We seek to improve estimates of the power spectrum covariance matrix from a limited number of simulations by employing a novel statistical technique known as shrinkage estimation. The shrinkage ...technique optimally combines an empirical estimate of the covariance with a model (the target) to minimize the total mean squared error compared to the true underlying covariance. We test this technique on N-body simulations and evaluate its performance by estimating cosmological parameters. Using a simple diagonal target, we show that the shrinkage estimator significantly outperforms both the empirical covariance and the target individually when using a small number of simulations. We find that reducing noise in the covariance estimate is essential for properly estimating the values of cosmological parameters as well as their confidence intervals. We extend our method to the jackknife covariance estimator and again find significant improvement, though simulations give better results. Even for thousands of simulations we still find evidence that our method improves estimation of the covariance matrix. Because our method is simple, requires negligible additional numerical effort, and produces superior results, we always advocate shrinkage estimation for the covariance of the power spectrum and other large-scale structure measurements when purely theoretical modeling of the covariance is insufficient.
The Marfan syndrome has been linked to the FBN1 gene encoding the microfibrillar glycoprotein fibrillin. To date, there have been no descriptions of microfibrillar abnormalities characteristic of ...this connective tissue disorder, although biochemical analyses have highlighted apparent abnormalities in fibrillin synthesis, secretion and processing. We have conducted a biochemical and ultrastructural investigation of fibrillin expression and assembly by a panel of dermal fibroblast lines from patients with Marfan syndrome and related diseases. The study has highlighted marked differences between cells in terms of secretion and aggregation of newly-synthesised fibrillin. In addition, electron microscopic visualization of fibrillin assemblies has clearly demonstrated for the first time the plethora of microfibrillar abnormalities that underlie this heterogeneous disorder. These data emphasize the molecular complexity that is a feature of the diverse clinical phenotypes exhibited by Marfan patients.
The human gastrointestinal tract consists of a dense and diverse microbial community, the composition of which is intimately linked to health. Extrinsic factors such as diet and host immunity are ...insufficient to explain the constituents of this community, and direct interactions between co-resident microorganisms have been implicated as important drivers of microbiome composition. The genomes of bacteria derived from the gut microbiome contain several pathways that mediate contact-dependent interbacterial antagonism
. Many members of the Gram-negative order Bacteroidales encode the type VI secretion system (T6SS), which facilitates the delivery of toxic effector proteins into adjacent cells
. Here we report the occurrence of acquired interbacterial defence (AID) gene clusters in Bacteroidales species that reside within the human gut microbiome. These clusters encode arrays of immunity genes that protect against T6SS-mediated intra- and inter-species bacterial antagonism. Moreover, the clusters reside on mobile elements, and we show that their transfer is sufficient to confer resistance to toxins in vitro and in gnotobiotic mice. Finally, we identify and validate the protective capability of a recombinase-associated AID subtype (rAID-1) that is present broadly in Bacteroidales genomes. These rAID-1 gene clusters have a structure suggestive of active gene acquisition and include predicted immunity factors of toxins derived from diverse organisms. Our data suggest that neutralization of contact-dependent interbacterial antagonism by AID systems helps to shape human gut microbiome ecology.
Climate change threatens to release abundant carbon that is sequestered at high latitudes, but the constraints on microbial metabolisms that mediate the release of methane and carbon dioxide are ...poorly understood
. The role of viruses, which are known to affect microbial dynamics, metabolism and biogeochemistry in the oceans
, remains largely unexplored in soil. Here, we aimed to investigate how viruses influence microbial ecology and carbon metabolism in peatland soils along a permafrost thaw gradient in Sweden. We recovered 1,907 viral populations (genomes and large genome fragments) from 197 bulk soil and size-fractionated metagenomes, 58% of which were detected in metatranscriptomes and presumed to be active. In silico predictions linked 35% of the viruses to microbial host populations, highlighting likely viral predators of key carbon-cycling microorganisms, including methanogens and methanotrophs. Lineage-specific virus/host ratios varied, suggesting that viral infection dynamics may differentially impact microbial responses to a changing climate. Virus-encoded glycoside hydrolases, including an endomannanase with confirmed functional activity, indicated that viruses influence complex carbon degradation and that viral abundances were significant predictors of methane dynamics. These findings suggest that viruses may impact ecosystem function in climate-critical, terrestrial habitats and identify multiple potential viral contributions to soil carbon cycling.
