The NBER Orange Book Dataset: A user's guide.

This paper introduces a newly digitized, open-access version of the Food and Drug Administration's "Orange Book"-a linkage between approved small-molecule drugs and the patents that protect them. The Orange Book also reports any applicable regulatory exclusivity that prevents competitive entry. We summarize the Orange Book's coverage and discuss the opportunities and challenges associated with using these data for research. Empirical validations against various administrative datasets suggest that Orange Book records are, largely, complete and accurate. We conclude with a specific use case-calculating legal exclusivity periods for drugs-to highlight the types of choices that researchers must make when using this resource.

Optimal vaccine subsidies for endemic diseases.

In Goodkin-Gold et al. (2021), we analyzed optimal subsidies for a vaccine against an epidemic outbreak like Covid-19. This companion paper alters the underlying epidemiological model to suit endemic diseases requiring continuous vaccination of new cohorts-also suiting an epidemic like Covid-19 if, following Gans (2020), one assumes peaks are leveled by social distancing. We obtain qualitatively similar results: across market structures ranging from perfect competition to monopoly, the subsidy needed to induce first-best vaccination coverage on the private market is highest for moderately infectious diseases, which invite the most free riding; extremely infectious diseases drive more consumers to become vaccinated, attenuating externalities. Stylized calibrations to HIV, among other diseases, suggest that first-best subsidies can be exorbitantly high when suppliers have market power, rationalizing alternative policies observed in practice such as bulk purchases negotiated by the government on behalf of the consumers.

Place-Based Drivers of Mortality: Evidence from Migration.

We estimate the effect of current location on elderly mortality by analyzing outcomes of movers in the Medicare population. We control for movers' origin locations as well as a rich vector of pre-move health measures. We also develop a novel strategy to adjust for remaining unobservables, using the correlation of residual mortality with movers' origins to gauge the importance of omitted variables. We estimate substantial effects of current location. Moving from a 10th to a 90th percentile location would increase life expectancy at age 65 by 1.1 years, and equalizing location effects would reduce cross-sectional variation in life expectancy by 15 percent. Places with favorable life expectancy effects tend to have higher quality and quantity of health care, less extreme climates, lower crime rates, and higher socioeconomic status.

Screening and Selection: The Case of Mammograms.

We analyze selection into screening in the context of recommendations that breast cancer screening start at age 40. Combining medical claims with a clinical oncology model, we document that compliers with the recommendation are less likely to have cancer than younger women who select into screening or women who never screen. We show this selection is quantitatively important: shifting the recommendation from age 40 to 45 results in three times as many deaths if compliers were randomly selected than under the estimated patterns of selection. The results highlight the importance of considering characteristics of compliers when making and designing recommendations.

How Do Patents Affect Follow-on Innovation? Evidence from the Human Genome.

We investigate whether patents on human genes have affected follow-on scientific research and product development. Using administrative data on successful and unsuccessful patent applications submitted to the US Patent and Trademark Office, we link the exact gene sequences claimed in each application with data measuring follow-on scientific research and commercial investments. Using this data, we document novel evidence of selection into patenting: patented genes appear more valuable-prior to being patented-than non-patented genes. This evidence of selection motivates two quasi-experimental approaches, both of which suggest that on average gene patents have had no quantitatively important effect on follow-on innovation.

How Do Patents Affect Follow-On Innovation? Evidence from the Human Genome.

We investigate whether patents on human genes have affected follow-on scientific research and product development. Using administrative data on successful and unsuccessful patent applications submitted to the US Patent and Trademark Office, we link the exact gene sequences claimed in each application with data measuring follow-on scientific research and commercial investments. Using these data, we document novel evidence of selection into patenting: patented genes appear more valuable--prior to being patented--than non-patented genes. This evidence of selection motivates two quasi-experimental approaches, both of which suggest that on average gene patents have had no quantitatively important effect on follow-on innovation.

PATENTS AND RESEARCH INVESTMENTS: ASSESSING THE EMPIRICAL EVIDENCE.

