Development of neuroendocrine components of the thyroid axis in the direct-developing frog Eleutherodactylus coqui: formation of the median eminence and onset of pituitary TSH production.

Direct-developing frogs lack, wholly or in part, a wide range of larval features found in metamorphosing species and form adult-specific features precociously, during embryogenesis. Most information on thyroid regulation of direct development relies on hormone manipulations; the ontogeny of many thyroid axis components has not been fully described. This analysis examines differentiation of the median eminence of the hypothalamus and production of thyroid-stimulating hormone (TSH) by the pituitary of the direct-developing frog Eleutherodactylus coqui. The median eminence is established two-thirds of the way through embryogenesis. Cells immunoreactive to human TSHb antibodies are first detected during embryogenesis and quantitative changes in TSHb-IR cells resemble those in metamorphosing amphibians. Formation of the median eminence of the hypothalamus and TSHb production by the pituitary precede or coincide with morphological changes during embryogenesis that occur during metamorphosis in biphasic anurans. Thus, while the onset of neuroendocrine regulation has changed during the evolution of direct development, it is likely that these thyroid axis components still mediate the formation of adult features

Preliminary observations of tool-processing behaviour in Hawaiian crows Corvus hawaiiensis

This project was funded through a BBSRC David Phillips Fellowship (BB/G023913/2 to C.R.), and a PhD studentship by the BBSRC and the University of St Andrews (to B.K.). Funding for the ‘Alalā conservation breeding programme was provided by the U.S. Fish and Wildlife Service, State of Hawai‘i Division of Forestry and Wildlife, Moore Family Foundation, several anonymous donors, and San Diego Zoo Global.Very few animal species habitually make and use foraging tools. We recently discovered that the Hawaiian crow is a highly skilled, natural tool user. Most captive adults in our experiment spontaneously used sticks to access out-of-reach food from a range of extraction tasks, exhibiting a surprising degree of dexterity. Moreover, many birds modified tools before or during deployment, and some even manufactured tools from raw materials. In this invited addendum article, we describe and discuss these observations in more detail. Our preliminary data, and comparisons with the better-studied New Caledonian crow, suggest that the Hawaiian crow has extensive tool-modification and manufacture abilities. To chart the full extent of the species’ natural tool-making repertoire, we have started conducting dedicated experiments where subjects are given access to suitable raw materials for tool manufacture, but not ready-to-use tools.Publisher PDFPeer reviewe

Analysis of lesion localisation at colonoscopy: outcomes from a multi-centre U.K. study

Background: Colonoscopy is currently the gold standard for detection of colorectal lesions, but may be limited in anatomically localising lesions. This audit aimed to determine the accuracy of colonoscopy lesion localisation, any subsequent changes in surgical management and any potentially influencing factors. Methods: Patients undergoing colonoscopy prior to elective curative surgery for colorectal lesion/s were included from 8 registered U.K. sites (2012–2014). Three sets of data were recorded: patient factors (age, sex, BMI, screener vs. symptomatic, previous abdominal surgery); colonoscopy factors (caecal intubation, scope guide used, colonoscopist accreditation) and imaging modality. Lesion localisation was standardised with intra-operative location taken as the gold standard. Changes to surgical management were recorded. Results: 364 cases were included; majority of lesions were colonic, solitary, malignant and in symptomatic referrals. 82% patients had their lesion/s correctly located at colonoscopy. Pre-operative CT visualised lesion/s in only 73% of cases with a reduction in screening patients (64 vs. 77%; p = 0.008). 5.2% incorrectly located cases at colonoscopy underwent altered surgical management, including conversion to open. Univariate analysis found colonoscopy accreditation, scope guide use, incomplete colonoscopy and previous abdominal surgery significantly influenced lesion localisation. On multi-variate analysis, caecal intubation and scope guide use remained significant (HR 0.35, 0.20–0.60 95% CI and 0.47; 0.25–0.88, respectively). Conclusion: Lesion localisation at colonoscopy is incorrect in 18% of cases leading to potentially significant surgical management alterations. As part of accreditation, colonoscopists need lesion localisation training and awareness of when inaccuracies can occur

Reproducibility in high-throughput density functional theory: a comparison of AFLOW, Materials Project, and OQMD

A central challenge in high throughput density functional theory (HT-DFT) calculations is selecting a combination of input parameters and post-processing techniques that can be used across all materials classes, while also managing accuracy-cost tradeoffs. To investigate the effects of these parameter choices, we consolidate three large HT-DFT databases: Automatic-FLOW (AFLOW), the Materials Project (MP), and the Open Quantum Materials Database (OQMD), and compare reported properties across each pair of databases for materials calculated using the same initial crystal structure. We find that HT-DFT formation energies and volumes are generally more reproducible than band gaps and total magnetizations; for instance, a notable fraction of records disagree on whether a material is metallic (up to 7%) or magnetic (up to 15%). The variance between calculated properties is as high as 0.105 eV/atom (median relative absolute difference, or MRAD, of 6%) for formation energy, 0.65 {\AA}$^3$/atom (MRAD of 4%) for volume, 0.21 eV (MRAD of 9%) for band gap, and 0.15 $\mu_{\rm B}$/formula unit (MRAD of 8%) for total magnetization, comparable to the differences between DFT and experiment. We trace some of the larger discrepancies to choices involving pseudopotentials, the DFT+U formalism, and elemental reference states, and argue that further standardization of HT-DFT would be beneficial to reproducibility.Comment: Authors VIH and CKHB contributed equally to this wor