The optimal timing of radiotherapy after radical prostatectomy for prostate cancer is uncertain. We aimed to compare the efficacy and safety of adjuvant radiotherapy versus an observation policy with ...salvage radiotherapy for prostate-specific antigen (PSA) biochemical progression.
We did a randomised controlled trial enrolling patients with at least one risk factor (pathological T-stage 3 or 4, Gleason score of 7–10, positive margins, or preoperative PSA ≥10 ng/mL) for biochemical progression after radical prostatectomy (RADICALS-RT). The study took place in trial-accredited centres in Canada, Denmark, Ireland, and the UK. Patients were randomly assigned in a 1:1 ratio to adjuvant radiotherapy or an observation policy with salvage radiotherapy for PSA biochemical progression (PSA ≥0·1 ng/mL or three consecutive rises). Masking was not deemed feasible. Stratification factors were Gleason score, margin status, planned radiotherapy schedule (52·5 Gy in 20 fractions or 66 Gy in 33 fractions), and centre. The primary outcome measure was freedom from distant metastases, designed with 80% power to detect an improvement from 90% with salvage radiotherapy (control) to 95% at 10 years with adjuvant radiotherapy. We report on biochemical progression-free survival, freedom from non-protocol hormone therapy, safety, and patient-reported outcomes. Standard survival analysis methods were used. A hazard ratio (HR) of less than 1 favoured adjuvant radiotherapy. This study is registered with ClinicalTrials.gov, NCT00541047.
Between Nov 22, 2007, and Dec 30, 2016, 1396 patients were randomly assigned, 699 (50%) to salvage radiotherapy and 697 (50%) to adjuvant radiotherapy. Allocated groups were balanced with a median age of 65 years (IQR 60–68). Median follow-up was 4·9 years (IQR 3·0–6·1). 649 (93%) of 697 participants in the adjuvant radiotherapy group reported radiotherapy within 6 months; 228 (33%) of 699 in the salvage radiotherapy group reported radiotherapy within 8 years after randomisation. With 169 events, 5-year biochemical progression-free survival was 85% for those in the adjuvant radiotherapy group and 88% for those in the salvage radiotherapy group (HR 1·10, 95% CI 0·81–1·49; p=0·56). Freedom from non-protocol hormone therapy at 5 years was 93% for those in the adjuvant radiotherapy group versus 92% for those in the salvage radiotherapy group (HR 0·88, 95% CI 0·58–1·33; p=0·53). Self-reported urinary incontinence was worse at 1 year for those in the adjuvant radiotherapy group (mean score 4·8 vs 4·0; p=0·0023). Grade 3–4 urethral stricture within 2 years was reported in 6% of individuals in the adjuvant radiotherapy group versus 4% in the salvage radiotherapy group (p=0·020).
These initial results do not support routine administration of adjuvant radiotherapy after radical prostatectomy. Adjuvant radiotherapy increases the risk of urinary morbidity. An observation policy with salvage radiotherapy for PSA biochemical progression should be the current standard after radical prostatectomy.
Cancer Research UK, MRC Clinical Trials Unit, and Canadian Cancer Society.
By bringing together a large group of participants with diverse skillsets, hackathons aim to make good headway into a particular research topic over a short period of time. This collaborative ...approach supports relationship building, cross team working and the development of technical skills across different areas.
