The central image of a gravitationally lensed quasar

A galaxy can act as a gravitational lens, producing multiple images of a background object. Theory predicts there should be an odd number of images but, paradoxically, almost all observed lenses have 2 or 4 images. The missing image should be faint and appear near the galaxy's center. These ``central images'' have long been sought as probes of galactic cores too distant to resolve with ordinary observations. There are five candidates, but in one case the third image is not necessarily a central image, and in the others, the central component might be a foreground source rather than a lensed image. Here we report the most secure identification of a central image, based on radio observations of PMN J1632-0033, one of the latter candidates. Lens models incorporating the central image show that the mass of the lens galaxy's central black hole is less than 2 x 10^8 M_sun, and the galaxy's surface density at the location of the central image is more than 20,000 M_sun per square parsec, in agreement with expectations based on observations of galaxies hundreds of times closer to the Earth.Comment: Nature, in press [7 pp, 2 figs]. Standard media embargo applies before publicatio

Reversal of aging-induced increases in aortic stiffness by targeting cytoskeletal protein-protein interfaces

Background: The proximal aorta normally functions as a critical shock absorber that protects small downstream vessels from damage by pressure and flow pulsatility generated by the heart during systole. This shock absorber function is impaired with age because of aortic stiffening. Methods and Results: We examined the contribution of common genetic variation to aortic stiffness in humans by interrogating results from the AortaGen Consortium genome-wide association study of carotid-femoral pulse wave velocity. Common genetic variation in the N-WASP (WASL) locus is associated with carotid-femoral pulse wave velocity (rs600420, P=0.0051). Thus, we tested the hypothesis that decoy proteins designed to disrupt the interaction of cytoskeletal proteins such as N-WASP with its binding partners in the vascular smooth muscle cytoskeleton could decrease ex vivo stiffness of aortas from a mouse model of aging. A synthetic decoy peptide construct of N-WASP significantly reduced activated stiffness in ex vivo aortas of aged mice. Two other cytoskeletal constructs targeted to VASP and talin-vinculin interfaces similarly decreased aging-induced ex vivo active stiffness by on-target specific actions. Furthermore, packaging these decoy peptides into microbubbles enables the peptides to be ultrasound-targeted to the wall of the proximal aorta to attenuate ex vivo active stiffness. Conclusions: We conclude that decoy peptides targeted to vascular smooth muscle cytoskeletal protein-protein interfaces and microbubble packaged can decrease aortic stiffness ex vivo. Our results provide proof of concept at the ex vivo level that decoy peptides targeted to cytoskeletal protein-protein interfaces may lead to substantive dynamic modulation of aortic stiffness

A report on the piloting of a novel computer-based medical case simulation for teaching and formative assessment of diagnostic laboratory testing

Objectives: Insufficient attention has been given to how information from computer-based clinical case simulations is presented, collected, and scored. Research is needed on how best to design such simulations to acquire valid performance assessment data that can act as useful feedback for educational applications. This report describes a study of a new simulation format with design features aimed at improving both its formative assessment feedback and educational function. Methods: Case simulation software (LabCAPS) was developed to target a highly focused and well-defined measurement goal with a response format that allowed objective scoring. Data from an eight-case computer-based performance assessment administered in a pilot study to 13 second-year medical students was analyzed using classical test theory and generalizability analysis. In addition, a similar analysis was conducted on an administration in a less controlled setting, but to a much large sample (n=143), within a clinical course that utilized two random case subsets from a library of 18 cases. Results: Classical test theory case-level item analysis of the pilot assessment yielded an average case discrimination of 0.37, and all eight cases were positively discriminating (range=0.11–0.56). Classical test theory coefficient alpha and the decision study showed the eight-case performance assessment to have an observed reliability of σ=G=0.70. The decision study further demonstrated that a G=0.80 could be attained with approximately 3 h and 15 min of testing. The less-controlled educational application within a large medical class produced a somewhat lower reliability for eight cases (G=0.53). Students gave high ratings to the logic of the simulation interface, its educational value, and to the fidelity of the tasks. Conclusions: LabCAPS software shows the potential to provide formative assessment of medical students’ skill at diagnostic test ordering and to provide valid feedback to learners. The perceived fidelity of the performance tasks and the statistical reliability findings support the validity of using the automated scores for formative assessment and learning. LabCAPS cases appear well designed for use as a scored assignment, for stimulating discussions in small group educational settings, for self-assessment, and for independent learning. Extension of the more highly controlled pilot assessment study with a larger sample will be needed to confirm its reliability in other assessment applications

