Germ-Line Gene Editing and Congressional Reaction in Context: Learning From Almost 50 Years of Congressional Reactions to Biomedical Breakthroughs

On December 18, 2015, President Obama signed into law a policy rider forestalling the therapeutic modification of the human germ line. The rider, motivated by the science’s potential unethical ends, is only the most recent instance in which the legislature cut short the ongoing national conversation on the acceptability of a developing science. This essay offers historical perspective on what bills were proposed and passed surrounding four other then-developing scientific breakthroughs—Recombinant DNA, in vitro fertilization, Cloning, Stem Cells—to better analyze how Congress is, and should, regulate this exciting and promising science

A Comparison of Two Open Source LiDAR Surface Classification Algorithms

With the progression of LiDAR (Light Detection and Ranging) towards a mainstream resource management tool, it has become necessary to understand how best to process and analyze the data. While most ground surface identification algorithms remain proprietary and have high purchase costs; a few are openly available, free to use, and are supported by published results. Two of the latter are the multiscale curvature classification and the Boise Center Aerospace Laboratory LiDAR (BCAL) algorithms. This study investigated the accuracy of these two algorithms (and a combination of the two) to create a digital terrain model from a raw LiDAR point cloud in a semi-arid landscape. Accuracy of each algorithm was assessed via comparison with \u3e7,000 high precision survey points stratified across six different cover types. The overall performance of both algorithms differed by only 2%; however, within specific cover types significant differences were observed in accuracy. The results highlight the accuracy of both algorithms across a variety of vegetation types, and ultimately suggest specific scenarios where one approach may outperform the other. Each algorithm produced similar results except in the ceanothus and conifer cover types where BCAL produced lower errors

Is the Universe Inflating? Dark Energy and the Future of the Universe

We consider the fate of the observable universe in the light of the discovery of a dark energy component to the cosmic energy budget. We extend results for a cosmological constant to a general dark energy component and examine the constraints on phenomena that may prevent the eternal acceleration of our patch of the universe. We find that the period of accelerated cosmic expansion has not lasted long enough for observations to confirm that we are undergoing inflation; such an observation will be possible when the dark energy density has risen to between 90% and 95% of the critical. The best we can do is make cosmological observations in order to verify the continued presence of dark energy to some high redshift. Having done that, the only possibility that could spoil the conclusion that we are inflating would be the existence of a disturbance (the surface of a true vacuum bubble, for example) that is moving toward us with sufficiently high velocity, but is too far away to be currently observable. Such a disturbance would have to move toward us with speed greater than about 0.8c in order to spoil the late-time inflation of our patch of the universe and yet avoid being detectable.Comment: 7 pages, 7 figure

Standard Model CP violation in Polarised b->d l^+ l^-

In the standard model, we study CP violating rate asymmetries in the decay b->d l^+ l^- when one of the leptons is polarised. We find an asymmetry of (5 -- 15)% in the polarised decay spectrum which is comparable to known results for the unpolarised case. In the kinematic region separating the rho-omega and $c \bar c$ resonances, which is also theoretically cleanest, the polarised contribution to the asymmetry is larger than the unpolarised results. In order to observe a 3 sigma signal for direct CP violation in the polarised spectrum, assuming 100% efficiency, about 10^10 $B \bar B$ pairs are required at a B factory. Our results indicate an asymmetric contribution from the individual polarisation states to the unpolarised CP asymmetry. Taking advantage of this, one can attribute any new physics to be most sensitive to a specific polarisation state.Comment: 23 pages, one reference adde

Calculation of two-loop virtual corrections to b --> s l+ l- in the standard model

We present in detail the calculation of the virtual O(alpha_s) corrections to the inclusive semi-leptonic rare decay b --> s l+ l-. We also include those O(alpha_s) bremsstrahlung contributions which cancel the infrared and mass singularities showing up in the virtual corrections. In order to avoid large resonant contributions, we restrict the invariant mass squared s of the lepton pair to the range 0.05 < s/mb^2 < 0.25. The analytic results are represented as expansions in the small parameters s/mb^2, z = mc^2/mb^2 and s/(4 mc^2). The new contributions drastically reduce the renormalization scale dependence of the decay spectrum. For the corresponding branching ratio (restricted to the above s-range) the renormalization scale uncertainty gets reduced from +/-13% to +/-6.5%.Comment: 41 pages including 9 postscript figures; in version 2 some typos and inconsistent notation correcte

Parentage test in broad-snouted caimans (Caiman latirostris, Crocodylidae) using microsatellite DNA

In this study, microsatellite markers, developed for Alligator mississipiensis and Caiman latirostris, were used to assess parentage among individuals from the captive colony of Caiman latirostris at the University of São Paulo, in Piracicaba, São Paulo, Brazil. Many of the females in the colony were full siblings, which made maternal identification difficult due to genotypic similarity. Even so, the most likely mother could be identified unambiguously among offspring in most of the clutches studied. Two non-parental females displayed maternal behavior which would have misled managers in assigning maternity based on behavior alone. This set of variable loci demonstrates the utility of parentage testing in captive propagation programs

