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Microsatellites are highly mutable sequences that can serve as markers for relationships among individuals or cells within a population. The accuracy and resolution of reconstructing these relationships depends on the fidelity of microsatellite profiling and the number of microsatellites profiled. However, current methods for targeted profiling of microsatellites incur significant "stutter" artifacts that interfere with accurate genotyping, and sequencing costs preclude whole-genome microsatellite profiling of a large number of samples. We developed a novel method for accurate and cost-effective targeted profiling of a panel of more than 150,000 microsatellites per sample, along with a computational tool for designing large-scale microsatellite panels. Our method addresses the greatest challenge for microsatellite profiling-"stutter" artifacts-with a low-temperature hybridization capture that significantly reduces these artifacts. We also developed a computational tool for accurate genotyping of the resulting microsatellite sequencing data that uses an ensemble approach integrating three microsatellite genotyping tools, which we optimize by analysis of de novo microsatellite mutations in human trios. Altogether, our suite of experimental and computational tools enables high-fidelity, large-scale profiling of microsatellites, which may find utility in diverse applications such as lineage tracing, population genetics, ecology, and forensics., (© 2024 Loh et al.; Published by Cold Spring Harbor Laboratory Press.)

Mutations accumulate in the genome of every cell of the body throughout life, causing cancer and other diseases 1,2 . Most mutations begin as nucleotide mismatches or damage in one of the two strands of the DNA before becoming double-strand mutations if unrepaired or misrepaired 3,4 . However, current DNA-sequencing technologies cannot accurately resolve these initial single-strand events. Here we develop a single-molecule, long-read sequencing method (Hairpin Duplex Enhanced Fidelity sequencing (HiDEF-seq)) that achieves single-molecule fidelity for base substitutions when present in either one or both DNA strands. HiDEF-seq also detects cytosine deamination-a common type of DNA damage-with single-molecule fidelity. We profiled 134 samples from diverse tissues, including from individuals with cancer predisposition syndromes, and derive from them single-strand mismatch and damage signatures. We find correspondences between these single-strand signatures and known double-strand mutational signatures, which resolves the identity of the initiating lesions. Tumours deficient in both mismatch repair and replicative polymerase proofreading show distinct single-strand mismatch patterns compared to samples that are deficient in only polymerase proofreading. We also define a single-strand damage signature for APOBEC3A. In the mitochondrial genome, our findings support a mutagenic mechanism occurring primarily during replication. As double-strand DNA mutations are only the end point of the mutation process, our approach to detect the initiating single-strand events at single-molecule resolution will enable studies of how mutations arise in a variety of contexts, especially in cancer and ageing., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Aims: Press freedom around the globe has deteriorated over the past decade, especially during the COVID-19 pandemic. This paper explores the effect of press freedom, as a cornerstone of democracy, on life expectancy., Methods: Exploring cross-country data, we use the ordinary least square method to estimate the association between press freedom and life expectancy. In addition, we adopt three novel instrumental variables to explore the causal relationship., Results: Our estimations indicate that a freer press leads to higher life expectancy, and the effect exists independently of the level of democracy. In addition, the effect of continuous exposure to press freedom is stronger than sporadic free press status. The results are robust to measurement errors, influential outliers, and country-specific heterogeneity., Conclusions: This study reveals the fundamental role of press freedom in promoting public health that was previously underexplored. Therefore, enhancing freedom of expression can be an effective tool to address three of the United Nations Millennium Development Goals, that is, reduce under-five mortality, improve maternal health, and combat HIV/AIDS. JEL: I1 H7 D02., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Mutations accumulate in the genome of every cell of the body throughout life, causing cancer and other genetic diseases 1-4 . Almost all of these mosaic mutations begin as nucleotide mismatches or damage in only one of the two strands of the DNA prior to becoming double-strand mutations if unrepaired or misrepaired 5 . However, current DNA sequencing technologies cannot resolve these initial single-strand events. Here, we developed a single-molecule, long-read sequencing method that achieves single-molecule fidelity for single-base substitutions when present in either one or both strands of the DNA. It also detects single-strand cytosine deamination events, a common type of DNA damage. We profiled 110 samples from diverse tissues, including from individuals with cancer-predisposition syndromes, and define the first single-strand mismatch and damage signatures. We find correspondences between these single-strand signatures and known double-strand mutational signatures, which resolves the identity of the initiating lesions. Tumors deficient in both mismatch repair and replicative polymerase proofreading show distinct single-strand mismatch patterns compared to samples deficient in only polymerase proofreading. In the mitochondrial genome, our findings support a mutagenic mechanism occurring primarily during replication. Since the double-strand DNA mutations interrogated by prior studies are only the endpoint of the mutation process, our approach to detect the initiating single-strand events at single-molecule resolution will enable new studies of how mutations arise in a variety of contexts, especially in cancer and aging., Competing Interests: Competing Interests A provisional patent application on HiDEF-seq has been filed (NYU Grossman School of Medicine). G.D.E. owns stock in DNA sequencing companies (Illumina, Oxford Nanopore Technologies, and Pacific Biosciences).

