Trimming the Judicial Oak : Rule 10b5-2(b)(1), Confidentiality Agreements, and the Proper Scope of Insider Trading Liability

In recent years the Securities and Exchange Commission, commonly known as the SEC, has been involved in a number of high- profile suits that have attracted a good deal of media attention. Among those prosecuted by the Commission are hedge fund billionaire and Galleon Group founder Raj Rajaratnam, investment/Ponzi- scheme guru Bernie Madoff, television host and magazine publisher Martha Stewart, and colorful Dallas Mavericks owner Mark Cuban. Although such notable suits may simply be the SEC\u27s attempt to justify its own existence and role in the market it polices in light of the financial disasters of the past decade, these cases do raise some significant questions regarding the amount of power delegated to the Commission by Congress. Specifically, what exactly is the scope of the SEC\u27s authority, and is there any limit on its ability to prosecute some of the most powerful and prominent people in the country? While the SEC seems to be engaged in some muscle-flexing with regard to whom it chooses to prosecute, the Commission has also attempted to broaden the scope of its statutory power, especially with regard to the doctrine of insider trading.6 Rule 10b-5-the provision utilized to prosecute inside traders-has experienced expansive growth since its creation, developing from a mere statutory catchall provision in the securities laws to one of the SEC\u27s chief weapons in combating insider trading and other fraudulent actions in the securities markets. In fact, the liberal expansion of Rule 10b-5 from its humble beginnings has been so vast that it led Chief Justice Rehnquist to remark that the Rule is a judicial oak which has grown from little more than a legislative acorn. Despite the significant growth that Rule 10b-5 has undergone since its enactment, the Supreme Court has always carefully limited the Rule to its statutory roots of prohibiting deceptive and manipulative conduct in the securities markets. Traditionally, to be liable for insider trading, the trader had to owe a fiduciary duty to the counterparty to the trade, or have a similar relationship of trust and confidence with him. In the late 1990s, the Court adopted an exception to this general rule known as the misappropriation theory. Under this theory, the scope of liability extends beyond those who owe a duty to the other transacting party to those who owe a duty only to the source of the information. Although the misappropriation theory recognizes liability where it did not previously exist, the theory is consistent with the statutory roots of Rule 10b-5 because self-dealing in confidential information, in breach of a duty owed to the source of the information, is clearly deceptive conduct

Rabies Surveillance Identifies Potential Risk Corridors and Enables Management Evaluation

Intensive efforts are being made to eliminate the raccoon variant of rabies virus (RABV) from the eastern United States and Canada. The United States Department of Agriculture (USDA) Wildlife Services National Rabies Management Program has implemented enhanced rabies surveillance (ERS) to improve case detection across the extent of the raccoon oral rabies vaccination (ORV) management area. We evaluated ERS and public health surveillance data from 2006 to 2017 in three northeastern USA states using a dynamic occupancy modeling approach. Our objectives were to examine potential risk corridors for RABV incursion from the U.S. into Canada, evaluate the effectiveness of ORV management strategies, and identify surveillance gaps. ORV management has resulted in a decrease in RABV cases over time within vaccination zones (from occupancy (ψ) of 0.60 standard error (SE) = 0.03 in the spring of 2006 to ψ of 0.33 SE = 0.10 in the spring 2017). RABV cases also reduced in the enzootic area (from ψ of 0.60 SE = 0.03 in the spring of 2006 to ψ of 0.45 SE = 0.05 in the spring 2017). Although RABV occurrence was related to habitat type, greater impacts were associated with ORV and trap–vaccinate–release (TVR) campaigns, in addition to seasonal and yearly trends. Reductions in RABV occupancy were more pronounced in areas treated with Ontario Rabies Vaccine Bait (ONRAB) compared to RABORAL V-RG®. Our approach tracked changes in RABV occurrence across space and time, identified risk corridors for potential incursions into Canada, and highlighted surveillance gaps, while evaluating the impacts of management actions. Using this approach, we are able to provide guidance for future RABV management

Depression in Parkinson\u27s disease: Perspectives from an Australian cohort

Introduction: Depression is often an under-recognised feature of Parkinson\u27s disease (PD). It is detrimental to physical and interpersonal functioning, negatively impacting a patient\u27s clinical management, quality of life and well-being. We aimed to identify clinical predictors and management implications of depression in Australian PD patients. Methods: 103 PD and 81 Healthy Control (HC) subjects were evaluated using the Beck Depression Inventory (BDI) and other validated PD motor and non-motor symptom (NMS) tools. Results: Nearly twice as many PD patients were depressed, (38.9% vs 20.1%, p = 0.009), with a corresponding increase in depression severity on the BDI (11.9; standard deviation (SD) 8.8 vs 5.2; SD 5.5, p\u3c0.001), and an odds ratio of 2.4 (95% confidence interval 1.2 - 4.7). Employment appeared to be a relative protective factor for depression, whilst patients requiring support services seemed to be more vulnerable to depression. Rapid Eye Movement Sleep Behaviour Disorder, dyskinesias, impulse control disorder, higher daily levodopa equivalent dose, increased motor severity, as well as catechol-O-methyltransferase inhibitor and amantadine use, all showed associations with depression (p\u3c0.05). Chronic pain, decreased physical activity, constipation and upper gastrointestinal dysfunction presented with an apparent increase in risk for developing depression and increased depression severity. Other NMS were also found to be associated with PD-related depression. Limitations: Potential selection bias of self-reporting data collection from specialist PD clinics in a single metropolitan area. Conclusion: Our findings provide novel insight into the prevalence of depression in PD, possible contributory factors and future treatment strategies targeting depression in PD

