A New Precision Measurement of the Small-Scale Line-of-Sight Power Spectrum of the Lyα{\alpha} Forest

We present a new measurement of the Ly${\alpha}$ forest power spectrum at $1.8 < z < 3.4$ using 74 Keck/HIRES and VLT/UVES high-resolution, high-S/N quasar spectra. We developed a custom pipeline to measure the power spectrum and its uncertainty, which fully accounts for finite resolution and noise, and corrects for the bias induced by masking missing data, DLAs, and metal absorption lines. Our measurement results in unprecedented precision on the small-scale modes $k > 0.02\,\mathrm{s\,km^{-1}}$, unaccessible to previous SDSS/BOSS analyses. It is well known that these high-$k$ modes are highly sensitive to the thermal state of the intergalactic medium, however contamination by narrow metal lines is a significant concern. We quantify the effect of metals on the small-scale power, and find a modest effect on modes with $k < 0.1\,\mathrm{s\,km^{-1}}$. As a result, by masking metals and restricting to $k < 0.1\,\mathrm{s\,km^{-1}}$ their impact is completely mitigated. We present an end-to-end Bayesian forward modeling framework whereby mock spectra with the same noise, resolution, and masking as our data are generated from Ly${\alpha}$ forest simulations. These mocks are used to build a custom emulator, enabling us to interpolate between a sparse grid of models and perform MCMC fits. Our results agree well with BOSS on scales $k < 0.02\,\mathrm{s\,km^{-1}}$ where the measurements overlap. The combination of BOSS' percent level low-$k$ precision with our $5-15\%$ high-$k$ measurements, results in a powerful new dataset for precisely constraining the thermal history of the intergalactic medium, cosmological parameters, and the nature of dark matter. The power spectra and their covariance matrices are provided as electronic tables.Comment: 24 pages, 12 figures, accepted for publication in ApJ, machine readable tables will be made available after publication in the journa

What if curriculum theorists were to share centre stage after school hours?

The after school hours time period is seen as a critical time for encouraging children between the ages of 5-7 to be active and play more sport. Often, existing age-appropriate junior sport programs represent a form of curriculum used in this time period. The curriculum in these programs is based on non-competitive, modified activities to minimise the risk of emotional harm to children and prepare them to play the mature form of the game. This paper uses Marsh and Willis' curriculum continuum to advocate an alternative perspective on addressing the needs of those children wishing to have rules and competition in the games they play as they participate in junior sports development programs. This perspective is supported by an analysis of two of the age-appropriate junior sport programs. Examples are drawn from the comments of Executive Officers, Program Officers, delivers, and parents. Key themes running through the comments were that some children were being discouraged from continued participation in sport due to the removal of competition and a feeling that they were not playing a version of the game they recognised

Discovery of three new near-pristine absorption clouds at z=2.6z=2.6-4.4

We report the discovery of three new "near-pristine" Lyman Limit Systems (LLSs), with metallicities ~1/1000 solar, at redshifts 2.6, 3.8 and 4.0, with a targeted survey at the Keck Observatory. High resolution echelle spectra of eight candidates yielded precise column densities of hydrogen and weak, but clearly detected, metal lines in seven LLSs; we previously reported the one remaining, apparently metal-free LLS, to have metallicity <1/10000 solar. Robust photoionisation modelling provides metallicities [Si/H] = -3.05 to -2.94, with 0.26 dex uncertainties (95% confidence) for three LLSs, and [Si/H] >~ -2.5 for the remaining four. Previous simulations suggest that near-pristine LLSs could be the remnants of PopIII supernovae, so comparing their detailed metal abundances with nucleosynthetic yields from supernovae models is an important goal. Unfortunately, at most two different metals were detected in each new system, despite their neutral hydrogen column densities (10^{19.2-19.4} cm^{-2}) being two orders of magnitude larger than the two previous, serendipitously discovered near-pristine LLSs. Nevertheless, the success of this first targeted survey for near-pristine systems demonstrates the prospect that a much larger, future survey could identify clear observational signatures of PopIII stars. With a well-understood selection function, such a survey would also yield the number density of near-pristine absorbers which, via comparison to future simulations, could reveal the origin(s) of these rare systems.Comment: Accepted by MNRAS. 21 pages, 27 figure

Interaction of Cryptococcus neoformans Rim101 and Protein Kinase A Regulates Capsule

Cryptococcus neoformans is a prevalent human fungal pathogen that must survive within various tissues in order to establish a human infection. We have identified the C. neoformans Rim101 transcription factor, a highly conserved pH-response regulator in many fungal species. The rim101Δ mutant strain displays growth defects similar to other fungal species in the presence of alkaline pH, increased salt concentrations, and iron limitation. However, the rim101Δ strain is also characterized by a striking defect in capsule, an important virulence-associated phenotype. This capsular defect is likely due to alterations in polysaccharide attachment to the cell surface, not in polysaccharide biosynthesis. In contrast to many other C. neoformans capsule-defective strains, the rim101Δ mutant is hypervirulent in animal models of cryptococcosis. Whereas Rim101 activation in other fungal species occurs through the conserved Rim pathway, we demonstrate that C. neoformans Rim101 is also activated by the cAMP/PKA pathway. We report here that C. neoformans uses PKA and the Rim pathway to regulate the localization, activation, and processing of the Rim101 transcription factor. We also demonstrate specific host-relevant activating conditions for Rim101 cleavage, showing that C. neoformans has co-opted conserved signaling pathways to respond to the specific niche within the infected host. These results establish a novel mechanism for Rim101 activation and the integration of two conserved signaling cascades in response to host environmental conditions

Beneficial effects of ivabradine in patients with heart failure, low ejection fraction, and heart rate above 77 b.p.m.

