The Quality of Mercy Is Not Strained: Interpreting the Notice Requirement of the Federal Tort Claims Act

Under the Federal Tort Claims Act of 1946 {FfCA), the United States is liable for tort claims in the same manner and to the same extent as a private individual under like circumstances. This limited waiver of sovereign immunity, subject to certain exceptions, grants federal district courts exclusive jurisdiction over civil tort actions against the United States for money damages. The Act requires a claimant suing the United States to file her claim first with the appropriate administrative agency. If the agency denies the claim, it mails a notice of final denial, and the claimant then has six months to file the claim against the United States in federal court. Failure to file suit within six months from the date of mailing and within two years after the claim accrues forever bar[s] the claimant from seeking relief in the courts under the FfCA. The Act does not specify to whom the agency must send the notice of denial. The Department of Justice (DOJ), charged by Congress with administering the Act, therefore promulgated 28 C.F.R. § 14.9(a), which requires that the agency send notice to the claimant, her attorney, or her legal representative. The courts have applied this regulation to claims arising under the Act nearly uniformly, interpreting it to permit an agency to send notice to any of the recipients enumerated in the regulation. They generally have dismissed claimants\u27 arguments that the notice of denial should have been sent only to them, or alternatively, to their attorneys, often with a succinct reference to the language of section 14.9. In late 1996, however, the Ninth Circuit let slip the dogs of war and held in Graham v. United States that section 14.9(a) requires that the notice of denial be sent only to the claimant\u27s attorney, if the agency knows that the claimant is represented. The court justified its override of the language of the regulation primarily on the grounds of prevailing ethical standards. Sending the notice to the claimant, the Ninth Circuit held, violates the ethical rule that attorneys may not communicate directly with parties they know to be represented. Because the Bureau of Prisons sent the notice of denial to Graham instead of to her attorney, the court permitted Graham\u27s suit to proceed despite its late filing

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Simplification: The Sims and Utopianism

'The Sims' is currently the best-selling computer game in which the players interact with a screen world, building and decorating houses, and striving to direct and control animated three-dimensional figures. The game's positioning of the player is very similar to the reader-positioning affected by the speculative genre of utopian narrative fiction

Adenovirus Vectors as Potent Adjuvants in Vaccine Development

Due to their ability to activate the immune system, replication-defective Adenoviruses (Ad) are potential vaccine vectors for several pathogens. The proinflammatory response to Ad contributes to the response to vaccine antigens. We found that reactive oxygen species (ROS) are an important signal in the proinflammatory response to Ad. We identified that serotype 5 adenovirus (Ad5) elicits ROS by inducing mitochondrial membrane damage, a process that is dependent on endosomal membrane rupture and Cathepsin release. This mitochondrial dysfunction contributes to NLRP3 inflammasome- and NFκB-dependent innate immune activation. The ROS-dependent inflammatory response likely contributes to the adaptive immune response by supporting DC maturation and activation, lymphocyte recruitment, and cytokine production influencing B and T cell proliferation and differentiation. We next exploited these immunostimulatory properties of Ad in vaccines to prevent transmission of malaria by Plasmodium falciparum. When combined with vaccines preventing infection, transmission-blocking vaccines (TBVs) could limit the spread of malaria. Our study explores how novel, Ad5-based TBVs enhance the humoral immune response to Pfs25, a vaccine antigen. Antibodies against Pfs25 can block transmission. While studies have designed Pfs25 protein-based vaccines with adjuvants, these vaccines do not efficiently elicit transmission-blocking antibodies. We hypothesized Ad5 would serve as a vaccine delivery platform and adjuvant for Pfs25 to generate a robust and prolonged Pfs25-specific antibody response. We found that Ad5-pfs25, which expresses pfs25, generated a robust Pfs25-specific antibody response characterized by a higher titer, higher relative affinity, and broader IgG subclass switching as compared to alum-adjuvanted Pfs25 protein vaccination. Ad5-specific T cell activation correlated with the observed increase in Pfs25-specific antibody titer following Ad5-pfs25 vaccination. Ad-based vectors enhance the humoral immune response to target antigens and likely do so by enhancing T cell activation. To further improve the Pfs25-specific antibody response we combined Ad5-pfs25 with Ad vectors displaying transmission-blocking Pfs25 epitopes within the viral capsid. These prime-boost vaccinations with Ad5-Pfs25 followed by capsid-displayed Pfs25 Ad vectors increase the Pfs25-specific antibody titer as compared to homologous prime-boost with Pfs25-alum. Ad-vectored prime-boosts also block transmission to the mosquito in vitro. In conclusion, we generated novel, Ad-based TBVs that improve the Pfs25-specific antibody response and block transmission

Objective definition of discharge thresholds for post-fire debris flows

Runoff-generated debris flows are a common post-fire hazard in the western United States and a growing number of regions around the world. As wildfire continues to emerge across a broader range of geographic regions and plant communities, there is an increasing need for generalizable methods to predict post-fire debris-flow initiation. The prediction of post-fire debris flow during intense rainstorms has traditionally relied upon empirical rainfall thresholds. Rainfall intensity-duration thresholds are often developed based on rainfall data and the hydrologic response to those rainstorms. They are most applicable to the specific regions where data are collected. Here, we present a new predictive approach that utilises processes-based models with fundamental physics and machine learning methods to estimate discharge thresholds for runoff-generated debris-flow initiation in four recently burned areas in the western United States. We assess the performance of the objectively defined discharge threshold-based predictions for post-fire debris-flow initiation from our hybrid framework, which utilises debris-flow timing within rainstorms, physically based numerical simulations of runoff, and the support vector machines method. The proposed thresholds have a good balance between true and false predictions for debris flow and floods. Importantly, our method permits the direct estimation of rainfall intensity-duration thresholds for areas where post-fire debris flow observations are limited

