\u3cem\u3eSamantar v. Yousuf\u3c/em\u3e: A False Summit in American Human Rights Civil Litigation

The quest to bring human rights abusers to justice is a challenge wrought with legal obstacles. One such obstacle is the common law principle of sovereign immunity, under which a foreign nation cannot be sued in a court outside of its own jurisdiction. In 1976, Congress sought to eliminate inconsistent application of such immunity by passing the Foreign Sovereign Immunities Act (FSIA). The inconsistency remained, however, as some circuit courts interpreted the FSIA immunity as applying to both foreign government officials, as well as foreign states. The U.S. Supreme Court settled the issue in 2010 in Samantar v. Yousuf, a civil suit against a former Somali general charged with torture, when it held that FSIA immunity does not apply to foreign officials sued in their individual capacity. While some lauded the decision as a landmark in human rights litigation, such optimism appears misplaced. Because of the various avenues of common law immunity still available to foreign officials, the possibility that the precedent of Samantar will prove to be a valuable tool in bringing justice to abuse victims remains highly remote

Wanted: A Practical Application of the Foreign Sovereign Immunities Act to Foreign Reward Offers

In 1976, Congress sought to codify the application of sovereign immunity with the passing of the Foreign Sovereign Immunities Act (FSIA). As foreign governments began to routinely act as participants in international commerce, Congress intended that the FSIA waive sovereign immunity when a foreign government engages in commercial activity that has a “direct effect” in the United States. This exception permits suits against foreign governments in U.S. courts when there is a breach a commercial contract that directly affects economic interests in the United States. Under U.S. contract law, a binding unilateral contract may form when one party performs the acts requested in an open offer, such as providing the whereabouts of a wanted fugitive in return for a reward. A recent Eleventh Circuit case, Guevara v. Republic of Peru, displayed the court’s inconsistent application of the FSIA’s commercial activity exception to fugitive reward offers, and prohibits the judicial enforcement of these contracts, even when offered by a foreign government and entered into on U.S. soil. The Guevara decision illustrates the unsettled interpretation and application of the FSIA by U.S. courts, and may have very damaging effects on U.S. participation in the pursuit of international fugitives

Pancreatic cancer patient survival correlates with DNA methylation of pancreas development genes.

DNA methylation is an epigenetic mark associated with regulation of transcription and genome structure. These markers have been investigated in a variety of cancer settings for their utility in differentiating normal tissue from tumor tissue. Here, we examine the direct correlation between DNA methylation and patient survival. We find that changes in the DNA methylation of key pancreatic developmental genes are strongly associated with patient survival

ESTABLISHING THE DISCRIMINATIVE STIMULUS PROPERTIES OF THE ATYPICAL ANTIPSYCHOTIC AMISULPRIDE IN C57BL/6 MICE

Abstract ESTABLISHING THE DISCRIMINATIVE STIMULUS PROPERTIES OF THE ATYPICAL ANTIPSYCHOTIC AMISULPRIDE IN C57BL/6 MICE Antipsychotic medications are used to treat schizophrenia. The present study used the drug discrimination paradigm to measure the subjective effects of the atypical antipsychotic amisulpride and to examine the underlying neuropharmacological mechanisms responsible for the discriminative stimulus property of the drug. Male C57BL/6 mice were trained to discriminate 10 mg/kg (-)S amisulpride from vehicle in a two-lever drug discrimination task. A dose effect curve for (-)S amisulpride yielded an ED50 = 1.77 mg/kg 95% CI [1.28, 2.45 mg/kg]. Substitution testing was conducted for the isomer (+)R amisulpride, racemic (±)SR amisulpride, the atypical antipsychotics clozapine, aripiprazole and the typical antipsychotic haloperidol. There was partial substitution for (+)R amisulpride, and full substitution for (±)SR amisulpride with a significant rightward shift in the dose effect curves. Clozapine, aripiprazole, and haloperidol failed to fully substitute with significant rate suppression at the higher doses. These results demonstrated that (-)S amisulpride has a unique discriminative stimulus that differs from other antipsychotic drugs

CHARACTERIZATION OF THE DISCRIMINATIVE STIMULUS PROPERTIES OF THE ATYPICAL ANTIPSYCHOTIC AMISULPRIDE IN C57BL/6 MICE

Amisulpride, a benzamide derivative, is an atypical antipsychotic drug used to treat both schizophrenia and depression. Amisulpride is a selective antagonist at dopamine D2 and D3 receptors and at serotonin 5-HT2B and 5-HT7 receptors and displays an atypical clinical profile with reduced extrapyramidal motor effects. The drug has a chiral center and is a mixture of two optical isomers: (S)-amisulpride and (R)-amisulpride. The present study used a two-lever drug discrimination assay to allow a direct comparison between amisulpride and its two isomers. Additionally, substitution testing was conducted with the typical antipsychotics, atypical antipsychotics, antidepressants, the anxiolytic chlordiazepoxide, several benzamide derivatives, and selective ligands with receptor mechanisms relevant to amisulpride. C57BL/6 mice were trained to discriminate 10 mg/kg rac-amisulpride from vehicle in a two-lever drug discrimination task for food reinforcement in an average of 35.7 sessions (range 6-89). The amisulpride dose-response curve (0.078 – 10.0 mg/kg) yielded an ED50 = 0.64 mg/kg, 95% CI [.47, 0.84 mg/kg]. The isomers fully substituted for amisulpride with a significant left-ward shift in the dose-response curve for (S)-amisulpride as compared to rac-amisulpride and (R)-amisulpride. The benzamide derivatives sulpiride and the (S)-sulpiride isomer fully substituted for amisulpride; tiapride produced partial substitution (76.4% DLR); none of the other tested drugs substituted for rac-amisulpride’s discriminative stimulus. These results showed that the rac-amisulpride stimulus was readily acquired in C57BL/6 mice, and that it has a unique and robust discriminative stimulus that is dose-dependent, time-dependent and stereoselective and is not shared with other antipsychotic or antidepressant drugs

