How hosts control worms

No abstract available

Cluster randomised trials in the medical literature: two bibliometric surveys

Background: Several reviews of published cluster randomised trials have reported that about half did not take clustering into account in the analysis, which was thus incorrect and potentially misleading. In this paper I ask whether cluster randomised trials are increasing in both number and quality of reporting. Methods: Computer search for papers on cluster randomised trials since 1980, hand search of trial reports published in selected volumes of the British Medical Journal over 20 years. Results: There has been a large increase in the numbers of methodological papers and of trial reports using the term 'cluster random' in recent years, with about equal numbers of each type of paper. The British Medical Journal contained more such reports than any other journal. In this journal there was a corresponding increase over time in the number of trials where subjects were randomised in clusters. In 2003 all reports showed awareness of the need to allow for clustering in the analysis. In 1993 and before clustering was ignored in most such trials. Conclusion: Cluster trials are becoming more frequent and reporting is of higher quality. Perhaps statistician pressure works

Natural genetic engineering: intelligence & design in evolution?

There are many things that I like about James Shapiro's new book "Evolution: A View from the 21st Century" (FT Press Science, 2011). He begins the book by saying that it is the creation of novelty, and not selection, that is important in the history of life. In the presence of heritable traits that vary, selection results in the evolution of a population towards an optimal composition of those traits. But selection can only act on changes - and where does this variation come from? Historically, the creation of novelty has been assumed to be the result of random chance or accident. And yet, organisms seem 'designed'. When one examines the data from sequenced genomes, the changes appear NOT to be random or accidental, but one observes that whole chunks of the genome come and go. These 'chunks' often contain functional units, encoding sets of genes that together can perform some specific function. Shapiro argues that what we see in genomes is 'Natural Genetic Engineering', or designed evolution: "Thinking about genomes from an informatics perspective, it is apparent that systems engineering is a better metaphor for the evolutionary process than the conventional view of evolution as a select-biased random walk through limitless space of possible DNA configurations" (page 6)

Utilization of a deoxynucleoside diphosphate substrate by HIV reverse transcriptase

Background: Deoxynucleoside triphosphates (dNTPs) are the normal substrates for DNA sysnthesis is catalyzed by polymerases such as HIV-1 reverse transcriptase (RT). However, substantial amounts of deoxynucleoside diphosphates (dNDPs) are also present in the cell. Use of dNDPs in HIV-1 DNA sysnthesis could have significant implications for the efficacy of nucleoside RT inhibitors such as AZT which are first line therapeutics fro treatment of HIV infection. Our earlier work on HIV-1 reverse transcriptase (RT) suggested that the interaction between the γ phosphate of the incoming dNTP and RT residue K65 in the active site is not essential for dNTP insertion, implying that this polymerase may be able to insert dNPs in addition to dNTPs. Methodology/Principal Findings: We examined the ability of recombinant wild type (wt) and mutant RTs with substitutions at residue K65 to utilize a dNDP substrate in primer extension reactions. We found that wild type HIV-1 RT indeed catalyzes incorporation of dNDP substrates whereas RT with mutations of residue K645 were unable to catalyze this reaction. Wild type HIV-1 RT also catalyzed the reverse reaction, inorganic phosphate-dependent phosphorolysis. Nucleotide-mediated phosphorolytic removal of chain-terminating 3′-terminal nucleoside inhibitors such as AZT forms the basis of HIV-1 resistance to such drugs, and this removal is enhanced by thymidine analog mutations (TAMs). We found that both wt and TAM-containing RTs were able to catalyze Pi-mediated phosphorolysis of 3′-terminal AZT at physiological levels of Pi with an efficacy similar to that for ATP-dependent AZT-excision. Conclusion: We have identified two new catalytic function of HIV-1 RT, the use of dNDPs as substrates for DNA synthesis, and the use of Pi as substrate for phosphorolytic removal of primer 3′-terminal nucleotides. The ability to insert dNDPs has been documented for only one other DNA polymerase The RB69 DNA polymerase and the reverse reaction employing inorganic phosphate has not been documented for any DNA polymerase. Importantly, our results show that Pi-mediated phosphorolysis can contribute to AZT resistance and indicates that factors that influence HIV resistance to AZT are more complex than previously appreciated. © 2008 Garforth et al