Gastrointestinal dysfunction in Parkinson\u27s disease

Background: Gastrointestinal (GI) dysfunction is prevalent in Parkinson’s disease (PD). Symptoms are evident throughout the disease course, affect the length of the GI tract and impact on patient quality of life and management. We clarify real-life differences in the frequency and severity of GI symptoms in a cohort of PD and healthy control (HC) subjects. Methods: 103 PD patients were compared to 81 HC subjects. Outcome measures collected from validated questionnaires included constipation severity, upper and lower GI symptoms and physical activity. Results: PD patients were three-times more likely to experience constipation than HC subjects, (78.6% vs 28.4%), exhibited a fourfold increase in constipation severity and formed harder stools. PD patients also reported increased symptoms of indigestion, nausea, excessive fullness and bloating, compared to the HCs. A higher mean Leeds Dyspepsia Questionnaire score for PD patients (8.3 (standard deviation (SD) 7.7) vs 4.6 (SD 6.1), p=0.001)) indicated increased symptom severity. Chronic pain was more frequently reported and correlated with constipation and upper GI dysfunction, being more prevalent and severe in women. Physical activity was notably decreased in the PD cohort (1823.6 (±1693.6) vs 2942.4 (±2620.9) metabolic equivalent-minutes/week, p=0.001) and correlated with constipation severity. PD therapies were associated with increased fullness and bloating and harder stools. Conclusions: PD patients report more prevalent and severe GI dysfunction, although our cohort comprised of many later stage participants. Earlier recognition of GI dysfunction in PD provides the opportunity to direct treatment for chronic pain and constipation, promote physical activity and rationalise PD therapies for optimal patient care

Attitude Control and Orbit Determination of a Crewed Spacecraft with Lunar Lander in near Rectilinear Halo Orbit

NASA's Gateway program plans to place a crew-tended spacecraft in cislunar Near Rectilinear Halo Orbit (NRHO). The craft will support arrivals of crews in Orion and the undocking and return of a crewed lunar lander. The impact to at-titude control of a Gateway with the addition of a lunar lander is investigated. Perturbations from Orion and a lander's docking and undocking from the Gate-way are considered. Deep Space Network (DSN) tracking is supplemented with optical measurements to lunar north pole craters to analyze the possible benefit in solution accuracy and/or DSN scheduling relief

Substrate Specificity, Metal Binding Properties, and Spectroscopic Characterization of the DapE-Encoded N-Succinyl-l,l-Diaminopimelic Acid Desuccinylase from \u3cem\u3eHaemophilus influenzae\u3c/em\u3e

The catalytic and structural properties of divalent metal ion cofactor binding sites in the dapE-encoded N-succinyl-l,l-diaminopimelic acid desuccinylase (DapE) from Haemophilus influenzae were investigated. Co(II)-substituted DapE enzyme was 25% more active than the Zn(II)-loaded form of the enzyme. Interestingly, Mn(II) can activate DapE, but only to ∼20% of the Zn(II)-loaded enzyme. The order of the observed kcat values are Co(II) \u3e Zn(II) \u3e Cd(II) \u3e Mn(II) \u3eNi(II) ∼ Cu(II) ∼ Mg(II). DapE was shown to only hydrolyze l,l-N-succinyl-diaminopimelic acid (l,l-SDAP) and was inactive toward d,l-, l,d-, and d,d-SDAP. DapE was also inactive toward several acetylated amino acids as well as d,l-succinyl aminopimelate, which differs from the natural substrate, l,l-SDAP, by the absence of the amine group on the amino acid side chain. These data imply that the carboxylate of the succinyl moiety and the amine form important interactions with the active site of DapE. The affinity of DapE for one versus two Zn(II) ions differs by nearly 2.2 × 103 times (Kd1 = 0.14 μM vs Kd2 = 300 μM). In addition, an Arrhenius plot was constructed from kcat values measured between 16 and 35 °C and was linear over this temperature range. The activation energy for [ZnZn(DapE)] was found to be 31 kJ/mol with the remaining thermodynamic parameters calculated at 25 °C being ΔG⧧ = 64 kJ/mol, ΔH⧧ = 28.5 kJ/mol, and ΔS⧧ = −119 J mol-1 K-1. Electronic absorption and EPR spectra of [Co_(DapE)] and [CoCo(DapE)] indicate that the first Co(II) binding site is five-coordinate, while the second site is octahedral. In addition, any spin−spin interaction between the two Co(II) ions in [CoCo(DapE)] is very weak. The kinetic and spectroscopic data presented herein suggest that the DapE from H. influenzae has similar divalent metal binding properties to the aminopeptidase from Aeromonas proteolytica (AAP), and the observed divalent metal ion binding properties are discussed with respect to their catalytic roles in SDAP hydrolysis