Space Transportation System Availability Relationships to Life Cycle Cost

Future space transportation architectures and designs must be affordable. Consequently, their Life Cycle Cost (LCC) must be controlled. For the LCC to be controlled, it is necessary to identify all the requirements and elements of the architecture at the beginning of the concept phase. Controlling LCC requires the establishment of the major operational cost drivers. Two of these major cost drivers are reliability and maintainability, in other words, the system's availability (responsiveness). Potential reasons that may drive the inherent availability requirement are the need to control the number of unique parts and the spare parts required to support the transportation system's operation. For more typical space transportation systems used to place satellites in space, the productivity of the system will drive the launch cost. This system productivity is the resultant output of the system availability. Availability is equal to the mean uptime divided by the sum of the mean uptime plus the mean downtime. Since many operational factors cannot be projected early in the definition phase, the focus will be on inherent availability which is equal to the mean time between a failure (MTBF) divided by the MTBF plus the mean time to repair (MTTR) the system. The MTBF is a function of reliability or the expected frequency of failures. When the system experiences failures the result is added operational flow time, parts consumption, and increased labor with an impact to responsiveness resulting in increased LCC. The other function of availability is the MTTR, or maintainability. In other words, how accessible is the failed hardware that requires replacement and what operational functions are required before and after change-out to make the system operable. This paper will describe how the MTTR can be equated to additional labor, additional operational flow time, and additional structural access capability, all of which drive up the LCC. A methodology will be presented that provides the decision makers with the understanding necessary to place constraints on the design definition. This methodology for the major drivers will determine the inherent availability, safety, reliability, maintainability, and the life cycle cost of the fielded system. This methodology will focus on the achievement of an affordable, responsive space transportation system. It is the intent of this paper to not only provide the visibility of the relationships of these major attribute drivers (variables) to each other and the resultant system inherent availability, but also to provide the capability to bound the variables, thus providing the insight required to control the system's engineering solution. An example of this visibility is the need to provide integration of similar discipline functions to allow control of the total parts count of the space transportation system. Also, selecting a reliability requirement will place a constraint on parts count to achieve a given inherent availability requirement, or require accepting a larger parts count with the resulting higher individual part reliability requirements. This paper will provide an understanding of the relationship of mean repair time (mean downtime) to maintainability (accessibility for repair), and both mean time between failure (reliability of hardware) and the system inherent availability

Low-Dose Continuous 5-Fluorouracil Combined with Leucovorin, nab-Paclitaxel, Oxaliplatin, and Bevacizumab for Patients with Advanced Pancreatic Cancer: A Retrospective Analysis.

BackgroundContinuous-infusion 5-fluorouracil (5FU) and calcium leucovorin plus nab-paclitaxel and oxaliplatin have been shown to be active in patients with pancreatic cancer. As a protracted low-dose infusion, 5FU is antiangiogenic, and has synergy with bevacizumab. As shown in the treatment of breast cancer, bevacizumab and nab-paclitaxel are also synergetic.ObjectiveIn this paper we retrospectively analyze the survival of 65 patients with advanced pancreatic cancer who were treated with low-dose continuous (metronomic) chemotherapy given in conjunction with conventional anti-VEGF therapy.Patients and methodsSince July of 2008, we have treated 65 patients with 5FU (180 mg/m2/day × 14 days) via an ambulatory pump. Calcium leucovorin (20 mg/m2 IV), nab-paclitaxel (60 mg/m2) IV as a 30-min infusion, and oxaliplatin (50 mg/m2) IV as a 60-min infusion were given on days 1, 8, and 15. Bevacizumab (5 mg/kg) IV over 30 min was administered on days 1 and 15. Cycles were repeated every 28-35 days. There were 42 women and 23 men, and the median age was 59 years. Forty-six patients had stage IV disease.ResultsThe median survival was 19 months, with 82% of patients surviving 12 months or longer. The overall response rate was 49%. There were 28 patients who had received prior treatment, 15 of whom responded to therapy. Fifty-two patients had elevated CA 19-9 prior to treatment. Of these, 21 patients had 90% or greater reduction in CA 19-9 levels. This cohort had an objective response rate of 71% and a median survival of 27 months. Thirty patients stopped treatment due to disease progression, and an additional 22 stopped because of toxicity. One patient died while on therapy.ConclusionsThis non-gemcitabine-based regimen resulted in higher response rates and better survival than what is commonly observed with therapy given at conventional dosing schedules. Low-dose continuous (metronomic therapy) cytotoxic chemotherapy combined with antiangiogenic therapy is safe and effective

Cosmogenic C-14 in Antarctic and non-Antarctic meteorites and lunar samples

We were able to develop measurements of C-14 in meteorites as a useful tool for estimates of terrestrial age. Prior to this accomplishment, only a few measurements of C-14 terrestrial ages had been made. The sample sizes were larger, and there had been no systematic study of the various parameters affecting production of C-14, such as depth dependence, and the production cross sections for C-14 from spallation amounted to a few data points. Presently, C-14 ages are an accepted terrestrial age estimate in the meteorite community, whereas before this work the few data available were difficult to interpret. We have obtained terrestrial ages not only on groups of meteorites from different geographic areas but also information on unique meteorites from particularly interesting groups, such as meteorites originating from the Moon, or SNC meteorites, which many researchers believe are derived from Mars