David A. Hoffman

Effect of allopurinol on NMDA receptor modification following recurrent asphyxia in newborn piglets

The present study tests the hypothesis that repeated episodes of asphyxia will lead to alterations in the characteristics of the N-methyl-d-aspartate (NMDA) receptor in the brain cell membrane of newborn piglets and that pre-treatment with allopurinol, a xanthine oxidase inhibitor, will prevent these modifications. Eighteen newborn piglets were studied. Six untreated and six allopurinol treated animals were subjected to eight asphyxial episodes and compared to six normoxic, normocapneic controls. Brain cell membrane Na+,K+-ATPase activity was determined to assess membrane function. Na+,K+-ATPase activity was decreased from control following asphyxia in both the untreated and treated animals (47.7+/-3.2 vs. 43.0+/-2.2 and 41.0+/-5.3 micromol Pi/mg protein/h, p<0.05, respectively). 3H-MK-801 binding studies were performed to measure NMDA receptor binding characteristics. The receptor density (Bmax) in the untreated asphyxia group was decreased compared to control animals (0.80+/-0.11 vs. 1.13+/-0.33, p<0.05); furthermore, the dissociation constant (Kd) was also decreased (3.8+/-0.7 vs. 9.2+/-2.2, p<0.05), indicating an increase in receptor affinity. In contrast, Bmax in the allopurinol treated asphyxia group was similar to control (1. 06+/-0.37); and Kd was higher (lower affinity) than in the untreated group (6.5+/-1.4, p<0.05). The data indicate that recurrent asphyxial episodes lead to alterations in NMDA receptor characteristics; and that despite cell membrane dysfunction as seen by a decrease in Na+,K+-ATPase activity, allopurinol prevents modification of NMDA receptor-ion channel binding characteristics induced by repeated episodes of asphyxia.

The Common Sense of Contract Formation

Legally, much depends on the moment that a negotiation becomes a deal. Unlike torts or civil procedure or any area of public law, the laws of promissory exchange only apply to parties who have manifested their assent to be bound. Even so, the moral norms of exchange and promise are quite firmly entrenched and more broadly applicable than just legal contracts. Norms of promise-keeping and reciprocity, interpersonal courtesy, community reputation — these kinds of intangible goods have real effects on contract behavior. For this reason it is especially surprising that intuitions about formation have gotten so little attention from legal and behavioral scholars. This paper offers five new empirical studies of commonsense approaches to contract formation. The first section of this Article surveys intuitions about what the law of formation is. In a world in which the vast majority of contracts are signed without the advice of counsel, most people have to draw inferences based on their background knowledge and beliefs. It turns out that the colloquial understanding of contract formation is about the formalization of an agreement rather than actual assent. In the second part of the Article, we tease out the intuitive relationship between formation and obligation. The law of contracts is very clear that parties’ obligations to one another turn entirely on whether or not they have mutually manifested assent to be bound. And, in fact, we find that behavioral results suggest that legal (or legalistic) formation does enhance commitment to a deal irrespective of its power to impose sanctions; it seems that the law has freestanding normative force. However, we also find that the subjective sense of obligation is not as black or white as the law would predict. Parties are influenced by the natural, informal obligations to one another that build over the course of a transaction, increasing their commitment to the partnership in stages rather than all at once at the moment of formation.

Building a Taxonomy of Litigation: Clusters of Causes of Action in Federal Complaints

This project empirically explores civil litigation from its inception by examining the content of civil complaints. We utilize spectral cluster analysis on a newly compiled federal district court data set of causes of action in complaints to illustrate the relationship of legal claims to one another, the broader composition of lawsuits in trial courts, and the breadth of pleading in individual complaints. Our results shed light not only on the networks of legal theories in civil litigation but also on how lawsuits are classified and the strategies that plaintiffs and their attorneys employ when commencing litigation. This approach permits us to lay the foundation for a more precise and useful taxonomy of federal litigation than has been previously available, one that, after the Supreme Court’s recent decisions in Bell Atlantic v. Twombly (2007) and Ashcroft v. Iqbal (2009), has also arguably never been more relevant than it is today.

From Promise to Form: How Contracting Online Changes Consumers

I hypothesize that different experiences with online contracting have led some consumers to see contracts — both online and offline — in distinctive ways. Experimenting on a large, nationally representative, sample, this paper provides evidence of age-based and experience-based differences in views of consumer contract formation and breach. I show that younger subjects who have entered into more online contracts are likelier than older ones to think that contracts can be formed online, that digital contracts are legitimate while oral contracts are not, and that contract law is unforgiving of breach. I argue that such individual differences in views of contract formation and enforceability might lead firms to discriminate among consumers. There is some evidence that businesses are already using variance in views of contract to induce consumers to purchase goods they would not otherwise have. I conclude by suggesting how the law might respond to such behavior.