SUSY, the Third Generation and the LHC

We develop a bottom-up approach to studying SUSY with light stops and sbottoms, but with other squarks and sleptons heavy and beyond reach of the LHC. We discuss the range of squark, gaugino and Higgsino masses for which the electroweak scale is radiatively stable over the "little hierarchy" below ~ 10 TeV. We review and expand on indirect constraints on this scenario, in particular from flavor and CP tests. We emphasize that in this context, R-parity violation is very well motivated. The phenomenological differences between Majorana and Dirac gauginos are also discussed. Finally, we focus on the light subsystem of stops, sbottom and neutralino with R-parity, in order to probe the current collider bounds. We find that 1/fb LHC bounds are mild and large parts of the motivated parameter space remain open, while the 10/fb data can be much more decisive.Comment: 42 pages, 8 figures, 1 table. V2: minor corrections, references adde

Improving fleet solution – a case study

Transportation management is a logistical activity with a high impact on a company’s ability to compete in the market. Although the focus on cost reduction is the most usual concern with this activity, lead times and the quality of the service provided should also be considered depending on the market to be served. The goal of this research was to compare different fleet alternatives for a specific construction materials company and discuss which scenario is the most suited to fulfil the company’s customer service policy. A case study approach was developed, and four alternative scenarios were considered. These were compared both regarding the costs they involve, which was analysed using a vehicle routing problem heuristic, and the quality of the customer service they allow, which was assessed based on their ability to provide flexibility in the fleet occupancy rate to respond to unexpected orders. Evidence showed that the current fleet solution is not adequate and investment should be made only if the demand level increases, otherwise outsourcing should be considered along with a minimum level of the self-owned fleet.info:eu-repo/semantics/acceptedVersio

An integrated general practice and pharmacy-based intervention to promote the use of appropriate preventive medications among individuals at high cardiovascular disease risk: protocol for a cluster randomized controlled trial

Background: Cardiovascular diseases (CVD) are responsible for significant morbidity, premature mortality, and economic burden. Despite established evidence that supports the use of preventive medications among patients at high CVD risk, treatment gaps remain. Building on prior evidence and a theoretical framework, a complex intervention has been designed to address these gaps among high-risk, under-treated patients in the Australian primary care setting. This intervention comprises a general practice quality improvement tool incorporating clinical decision support and audit/feedback capabilities; availability of a range of CVD polypills (fixed-dose combinations of two blood pressure lowering agents, a statin ± aspirin) for prescription when appropriate; and access to a pharmacy-based program to support long-term medication adherence and lifestyle modification. Methods: Following a systematic development process, the intervention will be evaluated in a pragmatic cluster randomized controlled trial including 70 general practices for a median period of 18 months. The 35 general practices in the intervention group will work with a nominated partner pharmacy, whereas those in the control group will provide usual care without access to the intervention tools. The primary outcome is the proportion of patients at high CVD risk who were inadequately treated at baseline who achieve target blood pressure (BP) and low-density lipoprotein cholesterol (LDL-C) levels at the study end. The outcomes will be analyzed using data from electronic medical records, utilizing a validated extraction tool. Detailed process and economic evaluations will also be performed. Discussion: The study intends to establish evidence about an intervention that combines technological innovation with team collaboration between patients, pharmacists, and general practitioners (GPs) for CVD prevention. Trial registration: Australian New Zealand Clinical Trials Registry ACTRN1261600023342

Non-global Structure of the O({\alpha}_s^2) Dijet Soft Function

High energy scattering processes involving jets generically involve matrix elements of light- like Wilson lines, known as soft functions. These describe the structure of soft contributions to observables and encode color and kinematic correlations between jets. We compute the dijet soft function to O({\alpha}_s^2) as a function of the two jet invariant masses, focusing on terms not determined by its renormalization group evolution that have a non-separable dependence on these masses. Our results include non-global single and double logarithms, and analytic results for the full set of non-logarithmic contributions as well. Using a recent result for the thrust constant, we present the complete O({\alpha}_s^2) soft function for dijet production in both position and momentum space.Comment: 55 pages, 8 figures. v2: extended discussion of double logs in the hard regime. v3: minor typos corrected, version published in JHEP. v4: typos in Eq. (3.33), (3.39), (3.43) corrected; this does not affect the main result, numerical results, or conclusion