A well-developed theoretical literature - dating back at least to Nordhaus (1969) - has analyzed optimal patent policy design. We re-present the core trade-off of the Nordhaus model and highlight an empirical question which emerges from the Nordhaus framework as a key input into optimal patent policy design: namely, what is the elasticity of R&D investment with respect to the patent term? We then review the - surprisingly small - body of empirical evidence that has been developed on this question over the nearly half century since the publication of Nordhaus's book.

Do firms underinvest in long-term research? Evidence from cancer clinical trials.

We investigate whether private research investments are distorted away from long-term projects. Our theoretical model highlights two potential sources of this distortion: short-termism and the fixed patent term. Our empirical context is cancer research, where clinical trials - and hence, project durations - are shorter for late-stage cancer treatments relative to early-stage treatments or cancer prevention. Using newly constructed data, we document several sources of evidence that together show private research investments are distorted away from long-term projects. The value of life-years at stake appears large. We analyze three potential policy responses: surrogate (non-mortality) clinicaltrial endpoints, targeted R&D subsidies, and patent design.

Do Firms Underinvest in Long-Term Research? Evidence from Cancer Clinical Trials.

We investigate whether private research investments are distorted away from long-term projects. Our theoretical model highlights two potential sources of this distortion: short-termism and the fixed patent term. Our empirical context is cancer research, where clinical trials--and hence, project durations--are shorter for late-stage cancer treatments relative to early-stage treatments or cancer prevention. Using newly constructed data, we document several sources of evidence that together show private research investments are distorted away from long-term projects. The value of life-years at stake appears large. We analyze three potential policy responses: surrogate (non-mortality) clinical-trial endpoints, targeted R&D subsidies, and patent design.

REPRESENTATION AND EXTRAPOLATION: EVIDENCE FROM CLINICAL TRIALS.

This article examines the consequences and causes of low enrollment of Black patients in clinical trials. We develop a simple model of similarity-based extrapolation that predicts that evidence is more relevant for decision-making by physicians and patients when it is more representative of the group being treated. This generates the key result that the perceived benefit of a medicine for a group depends not only on the average benefit from a trial but also on the share of patients from that group who were enrolled in the trial. In survey experiments, we find that physicians who care for Black patients are more willing to prescribe drugs tested in representative samples, an effect substantial enough to close observed gaps in the prescribing rates of new medicines. Black patients update more on drug efficacy when the sample that the drug is tested on is more representative, reducing Black-white patient gaps in beliefs about whether the drug will work as described. Despite these benefits of representative data, our framework and evidence suggest that those who have benefited more from past medical breakthroughs are less costly to enroll in the present, leading to persistence in who is represented in the evidence base.

Randomized controlled trial of osteoconductive fixation screws for anterior cruciate ligament reconstruction: a comparison of the Calaxo and Milagro screws.

PURPOSE: To compare the outcome of 2 bioabsorbable screws for tibial interference fixation in anterior cruciate ligament reconstruction with reference to rate of absorption, osteoconductive properties, and clinical outcome. METHODS: Patients undergoing primary anterior cruciate ligament reconstruction with hamstring autograft in a single unit were invited to participate in this study. Patients were randomized to receive either the Calaxo screw (Smith & Nephew, Andover, MA) or Milagro screw (DePuy Mitek, Raynham, MA) for tibial fixation. Patients were reviewed with subjective and objective evaluation by use of the International Knee Documentation Committee form, Lysholm score, KT-1000 arthrometry (MEDmetric, San Diego, CA), and clinical examination. Magnetic resonance imaging was performed at 1 year and computed tomography scanning at 1 week and at 6, 12, and 24 months. RESULTS: Sixty patients agreed to participate in the study, with 32 patients randomized to the Calaxo screw and 28 to the Milagro screw for tibial fixation. There was no significant difference in subjective or objective clinical outcome between the 2 groups. At 24 months, 88% of Calaxo screws showed complete screw resorption compared with 0% of Milagro screws (P < .001). Tibial cysts were present in 88% of the Calaxo group and 7% of the Milagro group (P = .001). At 24 months, the mean volume of new bone formation for the Calaxo group was 21% of original screw volume. Ossification of the Milagro screw was unable to be accurately assessed as a result of incomplete screw resorption. CONCLUSIONS: Both screws showed similar favorable objective and subjective outcomes at 2 years. The Calaxo screw resorbed completely over a period of 6 months and was associated with a high incidence of intra-tunnel cyst formation. The Milagro screw increased in volume over a period of 6 months, followed by a gradual resorption, which was still ongoing at 2 years. Both screws were associated with tunnel widening, and neither showed evidence of significant tunnel ossification. We conclude that, despite satisfactory clinical outcomes, the addition of "osteoconductive" materials to bioabsorbable screws is not associated with bone formation at the screw site at 2 years. LEVEL OF EVIDENCE: Level I, randomized controlled trial.