Aims: Ivabradine has been approved in heart failure with reduced ejection fraction (HFrEF) and elevated heart rate despite guideline‐directed medical therapy (GDMT) to reduce cardiovascular (CV) death and hospitalization for worsening HF. The median value of 77 b.p.m. is the lower bound selected for the regulatory approval in Canada, South Africa, and Australia. Patient‐reported outcomes (PROs) including symptoms, quality of life, and global assessment are considered of major interest in the global plan of care of patients with HF. However, the specific impact of GDMT, and specifically ivabradine, on PRO remains poorly studied. In the subgroup of patients from the Systolic Heart failure treatment with the If inhibitor ivabradine Trial (SHIFT) who had heart rate above the median of 77 b.p.m. (pre‐specified analysis) and for whom the potential for improvement was expected to be larger, we aimed (i) to evaluate the effects of ivabradine on PRO (symptoms, quality of life, and global assessment); (ii) to consolidate the effects of ivabradine on the primary composite endpoint of CV death and hospitalization for HF; and (iii) to reassess the effects of ivabradine on left ventricular (LV) remodelling. Methods and results: Comparisons were made according to therapy, and proportional hazards models (adjusted for baseline beta‐blocker therapy) were used to estimate the association between ivabradine and various outcomes. In SHIFT, n = 3357 (51.6%) patients had a baseline heart rate &gt; 77 b.p.m. After a median follow‐up of 22.9 months (inter‐quartile range 18–28 months), ivabradine on top of GDMT improved symptoms (28% vs. 23% improvement in New York Heart Association functional class, P = 0.0003), quality of life (5.3 vs. 2.2 improvement in Kansas City Cardiomyopathy Questionnaire overall summary score, P = 0.005), and global assessment [from both patient (improved in 72.3%) and physician (improved in 61.0%) perspectives] significantly more than did placebo (both P &lt; 0.0001). Ivabradine induced a 25% reduction in the combined endpoint of CV death and hospitalization for HF (hazard ratio 0.75; P &lt; 0.0001), which translates into a number of patients needed to be treated for 1 year of 17. Patients under ivabradine treatment demonstrated a significant reduction in LV dimensions when reassessed at 8 months (P &lt; 0.05). Conclusions: In patients with chronic HFrEF, sinus rhythm, and a heart rate &gt; 77 b.p.m. while on GDMT, the present analysis brings novel insights into the role of ivabradine in improving the management of HFrEF, particularly with regard to PRO (ISRCTN70429960)

Phylotastic! Making Tree-of-Life Knowledge Accessible, Reusable and Convenient

Scientists rarely reuse expert knowledge of phylogeny, in spite of years of effort to assemble a great "Tree of Life" (ToL). A notable exception involves the use of Phylomatic, which provides tools to generate custom phylogenies from a large, pre-computed, expert phylogeny of plant taxa. This suggests great potential for a more generalized system that, starting with a query consisting of a list of any known species, would rectify non-standard names, identify expert phylogenies containing the implicated taxa, prune away unneeded parts, and supply branch lengths and annotations, resulting in a custom phylogeny suited to the user's needs. Such a system could become a sustainable community resource if implemented as a distributed system of loosely coupled parts that interact through clearly defined interfaces. Results: With the aim of building such a "phylotastic" system, the NESCent Hackathons, Interoperability, Phylogenies (HIP) working group recruited 2 dozen scientist-programmers to a weeklong programming hackathon in June 2012. During the hackathon (and a three-month follow-up period), 5 teams produced designs, implementations, documentation, presentations, and tests including: (1) a generalized scheme for integrating components; (2) proof-of-concept pruners and controllers; (3) a meta-API for taxonomic name resolution services; (4) a system for storing, finding, and retrieving phylogenies using semantic web technologies for data exchange, storage, and querying; (5) an innovative new service, DateLife.org, which synthesizes pre-computed, time-calibrated phylogenies to assign ages to nodes; and (6) demonstration projects. These outcomes are accessible via a public code repository (GitHub.com), a website (www.phylotastic.org), and a server image. Conclusions: Approximately 9 person-months of effort (centered on a software development hackathon) resulted in the design and implementation of proof-of-concept software for 4 core phylotastic components, 3 controllers, and 3 end-user demonstration tools. While these products have substantial limitations, they suggest considerable potential for a distributed system that makes phylogenetic knowledge readily accessible in computable form. Widespread use of phylotastic systems will create an electronic marketplace for sharing phylogenetic knowledge that will spur innovation in other areas of the ToL enterprise, such as annotation of sources and methods and third-party methods of quality assessment.NESCent (the National Evolutionary Synthesis Center)NSF EF-0905606iPlant Collaborative (NSF) DBI-0735191Biodiversity Synthesis Center (BioSync) of the Encyclopedia of LifeComputer Science