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PIF1 is a 5′ to 3′ DNA helicase that can unwind double-stranded DNA and disrupt nucleic acid-protein complexes. In Saccharomyces cerevisiae, Pif1 plays important roles in mitochondrial and nuclear genome maintenance, telomere length regulation, unwinding of G-quadruplex structures, and DNA synthesis during break-induced replication. Some, but not all, of these functions are shared with other eukaryotes. To gain insight into the evolutionarily conserved functions of PIF1, we created pif1 null mutants in Drosophila melanogaster and assessed their phenotypes throughout development. We found that pif1 mutant larvae exposed to high concentrations of hydroxyurea, but not other DNA damaging agents, experience reduced survival to adulthood. Embryos lacking PIF1 fail to segregate their chromosomes efficiently during early nuclear divisions, consistent with a defect in DNA replication. Furthermore, loss of the BRCA2 protein, which is required for stabilization of stalled replication forks in metazoans, causes synthetic lethality in third instar larvae lacking either PIF1 or the polymerase delta subunit POL32. Interestingly, pif1 mutants have a reduced ability to synthesize DNA during repair of a double-stranded gap, but only in the absence of POL32. Together, these results support a model in which Drosophila PIF1 functions with POL32 during times of replication stress but acts independently of POL32 to promote synthesis during double-strand gap repair.

Since 2001, an aid consortium known as Gavi has accounted for over half of vaccines purchased in the 75 eligible countries with an initial GNI below $1,000 per capita. Regression discontinuity estimates suggest most aid for cheap, existing vaccines like hepatitis B and DPT was inframarginal: for instance, hepatitis B doses sufficient to vaccinate roughly 75% of infants raised vaccination rates by single-digit margins. These results are driven by middle-income countries near the eligibility threshold, and do not preclude larger gains for the poorest countries, global externalities via vaccine markets, or impacts on newer vaccines such as pneumococcal or rotavirus for which income eligibility rules were relaxed.

Accountable care organizations (ACOs) and bundled payments represent prominent value-based payment models, but the magnitude of overlap between the two models has not yet been described. Using Medicare data, we defined overlap based on attribution to Medicare Shared Savings Program (MSSP) ACOs and hospitalization for Bundled Payments for Care Improvement (BPCI) episodes at BPCI participant hospitals. Between 2013 and 2016, overlap as a share of ACO patients increased from 2.7% to 10% across BPCI episodes, while overlap as a share of all bundled payment patients increased from 19% to 27%. Overlap from the perspectives of both ACO and bundled payments varied by specific episode. In the first description of overlap between ACOs and bundled payments, one in every ten MSSP patients received care under BPCI by the end of our study period, whereas more than one in every four patients receiving care under BPCI were also attributed to MSSP. Policymakers should consider strategies to address the clinical and policy implications of increasing payment model overlap.

In 2016 Medicare implemented its first mandatory alternative payment model, the Comprehensive Care for Joint Replacement (CJR) program, in which the agency pays clinicians and hospitals a fixed amount for services provided in hip and knee replacement surgery episodes. Medicare made CJR mandatory, rather than voluntary, to produce generalizable evidence on what results Medicare might expect if it scaled bundled payment up nationally. However, it is unknown how markets and hospitals in CJR compare to others nationwide, particularly with respect to baseline quality and spending performance and the structural hospital characteristics associated with early savings in CJR. Using data from Medicare, the American Hospital Association, and the Health Resources and Services Administration, we found differences in structural market and hospital characteristics but largely similar baseline hospital episode quality and spending. Our findings suggest that despite heterogeneity in hospital characteristics associated with early savings in CJR, Medicare might nonetheless reasonably expect similar results by scaling CJR up to additional urban markets and increasing total program coverage to areas in which 71 percent of its beneficiaries reside. In contrast, different policy designs may be needed to extend market-level programs to other regions or enable different hospital types to achieve savings from bundled payment reimbursement.

PIF1 is a 5′ to 3′ DNA helicase that can unwind double-stranded DNA and disrupt nucleic acid-protein complexes. In Saccharomyces cerevisiae, Pif1 plays important roles in mitochondrial and nuclear genome maintenance, telomere length regulation, unwinding of G-quadruplex structures, and DNA synthesis during break-induced replication. Some, but not all, of these functions are shared with other eukaryotes. To gain insight into the evolutionarily conserved functions of PIF1, we created pif1 null mutants in Drosophila melanogaster and assessed their phenotypes throughout development. We found that pif1 mutant larvae exposed to high concentrations of hydroxyurea, but not other DNA damaging agents, experience reduced survival to adulthood. Embryos lacking PIF1 fail to segregate their chromosomes efficiently during early nuclear divisions, consistent with a defect in DNA replication. Furthermore, loss of the BRCA2 protein, which is required for stabilization of stalled replication forks in metazoans, causes synthetic lethality in third instar larvae lacking either PIF1 or the polymerase delta subunit POL32. Interestingly, pif1 mutants have a reduced ability to synthesize DNA during repair of a double-stranded gap, but only in the absence of POL32. Together, these results support a model in which Drosophila PIF1 functions with POL32 during times of replication stress but acts independently of POL32 to promote synthesis during double-strand gap repair.

