New Notions of Reduction and Non-Semantic Proofs of β-Strong Normalization in Typed λ-Calculi

Two new notions of reduction for terms of the λ-calculus are introduced and the question of whether a λ-term is beta-strongly normalizing is reduced to the question of whether a λ-term is merely normalizing under one of the new notions of reduction. This leads to a new way to prove beta-strong normalization for typed λ-calculi. Instead of the usual semantic proof style based on Girard's "candidats de réductibilité'', termination can be proved using a decreasing metric over a well-founded ordering in a style more common in the field of term rewriting. This new proof method is applied to the simply-typed λ-calculus and the system of intersection types.

Addendum to "New Notions of Reduction and Non-Semantic Proofs of β-Strong Normalization in Typed λ-Calculi"

This is an addendum to our technical report BUCS TR-94-014 of December 19, 1994. It clarifies some statements, adds information on some related research, includes a comparison with research be de Groote, and fixes two minor mistakes in a proof.

A New Version of Toom's Proof

There are several proofs now for the stability of Toom's example of a two-dimensional stable cellular automaton and its application to fault-tolerant computation. Simon and Berman simplified and strengthened Toom's original proof: the present report is simplified exposition of their proof.

Client-based Logging: A New Paradigm of Distributed Transaction Management

The proliferation of inexpensive workstations and networks has created a new era in distributed computing. At the same time, non-traditional applications such as computer-aided design (CAD), computer-aided software engineering (CASE), geographic-information systems (GIS), and office-information systems (OIS) have placed increased demands for high-performance transaction processing on database systems. The combination of these factors gives rise to significant challenges in the design of modern database systems. In this thesis, we propose novel techniques whose aim is to improve the performance and scalability of these new database systems. These techniques exploit client resources through client-based transaction management. Client-based transaction management is realized by providing logging facilities locally even when data is shared in a global environment. This thesis presents several recovery algorithms which utilize client disks for storing recovery related information (i.e., log records). Our algorithms work with both coarse and fine-granularity locking and they do not require the merging of client logs at any time. Moreover, our algorithms support fine-granularity locking with multiple clients permitted to concurrently update different portions of the same database page. The database state is recovered correctly when there is a complex crash as well as when the updates performed by different clients on a page are not present on the disk version of the page, even though some of the updating transactions have committed. This thesis also presents the implementation of the proposed algorithms in a memory-mapped storage manager as well as a detailed performance study of these algorithms using the OO1 database benchmark. The performance results show that client-based logging is superior to traditional server-based logging. This is because client-based logging is an effective way to reduce dependencies on server CPU and disk resources and, thus, prevents the server from becoming a performance bottleneck as quickly when the number of clients accessing the database increases.

Variation in the type and frequency of postoperative invasive Staphylococcus aureus infections according to type of surgical procedure.

OBJECTIVE: To determine the epidemiological characteristics of postoperative invasive Staphylococcus aureus infection following 4 types of major surgical procedures.design. Retrospective cohort study. SETTING: Eleven hospitals (9 community hospitals and 2 tertiary care hospitals) in North Carolina and Virginia. PATIENTS: Adults undergoing orthopedic, neurosurgical, cardiothoracic, and plastic surgical procedures. METHODS: We used previously validated, prospectively collected surgical surveillance data for surgical site infection and microbiological data for bloodstream infection. The study period was 2003 through 2006. We defined invasive S. aureus infection as either nonsuperficial incisional surgical site infection or bloodstream infection. Nonparametric bootstrapping was used to generate 95% confidence intervals (CIs). P values were generated using the Pearson chi2 test, Student t test, or Wilcoxon rank-sum test, as appropriate. RESULTS: In total, 81,267 patients underwent 96,455 procedures during the study period. The overall incidence of invasive S. aureus infection was 0.47 infections per 100 procedures (95% CI, 0.43-0.52); 227 (51%) of 446 infections were due to methicillin-resistant S.aureus. Invasive S. aureus infection was more common after cardiothoracic procedures (incidence, 0.79 infections per 100 procedures [95%CI, 0.62-0.97]) than after orthopedic procedures (0.37 infections per 100 procedures [95% CI, 0.32-0.42]), neurosurgical procedures (0.62 infections per 100 procedures [95% CI, 0.53-0.72]), or plastic surgical procedures (0.32 infections per 100 procedures [95% CI, 0.17-0.47]) (P < .001). Similarly, S. aureus bloodstream infection was most common after cardiothoracic procedures (incidence, 0.57 infections per 100 procedures [95% CI, 0.43-0.72]; P < .001, compared with other procedure types), comprising almost three-quarters of the invasive S. aureus infections after these procedures. The highest rate of surgical site infection was observed after neurosurgical procedures (incidence, 0.50 infections per 100 procedures [95% CI, 0.42-0.59]; P < .001, compared with other procedure types), comprising 80% of invasive S.aureus infections after these procedures. CONCLUSION: The frequency and type of postoperative invasive S. aureus infection varied significantly across procedure types. The highest risk procedures, such as cardiothoracic procedures, should be targeted for ongoing preventative interventions.

The price of innovation: new estimates of drug development costs.

The research and development costs of 68 randomly selected new drugs were obtained from a survey of 10 pharmaceutical firms. These data were used to estimate the average pre-tax cost of new drug development. The costs of compounds abandoned during testing were linked to the costs of compounds that obtained marketing approval. The estimated average out-of-pocket cost per new drug is 403 million US dollars (2000 dollars). Capitalizing out-of-pocket costs to the point of marketing approval at a real discount rate of 11% yields a total pre-approval cost estimate of 802 million US dollars (2000 dollars). When compared to the results of an earlier study with a similar methodology, total capitalized costs were shown to have increased at an annual rate of 7.4% above general price inflation.

Low Molecular Weight Opioid Peptide Esters Could be Developed as a New Class of Analgesics.

Low molecular weight opioid peptide esters (OPE) could become a class of analgesics with different side effect profiles than current opiates. OPE may have sufficient plasma stability to cross the blood brain barrier (BBB), undergo ester hydrolysis and produce analgesia. OPE of dipeptides, tyr-pro and tyr-gly conjugated to ethanol have a structure similar to the anesthestic agent, etomidate. Based upon the analgesic activity of dipeptide opioids, Lipinski's criteria, and permeability of select GABA esters to cross the BBB, opioid peptides (OP) conjugated to ethanol, cholesterol or 3-glucose are lead recommendations. Preliminary animal data suggests that tyr-pro-ethyl ester crosses the BBB and unexpectedly produces hyperalgesia. Currently, there are no approved OP analgesics available for clinical use. Clinical trials of good manufacturing practice OP administered to patients suffering from chronic pain with indwelling intrathecal pumps could resolve the issue that OP may be superior to opiates and may redirect research.