Review of deaths related to taking ecstasy, England and Wales, 1997-2000

Original article can be found at: http://www.bmj.com/archive/--Copyright BMJ Publishing Group Ltd DOI : 10.1136/bmj.326.7380.80Peer reviewe

Immunogenicity of a low-dose diphtheria, tetanus and acellular pertussis combination vaccine with either inactivated or oral polio vaccine compared to standard-dose diphtheria, tetanus, acellular pertussis when used as a pre-school booster in UK children : a 5-year follow-up of a randomised controlled study

This serological follow up study assessed the kinetics of antibody response in children who previously participated in a single centre, open-label, randomised controlled trial of low-dose compared to standard-dose diphtheria booster preschool vaccinations in the United Kingdom (UK). Children had previously been randomised to receive one of three combination vaccines: either a combined adsorbed tetanus, low-dose diphtheria, 5-component acellular pertussis and inactivated polio vaccine (IPV) (Tdap-IPV, Repevax(®); Sanofi Pasteur MSD); a combined adsorbed tetanus, low-dose diphtheria and 5-component acellular pertussis vaccine (Tdap, Covaxis(®); Sanofi Pasteur MSD) given concomitantly with oral polio vaccine (OPV); or a combined adsorbed standard-dose diphtheria, tetanus, 2-component acellular pertussis and IPV (DTap-IPV, Tetravac(®); Sanofi Pasteur MSD). Blood samples for the follow-up study were taken at 1, 3 and 5 years after participation in the original trial (median, 5.07 years of age at year 1), and antibody persistence to each vaccine antigen measured against defined serological thresholds of protection. All participants had evidence of immunity to diphtheria with antitoxin concentrations greater than 0.01IU/mL five years after booster vaccination and 75%, 67% and 79% of children who received Tdap-IPV, Tdap+OPV and DTap-IPV, respectively, had protective antitoxin levels greater than 0.1IU/mL. Long lasting protective immune responses to tetanus and polio antigens were also observed in all groups, though polio responses were lower in the sera of those who received OPV. Low-dose diphtheria vaccines provided comparable protection to the standard-dose vaccine and are suitable for use for pre-school booster vaccination

Computing Discrete Logarithms in an Interval

The discrete logarithm problem in an interval of size $N$ in a group $G$ is: Given $g, h \in G$ and an integer $N$ to find an integer $0 \le n \le N$, if it exists, such that $h = g^n$. Previously the best low-storage algorithm to solve this problem was the van Oorschot and Wiener version of the Pollard kangaroo method. The heuristic average case running time of this method is $(2 + o(1)) \sqrt{N}$ group operations. We present two new low-storage algorithms for the discrete logarithm problem in an interval of size $N$. The first algorithm is based on the Pollard kangaroo method, but uses 4 kangaroos instead of the usual two. We explain why this algorithm has heuristic average case expected running time of $(1.715 + o(1)) \sqrt{N}$ group operations. The second algorithm is based on the Gaudry-Schost algorithm and the ideas of our first algorithm. We explain why this algorithm has heuristic average case expected running time of $(1.661 + o(1)) \sqrt{N}$ group operations. We give experimental results that show that the methods do work close to that predicted by the theoretical analysis. This is a revised version since the published paper that contains a corrected proof of Theorem 6 (the statement of Theorem 6 is unchanged). We thank Ravi Montenegro for pointing out the errors

Descriptive oceanography during the Frontal Air‐Sea Interaction Experiment: Medium‐ to large‐scale variability

