The Special Study of Securities Markets of the Securities and Exchange Commission

Moved perhaps by a certain institutional egoism, the Securities and Exchange Commission welcomes this thorough symposium upon the Report of Special Study of Securities Markets. Although the product of a separate study group, this report has nevertheless been the focal point of debate throughout the Commission during the past eighteen months. Representing both an intensive and extensive inquiry into the securities markets, it is unquestionably the most ambitious and comprehensive study since the passage of the securities acts thirty years ago. It is not a sensational document-quite consciously. In our opinion, raising standards in the securities industry could best be achieved by thorough documentation, responsible analysis, and constructive criticism. Upon this premise it warrants thoughtful but critical review

Evaluation of the Algorithms and Parameterizations for Ground Thawing and Freezing Simulation in Permafrost Regions

Ground thawing and freezing depths (GTFDs) strongly influence the hydrology and energy balances of permafrost regions. Current methods to simulate GTFD differ in algorithm type, soil parameterization, representation of latent heat, and unfrozen water content. In this study, five algorithms (one semiempirical, two analytical, and two numerical), three soil thermal conductivity parameterizations, and three unfrozen water parameterizations were evaluated against detailed field measurements at four field sites in Canada’s discontinuous permafrost region. Key findings include: (1) de Vries’ parameterization is recommended to determine the thermal conductivity in permafrost soils; (2) the three unfrozen water parameterization methods exhibited little difference in terms of GTFD simulations, yet the segmented linear function is the simplest to be implemented; (3) the semiempirical algorithm reasonably simulates thawing at permafrost sites and freezing at seasonal frost sites with site-specific calibration. However, large interannual and intersite variations in calibration coefficients limit its applicability for dynamic analysis; (4) when driven by surface forcing, analytical algorithms performed marginally better than the semiempirical algorithm. The inclusion of bottom forcing improved analytical algorithm performance, yet their results were still poor compared with those achieved by numerical algorithms; (5) when supplied with the optimal inputs, soil parameterizations, and model configurations, the numerical algorithm with latent heat treated as an apparent heat capacity achieved the best GTFD simulations among all algorithms at all sites. Replacing the observed bottom temperature with a zero heat flux boundary condition did not significantly reduce simulation accuracy, while assuming a saturated profile caused large errors at several sites

Genetic Architecture of Soybean Yield and Agronomic Traits

Soybean is the world’s leading source of vegetable protein and demand for its seed continues to grow. Breeders have successfully increased soybean yield, but the genetic architecture of yield and key agronomic traits is poorly understood. We developed a 40-mating soybean nested association mapping (NAM) population of 5,600 inbred lines that were characterized by single nucleotide polymorphism (SNP) markers and six agronomic traits in field trials in 22 environments. Analysis of the yield, agronomic, and SNP data revealed 23 significant marker-trait associations for yield, 19 for maturity, 15 for plant height, 17 for plant lodging, and 29 for seed mass. A higher frequency of estimated positive yield alleles was evident from elite founder parents than from exotic founders, although unique desirable alleles from the exotic group were identified, demonstrating the value of expanding the genetic base of US soybean breeding

Effect of natalizumab on disease progression in secondary progressive multiple sclerosis (ASCEND). a phase 3, randomised, double-blind, placebo-controlled trial with an open-label extension

Background: Although several disease-modifying treatments are available for relapsing multiple sclerosis, treatment effects have been more modest in progressive multiple sclerosis and have been observed particularly in actively relapsing subgroups or those with lesion activity on imaging. We sought to assess whether natalizumab slows disease progression in secondary progressive multiple sclerosis, independent of relapses. Methods: ASCEND was a phase 3, randomised, double-blind, placebo-controlled trial (part 1) with an optional 2 year open-label extension (part 2). Enrolled patients aged 18–58 years were natalizumab-naive and had secondary progressive multiple sclerosis for 2 years or more, disability progression unrelated to relapses in the previous year, and Expanded Disability Status Scale (EDSS) scores of 3·0–6·5. In part 1, patients from 163 sites in 17 countries were randomly assigned (1:1) to receive 300 mg intravenous natalizumab or placebo every 4 weeks for 2 years. Patients were stratified by site and by EDSS score (3·0–5·5 vs 6·0–6·5). Patients completing part 1 could enrol in part 2, in which all patients received natalizumab every 4 weeks until the end of the study. Throughout both parts, patients and staff were masked to the treatment received in part 1. The primary outcome in part 1 was the proportion of patients with sustained disability progression, assessed by one or more of three measures: the EDSS, Timed 25-Foot Walk (T25FW), and 9-Hole Peg Test (9HPT). The primary outcome in part 2 was the incidence of adverse events and serious adverse events. Efficacy and safety analyses were done in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT01416181. Findings: Between Sept 13, 2011, and July 16, 2015, 889 patients were randomly assigned (n=440 to the natalizumab group, n=449 to the placebo group). In part 1, 195 (44%) of 439 natalizumab-treated patients and 214 (48%) of 448 placebo-treated patients had confirmed disability progression (odds ratio [OR] 0·86; 95% CI 0·66–1·13; p=0·287). No treatment effect was observed on the EDSS (OR 1·06, 95% CI 0·74–1·53; nominal p=0·753) or the T25FW (0·98, 0·74–1·30; nominal p=0·914) components of the primary outcome. However, natalizumab treatment reduced 9HPT progression (OR 0·56, 95% CI 0·40–0·80; nominal p=0·001). In part 1, 100 (22%) placebo-treated and 90 (20%) natalizumab-treated patients had serious adverse events. In part 2, 291 natalizumab-continuing patients and 274 natalizumab-naive patients received natalizumab (median follow-up 160 weeks [range 108–221]). Serious adverse events occurred in 39 (13%) patients continuing natalizumab and in 24 (9%) patients initiating natalizumab. Two deaths occurred in part 1, neither of which was considered related to study treatment. No progressive multifocal leukoencephalopathy occurred. Interpretation: Natalizumab treatment for secondary progressive multiple sclerosis did not reduce progression on the primary multicomponent disability endpoint in part 1, but it did reduce progression on its upper-limb component. Longer-term trials are needed to assess whether treatment of secondary progressive multiple sclerosis might produce benefits on additional disability components. Funding: Biogen