Amici Brief of Certain Academics in Law, Medicine, Health Policy, and Clinical Genetics in Support of Petitioners

Brief of Amici Curiae ("friend of the court") submitted by certain academics in law, medicine, health policy, and clinical genetics in support of petitioners on petition for a Writ of Certiorari (No. 11-725

GWIPS-viz: 2018 update

The GWIPS-viz browser (http://gwips.ucc.ie/) is an on-line genome browser which is tailored for exploring ribosome profiling (Ribo-seq) data. Since its publication in 2014, GWIPS-viz provides Ribo-seq data for an additional 14 genomes bringing the current total to 23. The integration of new Ribo-seq data has been automated thereby increasing the number of available tracks to 1792, a 10-fold increase in the last three years. The increase is particularly substantial for data derived from human sources. Following user requests, we added the functionality to download these tracks in bigWig format. We also incorporated new types of data (e.g. TCP-seq) as well as auxiliary tracks from other sources that help with the interpretation of Ribo-seq data. Improvements in the visualization of the data have been carried out particularly for bacterial genomes where the Ribo-seq data are now shown in a strand specific manner. For higher eukaryotic datasets, we provide characteristics of individual datasets using the RUST program which includes the triplet periodicity, sequencing biases and relative inferred A-site dwell times. This information can be used for assessing the quality of Ribo-seq datasets. To improve the power of the signal, we aggregate Ribo-seq data from several studies into Global aggregate tracks for each genome

GWIPS-viz: development of a ribo-seq genome browser

We describe the development of GWIPS-viz (http://gwips.ucc.ie), an online genome browser for viewing ribosome profiling data. Ribosome profiling (ribo-seq) is a recently developed technique that provides genome-wide information on protein synthesis (GWIPS) in vivo. It is based on the deep sequencing of ribosome-protected messenger RNA (mRNA) fragments, which allows the ribosome density along all mRNA transcripts present in the cell to be quantified. Since its inception, ribo-seq has been carried out in a number of eukaryotic and prokaryotic organisms. Owing to the increasing interest in ribo-seq, there is a pertinent demand for a dedicated ribo-seq genome browser. GWIPS-viz is based on The University of California Santa Cruz (UCSC) Genome Browser. Ribo-seq tracks, coupled with mRNA-seq tracks, are currently available for several genomes: human, mouse, zebrafish, nematode, yeast, bacteria (Escherichia coli K12, Bacillus subtilis), human cytomegalovirus and bacteriophage lambda. Our objective is to continue incorporating published ribo-seq data sets so that the wider community can readily view ribosome profiling information from multiple studies without the need to carry out computational processing

X-rays in the Orion Nebula Cluster: Constraints on the origins of magnetic activity in pre-main sequence stars

A recent Chandra/ACIS observation of the Orion Nebula Cluster detected 1075 sources (Feigelson et al. 2002), providing a uniquely large and well-defined sample to study the dependence of magnetic activity on bulk properties for stars descending the Hayashi tracks. The following results are obtained: (1) X-ray luminosities L_t in the 0.5-8 keV band are strongly correlated with bolometric luminosity with = -3.8 for stars with masses 0.7<M<2 Mo, an order of magnitude below the main sequence saturation level; (2) the X-ray emission drops rapidly below this level in some or all stars with 2<M<3 Mo; (3) the presence or absence of infrared circumstellar disks has no apparent relation to X-ray levels; and (4) X-ray luminosities exhibit a slight rise as rotational periods increase from 0.4 to 20 days. This last finding stands in dramatic contrast to the strong anticorrelation between X-rays and period seen in main sequence stars. The absence of a strong X-ray/rotation relationship in PMS stars, and particularly the high X-ray values seen in some very slowly rotating stars, is a clear indication that the mechanisms of magnetic field generation differ from those operating in main sequence stars. The most promising possibility is a turbulent dynamo distributed throughout the deep convection zone, but other models such as alpha-Omega dynamo with `supersaturation' or relic core fields are not immediately excluded. The drop in magnetic activity in intermediate-mass stars may reflect the presence of a significant radiative core. The evidence does not support X-ray production in large-scale star-disk magnetic fields.Comment: 51 pages, 8 figures. To appear in the Astrophysical Journa