Medium‐ and large‐scale oceanographic variability in the Sargasso Sea is examined during the Frontal Air‐Sea Interaction Experiment (FASINEX), focusing primarily on processes that influence the formation of subtropical fronts. From Fall to Spring the mean meridional gradient of meridional Ekman transport in the Subtropical Convergence Zone (STCZ) enhances the meridional sea surface temperature (Ts) gradients between 26° and 32°N. In the presence of this enhanced mean gradient, baroclinic eddies with zonal wavelengths of ≈800 km and periods of ≈200 days exert the dominant influence on the formation of subtropical fronts at medium and large scales. These eddies generate westward propagating Ts anomaly features with the same dominant wavelengths and periods. They are confined between 26° and 32°N and have amplitudes that occasionally exceed ±1°C. Ts fronts tend to be found within bands ≈200 km wide that roughly follow the periphery of these anomaly features. Deformation in the horizontal eddy current field is primarily responsible for the existence of these frontal bands. The migration of the strong front originally bracketed by the FASINEX moored array was related to the westward propagation of the larger‐scale eddy/anomaly/frontal‐band pattern. The moored array was located within a warm‐anomaly feature during most of the experiment, which produced exceptionally warm conditions in the upper ocean. These anomalies are confined between 26° and 32°N, not only because the relatively large seasonal mean Tsy there allows horizontal eddy currents to force strong anomalies, but also because the baroclinic eddies with wavelengths of ≈800 km and periods of ≈200 days are confined to the STCZ. Large meridional variability exists in many properties of the eddy field, much of which can be traced to the influence of the Sargasso Sea mean current field on eddy variability

An Exactly Conservative Integrator for the n-Body Problem

The two-dimensional n-body problem of classical mechanics is a non-integrable Hamiltonian system for n > 2. Traditional numerical integration algorithms, which are polynomials in the time step, typically lead to systematic drifts in the computed value of the total energy and angular momentum. Even symplectic integration schemes exactly conserve only an approximate Hamiltonian. We present an algorithm that conserves the true Hamiltonian and the total angular momentum to machine precision. It is derived by applying conventional discretizations in a new space obtained by transformation of the dependent variables. We develop the method first for the restricted circular three-body problem, then for the general two-dimensional three-body problem, and finally for the planar n-body problem. Jacobi coordinates are used to reduce the two-dimensional n-body problem to an (n-1)-body problem that incorporates the constant linear momentum and center of mass constraints. For a four-body choreography, we find that a larger time step can be used with our conservative algorithm than with symplectic and conventional integrators.Comment: 17 pages, 3 figures; to appear in J. Phys. A.: Math. Ge

Twelve years of SAMtools and BCFtools.

BACKGROUND: SAMtools and BCFtools are widely used programs for processing and analysing high-throughput sequencing data. They include tools for file format conversion and manipulation, sorting, querying, statistics, variant calling, and effect analysis amongst other methods. FINDINGS: The first version appeared online 12 years ago and has been maintained and further developed ever since, with many new features and improvements added over the years. The SAMtools and BCFtools packages represent a unique collection of tools that have been used in numerous other software projects and countless genomic pipelines. CONCLUSION: Both SAMtools and BCFtools are freely available on GitHub under the permissive MIT licence, free for both non-commercial and commercial use. Both packages have been installed >1 million times via Bioconda. The source code and documentation are available from https://www.htslib.org

A Model-Based Analysis of GC-Biased Gene Conversion in the Human and Chimpanzee Genomes

GC-biased gene conversion (gBGC) is a recombination-associated process that favors the fixation of G/C alleles over A/T alleles. In mammals, gBGC is hypothesized to contribute to variation in GC content, rapidly evolving sequences, and the fixation of deleterious mutations, but its prevalence and general functional consequences remain poorly understood. gBGC is difficult to incorporate into models of molecular evolution and so far has primarily been studied using summary statistics from genomic comparisons. Here, we introduce a new probabilistic model that captures the joint effects of natural selection and gBGC on nucleotide substitution patterns, while allowing for correlations along the genome in these effects. We implemented our model in a computer program, called phastBias, that can accurately detect gBGC tracts about 1 kilobase or longer in simulated sequence alignments. When applied to real primate genome sequences, phastBias predicts gBGC tracts that cover roughly 0.3% of the human and chimpanzee genomes and account for 1.2% of human-chimpanzee nucleotide differences. These tracts fall in clusters, particularly in subtelomeric regions; they are enriched for recombination hotspots and fast-evolving sequences; and they display an ongoing fixation preference for G and C alleles. They are also significantly enriched for disease-associated polymorphisms, suggesting that they contribute to the fixation of deleterious alleles. The gBGC tracts provide a unique window into historical recombination processes along the human and chimpanzee lineages. They supply additional evidence of long-term conservation of megabase-scale recombination rates accompanied by rapid turnover of hotspots. Together, these findings shed new light on the evolutionary, functional, and disease implications of gBGC. The phastBias program and our predicted tracts are freely available. © 2013 Capra et al