The recent growth in the globalization of medical services has attracted broad attention from scholars and policymakers. The intimacy and risk associated with many medical services makes these markets especially sensitive to trade barriers, transaction costs and asymmetric information. This paper uses a gravity model to investigate the factors associated with the global pattern of bilateral trade in medical services. Using data from the United Nations International Trade in Services Database, we differentiate between trade flows in which the recipient travels to the service provider, 'medical tourism,' and those trade flows in which the service is delivered to the recipient, 'other health services.' Our findings indicate that, after controlling for various economic, historical and geographic linkages, linguistic proximity and international accreditation are not significant predictors of the bilateral pattern of medical tourism, though they are associated with greater trade in other health services. We argue the key difference is that trade in other health services, including medical transcription, diagnostic analysis and laboratory services, is akin to trade in intermediate inputs. The medical service providers contracting for these services are especially sensitive to risk and have strong incentives to monitor quality. By contrast, medical tourism is a market in which patients do not have strong incentives to engage in costly monitoring or information gathering. Providers seeking to market their services to patients abroad have mitigated the effects of linguistic dissimilarity and asymmetric information by exploiting the strong complementarities between medical and non-medical tourism services., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Fast-tracking is an approach adopted by Mayo Clinic in Florida's (MCF) liver transplant (LT) program, which consists of early tracheal extubation and transfer of patients to surgical ward, eliminating a stay in the intensive care unit in select patients. Since adopting this approach in 2002, MCF has successfully fast-tracked 54.3% of patients undergoing LT. Objectives: This study evaluated the reduction in post-operative length of stay (LOS) that resulted from the fast-tracking protocol and assessed the potential cost saving in the case of nationwide implementation. Methods: A propensity score for fast-tracking was generated based on MCF liver transplant databases during 2011-2013. Various propensity score matching algorithms were used to form control groups from the United Network of Organ Sharing Standard Analysis and Research (STAR) file that had comparable demographic characteristics and health status to the treatment group identified in MCF. Multiple regression and matching estimators were employed for evaluation of the post-surgery LOS. The algorithm generated from the analysis was also applied to the STAR data to determine the proportion of patients in the US who could potentially be candidates for fast-tracking, and the potential savings. Results: The effect of the fast-tracking on the post-transplant LOS was estimated at approximately from 2.5 ( p -value = 0.001) to 3.2 ( p -value < 0.001) days based on various matching algorithms. The cost saving from a nationwide implementation of fast-tracking of liver transplant patients was estimated to be at least $78 million during the 2-year period. Conclusion: The fast-track program was found to be effective in reducing post-transplant LOS, although the reduction appeared to be less than previously reported. Nationwide implementation of fast-tracking could result in substantial cost savings without compromising the patient outcome.

The shift from a fee-for-service payment to a value-based payment scheme, sparked by the Patient Protection and Affordable Care Act, introduced pay-for-performance programs such Hospital Value Based Purchasing. Previous inquiry has not considered how local community factors may affect hospital system performance. This study investigated the association between local health performance and minority population in a hospital referral region (HRR). The primary objective was to ascertain whether community diversity levels are significantly associated to local health performance guided by the ecological model. Secondary data analysis collected from the 2016 American Hospital Association, Area Health Resource File, Commonwealth Fund Scorecard on Local Health System Performance, and the Dartmouth Atlas HRR dataset was used. Our primary findings show that the more diverse a HRR is, the more likely it is to be associated with lower ranking for access and affordability prevention and treatment avoidable hospital use and cost as well as healthy lives. Total performance score was significantly related to a better health ranking on prevention and treatment, hospital use, and cost, as well as healthy lives. This research supports the assertion that communities, particularly minorities in those communities, affect local health care performance in a variety of ways., (© 2018 John Wiley & Sons, Ltd.)