Where and with whom does a brief social-belonging intervention promote progress in college?

A promising way to mitigate inequality is by addressing students' worries about belonging. But where and with whom is this social-belonging intervention effective? Here we report a team-science randomized controlled experiment with 26,911 students at 22 diverse institutions. Results showed that the social-belonging intervention, administered online before college (in under 30 minutes), increased the rate at which students completed the first year as full-time students, especially among students in groups that had historically progressed at lower rates. The college context also mattered: The intervention was effective only when students' groups were afforded opportunities to belong. This study develops methods for understanding how student identities and contexts interact with interventions. It also shows that a low-cost, scalable intervention generalizes its effects to 749 4-year institutions in the United States.

Counterfeit diversity: How strategically misrepresenting gender diversity dampens organizations' perceived sincerity and elevates women's identity threat concerns.

Women remain underrepresented in technology and computing fields. Aware of this problem, many tech organizations seek diversification strategies. Several academic sources recommend including gender diverse images in recruitment materials as a low-cost way to potentially attract female workers. However, for gender nondiverse organizations, this strategy means misrepresenting the current on-the-ground diversity of their organization. Four experiments investigate how women and men perceive organizations that counterfeit diversity (i.e., exaggerate gender diversity in recruitment advertisements) relative to organizations that (a) authentically portray a high degree of gender diversity (authentic diversity; Experiments 1-3); (b) authentically portray a low degree of gender diversity (authentic nondiversity; Experiments 2 and 3); and (c) acknowledge a lack of diversity in the present, but aspire to increase diversity in the future (aspirational diversity; Experiment 3). Results reveal that women and men perceive counterfeit diversity as insincere. This perceived insincerity, in turn, decreases women's and men's interest in the organization and engenders identity threat concerns among women (Experiments 1-4). Taken together, these findings complicate scholarly discussions of diversity and inclusion strategies by highlighting the role of perceived sincerity. When recruitment strategies are deemed insincere, these strategies can backfire-decreasing interest in the organization, fomenting threat, and perpetuating underrepresentation. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

A diagnostic PCR assay for the detection of an Australian epidemic strain of Pseudomonas aeruginosa.

BACKGROUND: Chronic lung infection with the bacterium Pseudomonas aeruginosa is one of the hallmarks of cystic fibrosis (CF) and is associated with worsening lung function, increased hospitalisation and reduced life expectancy. A virulent clonal strain of P. aeruginosa (Australian epidemic strain I; AES-I) has been found to be widespread in CF patients in eastern Australia. METHODS: Suppression subtractive hybridization (SSH) was employed to identify genetic sequences that are present in the AES-I strain but absent from the sequenced reference strain PAO1. We used PCR to evaluate the distribution of several of the AES-I loci amongst a collection of 188 P. aeruginosa isolates which was comprised of 35 AES-I isolates (as determined by PFGE), 78 non-AES-I CF isolates including other epidemic CF strains as well as 69 P. aeruginosa isolates from other clinical and environmental sources. RESULTS: We have identified a unique AES-I genetic locus that is present in all 35 AES-I isolates tested and not present in any of the other 153 P. aeruginosa strains examined. We have used this unique AES-I locus to develop a diagnostic PCR and a real-time PCR assay to detect the presence of P. aeruginosa and AES-I in patient sputum samples. CONCLUSIONS: We have developed diagnostic PCR assays that are 100% sensitive and 100% specific for the P. aeruginosa strain AES-I. We have also shown that Whatman FTA Elute cards may be used with PCR-based assays to rapidly detect the presence of P. aeruginosa strains in CF sputum.

