Fraudulent Concealment, Self-Concealing Conspiracies, and the Clayton Act

This Note argues that courts should apply a self-concealment standard to section 4B of the Clayton Act rather than require a showing of additional affirmative acts. Part I examines the history of the fraudulent concealment doctrine and its application to antitrust cases. It identifies three different standards used by courts to satisfy the concealment element and finds that courts apply the doctrine inconsistently. Part II analyzes the relationship between the fraudulent concealment doctrine and the self-concealment standard in antitrust cases by examining the judicial development of the doctrine and Congress\u27 intent in enacting section 4B. Part II concludes that the self-concealment standard is an integral part of the fraudulent concealment doctrine and thus should apply to section 4B cases. Part III addresses the policies behind statutes of limitation generally and section 4B specifically, and finds that the self-concealment standard best achieves these policy goals. This Note concludes that courts should toll the antitrust limitation period when the defendant either has affirmatively concealed his wrong or has committed a wrong that inherently conceals itself

Angiotensin II for the Treatment of Vasodilatory Shock

BACKGROUND Vasodilatory shock that does not respond to high-dose vasopressors is associated with high mortality. We investigated the effectiveness of angiotensin II for the treatment of patients with this condition. METHODS We randomly assigned patients with vasodilatory shock who were receiving more than 0.2 mu g of norepinephrine per kilogram of body weight per minute or the equivalent dose of another vasopressor to receive infusions of either angiotensin II or placebo. The primary end point was a response with respect to mean arterial pressure at hour 3 after the start of infusion, with response defined as an increase from baseline of at least 10 mm Hg or an increase to at least 75 mm Hg, without an increase in the dose of background vasopressors. RESULTS A total of 344 patients were assigned to one of the two regimens; 321 received a study intervention (163 received angiotensin II, and 158 received placebo) and were included in the analysis. The primary end point was reached by more patients in the angiotensin II group (114 of 163 patients, 69.9%) than in the placebo group (37 of 158 patients, 23.4%) (odds ratio, 7.95; 95% confidence interval [CI], 4.76 to 13.3; P<0.001). At 48 hours, the mean improvement in the cardiovascular Sequential Organ Failure Assessment (SOFA) score (scores range from 0 to 4, with higher scores indicating more severe dysfunction) was greater in the angiotensin II group than in the placebo group (-1.75 vs. -1.28, P = 0.01). Serious adverse events were reported in 60.7% of the patients in the angiotensin II group and in 67.1% in the placebo group. Death by day 28 occurred in 75 of 163 patients (46%) in the angiotensin II group and in 85 of 158 patients (54%) in the placebo group (hazard ratio, 0.78; 95% CI, 0.57 to 1.07; P = 0.12). CONCLUSIONS Angiotensin II effectively increased blood pressure in patients with vasodilatory shock that did not respond to high doses of conventional vasopressors. (Funded by La Jolla Pharmaceutical Company; ATHOS-3 ClinicalTrials.gov number, NCT02338843.)Peer reviewe

Transcription Regulation of Sex-Biased Genes during Ontogeny in the Malaria Vector Anopheles gambiae

In Anopheles gambiae, sex-regulated genes are responsible for controlling gender dimorphism and are therefore crucial in determining the ability of female mosquitoes to transmit human malaria. The identification and functional characterization of these genes will shed light on the sexual development and maturation of mosquitoes and provide useful targets for genetic control measures aimed at reducing mosquito fertility and/or distorting the sex ratio

Fraudulent Concealment, Self-Concealing Conspiracies, and the Clayton Act

This Note argues that courts should apply a self-concealment standard to section 4B of the Clayton Act rather than require a showing of additional affirmative acts. Part I examines the history of the fraudulent concealment doctrine and its application to antitrust cases. It identifies three different standards used by courts to satisfy the concealment element and finds that courts apply the doctrine inconsistently. Part II analyzes the relationship between the fraudulent concealment doctrine and the self-concealment standard in antitrust cases by examining the judicial development of the doctrine and Congress\u27 intent in enacting section 4B. Part II concludes that the self-concealment standard is an integral part of the fraudulent concealment doctrine and thus should apply to section 4B cases. Part III addresses the policies behind statutes of limitation generally and section 4B specifically, and finds that the self-concealment standard best achieves these policy goals. This Note concludes that courts should toll the antitrust limitation period when the defendant either has affirmatively concealed his wrong or has committed a wrong that inherently conceals itself

Use of circulating tumor cell technology (CELLSEARCH) for the diagnosis of malignant pleural effusions.

