LNA (locked nucleic acid) and the diastereoisomeric alpha-L-LNA: conformational tuning and high-affinity recognition of DNA/RNA targets.

The remarkable binding properties of LNA (Locked Nucleic Acid) and alpha-L-LNA (the alpha-L-ribo configured diastereoisomer of LNA) are summarized, and hybridization results for LNA/2'-O-Me-RNA chimera and LNAs with a "dangling" nucleotide are introduced. In addition, results from NMR investigations on the furanose conformations of the individual nucleotide monomers in different duplexes are presented. All these data are discussed with focus on the importance of conformational steering of unmodified nucleotides in partly modified LNA and alpha-L-LNA sequences in relation to the unprecedented binding properties of LNA and alpha-L-LNA.

Endogenous fringe benefits, compensating wage differentials and older workers.

Employers are the principal source of health insurance for Americans under age 65. Economic theory argues that workers pay for health insurance in the form of lower wages or reductions in other forms of compensation. This paper uses 1994 and 1998 Health and Retirement Survey data to examine the wage-health insurance trade-off for older U.S. workers. Job and insurance choice are treated as endogenous in a two stage least squares framework. There is strong evidence supporting the treatment of nonwage benefits as endogenous. The preferred specification indicates an annual health insurance wage adjustment of $6,300. The magnitude of the trade-off is fragile, however.

Medical malpractice among physicians: who will be sued and who will pay?

This paper examines whether a physician's future claims of medical malpractice are predictable from information on the physician's recent claims history, training credentials, practice characteristics, and demographics. Data on the medical malpractice experience of 8,733 Michigan physicians between 1980 and 1989 is analyzed. We find strong evidence of repetition over time regarding who was sued and who paid claims. The worse a physician's malpractice litigation record during 1980-1984, the worse was his record during 1985-1989. Training credentials were also highly predictive of future malpractice experience. Physicians trained at lower ranked medical schools or who went through lower-ranked residency programs faced higher odds of developing adverse malpractice records, even after controlling for their previous litigation record. Growing internet access to information on these characteristics will help inform prospective patients if they wish to avoid physicians likely to be sued and likely to make payments in the future for malpractice.

Medicaid and crowding out of private insurance: a re-examination using firm level data.

While previous research has identified a relationship between expanded Medicaid eligibility and falling private health insurance coverage, the exact mechanism by which this "crowding out" occurs is largely unexplained. We combine individual and firm-level data to investigate possible responses to the Medicaid expansions by firms and workers. We find no evidence that the expansions affected employer offers of insurance to workers. However, we find some evidence of an effect on the probability that a firm offers family coverage, and on the percentage of full-time workers accepting employer-sponsored coverage offered to them.

The conformations of locked nucleic acids (LNA).

We have used 2D NMR spectroscopy to study the sugar conformations of oligonucleotides containing a conformationally restricted nucleotide (LNA) with a 2'-O, 4'-C-methylene bridge. We have investigated a modified 9-mer single stranded oligonucleotide as well as three 9- and 10-mer modified oligonucleotides hybridized to unmodified DNA. The single-stranded LNA contained three modifications whereas the duplexes contained one, three and four modifications, respectively. The LNA:DNA duplexes have normal Watson-Crick base-pairing with all the nucleotides in anti-conformation. By use of selective DQF-COSY spectra we determined the ratio between the N-type (C3'-endo) and S-type (C2'-endo) sugar conformations of the nucleotides. In contrast to the corresponding single-stranded DNA (ssDNA), we found that the sugar conformations of the single-stranded LNA oligonucleotide (ssLNA) cannot be described by a major S-type conformer of all the nucleotides. The nucleotides flanking an LNA nucleotide have sugar conformations with a significant population of the N-type conformer. Similarly, the sugar conformations of the nucleotides in the LNA:DNA duplexes flanking a modification were also shown to have significant contributions from the N-type conformation. In all cases, the sugar conformations of the nucleotides in the complementary DNA strand in the duplex remain in the S-type conformation. We found that the locked conformation of the LNA nucleotides both in ssLNA and in the duplexes organize the phosphate backbone in such a way as to introduce higher population of the N-type conformation. These conformational changes are associated with an improved stacking of the nucleobases. Based on the results reported herein, we propose that the exceptional stability of the LNA modified duplexes is caused by a quenching of concerted local backbone motions (preorganization) by the LNA nucleotides in ssLNA so as to decrease the entropy loss on duplex formation combined with a more efficient stacking of the nucleobases.

Small group reform and insurance provision by small firms, 1989-1995.

Since 1989, states have enacted legislation to dismantle barriers facing small businesses that wish to purchase health insurance. Using data on the insurance offerings of 2,472 small firms (one to 49 employees) observed from 1989 to 1995, we assess whether state reforms encouraged more small firms to sponsor health benefits. We find that small group reforms did not spur uninsured firms to offer insurance. Firms without health insurance say that the high price of coverage is still the major barrier they face to offering a plan. Our findings suggest that the small group reforms within the 1996 Health Insurance Portability and Accountability Act are not likely to have an effect on the small group market. Most states already had implemented measures similar to those found in the act, and not much changed.

Health Insurance Portability and Accountability Act of 1996: lessons from the States.