Modelling interactions of acid-base balance and respiratory status in the toxicity of metal mixtures in the American oyster Crassostrea virginica.

Heavy metals, such as copper, zinc and cadmium, represent some of the most common and serious pollutants in coastal estuaries. In the present study, we used a combination of linear and artificial neural network (ANN) modelling to detect and explore interactions among low-dose mixtures of these heavy metals and their impacts on fundamental physiological processes in tissues of the Eastern oyster, Crassostrea virginica. Animals were exposed to Cd (0.001-0.400 microM), Zn (0.001-3.059 microM) or Cu (0.002-0.787 microM), either alone or in combination for 1 to 27 days. We measured indicators of acid-base balance (hemolymph pH and total CO(2)), gas exchange (Po(2)), immunocompetence (total hemocyte counts, numbers of invasive bacteria), antioxidant status (glutathione, GSH), oxidative damage (lipid peroxidation; LPx), and metal accumulation in the gill and the hepatopancreas. Linear analysis showed that oxidative membrane damage from tissue accumulation of environmental metals was correlated with impaired acid-base balance in oysters. ANN analysis revealed interactions of metals with hemolymph acid-base chemistry in predicting oxidative damage that were not evident from linear analyses. These results highlight the usefulness of machine learning approaches, such as ANNs, for improving our ability to recognize and understand the effects of sub-acute exposure to contaminant mixtures.

Acupuncture during pregnancy and the perinatal period: Women's attitudes, beliefs and practices.

BACKGROUND: Acupuncture during pregnancy and the perinatal period aims to increase normal birth and enhance a woman's birth experience by decreasing intervention and adverse birth outcomes. Acupuncture in Australian maternity services has not been well accepted, and there is limited research evidence as to whether women are supportive of acupuncture treatment. OBJECTIVE: The aims of this study were to understand childbearing aged women's attitudes, beliefs and practices to using acupuncture during pregnancy and the perinatal period, and possible acceptance of a midwife providing acupuncture treatments. DESIGN: A descriptive/explorative quantitative methodology was used to gather data from childbearing aged women using an online survey. Statistical analysis was used for quantitative data and content analysis for the free-text responses. Recruitment of respondents took place in 2017 via Facebook birth and parenting groups and pages. FINDINGS: Of 304 respondents, 68% (n = 206) had used acupuncture, and of these, 68% (n = 140) used acupuncture for concerns during pregnancy and the perinatal period. The majority of respondents indicated they would consider acupuncture during pregnancy and the perinatal period (89%) and 62% indicated they would have a midwife provide a treatment. The free-text responses provided mostly positive comments on the outcomes and satisfaction of acupuncture treatments (84% n = 199). CONCLUSION: The majority of respondents would consider acupuncture during pregnancy and the perinatal period, were positive to trying acupuncture for various concerns, and were positive towards a midwife providing treatments. These findings raise awareness of women's desire for the choice of an acupuncture treatment during pregnancy and the perinatal period.

WHO PROFITS FROM PATENTS? RENT-SHARING AT INNOVATIVE FIRMS.

This article analyzes how patent-induced shocks to labor productivity propagate into worker compensation using a new linkage of U.S. patent applications to U.S. business and worker tax records. We infer the causal effects of patent allowances by comparing firms whose patent applications were initially allowed to those whose patent applications were initially rejected. To identify patents that are ex ante valuable, we extrapolate the excess stock return estimates of Kogan et al. (2017) to the full set of accepted and rejected patent applications based on predetermined firm and patent application characteristics. An initial allowance of an ex ante valuable patent generates substantial increases in firm productivity and worker compensation. By contrast, initial allowances of lower ex ante value patents yield no detectable effects on firm outcomes. Patent allowances lead firms to increase employment, but entry wages and workforce composition are insensitive to patent decisions. On average, workers capture roughly 30 cents of every dollar of patent-induced surplus in higher earnings. This share is roughly twice as high among workers present since the year of application. These earnings effects are concentrated among men and workers in the top half of the earnings distribution and are paired with corresponding improvements in worker retention among these groups. We interpret these earnings responses as reflecting the capture of economic rents by senior workers, who are most costly for innovative firms to replace.