treatment goals. (Endocr Pract. 2008;14: 143-154)