Seasonal kinetic energy variability of near-inertial motions

Author Posting. © American Meteorological Society, 2009. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Journal of Physical Oceanography 39 (2009): 1035-1049, doi:10.1175/2008JPO3920.1.Seasonal variability of near-inertial horizontal kinetic energy is examined using observations from a series of McLane Moored Profiler moorings located at 39°N, 69°W in the western North Atlantic Ocean in combination with a one-dimensional, depth-integrated kinetic energy model. The time-mean kinetic energy and shear vertical wavenumber spectra of the high-frequency motions at the mooring site are in reasonable agreement with the Garrett–Munk internal wave description. Time series of depth-dependent and depth-integrated near-inertial kinetic energy are calculated from available mooring data after filtering to isolate near-inertial-frequency motions. These data document a pronounced seasonal cycle featuring a wintertime maximum in the depth-integrated near-inertial kinetic energy deriving chiefly from the variability in the upper 500 m of the water column. The seasonal signal in the near-inertial kinetic energy is most prominent for motions with vertical wavelengths greater than 100 m but observable wintertime enhancement is seen down to wavelengths of the order of 10 m. Rotary vertical wavenumber spectra exhibit a dominance of clockwise-with-depth energy, indicative of downward energy propagation and implying a surface energy source. A simple depth-integrated near-inertial kinetic energy model consisting of a wind forcing term and a dissipation term captures the order of magnitude of the observed near-inertial kinetic energy as well as its seasonal cycle.Funding to initiate the McLane Moored Profiler observations at Line W were provided by grants from the G. Unger Vetlesen Foundation and the Comer Charitable Fund to the Woods Hole Oceanographic Institution’s Ocean and Climate Change Institute. Ongoing moored observations at Line W are supported by the National Science Foundation (NSF Grant OCE-0241354)

Common cancer-associated imbalances in the DNA damage response confer sensitivity to single agent ATR inhibition

ATR is an attractive target in cancer therapy because it signals replication stress and DNA lesions for repair and to S/G2 checkpoints. Cancer-specific defects in the DNA damage response (DDR) may render cancer cells vulnerable to ATR inhibition alone. We determined the cytotoxicity of the ATR inhibitor VE-821 in isogenically matched cells with DDR imbalance. Cell cycle arrest, DNA damage accumulation and repair were determined following VE-821 exposure. Defects in homologous recombination repair (HRR: ATM, BRCA2 and XRCC3) and base excision repair (BER: XRCC1) conferred sensitivity to VE-821. Surprisingly, the loss of different components of the trimeric non-homologous end-joining (NHEJ) protein DNA-PK had opposing effects. Loss of the DNA-binding component, Ku80, caused hypersensitivity to VE-821, but loss of its partner catalytic subunit, DNA-PKcs, did not. Unexpectedly, VE-821 was particularly cytotoxic to human and hamster cells expressing high levels of DNA-PKcs. High DNA-PKcs was associated with replicative stress and activation of the DDR. VE-821 suppressed HRR, determined by RAD51 focus formation, to a greater extent in cells with high DNA-PKcs. Defects in HRR and BER and high DNA-PKcs expression, that are common in cancer, confer sensitivity to ATR inhibitor monotherapy and may be developed as predictive biomarkers for personalised medicine