The Program Assessment Rating Tool and its Role in Evaluating the Effectiveness of U.S. Government Programs

Over the past 50 years, the United States government has engaged in a number of efforts designed to focus on the results of federal agencies and programs.  Starting in the 1950s with “performance budgeting” and continuing through the 1960s and 1970s program budgeting and zero-based budgeting efforts, the goal of these has been a closer linkage between resources provided and results achieved.  In 1993, during the administration of President Bill Clinton, the Government Performance and Results Act (GPRA) was signed into law.  This act required federal agencies to engage in strategic planning, performance planning, and performance reporting

Calibration uncertainty in molecular dating analyses: there is no substitute for the prior evaluation of time priors

Calibration is the rate-determining step in every molecular clock analysis and, hence, considerable effort has been expended in the development of approaches to distinguish good from bad calibrations. These can be categorized into a priori evaluation of the intrinsic fossil evidence, and a posteriori evaluation of congruence through cross-validation. We contrasted these competing approaches and explored the impact of different interpretations of the fossil evidence upon Bayesian divergence time estimation. The results demonstrate that a posteriori approaches can lead to the selection of erroneous calibrations. Bayesian posterior estimates are also shown to be extremely sensitive to the probabilistic interpretation of temporal constraints. Furthermore, the effective time priors implemented within an analysis differ for individual calibrations when employed alone and in differing combination with others. This compromises the implicit assumption of all calibration consistency methods, that the impact of an individual calibration is the same when used alone or in unison with others. Thus, the most effective means of establishing the quality of fossil-based calibrations is through a priori evaluation of the intrinsic palaeontological, stratigraphic, geochronological and phylogenetic data. However, effort expended in establishing calibrations will not be rewarded unless they are implemented faithfully in divergence time analyses

Milky Way demographics with the VVV survey. IV. PSF photometry from almost one billion stars in the Galactic bulge and adjacent southern disk

Accepted for publication in a forthcoming issue of Astronomy & Astrophysics. Reproduced with permission from Astronomy & Astrophysics. © 2018 ESO.Context. The inner regions of the Galaxy are severely affected by extinction, which limits our capability to study the stellar populations present there. The Vista Variables in the Vía Láctea (VVV) ESO Public Survey has observed this zone at near-infrared wavelengths where reddening is highly diminished. Aims. By exploiting the high resolution and wide field-of-view of the VVV images we aim to produce a deep, homogeneous, and highly complete database of sources that cover the innermost regions of our Galaxy. Methods. To better deal with the high crowding in the surveyed areas, we have used point spread function (PSF)-fitting techniques to obtain a new photometry of the VVV images, in the ZY JHK s near-infrared filters available. Results. Our final catalogs contain close to one billion sources, with precise photometry in up to five near-infrared filters, and they are already being used to provide an unprecedented view of the inner Galactic stellar populations. We make these catalogs publicly available to the community. Our catalogs allow us to build the VVV giga-CMD, a series of color-magnitude diagrams of the inner regions of the Milky Way presented as supplementary videos. We provide a qualitative analysis of some representative CMDs of the inner regions of the Galaxy, and briefly mention some of the studies we have developed with this new dataset so far.Peer reviewe

Evaluation of the London Measure of Unplanned Pregnancy in a United States population of women

Copyright @ 2012 Morof et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Objective: To evaluate the reliability and validity of the London Measure of Unplanned Pregnancy (a U.K.-developed measure of pregnancy intention), in English and Spanish translation, in a U.S. population of women. Methods: A psychometric evaluation study of the London Measure of Unplanned Pregnancy (LMUP), a six-item, self-completion paper measure was conducted with 346 women aged 15–45 who presented to San Francisco General Hospital for termination of pregnancy or antenatal care. Analyses of the two language versions were carried out separately. Reliability (internal consistency) was assessed using Cronbach’s alpha and item-total correlations. Test-retest reliability (stability) was assessed using weighted Kappa. Construct validity was assessed using principal components analysis and hypothesis testing. Results: Psychometric testing demonstrated that the LMUP was reliable and valid in both U.S. English (alpha = 0.78, all item-total correlations .0.20, weighted Kappa = 0.72, unidimensionality confirmed, hypotheses met) and Spanish translation (alpha = 0.84, all item-total correlations .0.20, weighted Kappa = 0.77, unidimensionality confirmed, hypotheses met). Conclusion: The LMUP was reliable and valid in U.S. English and Spanish translation and therefore may now be used with U.S. women.The study was funded by an anonymous donation

Callous-unemotional traits and anxiety in adolescents: a latent profile analysis to identify different types of antisocial behavior in a high-risk community sample