RATIONALE: Cytological analysis of pleural effusions (PEs) has a sensitivity of approximately 60%. We hypothesized that the CELLSEARCH technology (Janssen Research and Development, Huntingdon Valley, PA) currently used to detect circulating tumor cells could be adapted for the identification of tumor cells in PEs. METHODS: This was a single-center, prospective, observational study. Pleural fluid from subjects with undiagnosed PEs were analyzed by CELLSEARCH technology, which uses an epithelial cell adhesion molecule antibody-based capture system/cytokeratin antibodies to identify tumor cells. Subjects were prospectively monitored by periodic chart review to determine the etiology of the PE. MEASUREMENTS AND MAIN RESULTS: One hundred thirty-two subjects were analyzed. A malignant etiology was established in 81 subjects. The median number of positive pleural epithelial cells (PECs) detected per milliliter of pleural fluid was 6 in the benign group. The number of PECs was 52 in the malignant nonepithelial group (NS) and 526 in the malignant epithelial group (P \u3c 0.001). Unlike blood, there was a baseline number of positive cells in benign pleural fluids; however, any cutoff greater than 852 positive cells/ml had 100% specificity. The area under the receiver operating characteristic curve was 0.86. Nine percent of our cancer cases had high numbers of PECs (\u3e280/ml) but a negative or nondefinitive cancer diagnosis by cytology. CONCLUSIONS: The pleural CELLSEARCH assay may serve as a valuable addition to traditional cytology and provide useful information regarding the diagnosis of malignant effusions. Major advantages include that it is well standardized, relatively inexpensive, has a rapid turnaround, and is easily available. Our data support the conduct of additional studies of this approach to assist in the diagnosis of malignant PEs

Immunological effects of the TGFβ-blocking antibody GC1008 in malignant pleural mesothelioma patients

We evaluated a neutralizing anti-TGFβ antibody (GC1008) in cancer patients with malignant pleura mesothelioma (MPM). The goal of this study was to assess immunoregulatory effects in relation to clinical safety and clinical response. Patients with progressive MPM and 1–2 prior systemic therapies received GC1008 at 3mg/kg IV over 90 min every 21 d as part of an open-label, two-center Phase II trial. Following TGFβ blockade therapy, clinical safety and patient survival were monitored along with the effects of anti-TGFβ antibodies on serum biomarkers and peripheral blood mononuclear cells (PBMC). Although designed as a larger trial, only 13 patients were enrolled when the manufacturer discontinued further development of the antibody for oncology indications. All participants tolerated therapy. Although partial or complete radiographic responses were not observed, three patients showed stable disease at 3 mo. GC1008 had no effect in the expression of NK, CD4(+), or CD8(+) T cell activating and inhibitory markers, other than a decrease in the expression of 2B4 and DNAM-1 on NK cells. However, serum from 5 patients showed new or enhanced levels of antibodies against MPM tumor lysates as measured by immunoblotting. Patients who produced anti-tumor antibodies had increased median overall survival (OS) (15 vs 7.5 mo, p < 0.03) compared with those who did not. To our knowledge, these data represent the first immune analysis of TGFβ- blockade in human cancer patients

Immunological effects of the TGFβ-blocking antibody GC1008 in malignant pleural mesothelioma patients.

We evaluated a neutralizing anti-TGFβ antibody (GC1008) in cancer patients with malignant pleura mesothelioma (MPM). The goal of this study was to assess immunoregulatory effects in relation to clinical safety and clinical response. Patients with progressive MPM and 1-2 prior systemic therapies received GC1008 at 3mg/kg IV over 90 min every 21 d as part of an open-label, two-center Phase II trial. Following TGFβ blockade therapy, clinical safety and patient survival were monitored along with the effects of anti-TGFβ antibodies on serum biomarkers and peripheral blood mononuclear cells (PBMC). Although designed as a larger trial, only 13 patients were enrolled when the manufacturer discontinued further development of the antibody for oncology indications. All participants tolerated therapy. Although partial or complete radiographic responses were not observed, three patients showed stable disease at 3 mo. GC1008 had no effect in the expression of NK, CD