Massive Spin-2 States as the Origin of the Top Quark Forward-Backward Asymmetry

We show that the anomalously large top quark forward-backward asymmetry observed by CDF and D\O\, can naturally be accommodated in models with flavor-violating couplings of a new massive spin-2 state to quarks. Regardless of its origin, the lowest-order couplings of a spin-2 boson to fermions are analogous to the coupling of the graviton to energy/momentum, leading to strong sensitivity of the effects associated with its virtual exchange to the energy scales at hand. Precisely due to this fact, the observed dependence of the asymmetry on the $t\bar t$ invariant mass fits nicely into the proposed framework. In particular, we find a vast parameter space which can lead to the central value for the observed forward-backward asymmetry in the high mass bin, while being in accord with all of the existing experimental constraints.Comment: added discussion of differential observables at the LHC, matches version accepted for publication in JHE

ENIGMA and global neuroscience: A decade of large-scale studies of the brain in health and disease across more than 40 countries.

This review summarizes the last decade of work by the ENIGMA (Enhancing NeuroImaging Genetics through Meta Analysis) Consortium, a global alliance of over 1400 scientists across 43 countries, studying the human brain in health and disease. Building on large-scale genetic studies that discovered the first robustly replicated genetic loci associated with brain metrics, ENIGMA has diversified into over 50 working groups (WGs), pooling worldwide data and expertise to answer fundamental questions in neuroscience, psychiatry, neurology, and genetics. Most ENIGMA WGs focus on specific psychiatric and neurological conditions, other WGs study normal variation due to sex and gender differences, or development and aging; still other WGs develop methodological pipelines and tools to facilitate harmonized analyses of "big data" (i.e., genetic and epigenetic data, multimodal MRI, and electroencephalography data). These international efforts have yielded the largest neuroimaging studies to date in schizophrenia, bipolar disorder, major depressive disorder, post-traumatic stress disorder, substance use disorders, obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, autism spectrum disorders, epilepsy, and 22q11.2 deletion syndrome. More recent ENIGMA WGs have formed to study anxiety disorders, suicidal thoughts and behavior, sleep and insomnia, eating disorders, irritability, brain injury, antisocial personality and conduct disorder, and dissociative identity disorder. Here, we summarize the first decade of ENIGMA's activities and ongoing projects, and describe the successes and challenges encountered along the way. We highlight the advantages of collaborative large-scale coordinated data analyses for testing reproducibility and robustness of findings, offering the opportunity to identify brain systems involved in clinical syndromes across diverse samples and associated genetic, environmental, demographic, cognitive, and psychosocial factors

Expression of Distal-less, dachshund, and optomotor blind in Neanthes arenaceodentata (Annelida, Nereididae) does not support homology of appendage-forming mechanisms across the Bilateria

The similarity in the genetic regulation of arthropod and vertebrate appendage formation has been interpreted as the product of a plesiomorphic gene network that was primitively involved in bilaterian appendage development and co-opted to build appendages (in modern phyla) that are not historically related as structures. Data from lophotrochozoans are needed to clarify the pervasiveness of plesiomorphic appendage forming mechanisms. We assayed the expression of three arthropod and vertebrate limb gene orthologs, Distal-less (Dll), dachshund (dac), and optomotor blind (omb), in direct-developing juveniles of the polychaete Neanthes arenaceodentata. Parapodial Dll expression marks premorphogenetic notopodia and neuropodia, becoming restricted to the bases of notopodial cirri and to ventral portions of neuropodia. In outgrowing cephalic appendages, Dll activity is primarily restricted to proximal domains. Dll expression is also prominent in the brain. dac expression occurs in the brain, nerve cord ganglia, a pair of pharyngeal ganglia, presumed interneurons linking a pair of segmental nerves, and in newly differentiating mesoderm. Domains of omb expression include the brain, nerve cord ganglia, one pair of anterior cirri, presumed precursors of dorsal musculature, and the same pharyngeal ganglia and presumed interneurons that express dac. Contrary to their roles in outgrowing arthropod and vertebrate appendages, Dll, dac, and omb lack comparable expression in Neanthes appendages, implying independent evolution of annelid appendage development. We infer that parapodia and arthropodia are not structurally or mechanistically homologous (but their primordia might be), that Dll’s ancestral bilaterian function was in sensory and central nervous system differentiation, and that locomotory appendages possibly evolved from sensory outgrowths