Giant magnetoresistance of Dirac plasma in high-mobility graphene

The most recognizable feature of graphene's electronic spectrum is its Dirac point around which interesting phenomena tend to cluster. At low temperatures, the intrinsic behavior in this regime is often obscured by charge inhomogeneity but thermal excitations can overcome the disorder at elevated temperatures and create electron-hole plasma of Dirac fermions. The Dirac plasma has been found to exhibit unusual properties including quantum critical scattering and hydrodynamic flow. However, little is known about the plasma's behavior in magnetic fields. Here we report magnetotransport in this quantum-critical regime. In low fields, the plasma exhibits giant parabolic magnetoresistivity reaching >100% in 0.1 T even at room temperature. This is orders of magnitude higher than magnetoresistivity found in any other system at such temperatures. We show that this behavior is unique to monolayer graphene, being underpinned by its massless spectrum and ultrahigh mobility, despite frequent (Planckian-limit) scattering. With the onset of Landau quantization in a few T, where the electron-hole plasma resides entirely on the zeroth Landau level, giant linear magnetoresistivity emerges. It is nearly independent of temperature and can be suppressed by proximity screening, indicating a many-body origin. Clear parallels with magnetotransport in strange metals and so-called quantum linear magnetoresistance predicted for Weyl metals offer an interesting playground to further explore relevant physics using this well-defined quantum-critical 2D system.Comment: 8 pages, 3 figure

A permethrin metabolite is associated with adaptive immune responses in Gulf War Illness

Gulf War Illness (GWI), affecting 30% of veterans from the 1991 Gulf War (GW), is a multi-symptom illness with features similar to those of patients with autoimmune diseases. The objective of the current work is to determine if exposure to GW-related pesticides, such as permethrin (PER), activates peripheral and central nervous system (CNS) adaptive immune responses. In the current study, we focused on a PER metabolite, 3-phenoxybenzoic acid (3-PBA), as this is a common metabolite previously shown to form adducts with endogenous proteins. We observed the presence of 3-PBA and 3-PBA modified lysine of protein peptides in the brain, blood and liver of pyridostigmine bromide (PB) and  PER (PB+PER) exposed mice at acute and chronic post-exposure timepoints. We tested whether 3-PBA-haptenated albumin (3-PBA-albumin) can activate immune cells since it is known that chemically haptenated proteins can stimulate immune responses. We detected autoantibodies against 3-PBA-albumin in plasma from PB + PER exposed mice and veterans with GWI at chronic post-exposure timepoints. We also observed that in vitro treatment of blood with 3-PBA-albumin resulted in the activation of B- and T-helper lymphocytes and that these immune cells were also increased in blood of PB + PER exposed mice and veterans with GWI. These immune changes corresponded with elevated levels of infiltrating monocytes in the brain and blood of PB + PER exposed mice which coincided with alterations in the markers of blood-brain barrier disruption, brain macrophages and neuroinflammation. These studies suggest that pesticide exposure associated with GWI may have resulted in the activation of the peripheral and CNS adaptive immune responses, possibly contributing to an autoimmune-type phenotype in veterans with GWI

The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

Metallicity and Temperature Indicators in M dwarf K band Spectra: Testing New & Updated Calibrations With Observations of 133 Solar Neighborhood M dwarfs

