Showing papers by "David Reich published in 2021"

AKI in hospitalized patients with COVID-19

Abstract: Background Early reports indicate that AKI is common among patients with coronavirus disease 2019 (COVID-19) and associated with worse outcomes. However, AKI among hospitalized patients with COVID-19 in the United States is not well described. Methods This retrospective, observational study involved a review of data from electronic health records of patients aged ≥18 years with laboratory-confirmed COVID-19 admitted to the Mount Sinai Health System from February 27 to May 30, 2020. We describe the frequency of AKI and dialysis requirement, AKI recovery, and adjusted odds ratios (aORs) with mortality. Results Of 3993 hospitalized patients with COVID-19, AKI occurred in 1835 (46%) patients; 347 (19%) of the patients with AKI required dialysis. The proportions with stages 1, 2, or 3 AKI were 39%, 19%, and 42%, respectively. A total of 976 (24%) patients were admitted to intensive care, and 745 (76%) experienced AKI. Of the 435 patients with AKI and urine studies, 84% had proteinuria, 81% had hematuria, and 60% had leukocyturia. Independent predictors of severe AKI were CKD, men, and higher serum potassium at admission. In-hospital mortality was 50% among patients with AKI versus 8% among those without AKI (aOR, 9.2; 95% confidence interval, 7.5 to 11.3). Of survivors with AKI who were discharged, 35% had not recovered to baseline kidney function by the time of discharge. An additional 28 of 77 (36%) patients who had not recovered kidney function at discharge did so on posthospital follow-up. Conclusions AKI is common among patients hospitalized with COVID-19 and is associated with high mortality. Of all patients with AKI, only 30% survived with recovery of kidney function by the time of discharge.

Genomic insights into the formation of human populations in East Asia

Abstract: The deep population history of East Asia remains poorly understood owing to a lack of ancient DNA data and sparse sampling of present-day people1,2. Here we report genome-wide data from 166 East Asian individuals dating to between 6000 bc and ad 1000 and 46 present-day groups. Hunter-gatherers from Japan, the Amur River Basin, and people of Neolithic and Iron Age Taiwan and the Tibetan Plateau are linked by a deeply splitting lineage that probably reflects a coastal migration during the Late Pleistocene epoch. We also follow expansions during the subsequent Holocene epoch from four regions. First, hunter-gatherers from Mongolia and the Amur River Basin have ancestry shared by individuals who speak Mongolic and Tungusic languages, but do not carry ancestry characteristic of farmers from the West Liao River region (around 3000 bc), which contradicts theories that the expansion of these farmers spread the Mongolic and Tungusic proto-languages. Second, farmers from the Yellow River Basin (around 3000 bc) probably spread Sino-Tibetan languages, as their ancestry dispersed both to Tibet—where it forms approximately 84% of the gene pool in some groups—and to the Central Plain, where it has contributed around 59–84% to modern Han Chinese groups. Third, people from Taiwan from around 1300 bc to ad 800 derived approximately 75% of their ancestry from a lineage that is widespread in modern individuals who speak Austronesian, Tai–Kadai and Austroasiatic languages, and that we hypothesize derives from farmers of the Yangtze River Valley. Ancient people from Taiwan also derived about 25% of their ancestry from a northern lineage that is related to, but different from, farmers of the Yellow River Basin, which suggests an additional north-to-south expansion. Fourth, ancestry from Yamnaya Steppe pastoralists arrived in western Mongolia after around 3000 bc but was displaced by previously established lineages even while it persisted in western China, as would be expected if this ancestry was associated with the spread of proto-Tocharian Indo-European languages. Two later gene flows affected western Mongolia: migrants after around 2000 bc with Yamnaya and European farmer ancestry, and episodic influences of later groups with ancestry from Turan. Genome-wide data from 166 East Asian individuals dating to between 6000 bc and ad 1000 and from 46 present-day groups provide insights into the histories of mixture and migration of human populations in East Asia.

Use of Physiological Data From a Wearable Device to Identify SARS-CoV-2 Infection and Symptoms and Predict COVID-19 Diagnosis: Observational Study.