Participation and satisfaction after spinal cord injury: results of a vocational and leisure outcome study

Study design: Survey. Objectives: Insight in (1) the changes in participation in vocational and leisure activities and (2) satisfaction with the current participation level of people with spinal cord injuries (SCIs) after reintegration in society. Design: Descriptive analysis of data from a questionnaire. Setting: Rehabilitation centre with special department for patients with SCIs, Groningen, The Netherlands. Subjects: A total of 57 patients with traumatic SCI living in the community, who were admitted to the rehabilitation centre two to 12 years before the current assessment. Main outcome measures: Changes in participation in activities; current life satisfaction; support and unmet needs. Results: Participation expressed in terms of hours spent on vocational and leisure activities changed to a great extent after the SCI. This was mainly determined by a large reduction of hours spent on paid work. While 60% of the respondents successfully reintegrated in work, many changes took place in the type and extent of the job. Loss of work was partially compensated with domestic and leisure activities. Sports activities were reduced substantially. The change in participation level and compensation for the lost working hours was not significantly associated with the level of SCI-specific health problems and disabilities. As was found in other studies, most respondents were satisfied with their lives. Determinants of a negative life satisfaction several years following SCI were not easily indicated. Reduced quality of life was particularly related to an unsatisfactory work and leisure situation. Conclusions: Most people with SCI in this study group were able to resume work and were satisfied with their work and leisure situation

Variations in 24-mu m morphologies among galaxies in the Spitzer Infrared Nearby Galaxies Survey: new insights into the Hubble sequence

To study the distribution of star formation and dust emission within nearby galaxies, we measured five morphological parameters in the 3.6- and 24-μm wavebands for 65 galaxies in the Spitzer Infrared Nearby Galaxies Survey (SINGS) and eight galaxies that were serendipitously observed by SINGS. The morphological parameters demonstrate strong variations along the Hubble sequence, including statistically significant differences between S0/a-Sab and Sc-Sd galaxies. Early-type galaxies are generally found to be compact, centralized, symmetric sources in the 24-μm band, while late-type galaxies are generally found to be extended, asymmetric sources. These results suggest that the processes that increase the real or apparent sizes of galaxies\u27 bulges also lead to more centralized 24-μm dust emission. Several phenomena, such as strong nuclear star formation, Seyfert activity, or outer ring structures, may cause galaxies to deviate from the general morphological trends observed at 24 μm. We also note that the 24-μm morphologies of Sdm-Im galaxies are quite varied, with some objects appearing very compact and symmetric but others appearing diffuse and asymmetric. These variations reflect the wide variation in star formation in irregular galaxies as observed at other wavelengths. The variations in the 24-μm morphological parameters across the Hubble sequence mirror many of the morphological trends seen in other tracers of the ISM and in stellar emission. However, the 24-μm morphological parameters for the galaxies in this sample do not match the morphological parameters measured in the stellar wavebands. This implies that the distribution of dust emission is related to but not equivalent to the distribution of stellar emission

Glueball masses in the large N limit

The lowest-lying glueball masses are computed in SU($N$) gauge theory on a spacetime lattice for constant value of the lattice spacing $a$ and for $N$ ranging from 3 to 8. The lattice spacing is fixed using the deconfinement temperature at temporal extension of the lattice $N_T = 6$. The calculation is conducted employing in each channel a variational ansatz performed on a large basis of operators that includes also torelon and (for the lightest states) scattering trial functions. This basis is constructed using an automatic algorithm that allows us to build operators of any size and shape in any irreducible representation of the cubic group. A good signal is extracted for the ground state and the first excitation in several symmetry channels. It is shown that all the observed states are well described by their large $N$ values, with modest ${\cal O}(1/N^2)$ corrections. In addition spurious states are identified that couple to torelon and scattering operators. As a byproduct of our calculation, the critical couplings for the deconfinement phase transition for N=5 and N=7 and temporal extension of the lattice $N_T=6$ are determined.Comment: 1+36 pages, 22 tables, 21 figures. Typos corrected, conclusions unchanged, matches the published versio