Seeded Growth of Highly Luminescent CdSe/CdS Nano-Heterostructures with Rod and Tetrapod Morphologies

We have demonstrated that seeded growth of nanocrystals offers a convenient way to design nanoheterostructures with complex shapes and morphologies by changing the crystalline structure of the seed. By using Use nanocrystals with wurtzite and zinc blende structure as seeds for growth of US nanorods, we synthesized CdSe/CdS heterostructure nanorods and nanotetrapods, respectively. Both of these structures showed excellent luminescentproperties, combining high photoluminescence efficiency (similar to 80 and similar to 50percent for nanorods and nanotetrapods, correspondingly), giant extinction coefficients (similar to 2 x 10(7) and similar to 1.5 x 10(8) M-1 cm (-1) at 350 nm for nanorods and nanotetrapods, correspondingly), and efficient energy transfer from the US arms into the emitting CdSe Core

The Pan-STARRS Moving Object Processing System

We describe the Pan-STARRS Moving Object Processing System (MOPS), a modern software package that produces automatic asteroid discoveries and identifications from catalogs of transient detections from next-generation astronomical survey telescopes. MOPS achieves > 99.5% efficiency in producing orbits from a synthetic but realistic population of asteroids whose measurements were simulated for a Pan-STARRS4-class telescope. Additionally, using a non-physical grid population, we demonstrate that MOPS can detect populations of currently unknown objects such as interstellar asteroids. MOPS has been adapted successfully to the prototype Pan-STARRS1 telescope despite differences in expected false detection rates, fill-factor loss and relatively sparse observing cadence compared to a hypothetical Pan-STARRS4 telescope and survey. MOPS remains >99.5% efficient at detecting objects on a single night but drops to 80% efficiency at producing orbits for objects detected on multiple nights. This loss is primarily due to configurable MOPS processing limits that are not yet tuned for the Pan-STARRS1 mission. The core MOPS software package is the product of more than 15 person-years of software development and incorporates countless additional years of effort in third-party software to perform lower-level functions such as spatial searching or orbit determination. We describe the high-level design of MOPS and essential subcomponents, the suitability of MOPS for other survey programs, and suggest a road map for future MOPS development.Comment: 57 Pages, 26 Figures, 13 Table

De Novo Mutations in SIK1 Cause a Spectrum of Developmental Epilepsies

Developmental epilepsies are age-dependent seizure disorders for which genetic causes have been increasingly identified. Here we report six unrelated individuals with mutations in salt-inducible kinase 1 (SIK1) in a series of 101 persons with early myoclonic encephalopathy, Ohtahara syndrome, and infantile spasms. Individuals with SIK1 mutations had short survival in cases with neonatal epilepsy onset, and an autism plus developmental syndrome after infantile spasms in others. All six mutations occurred outside the kinase domain of SIK1 and each of the mutants displayed autophosphorylation and kinase activity toward HDAC5. Three mutations generated truncated forms of SIK1 that were resistant to degradation and also showed changes in sub-cellular localization compared to wild-type SIK1. We also report the human neuropathologic examination of SIK1-related developmental epilepsy, with normal neuronal morphology and lamination but abnormal SIK1 protein cellular localization. Therefore, these results expand the genetic etiologies of developmental epilepsies by demonstrating SIK1 mutations as a cause of severe developmental epilepsy

Levels and equivalence in credit and qualifications frameworks: Contrasting the prescribed and enacted curriculum in school and college

Drawing on data from an empirical study of three matched subjects in upper secondary school and further education college in Scotland, this article explores some of the factors that result in differences emerging from the translation of the prescribed curriculum into the enacted curriculum. We argue that these differences raise important questions about equivalences which are being promoted through the development of credit and qualifications frameworks. The article suggests that the standardisation associated with the development of a rational credit and qualifications framework and an outcomes-based prescribed curriculum cannot be achieved precisely because of the multiplicity that emerges from the practices of translation

IFNAR1-Signalling Obstructs ICOS-mediated Humoral Immunity during Non-lethal Blood-Stage Plasmodium Infection

Funding: This work was funded by a Career Development Fellowship (1028634) and a project grant (GRNT1028641) awarded to AHa by the Australian National Health & Medical Research Council (NHMRC). IS was supported by The University of Queensland Centennial and IPRS Scholarships. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

Germline Analysis from Tumor–Germline Sequencing Dyads to Identify Clinically Actionable Secondary Findings

To evaluate germline variants in hereditary cancer susceptibility genes among unselected cancer patients undergoing tumor-germline sequencing