Lost horizons: The noncooperative management of an evolutionary biological system

This paper studies the interaction between two dynamic domains, (1) an evolutionary biological system ('the environment') whose behaviour determines the availability of a resource stock, and (2) an industry where access to the resource stock is determined by the outcome of a patent race. The specific setting of the model is that of managing microbial resistance to antibiotics. Here, resistance develops in response to the use of antibiotics above a threshold level. We show that the optimal policy from society's point of view is to generate through R&D a diversified portfolio of antibiotics that maintains a steady-state of resistance. In practice, however, the management of the resistance stock is left to an industry operating under a system of intellectual property rights (IPR). There, firms are involved in a sequence of patent races to supply the antibiotic with the best cost-effectiveness ratio. The paper studies the structure of the patent race within the industry against the background of pathogen evolution. We show that a multi-firm industry operating under an IPR-based incentive mechanism is unlikely to generate the socially optimal number of antibiotics because IPR systems (1) create incentives for sequential rather than simultaneous innovation; (2) generate incentives that decline with the number of previous (shelved) discoveries; and (3) generate incentives that respond perversely to increases in biological system velocity. These results highlight the importance of well-designed dynamic incentives for managing resource stock dynamics

The Residential Tenant\u27s Right to Freedom of Political Expression

This Article outlines the arguments to be made on behalf of residential tenants who display political signs and who encounter threats of eviction, rent increases, and other forms of landlord opposition. In Section II, the Article describes the development of the general principles of constitutional law applicable to disputes between property owners and tenants who wish to use the property owners’ premises as a forum for the expression of the tenants’ ideas and beliefs. Tracing the history of the United States Supreme Court rulings in this area, the authors analyze the waxing and waning of first amendment speech rights, the development of property-based first amendment speech rights, and the recognition of state constitutional free speech rights that are broader than their first amendment counterparts. Section III analyzes the application of freedom of speech principles to disputes between landlords and residential tenants, when the tenants wish to display political signs on the leased property. Section III also presents and analyzes the arguments frequently relied upon by landlords. For the benefit of those tenants residing in states where state constitutional free speech rights have not been liberally construed, the authors discuss the common law property rights of tenants, citing reasons why those rights are superior to the property rights of landlords in the context of disputes over tenant political expression. Finally, in Section IV, the Article concludes with an assessment of the public policy justifications for refusing to enforce contractual waivers (such as rule 13 of the lease in Paulsen v. Seamark) of a tenant’s right to freedom of political expression

The Residential Tenant\u27s Right to Freedom of Political Expression

This Article outlines the arguments to be made on behalf of residential tenants who display political signs and who encounter threats of eviction, rent increases, and other forms of landlord opposition. In Section II, the Article describes the development of the general principles of constitutional law applicable to disputes between property owners and tenants who wish to use the property owners’ premises as a forum for the expression of the tenants’ ideas and beliefs. Tracing the history of the United States Supreme Court rulings in this area, the authors analyze the waxing and waning of first amendment speech rights, the development of property-based first amendment speech rights, and the recognition of state constitutional free speech rights that are broader than their first amendment counterparts. Section III analyzes the application of freedom of speech principles to disputes between landlords and residential tenants, when the tenants wish to display political signs on the leased property. Section III also presents and analyzes the arguments frequently relied upon by landlords. For the benefit of those tenants residing in states where state constitutional free speech rights have not been liberally construed, the authors discuss the common law property rights of tenants, citing reasons why those rights are superior to the property rights of landlords in the context of disputes over tenant political expression. Finally, in Section IV, the Article concludes with an assessment of the public policy justifications for refusing to enforce contractual waivers (such as rule 13 of the lease in Paulsen v. Seamark) of a tenant’s right to freedom of political expression

Concepts of Sliding and Lifting Tissue Movement in Flap Reconstruction

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/94457/1/j.1524-4725.2000.09172.x.pd

The anatomy of exhumed river-channel belts: Bedform to belt‐scale river kinematics of the Ruby Ranch Member, Cretaceous Cedar Mountain Formation, Utah, USA

Many published interpretations of ancient fluvial systems have relied on observations of extensive outcrops of thick successions. This paper, in contrast, demonstrates that a regional understanding of palaeoriver kinematics, depositional setting and sedimentation rates can be interpreted from local sedimentological measurements of bedform and barform strata. Dune and bar strata, channel planform geometry and bed topography are measured within exhumed fluvial strata exposed as ridges in the Ruby Ranch Member of the Cretaceous Cedar Mountain Formation, Utah, USA. The ridges are composed of lithified stacked channel belts, representing at least five or six re‐occupations of a single‐strand channel. Lateral sections reveal well‐preserved barforms constructed of subaqueous dune cross‐sets. The topography of palaeobarforms is preserved along the top surface of the outcrops. Comparisons of the channel‐belt centreline to local palaeotransport directions indicate that channel planform geometry was preserved through the re‐occupations, rather than being obscured by lateral migration. Rapid avulsions preserved the state of the active channel bed and its individual bars at the time of abandonment. Inferred minimum sedimentation durations for the preserved elements, inferred from cross‐set thickness distributions and assumed bedform migration rates, vary within a belt from one to ten days. Using only these local sedimentological measurements, the depositional setting is interpreted as a fluvial megafan, given the similarity in river kinematics. This paper provides a systematic methodology for the future synthesis of vertical and planview data, including the drone‐equipped 2020 Mars Rover mission, to exhumed fluvial and deltaic strata

Prognostic Significance of Growth Kinetics in Newly Diagnosed Glioblastomas Revealed by Combining Serial Imaging with a Novel Biomathematical Model