Abstract: Background: Changes in autonomic nervous system function, characterized by heart rate variability (HRV), have been associated with infection and observed prior to its clinical identification. Objective: We performed an evaluation of HRV collected by a wearable device to identify and predict COVID-19 and its related symptoms. Methods: Health care workers in the Mount Sinai Health System were prospectively followed in an ongoing observational study using the custom Warrior Watch Study app, which was downloaded to their smartphones. Participants wore an Apple Watch for the duration of the study, measuring HRV throughout the follow-up period. Surveys assessing infection and symptom-related questions were obtained daily. Results: Using a mixed-effect cosinor model, the mean amplitude of the circadian pattern of the standard deviation of the interbeat interval of normal sinus beats (SDNN), an HRV metric, differed between subjects with and without COVID-19 (P=.006). The mean amplitude of this circadian pattern differed between individuals during the 7 days before and the 7 days after a COVID-19 diagnosis compared to this metric during uninfected time periods (P=.01). Significant changes in the mean and amplitude of the circadian pattern of the SDNN was observed between the first day of reporting a COVID-19–related symptom compared to all other symptom-free days (P=.01). Conclusions: Longitudinally collected HRV metrics from a commonly worn commercial wearable device (Apple Watch) can predict the diagnosis of COVID-19 and identify COVID-19–related symptoms. Prior to the diagnosis of COVID-19 by nasal swab polymerase chain reaction testing, significant changes in HRV were observed, demonstrating the predictive ability of this metric to identify COVID-19 infection.

Assessing the Performance of qpAdm: A Statistical Tool for Studying Population Admixture

Abstract: qpAdm is a statistical tool for studying the ancestry of populations with histories that involve admixture between two or more source populations. Using qpAdm, it is possible to identify plausible models of admixture that fit the population history of a group of interest and to calculate the relative proportion of ancestry that can be ascribed to each source population in the model. Although qpAdm is widely used in studies of population history of human (and nonhuman) groups, relatively little has been done to assess its performance. We performed a simulation study to assess the behavior of qpAdm under various scenarios in order to identify areas of potential weakness and establish recommended best practices for use. We find that qpAdm is a robust tool that yields accurate results in many cases, including when data coverage is low, there are high rates of missing data or ancient DNA damage, or when diploid calls cannot be made. However, we caution against co-analyzing ancient and present-day data, the inclusion of an extremely large number of reference populations in a single model, and analyzing population histories involving extended periods of gene flow. We provide a user guide suggesting best practices for the use of qpAdm.

A genetic history of the pre-contact Caribbean

Abstract: Humans settled the Caribbean about 6,000 years ago, and ceramic use and intensified agriculture mark a shift from the Archaic to the Ceramic Age at around 2,500 years ago1–3. Here we report genome-wide data from 174 ancient individuals from The Bahamas, Haiti and the Dominican Republic (collectively, Hispaniola), Puerto Rico, Curacao and Venezuela, which we co-analysed with 89 previously published ancient individuals. Stone-tool-using Caribbean people, who first entered the Caribbean during the Archaic Age, derive from a deeply divergent population that is closest to Central and northern South American individuals; contrary to previous work4, we find no support for ancestry contributed by a population related to North American individuals. Archaic-related lineages were >98% replaced by a genetically homogeneous ceramic-using population related to speakers of languages in the Arawak family from northeast South America; these people moved through the Lesser Antilles and into the Greater Antilles at least 1,700 years ago, introducing ancestry that is still present. Ancient Caribbean people avoided close kin unions despite limited mate pools that reflect small effective population sizes, which we estimate to be a minimum of 500–1,500 and a maximum of 1,530–8,150 individuals on the combined islands of Puerto Rico and Hispaniola in the dozens of generations before the individuals who we analysed lived. Census sizes are unlikely to be more than tenfold larger than effective population sizes, so previous pan-Caribbean estimates of hundreds of thousands of people are too large5,6. Confirming a small and interconnected Ceramic Age population7, we detect 19 pairs of cross-island cousins, close relatives buried around 75 km apart in Hispaniola and low genetic differentiation across islands. Genetic continuity across transitions in pottery styles reveals that cultural changes during the Ceramic Age were not driven by migration of genetically differentiated groups from the mainland, but instead reflected interactions within an interconnected Caribbean world1,8. Ancient DNA reveals genetic differences between stone-tool users and people associated with ceramic technology in the Caribbean and provides substantially lower estimates of population sizes in the region before European contact.