Distinct immune signatures in directly treated and distant tumors result from TLR adjuvants and focal ablation.

Both adjuvants and focal ablation can alter the local innate immune system and trigger a highly effective systemic response. Our goal is to determine the impact of these treatments on directly treated and distant disease and the mechanisms for the enhanced response obtained by combinatorial treatments. Methods: We combined RNA-sequencing, flow cytometry and TCR-sequencing to dissect the impact of immunotherapy and of immunotherapy combined with ablation on local and systemic immune components. Results: With administration of a toll-like receptor agonist agonist (CpG) alone or CpG combined with same-site ablation, we found dramatic differences between the local and distant tumor environments, where the directly treated tumors were skewed to high expression of F4/80, Cd11b and Tnf and the distant tumors to enhanced Cd11c, Cd3 and Ifng. When ablation was added to immunotherapy, 100% (n=20/20) of directly treated tumors and 90% (n=18/20) of distant tumors were responsive. Comparing the combined ablation-immunotherapy treatment to immunotherapy alone, we find three major mechanistic differences. First, while ablation alone enhanced intratumoral antigen cross-presentation (up to ~8% of CD45+ cells), systemic cross-presentation of tumor antigen remained low. Combining same-site ablation with CpG amplified cross-presentation in the draining lymph node (~16% of CD45+ cells) compared to the ablation-only (~0.1% of CD45+ cells) and immunotherapy-only cohorts (~10% of CD45+ cells). Macrophages and DCs process and present this antigen to CD8+ T-cells, increasing the number of unique T-cell receptor rearrangements in distant tumors. Second, type I interferon (IFN) release from tumor cells increased with the ablation-immunotherapy treatment as compared with ablation or immunotherapy alone. Type I IFN release is synergistic with toll-like receptor activation in enhancing cytokine and chemokine expression. Expression of genes associated with T-cell activation and stimulation (Eomes, Prf1 and Icos) was 27, 56 and 89-fold higher with ablation-immunotherapy treatment as compared to the no-treatment controls (and 12, 32 and 60-fold higher for immunotherapy-only treatment as compared to the no-treatment controls). Third, we found that the ablation-immunotherapy treatment polarized macrophages and dendritic cells towards a CD169 subset systemically, where CD169+ macrophages are an IFN-enhanced subpopulation associated with dead-cell antigen presentation. Conclusion: While the local and distant responses are distinct, CpG combined with ablative focal therapy drives a highly effective systemic immune response

A Pre-Exercise Dose of Melatonin Can Alter Substrate Use During Exercise

International Journal of Exercise Science 10(7): 1029-1037, 2017. Notwithstanding the lack of exercise research, several reviews have championed the use of melatonin to combat metabolic syndrome. Therefore, this study compared substrate utilization during a 30-minute (min) graded exercise protocol following the ingestion of either 6 mg melatonin (M) or a placebo (P). Participants (12 women, 12 men) performed stages 1-5 of the Naughton graded exercise protocol (6 min per stage). The protocol was repeated 4 times (2x M, 2x P) at the same time of day with one week separating each session. Expired gases were monitored, VO2 and respiratory exchange ratio (RER) output was provided every 30s. Total, carbohydrate (CHO), and fat energy expenditures were obtained from the RER values using the formulae of Lusk. The VO2 at which CHO accounted for 50% of the total caloric expenditure was calculated by a VO2: RER regression line. Additionally, the energy derived was calculated by multiplying VO2 and the respective energy expenditures. Then, the total, CHO, and fat energies consumed during the 30 min of exercise were determined by calculating the area under the kJ/min: time curve using the trapezoid rule. The final data for the two similar trials were averaged and a paired-T test was used for statistical comparison. The average VO2 for 50% CHO usage was significantly lower following M (0.84 ± 0.54 l·min-1) than after P (1.21 ± 0.52 l·min-1). Also, average CHO kJ for M (627 ± 284) was significantly (p \u3c 0.004) greater than P (504 ± 228), and accounted for a significantly greater contribution of total kJ consumed (M = 68% ±15 vs. P = 61% ± 18). Ingestion of melatonin 30 min prior to an aerobic exercise bout elevates CHO use during exercise