Constraining post-fire debris-flow volumes in the southwestern United States

Debris flows pose a serious threat to human life and infrastructure in downstream areas following wildfire. This underscores the necessity for having a hazard assessment framework in place that can be used to estimate the impacts of post-wildfire debris flows. Current hazard assessments in the western United States (USA) use empirical models to assess the volume of potential post-wildfire debris flows. Volume models provide information regarding the magnitude and potential downstream impacts of debris flows. In this study, we gathered post-wildfire debris-flow volume data from 54 watersheds across the states of Arizona (AZ) and New Mexico (NM), USA, and compared these data to the output of a widely used empirical post-wildfire debris-flow volume model. Results show that the volume model, which was developed using data from the Transverse Ranges of southern California (CA), tends to overestimate observed volumes from AZ and NM, sometimes by several orders of magnitude. This disparity may be explained by regional differences between southern CA and AZ and NM, including differences in sediment supply. However, we found a power- law relationship between debris-flow volume and watershed area that can be used to put first-order constraints on debris-flow volume in AZ and NM

Triggering rainfall intensities for post-wildfire debris flows in the Sonoran Desertscrub plant community

Wildfire makes landscapes more vulnerable to debris flows by reducing soil infiltration capacity and decreasing vegetation cover. The extent to which fire affects debris-flow processes depends on the severity of the fire, the climatology of intense rainfall, the pre-fire plant community, and sediment supply, among other factors. As fire expands into new plant communities and geographic regions, there is a corresponding need to expand efforts to document fire-induced changes and their impacts on debris-flow processes. In recent years, several large wildfires have impacted portions of the Sonoran Desertscrub plant community in Arizona, USA, a plant community where fire has been historically infrequent. Following two of these fires, we monitored debris-flow activity at the watershed scale and quantified wildfire-driven changes in soil hydraulic properties using in-situ measurements with mini disk tension infiltrometers. Results indicate that rainfall intensity-duration thresholds for the initiation of post-fire debris flows in recently burned watersheds within the Sonoran Desertscrub plant community are substantially greater than those in nearby areas dominated by other plant communities, such as chaparral. Results provide insight into the impact of fire on debris-flow processes in a plant community where it is likely to be more impactful in the future and help expand existing post-fire debris flow databases into a plant community where there is a paucity of observations

Maporal Hantavirus Causes Mild Pathology in Deer Mice (\u3ci\u3ePeromyscus maniculatus\u3c/i\u3e)

Rodent-borne hantaviruses can cause two human diseases with many pathological similarities: hantavirus cardiopulmonary syndrome (HCPS) in the western hemisphere and hemorrhagic fever with renal syndrome in the eastern hemisphere. Each virus is hosted by specific reservoir species without conspicuous disease. HCPS-causing hantaviruses require animal biosafety level-4 (ABSL-4) containment, which substantially limits experimental research of interactions between the viruses and their reservoir hosts. Maporal virus (MAPV) is a South American hantavirus not known to cause disease in humans, thus it can be manipulated under ABSL-3 conditions. The aim of this study was to develop an ABSL-3 hantavirus infection model using the deer mouse (Peromyscus maniculatus), the natural reservoir host of Sin Nombre virus (SNV), and a virus that is pathogenic in another animal model to examine immune response of a reservoir host species. Deer mice were inoculated with MAPV, and viral RNA was detected in several organs of all deer mice during the 56 day experiment. Infected animals generated both nucleocapsid-specific and neutralizing antibodies. Histopathological lesions were minimal to mild with the peak of the lesions detected at 7–14 days postinfection, mainly in the lungs, heart, and liver. Low to modest levels of cytokine gene expression were detected in spleens and lungs of infected deer mice, and deer mouse primary pulmonary cells generated with endothelial cell growth factors were susceptible to MAPV with viral RNA accumulating in the cellular fraction compared to infected Vero cells. Most features resembled that of SNV infection of deer mice, suggesting this model may be an ABSL-3 surrogate for studying the host response of a New World hantavirus reservoir

Maporal Hantavirus Causes Mild Pathology in Deer Mice (\u3ci\u3ePeromyscus maniculatus\u3c/i\u3e)

Rodent-borne hantaviruses can cause two human diseases with many pathological similarities: hantavirus cardiopulmonary syndrome (HCPS) in the western hemisphere and hemorrhagic fever with renal syndrome in the eastern hemisphere. Each virus is hosted by specific reservoir species without conspicuous disease. HCPS-causing hantaviruses require animal biosafety level-4 (ABSL-4) containment, which substantially limits experimental research of interactions between the viruses and their reservoir hosts. Maporal virus (MAPV) is a South American hantavirus not known to cause disease in humans, thus it can be manipulated under ABSL-3 conditions. The aim of this study was to develop an ABSL-3 hantavirus infection model using the deer mouse (Peromyscus maniculatus), the natural reservoir host of Sin Nombre virus (SNV), and a virus that is pathogenic in another animal model to examine immune response of a reservoir host species. Deer mice were inoculated with MAPV, and viral RNA was detected in several organs of all deer mice during the 56 day experiment. Infected animals generated both nucleocapsid-specific and neutralizing antibodies. Histopathological lesions were minimal to mild with the peak of the lesions detected at 7–14 days postinfection, mainly in the lungs, heart, and liver. Low to modest levels of cytokine gene expression were detected in spleens and lungs of infected deer mice, and deer mouse primary pulmonary cells generated with endothelial cell growth factors were susceptible to MAPV with viral RNA accumulating in the cellular fraction compared to infected Vero cells. Most features resembled that of SNV infection of deer mice, suggesting this model may be an ABSL-3 surrogate for studying the host response of a New World hantavirus reservoir