Glioblastomas (GBMs) are the most aggressive primary brain tumors characterized by their rapid proliferation and diffuse infiltration of the brain tissue. Survival patterns in patients with GBM have been associated with a number of clinico-pathologic factors, including age and neurological status, yet a significant quantitative link to in vivo growth kinetics of each glioma has remained elusive. Exploiting a recently developed tool for quantifying glioma net proliferation and invasion rates in individual patients using routinely available magnetic resonance images (MRIs), we propose to link these patient-specific kinetic rates of biological aggressiveness to prognostic significance. Using our biologically-based mathematical model for glioma growth and invasion, examination of serial pre-treatment MRIs of 32 GBM patients allowed quantification of these rates for each patient’s tumor. Survival analyses revealed that even when controlling for standard clinical parameters (e.g., age, KPS) these model-defined parameters quantifying biologically aggressiveness (net proliferation and invasion rates) were significantly associated with prognosis. One hypothesis generated was that the ratio of the actual survival time after whatever therapies were employed to the duration of survival predicted (by the model) without any therapy would provide a “Therapeutic Response Index” (TRI) of the overall effectiveness of the therapies. The TRI may provided important information, not otherwise available, as to the effectiveness of the treatments in individual patients. To our knowledge, this is the first report indicating that dynamic insight from routinely obtained pre-treatment imaging may be quantitatively useful in characterizing survival of individual patients with GBM. Such a hybrid tool bridging mathematical modeling and clinical imaging may allow for statifying patients for clinical studies relative to their pretreatment biological aggressiveness

Resolution of Clinical and Laboratory Abnormalities after Diagnosis of Ventilator-Associated Pneumonia in Trauma Patients

Background: Guidelines advise that patients with ventilator-associated pneumonia (VAP) should respond clinically by Day 3 of antibiotics. White blood cell (WBC) count, maximum temperature (Tmax), and PaO2:FIO2 ratio are all said to respond significantly by Day 6. Resolution of abnormalities has not been evaluated in trauma patients. Methods: Retrospective review of trauma patients with VAP. The WBC count, Tmax, and PaO2:FIO2 were evaluated for 16 days after diagnosis. Patients were grouped into uncomplicated VAP, complicated VAP (those with inadequate empirical therapy [IEAT], VAP relapse/superinfection, or acute respiratory distress syndrome), and concurrent infection +VAP (those also infected at another site). Results: There were 126 patients (uncomplicated VAP= 29, complicated VAP = 69, and concurrent infection + VAP = 28). The mean Tmax in patients with uncomplicated VAP decreased significantly from diagnosis to Day 4 (Day 1: 39 – 0.5°C vs. Day 4: 38.6 – 0.7°C; p = 0.028) but never normalized. Their WBC counts and PaO2:FIO2 did not change significantly over the 16-day follow-up and never normalized.When comparing the three groups, the probability of resolving all three abnormalities was not different (p = 0.5). Conclusions: Clinical and laboratory abnormalities in critically injured patients with VAP do not resolve as quickly as suggested in the guidelines. Future studies should evaluate new methods to determine the response to antibiotic therapy in critically injured patients with VAP

Child and Parent Predictors of Perceptions of Parent–Child Relationship Quality

Objective/Method: Predictors of perceptions of parent–child relationship quality were examined for 175 children with ADHD, 119 comparison children, and parents of these children, drawn from the follow-up phase of the Multimodal Treatment Study of Children with ADHD. Results/Conclusion: Children with ADHD perceived their mothers and fathers as more power assertive than comparison children. Children higher on depressive symptomatology also perceived their mothers and fathers as less warm and more power assertive. Mothers perceived themselves as more power assertive and fathers perceived themselves as less warm if they were higher on depressive symptomatology themselves or had children with ADHD or higher levels of depressive symptomatology. Several interactions indicated that the association between child factors and parental perceptions of warmth and power assertion often depended on parental depressive symptomatology. The findings resolve a previous contradiction in the literature regarding the relationship between child depressive symptoms and parental perceptions of parent–child relationship quality

Parent Agreement on Ratings of Children's Attention Deficit/Hyperactivity Disorder and Broadband Externalizing Behaviors

Mothers and fathers often disagree in their ratings of child behavior, as evidenced clinically and as supported by a substantial literature examining parental agreement on broadband rating scales. The present study examined mother-father agreement on Diagnostic and Statistical Manual-based symptom-specific ratings of Attention-Deficit/Hyperactivity Disorder (ADHD), as compared to agreement on broadband ratings of externalizing behavior. Based on mother and father ratings of 324 children who participated in the Multimodal Treatment Study of Children with ADHD (MTA), parental agreement was computed and patterns of disagreement examined. Mother-father ratings were significantly correlated; however, a clear pattern of higher ratings by mothers was present. Agreement on attention-deficit/hyperactivity disorder symptom-specific ratings was significantly lower than that for broadband externalizing behaviors and oppositional defiant disorder symptoms. Of several moderator variables tested, parental stress was the only one that predicted the discrepancy in ratings. Disagreement between parents is clinically significant and may pose complications to the diagnostic process

Spotted-Fever Group Rickettsia in Dermacentor variabilis, Maryland

Three-hundred ninety-two adult Dermacentor variabilis were collected from six Maryland counties during the spring, summer, and fall of 2002. Infection prevalence for spotted fever group Rickettsia was 3.8%, as determined by polymerase chain reaction. Single strand conformational polymorphism (SSCP) analysis followed by sequencing indicated that all infections represented a single rickettsial taxon, Rickettsia montanensis