Across the globe, wild bees are threatened by ongoing natural habitat loss, risking the maintenance of plant biodiversity and agricultural production. Despite the ecological and economic importance ...of wild bees and the fact that several species are now managed for pollination services worldwide, little is known about how land use and beekeeping practices jointly influence gene flow. Using stingless bees as a model system, containing wild and managed species that are presumed to be particularly susceptible to habitat degradation, here we examine the main drivers of tropical bee gene flow. We employ a novel landscape genetic approach to analyse data from 135 populations of 17 stingless bee species distributed across diverse tropical biomes within the Americas. Our work has important methodological implications, as we illustrate how a maximum‐likelihood approach can be applied in a meta‐analysis framework to account for multiple factors, and weight estimates by sample size. In contrast to previously held beliefs, gene flow was not related to body size or deforestation, and isolation by geographic distance (IBD) was significantly affected by management, with managed species exhibiting a weaker IBD than wild ones. Our study thus reveals the critical importance of beekeeping practices in shaping the patterns of genetic differentiation across bee species. Additionally, our results show that many stingless bee species maintain high gene flow across heterogeneous landscapes. We suggest that future efforts to preserve wild tropical bees should focus on regulating beekeeping practices to maintain natural gene flow and enhancing pollinator‐friendly habitats, prioritizing species showing a limited dispersal ability.
We present the design and performance of the multi-object fiber spectrographs for the Sloan Digital Sky Survey (SDSS) and their upgrade for the Baryon Oscillation Spectroscopic Survey (BOSS). ...Originally commissioned in Fall 1999 on the 2.5-m aperture Sloan Telescope at Apache Point Observatory, the spectrographs produced more than 1.5 million spectra for the SDSS and SDSS-II surveys, enabling a wide variety of Galactic and extra-galactic science including the first observation of baryon acoustic oscillations in 2005. The spectrographs were upgraded in 2009 and are currently in use for BOSS, the flagship survey of the third-generation SDSS-III project. BOSS will measure redshifts of 1.35 million massive galaxies to redshift 0.7 and Lyman-alpha absorption of 160,000 high redshift quasars over 10,000 square degrees of sky, making percent level measurements of the absolute cosmic distance scale of the Universe and placing tight constraints on the equation of state of dark energy. The twin multi-object fiber spectrographs utilize a simple optical layout with reflective collimators, gratings, all-refractive cameras, and state-of-the-art CCD detectors to produce hundreds of spectra simultaneously in two channels over a bandpass covering the near ultraviolet to the near infrared, with a resolving power R = \lambda/FWHM ~ 2000. Building on proven heritage, the spectrographs were upgraded for BOSS with volume-phase holographic gratings and modern CCD detectors, improving the peak throughput by nearly a factor of two, extending the bandpass to cover 360 < \lambda < 1000 nm, and increasing the number of fibers from 640 to 1000 per exposure. In this paper we describe the original SDSS spectrograph design and the upgrades implemented for BOSS, and document the predicted and measured performances.
Astrophys.J. 606 (2004) 1-24 Eigenmode analysis is one of the most promising methods of analyzing large
data sets in ongoing and near-future galaxy surveys. In such analyses, a fast
evaluation of the ...correlation matrix in arbitrary cosmological models is
crucial. The observational effects, including peculiar velocity distortions in
redshift space, light-cone effects, selection effects, and effects of the
complex shape of the survey geometry, should be taken into account in the
analysis. In the framework of the linear theory of gravitational instability,
we provide the methodology to quickly compute the correlation matrix. Our
methods are not restricted to shallow redshift surveys, arbitrarily deep
samples can be dealt with as well. Therefore, our methods are useful in
constraining the geometry of the universe and the dark energy component, as
well as the power spectrum of galaxies, since ongoing and near-future galaxy
surveys probe the universe at intermediate to deep redshifts, z ~ 0.2--5. In
addition to the detailed methods to compute the correlation matrix in
3-dimensional redshift surveys, methods to calculate the matrix in
2-dimensional projected samples are also provided. Prospects of applying our
methods to likelihood estimation of the cosmological parameters are discussed.
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