Transient Renal Medullary Hyperechoic Foci in the Neonate: Normal Variation Found in the First Few Days of Life

Transient Renal Medullary Hyperechoic Foci in the Neonate: Normal Variation Found in the First Few Days of Life

Law and Psychology Grows Up, Goes Online, and Replicates

Over the last thirty years, legal scholars have increasingly deployed experimental studies, particularly hypothetical scenarios, to test intuitions about legal reasoning and behavior. That movement has accelerated in the last decade, facilitated in large part by cheap and convenient Internet participant recruiting platforms like Amazon Mechanical Turk. The widespread use of MTurk subjects, a practice that dramatically lowers the barriers to entry for experimental research, has been controversial. At the same time, law and psychology’s home discipline is experiencing a public crisis of confidence widely discussed in terms of the “replication crisis.” At present, law and psychology research is arguably in a new era, in which it is both an accepted feature of the legal landscape and also a target of fresh skepticism. The moment is ripe for taking stock. In this paper, we bring an empirical approach to these problems. Using three canonical law and psychology findings, we document the challenges and the feasibility of reproducing results across platforms. We evaluate the extent to which we are able to reproduce the original findings with contemporary subject pools (MTurk, other national online platforms, and in-person labs). We partially replicate the results, and show marked similarities in subject responses across platforms. In the context of the experiments here, we conclude that meaningful replication requires active intervention in order to keep the materials relevant and sensible. The second aim is to compare Turk subjects to the original samples and to the replication samples. We find, consistent with the weight of recent evidence, that MTurk samples are highly reliable and useful. Subjects are highly similar to subjects on other online platforms an in-person samples, but they differ in their high level of attentiveness. Finally, we review the growing replication literature across disciplines, as well as our firsthand experience, to propose a set of standard practices for the publication of results in law and psychology.

NEUROPROTECTIVE EFFECT OF ANTEPARTUM MAGNESIUM ON NMDA RECEPTOR OF FETAL GUINEA PIG BRAIN DURING HYPOXIA. |[utrif]| 453

Previously we have shown that hypoxia modifies the N-methyl-D-aspartate receptor-ion channel in the fetal guinea pig brain. The present study tests the hypothesis that clinical doses of magnesium (Mg) administered to pregnant guinea pigs will prevent the hypoxia-induced modification of NMDA receptor in the fetal brain. 3H-MK-801 binding was used as an index of NMDA receptor modification. Pregnant term guinea pigs were grouped as follows: group (Gr) I, Mg-controls; Gr II, Mg-hypoxia; Gr III, saline-hypoxia. Intraperitoneal Mg was given as a 300mg/kg loading dose followed by 100mg/kg per hour for four hours. Maternal serum Mg levels ranged from 7.2 to 7.9mg/dL for the Mg-infused groups and 3.4 to 3.9mg/dL for the saline-infused group. Hypoxia was induced by decreasing maternal FiO2 to 7% for one hour. Fetal brain tissue hypoxia was confirmed biochemically by ATP and phosphocreatine. P2 membranes were prepared from 7 fetuses of Gr I, 8 of Gr II, and 10 of Gr III. 3H-MK-801 binding was performed in a medium containing 100μM glutamate, 100μM glycine, 10mM HEPES, 75μg membrane protein, and 0.5 to 50nM 3H-MK-801. Non-specific binding was determined in the presence of 10μM unlabeled MK-801. Kd (dissociation constant) and Bmax (number of receptors) were determined from Scatchard plots using linear regression with R2 values ranging from 0.74 to 0.84. Results are as follows (mean±sd): for groups I, II, and III, Bmax was 0.77±0.17, 0.79±0.16, and 0.78±0.08pmol/mg protein respectively; for same groups, Kd was 4.4±0.1, 4.5±0.1, and 3.2±0.1nM respectively. While there was no statistical difference in Bmax among the three groups, a significant decrease in Kd (p < 0.001) was observed when comparing the saline-treated hypoxic group to the other two groups. No difference in Kd was observed between the Mg-treated normoxic and the Mg-treated hypoxic groups suggesting a protective effect of Mg at clinical doses on the NMDA receptor during hypoxia. We speculate that blockade of NMDA receptor-ion channel by Mg will prevent the ion channel mediated influx of Ca++, thus preventing activation of phospholipase A2 and nitric oxide synthase resulting in free radical generation, a mechanism of neuronal injury. Funded by NIH-HD-20337, MOD#6-FY94-0135, UCPR 506-93.