OBJECTIVES: To assess the likely effects of the 1996 Health Insurance Portability and Accessibility Act (HIPAA), based on small firms' experiences under state small group insurance reforms that were similar in design to HIPAA. METHODS: Data on 17,818 small businesses (range, 2-50 employees) nationwide from the 1994 National Employer Health Insurance Survey were analyzed to examine the effects of state small group reforms on the following: (1) employers' provision of coverage; (2) the percentage of workers in insured firms who were covered by plans; and (3) insurer practices of "enrollee exclusion." Logistic regression models were estimated and used to quantify the marginal effects of state small-group reform. Reform effects were examined for all small firms, for small firms by size category, and for small firms in redlined industries. RESULTS: Under full reform for at least 3 years (full reform includes guaranteed issue and renewal, portability, limits on pre-existing condition waits, and rating restrictions), employers were slightly more likely to sponsor health plans; however, employee participation in employer plans was no higher and the prevalence of enrollee-exclusion provisions was unchanged. Businesses in redlined industries clearly benefitted from all types of small group reform. For other subgroups of businesses, however, there were advantages and disadvantages associated with reforms, which varied with the scope of the measures and time since their implementation. CONCLUSION: Widespread small group reform may eventually help raise the proportion of small firms that sponsor health benefits, but not by much.

Employer-sponsored health insurance and mandated benefit laws.

Regulations for the content of private health plans, called mandated benefit laws, are widespread and growing in the United States, at both state and federal levels. Three aspects of these laws are examined: their current scope; some economic reasons for their existence; and the theory and empirical evidence for their effects in health insurance markets. A growing body of literature suggests that society is paying a high price for enhanced coverage via mandated benefits. These laws increase insurance premiums, cause declines in wages and other fringe benefits, and lead some employers and their workers to forgo health benefits altogether. The cost of mandated benefit laws falls disproportionately on workers in small firms.

Employer-sponsored health insurance for chiropractic services.

The use of chiropractors has increased substantially in recent years, and there is growing scientific evidence on the effectiveness of chiropractic treatment for common low back ailments. Despite the increased acceptance of chiropractic care, little is known about the prevalence of chiropractic coverage in employer health plans and the nature of such benefits when they are provided. This article reports on the extent and composition of chiropractic insurance among workers with employer-sponsored health insurance in 1993. The prevalence of the benefits in employer plans was examined, as was the extent to which plans are in compliance with state mandated benefits in this area. The authors also examined what the actual benefits consist of and how they compare with those for physician office visits and physical therapy.

Switching to managed care in the small employer market.

In 1993, only 22% of small employers offered a managed care product; by 1995, nearly 70% did. This study uses nationally representative data on small firms in 1993 and 1995 to examine the factors underlying this dramatic shift. Two explanations emerge from the regression work. Adoption of managed care by large employers appears to have served as a signal, certifying the acceptance of managed care among workers. Second, lower prices for managed care products, relative to conventional insurance, increased the adoption of managed care, particularly in 1995. There is little evidence that state insurance reforms prompted the switch, although they may have helped set the stage for it.

Small group reform in a competitive managed care market: the case of California, 1993 to 1995.

State-level insurance reforms designed to make health insurance more accessible for small businesses and their employees have become common in the 1990s. This study examines the effects of small group reform legislation enacted in California in 1993. Using survey data on health benefits in small firms, we look at changes in health insurance coverage that occurred between spring 1993 (just before reform) and spring 1995. Our results indicate that insurance became slightly more affordable and, among businesses with three to nine employees, employer provision increased more than 10 percentage points. Provision was unchanged among larger-sized businesses, however. Managed care penetration increased considerably. We argue that California's competitive health insurance market, which already was dominated by managed care, represented a favorable environment for small group reform. In this context, the modest growth in insurance provision highlights the limited potential of incremental reforms for expanding insurance coverage.

The heart of aging: special challenges of cardiac ischemic disease and failure in the elderly.

The elderly are the fastest-growing segment of society, and heart disease is the single-most common cause of death in this population. In this article, age-related structural and functional changes that occur in the heart are discussed, including changes in the heart muscle, valves, conduction system and major arteries. Coronary artery disease affects half of those older than 65, resulting in acute myocardial infarction, angina pectoris, dysrhythmias, congestive heart failure and sudden death. Each of these is discussed, including altered presentation in the elderly and implications for practice derived from national and international studies.

Why medical savings accounts deserve a closer look.

Dismissed as a luxury only for the young or wealthy, medical savings accounts could be used by a majority of Americans--who are neither poor or chronically ill--to make cost-conscious choices about their health care. Current federal tax laws and insurers' inability to sell catastrophic group coverage policies pose obstacles to their widespread use and should be removed.

How Clinton's health benefit package compares to today's employer-sponsored plans.

Will you and your employees be better or worse off under the Clinton Health Security Act? A national survey of nearly 2,000 large and small businesses finds that a few workers will pay a lot less and receive a lot more insurance coverage than they receive today, while those who lose ground will just be a little worse off.

Small employers and the health insurance market.

In 1993 half of all small businesses (fewer than fifty workers) sponsored a health plan for their employees, up from 41 percent in 1989. While not as deep, the benefits offered by small firms are nearly as broad as benefits offered by large firms, and they have expanded since 1989. Small businesses pay more for coverage, however. Although coverage restrictions based on health status and preexisting conditions are a significant concern of small firms, actual limits of this type in the small-group market are modest. Firms not offering insurance report that they have wide access to coverage, and many would sponsor a plan if only prices were lower.

Small businesses' changing views on health reform.

Our national sample of 750 randomly chosen firms with fewer than 50 employees reveals surprising findings about the traditional views of small business on health care reform. A substantial segment of the small business community is sympathetic to health care reform, including such controversial measures as mandating that all employers contribute to the coverage of their workers, limits on health care spending, and altering the tax treatment of employer contributions for health insurance. Without premium savings, fewer than half of small businesses support the concept of health insurance purchasing cooperatives. With premium savings, a majority support it.