We present K band spectra for 133 nearby (d < 33 parsecs) M dwarfs, including 18 M dwarfs with reliable metallicity estimates (as inferred from an FGK type companion), 11 M dwarf planet hosts, more than 2/3 of the M dwarfs in the Northern 8 pc sample, and several M dwarfs from the LSPM catalog. From these spectra, we measure equivalent widths of the Ca and Na lines, and a spectral index quantifying the absorption due to H2O opacity (the H2O-K2 index). Using empirical spectral types standards and synthetic models, we calibrate the H2O-K2 index as an indicator of an M dwarf's spectral type and effective temperature. We also present a revised relationship that estimates the [Fe/H] and [M/H] metallicities of M dwarfs from their Na I, Ca I, and H2O-K2 measurements. Comparisons to model atmosphere provide a qualitative validation of our approach, but also reveal an overall offset between the atomic line strengths predicted by models as compared to actual observations. Our metallicity estimates also reproduce expected correlations with Galactic space motions and H alpha emission line strengths, and return statistically identical metallicities for M dwarfs within a common multiple system. Finally, we find systematic residuals between our H2O-based spectral types and those derived from optical spectral features with previously known sensitivity to stellar metallicity, such as TiO, and identify the CaH1 index as a promising optical index for diagnosing the metallicities of near-solar M dwarfs.Comment: 132 pages, 48 figures. Paper resubmitted to Ap

A qualitative exploration of the human resource policy implications of voluntary counselling and testing scale-up in Kenya: applying a model for policy analysis

Background: Kenya experienced rapid scale up of HIV testing and counselling services in government health services from 2001. We set out to examine the human resource policy implications of scaling up HIV testing and counselling in Kenya and to analyse the resultant policy against a recognised theoretical framework of health policy reform (policy analysis triangle). Methods: Qualitative methods were used to gain in-depth insights from policy makers who shaped scale up. This included 22 in-depth interviews with Voluntary Counselling and Testing (VCT) task force members, critical analysis of 53 sets of minutes and diary notes. We explore points of consensus and conflict amongst policymakers in Kenya and analyse this content to assess who favoured and resisted new policies, how scale up was achieved and the importance of the local context in which scale up occurred. Results: The scale up of VCT in Kenya had a number of human resource policy implications resulting from the introduction of lay counsellors and their authorisation to conduct rapid HIV testing using newly introduced rapid testing technologies. Our findings indicate that three key groups of actors were critical: laboratory professionals, counselling associations and the Ministry of Health. Strategic alliances between donors, NGOs and these three key groups underpinned the process. The process of reaching consensus required compromise and time commitment but was critical to a unified nationwide approach. Policies around quality assurance were integral in ensuring standardisation of content and approach. Conclusion: The introduction and scale up of new health service initiatives such as HIV voluntary counselling and testing necessitates changes to existing health systems and modification of entrenched interests around professional counselling and laboratory testing. Our methodological approach enabled exploration of complexities of scale up of HIV testing and counselling in Kenya. We argue that a better understanding of the diverse actors, the context and the process, is required to mitigate risks and maximise impact

Assessing the Quality of Clinical Teachers: A Systematic Review of Content and Quality of Questionnaires for Assessing Clinical Teachers

BACKGROUND: Learning in a clinical environment differs from formal educational settings and provides specific challenges for clinicians who are teachers. Instruments that reflect these challenges are needed to identify the strengths and weaknesses of clinical teachers. OBJECTIVE: To systematically review the content, validity, and aims of questionnaires used to assess clinical teachers. DATA SOURCES: MEDLINE, EMBASE, PsycINFO and ERIC from 1976 up to March 2010. REVIEW METHODS: The searches revealed 54 papers on 32 instruments. Data from these papers were documented by independent researchers, using a structured format that included content of the instrument, validation methods, aims of the instrument, and its setting. Results : Aspects covered by the instruments predominantly concerned the use of teaching strategies (included in 30 instruments), supporter role (29), role modeling (27), and feedback (26). Providing opportunities for clinical learning activities was included in 13 instruments. Most studies referred to literature on good clinical teaching, although they failed to provide a clear description of what constitutes a good clinical teacher. Instrument length varied from 1 to 58 items. Except for two instruments, all had to be completed by clerks/residents. Instruments served to provide formative feedback ( instruments) but were also used for resource allocation, promotion, and annual performance review (14 instruments). All but two studies reported on internal consistency and/or reliability; other aspects of validity were examined less frequently. CONCLUSIONS: No instrument covered all relevant aspects of clinical teaching comprehensively. Validation of the instruments was often limited to assessment of internal consistency and reliability. Available instruments for assessing clinical teachers should be used carefully, especially for consequential decisions. There is a need for more valid comprehensive instruments