OBJECTIVE: Callous-unemotional (CU) traits are associated with a more severe and chronic trajectory of antisocial behavior. The present study aimed to identify different classes of CU and anxiety and to compare these classes on overt and covert antisocial behavior and several clinical correlates. METHOD: In a prospective high-risk cohort of adolescents (N = 679; mean age = 14.77, SD = 0.81), latent profile analysis was conducted using CU traits and anxiety symptoms as indicators, and multi-informant aggressive and rule breaking behavior as distal outcomes. Post-hoc analyses with binary logistic regression and a series of ANCOVA were performed on identified classes assessing violent aggression, property offending, and clinical correlates. RESULTS: Three classes were found, a reference group (low CU, low anxiety; N = 500), a high CU-low anxiety group (N = 98), and an intermediate CU-high anxious group (N = 81). The high CU-low anxiety group scored highest on property offenses, while the intermediate CU-high anxious group scored highest on aggressive behavior. The intermediate CU-high anxious group scored highest on psychotic experiences, while the high CU group scored highest on internet gaming addiction problems and bullying victimization. CONCLUSION: These findings provide further evidence for diverse variants of CU traits in a high-risk community sample. Future prospective studies should point out whether and to what extent adolescents with CU traits with and without anxiety develop criminal careers and psychiatric disorders in adulthood

Global redox proteome and phosphoproteome analysis reveals redox switch in Akt.

Protein oxidation sits at the intersection of multiple signalling pathways, yet the magnitude and extent of crosstalk between oxidation and other post-translational modifications remains unclear. Here, we delineate global changes in adipocyte signalling networks following acute oxidative stress and reveal considerable crosstalk between cysteine oxidation and phosphorylation-based signalling. Oxidation of key regulatory kinases, including Akt, mTOR and AMPK influences the fidelity rather than their absolute activation state, highlighting an unappreciated interplay between these modifications. Mechanistic analysis of the redox regulation of Akt identified two cysteine residues in the pleckstrin homology domain (C60 and C77) to be reversibly oxidized. Oxidation at these sites affected Akt recruitment to the plasma membrane by stabilizing the PIP3 binding pocket. Our data provide insights into the interplay between oxidative stress-derived redox signalling and protein phosphorylation networks and serve as a resource for understanding the contribution of cellular oxidation to a range of diseases

Novel mutations in human and mouse SCN4A implicate AMPK in myotonia and periodic paralysis

Mutations in the skeletal muscle channel (SCN4A), encoding the Nav1.4 voltage-gated sodium channel, are causative of a variety of muscle channelopathies, including non-dystrophic myotonias and periodic paralysis. The effects of many of these mutations on channel function have been characterized both in vitro and in vivo. However, little is known about the consequences of SCN4A mutations downstream from their impact on the electrophysiology of the Nav1.4 channel. Here we report the discovery of a novel SCN4A mutation (c.1762A>G; p.I588V) in a patient with myotonia and periodic paralysis, located within the S1 segment of the second domain of the Nav1.4 channel. Using N-ethyl-N-nitrosourea mutagenesis, we generated and characterized a mouse model (named draggen), carrying the equivalent point mutation (c.1744A>G; p.I582V) to that found in the patient with periodic paralysis and myotonia. Draggen mice have myotonia and suffer from intermittent hind-limb immobility attacks. In-depth characterization of draggen mice uncovered novel systemic metabolic abnormalities in Scn4a mouse models and provided novel insights into disease mechanisms. We discovered metabolic alterations leading to lean mice, as well as abnormal AMP-activated protein kinase activation, which were associated with the immobility attacks and may provide a novel potential therapeutic target

The Fossil Calibration Database—A New Resource for Divergence Dating

Fossils provide the principal basis for temporal calibrations, which are critical to the accuracy of divergence dating analyses. Translating fossil data into minimum and maximum bounds for calibrations is the most important—often least appreciated—step of divergence dating. Properly justified calibrations require the synthesis of phylogenetic, paleontological, and geological evidence and can be difficult for nonspecialists to formulate. The dynamic nature of the fossil record (e.g., new discoveries, taxonomic revisions, updates of global or local stratigraphy) requires that calibration data be updated continually lest they become obsolete. Here, we announce the Fossil Calibration Database (http://fossilcalibrations.org), a new open-access resource providing vetted fossil calibrations to the scientific community. Calibrations accessioned into this database are based on individual fossil specimens and follow best practices for phylogenetic justification and geochronological constraint. The associated Fossil Calibration Series, a calibration-themed publication series at Palaeontologia Electronica, will serve as a key pipeline for peer-reviewed calibrations to enter the databas

Genome-wide association and HLA fine-mapping studies identify risk loci and genetic pathways underlying allergic rhinitis

Allergic rhinitis is the most common clinical presentation of allergy, affecting 400 million people worldwide, with increasing incidence in westernized countries1,2. To elucidate the genetic architecture and understand the underlying disease mechanisms, we carried out a meta-analysis of allergic rhinitis in 59,762 cases and 152,358 controls of European ancestry and identified a total of 41 risk loci for allergic rhinitis, including 20 loci not previously associated with allergic rhinitis, which were confirmed in a replication phase of 60,720 cases and 618,527 controls. Functional annotation implicated genes involved in various immune pathways, and fine mapping of the HLA region suggested amino acid variants important for antigen binding. We further performed genome-wide association study (GWAS) analyses of allergic sensitization against inhalant allergens and nonallergic rhinitis, which suggested shared genetic mechanisms across rhinitis-related traits. Future studies of the identified loci and genes might identify novel targets for treatment and prevention of allergic rhinitis