PIF1 is a 5’ to 3’ DNA helicase that can unwind double-stranded DNA and disrupt nucleic acid-protein complexes. InSaccharomyces cerevisiae, Pif1 plays important roles in mitochondrial and nuclear genome maintenance, telomere length regulation, unwinding of G-quadruplex structures, and DNA synthesis during break-induced replication. Some, but not all, of these functions are shared with other eukaryotes. To gain insight into the evolutionarily conserved functions of PIF1, we createdpif1null mutants inDrosophila melanogasterand assessed their phenotypes throughout development. We found thatpif1mutant larvae exposed to high concentrations of hydroxyurea, but not other DNA damaging agents, experience reduced survival to adulthood. Embryos lacking PIF1 fail to segregate their chromosomes efficiently during early nuclear divisions, consistent with a defect in DNA replication. Furthermore, loss of the BRCA2 protein, which is required for stabilization of stalled replication forks in metazoans, causes synthetic lethality in third instar larvae lacking either PIF1 or the polymerase delta subunit POL32. Interestingly,pif1mutants have a reduced ability to synthesize DNA during repair of a double-stranded gap, but only in the absence of POL32. Together, these results support a model in which Drosophila PIF1 functions with POL32 during times of replication stress but acts independently of POL32 to promote synthesis during double-strand gap repair.

Importance Medicare’s Bundled Payments for Care Improvement (BPCI) initiative for lower extremity joint replacement (LEJR) surgery has been associated with a reduction in episode spending and stable-to-improved quality. However, BPCI may create unintended effects by prompting participating hospitals to increase the overall volume of episodes paid for by Medicare, which could potentially eliminate program-related savings or prompt them to shift case mix to lower-risk patients. Objective To evaluate whether hospital BPCI participation for LEJR was associated with changes in overall volume and case mix. Design, Setting, and Participants Observational study using Medicare claims data and a difference-in-differences method to compare 131 markets (hospital referral regions) with at least 1 BPCI participant hospital (n = 322) and 175 markets with no participating hospitals (n = 1340), accounting for 580 043 Medicare beneficiaries treated before (January 2011-September 2013) and 462 161 after (October 2013-December 2015) establishing the BPCI initiative. Hospital-level case-mix changes were assessed by comparing 265 participating hospitals with a 1:1 propensity-matched set of nonparticipating hospitals from non-BPCI markets. Exposures Hospital BPCI participation. Main Outcomes and Measures Changes in market-level LEJR volume in the before vs after BPCI periods and changes in hospital-level case mix based on demographic, socioeconomic, clinical, and utilization factors. Results Among the 1 717 243 Medicare beneficiaries who underwent LEJR (mean age, 75 years; 64% women; and 95% nonblack race/ethnicity), BPCI participation was not significantly associated with a change in overall market-level volume. The mean quarterly market volume in non-BPCI markets increased 3.8% from 3.8 episodes per 1000 beneficiaries before BPCI to 3.9 episodes per 1000 beneficiaries after BPCI was launched. For BPCI markets, the mean quarterly market volume increased 4.4% from 3.6 episodes per 1000 beneficiaries before BPCI to 3.8 episodes per 1000 beneficiaries after BPCI was launched. The adjusted difference-in-differences estimate between the market types was 0.32% (95% CI, −0.06% to 0.69%;P = .10). Among 20 demographic, socioeconomic, clinical, and utilization factors, BPCI participation was associated with differential changes in hospital-level case mix for only 1 factor, prior skilled nursing facility use (adjusted difference-in-differences estimate, −0.53%; 95% CI, −0.96% to −0.10%;P = .01) in BPCI vs non-BPCI markets. Conclusions and Relevance In this observational study of Medicare beneficiaries who underwent LEJR, hospital participation in Bundled Payments for Care Improvement was not associated with changes in market-level lower extremity joint replacement volume and largely was not associated with changes in hospital case mix. These findings may provide reassurance regarding 2 potential unintended effects associated with bundled payments for LEJR.

Much of the data underlying global poverty and inequality estimates is not in the public domain, but can be accessed in small pieces using the World Bank’s PovcalNet online tool. To overcome these limitations and reproduce this database in a format more useful to researchers, we ran approximately 23 million queries of the World Bank’s web site, accessing only information that was already in the public domain. This web scraping exercise produced 10,000 points on the cumulative distribution of income or consumption from each of 942 surveys spanning 127 countries over the period 1977 to 2012. This short note describes our methodology, briefly discusses some of the relevant intellectual property issues, and illustrates the kind of calculations that are facilitated by this data set, including growth incidence curves and poverty rates using alternative PPP indices. The full data can be downloaded at www.