Prenatal origin of childhood AML occurs less frequently than in childhood ALL

Background While there is enough convincing evidence in childhood acute lymphoblastic leukemia (ALL), the data on the pre-natal origin in childhood acute myeloid leukemia (AML) are less comprehensive. Our study aimed to screen Guthrie cards (neonatal blood spots) of non-infant childhood AML and ALL patients for the presence of their respective leukemic markers. Methods We analysed Guthrie cards of 12 ALL patients aged 2–6 years using immunoglobulin (Ig) and T-cell receptor (TCR) gene rearrangements (n = 15) and/or intronic breakpoints of TEL/AML1 fusion gene (n = 3). In AML patients (n = 13, age 1–14 years) PML/RARalpha (n = 4), CBFbeta/MYH11 (n = 3), AML1/ETO (n = 2), MLL/AF6 (n = 1), MLL/AF9 (n = 1) and MLL/AF10 (n = 1) fusion genes and/or internal tandem duplication of FLT3 gene (FLT3/ITD) (n = 2) were used as clonotypic markers. Assay sensitivity determined using serial dilutions of patient DNA into the DNA of a healthy donor allowed us to detect the pre-leukemic clone in Guthrie card providing 1–3 positive cells were present in the neonatal blood spot. Results In 3 patients with ALL (25%) we reproducibly detected their leukemic markers (Ig/TCR n = 2; TEL/AML1 n = 1) in the Guthrie card. We did not find patient-specific molecular markers in any patient with AML. Conclusion In the largest cohort examined so far we used identical approach for the backtracking of non-infant childhood ALL and AML. Our data suggest that either the prenatal origin of AML is less frequent or the load of pre-leukemic cells is significantly lower at birth in AML compared to ALL cases

Intrinsic ripples in graphene

The stability of two-dimensional (2D) layers and membranes is subject of a long standing theoretical debate. According to the so called Mermin-Wagner theorem, long wavelength fluctuations destroy the long-range order for 2D crystals. Similarly, 2D membranes embedded in a 3D space have a tendency to be crumpled. These dangerous fluctuations can, however, be suppressed by anharmonic coupling between bending and stretching modes making that a two-dimensional membrane can exist but should present strong height fluctuations. The discovery of graphene, the first truly 2D crystal and the recent experimental observation of ripples in freely hanging graphene makes these issues especially important. Beside the academic interest, understanding the mechanisms of stability of graphene is crucial for understanding electronic transport in this material that is attracting so much interest for its unusual Dirac spectrum and electronic properties. Here we address the nature of these height fluctuations by means of straightforward atomistic Monte Carlo simulations based on a very accurate many-body interatomic potential for carbon. We find that ripples spontaneously appear due to thermal fluctuations with a size distribution peaked around 70 \AA which is compatible with experimental findings (50-100 \AA) but not with the current understanding of stability of flexible membranes. This unexpected result seems to be due to the multiplicity of chemical bonding in carbon.Comment: 14 pages, 6 figure

Intraspecfic variation in cold-temperature metabolic phenotypes of Arabidopsis lyrata ssp petraea

Atmospheric temperature is a key factor in determining the distribution of a plant species. Alongside this, plant populations growing at the margin of their range may exhibit traits that indicate genetic differentiation and adaptation to their local abiotic environment. We investigated whether geographically separated marginal populations of Arabidopsis lyrata ssp. petraea have distinct metabolic phenotypes associated with exposure to cold temperatures. Seeds of A. petraea were obtained from populations along a latitudinal gradient, namely Wales, Sweden and Iceland and grown in a controlled cabinet environment. Mannose, glucose, fructose, sucrose and raffinose concentrations were different between cold treatments and populations, especially in the Welsh population, but polyhydric alcohol concentrations were not. The free amino acid compositions were population specific, with fold differences in most amino acids, especially in the Icelandic populations, with gross changes in amino acids, particularly those associated with glutamine metabolism. Metabolic fingerprints and profiles were obtained. Principal component analysis (PCA) of metabolite fingerprints revealed metabolic characteristic phenotypes for each population and temperature. It is suggested that amino acids and carbohydrates were responsible for discriminating populations within the PCA. Metabolite fingerprinting and profiling has proved to be sufficiently sensitive to identify metabolic differences between plant populations at different atmospheric temperatures. These findings show that there is significant natural variation in cold metabolism among populations of A. l. petraea which may signify plant adaptation to local climates