Fenfluramine for Treatment-Resistant Seizures in Patients With Dravet Syndrome Receiving Stiripentol-Inclusive Regimens A Randomized Clinical Trial

IMPORTANCE Fenfluramine treatment may reduce monthly convulsive seizure frequency in patients with Dravet syndrome who have poor seizure control with their current stiripentol-containing antiepileptic drug regimens. OBJECTIVE To determine whether fenfluramine reduced monthly convulsive seizure frequency relative to placebo in patients with Dravet syndrome who were taking stiripentol-inclusive regimens. DESIGN, SETTING, AND PARTICIPANTS This double-blind, placebo-controlled, parallel-group randomized clinical trial was conducted in multiple centers. Eligible patients were children aged 2 to 18 years with a confirmed clinical diagnosis of Dravet syndrome who were receiving stable, stiripentol-inclusive antiepileptic drug regimens. INTERVENTIONS Patients with 6 or more convulsive seizures during the 6-week baseline period were randomly assigned to receive fenfluramine, 0.4 mg/kg/d (maximum, 17 mg/d), or a placebo. After titration (3 weeks), patients’ assigned dosages were maintained for 12 additional weeks. Caregivers recorded seizures via a daily electronic diary. MAIN OUTCOMES AND MEASURES The primary efficacy end point was the change in mean monthly convulsive seizure frequency between fenfluramine and placebo during the combined titration and maintenance periods relative to baseline. RESULTS A total of 115 eligible patients were identified; of these, 87 patients (mean [SD], age 9.1 [4.8] years; 50 male patients [57%]; mean baseline frequency of seizures, approximately 25 convulsive seizures per month) were enrolled and randomized to fenfluramine, 0.4 mg/kg/d (n = 43) or placebo (n = 44). Patients treated with fenfluramine achieved a 54.0% (95% CI, 35.6%-67.2%; P < .001) greater reduction in mean monthly convulsive seizure frequency than those receiving the placebo. With fenfluramine, 54% of patients demonstrated a clinically meaningful (50%) reduction in monthly convulsive seizure frequency vs 5% with placebo (P < .001). The median (range) longest seizure-free interval was 22 (3.0-105.0) days with fenfluramine and 13 (1.0-40.0) days with placebo (P = .004). The most common adverse events were decreased appetite (19 patients taking fenfluramine [44%] vs 5 taking placebo [11%]), fatigue (11 [26%] vs 2 [5%]), diarrhea (10 [23%] vs 3 [7%]), and pyrexia (11 [26%] vs 4 [9%]). Cardiac monitoring demonstrated no clinical or echocardiographic evidence of valvular heart disease or pulmonary arterial hypertension. CONCLUSIONS AND RELEVANCE Fenfluramine demonstrated significant improvements in monthly convulsive seizure frequency in patients with Dravet syndrome whose conditions were insufficiently controlled with stiripentol-inclusive antiepileptic drug regimens. Fenfluramine was generally well tolerated. Fenfluramine may represent a new treatment option for Dravet syndrome. TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT0292689

HerMES: The contribution to the cosmic infrared background from galaxies selected by mass and redshift

The cosmic infrared background (CIB), discovered in Far Infrared Absolute Spectrophotometer (FIRAS) data from the Cosmic Background Explorer (COBE; Puget et al. 1996; Fixsen et al. 1998), originates from thermal re-radiation of imagine cutting out hundreds of thumbnails from a map centered on the positions where galaxies are known to be, and averaging those thumbnails together until an image of the average galaxy emerges from the noise. These positional priors can come in many forms, e.g., they could be catalogs of UV, optical, IR, or radio sources. Note that the output is the average of that population in the stacked maps, i.e., there will likely be sources whose actual fluxes are higher or lower. Thus, the more homogeneous the sources comprising the input list, the more meaningful the stacked flux will be.Web of Scienc

Centrality Dependence of the High p_T Charged Hadron Suppression in Au+Au collisions at sqrt(s_NN) = 130 GeV

PHENIX has measured the centrality dependence of charged hadron p_T spectra from central Au+Au collisions at sqrt(s_NN)=130 GeV. The truncated mean p_T decreases with centrality for p_T > 2 GeV/c, indicating an apparent reduction of the contribution from hard scattering to high p_T hadron production. For central collisions the yield at high p_T is shown to be suppressed compared to binary nucleon-nucleon collision scaling of p+p data. This suppression is monotonically increasing with centrality, but most of the change occurs below 30% centrality, i.e. for collisions with less than about 140 participating nucleons. The observed p_T and centrality dependence is consistent with the particle production predicted by models including hard scattering and subsequent energy loss of the scattered partons in the dense matter created in the collisions.Comment: 7 pages text, LaTeX, 6 figures, 2 tables, 307 authors, resubmitted to Phys. Lett. B. Revised to address referee concerns. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are publicly available at http://www.phenix.bnl.gov/phenix/WWW/run/phenix/papers.htm

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types