Dairying enabled Early Bronze Age Yamnaya steppe expansions

Abstract: During the Early Bronze Age, populations of the western Eurasian steppe expanded across an immense area of northern Eurasia. Combined archaeological and genetic evidence supports widespread Early Bronze Age population movements out of the Pontic–Caspian steppe that resulted in gene flow across vast distances, linking populations of Yamnaya pastoralists in Scandinavia with pastoral populations (known as the Afanasievo) far to the east in the Altai Mountains1,2 and Mongolia3. Although some models hold that this expansion was the outcome of a newly mobile pastoral economy characterized by horse traction, bulk wagon transport4–6 and regular dietary dependence on meat and milk5, hard evidence for these economic features has not been found. Here we draw on proteomic analysis of dental calculus from individuals from the western Eurasian steppe to demonstrate a major transition in dairying at the start of the Bronze Age. The rapid onset of ubiquitous dairying at a point in time when steppe populations are known to have begun dispersing offers critical insight into a key catalyst of steppe mobility. The identification of horse milk proteins also indicates horse domestication by the Early Bronze Age, which provides support for its role in steppe dispersals. Our results point to a potential epicentre for horse domestication in the Pontic–Caspian steppe by the third millennium bc, and offer strong support for the notion that the novel exploitation of secondary animal products was a key driver of the expansions of Eurasian steppe pastoralists by the Early Bronze Age. Analysis of ancient proteins suggests that Early Bronze Age dairying and horse domestication catalysed eastern Yamnaya migrations.

The Association Between Obesity and Peak Antibody Titer Response in COVID-19 Infection.

Abstract: OBJECTIVE: Obesity is associated with severe COVID-19 infection. Disease severity is associated with a higher COVID-19 antibody titer. We compared the COVID-19 antibody titer response of patients with obesity versus patients without obesity. METHODS: We retrospectively retrieved data of individuals tested for COVID-19 serology at the Mount Sinai Health System in New York City between March 1st, 2020, and December 14th, 2021. The primary outcome was peak antibody titer, assessed as a binary variable (1:2880, which was the highest detected titer, versus lower than 1:2880). In patients with positive serology test, peak titer rates were compared between BMI groups (<18.5, 18.5-25, 25-30, 30-40, ≥40 kg/m2 ). A multivariable logistic regression model was used to analyze the independent association between different BMI groups and peak titer. RESULTS: Overall, 39,342 individuals underwent serology testing and had BMI measurements. Positive serology test was present in 12,314 patients. Peak titer rates were associated with obesity (<18.5:34.5%, 18.5-25:29.2%, 25-30:37.7%; 30-40:44.7%; ≥40:52.0%, p<0.001). In multivariable analysis, severe obesity had the highest adjusted odds ratio for peak titer (aOR 2.5, 95% CI 2.1-3.0). CONCLUSION: COVID-19 neutralizing antibody titer is associated with obesity. This has implications on the understanding of the role of obesity in COVID-19 severity.

Dynamic changes in genomic and social structures in third millennium BCE central Europe.

Abstract: Europe’s prehistory oversaw dynamic and complex interactions of diverse societies, hitherto unexplored at detailed regional scales. Studying 271 human genomes dated ~4900 to 1600 BCE from the European heartland, Bohemia, we reveal unprecedented genetic changes and social processes. Major migrations preceded the arrival of “steppe” ancestry, and at ~2800 BCE, three genetically and culturally differentiated groups coexisted. Corded Ware appeared by 2900 BCE, were initially genetically diverse, did not derive all steppe ancestry from known Yamnaya, and assimilated females of diverse backgrounds. Both Corded Ware and Bell Beaker groups underwent dynamic changes, involving sharp reductions and complete replacements of Y-chromosomal diversity at ~2600 and ~2400 BCE, respectively, the latter accompanied by increased Neolithic-like ancestry. The Bronze Age saw new social organization emerge amid a ≥40% population turnover.

Ethics of DNA research on human remains: five globally applicable guidelines.

Abstract: We are a group of archaeologists, anthropologists, curators and geneticists representing diverse global communities and 31 countries. All of us met in a virtual workshop dedicated to ethics in ancient DNA research held in November 2020. There was widespread agreement that globally applicable ethical guidelines are needed, but that recent recommendations grounded in discussion about research on human remains from North America are not always generalizable worldwide. Here we propose the following globally applicable guidelines, taking into consideration diverse contexts. These hold that: (1) researchers must ensure that all regulations were followed in the places where they work and from which the human remains derived; (2) researchers must prepare a detailed plan prior to beginning any study; (3) researchers must minimize damage to human remains; (4) researchers must ensure that data are made available following publication to allow critical re-examination of scientific findings; and (5) researchers must engage with other stakeholders from the beginning of a study and ensure respect and sensitivity to stakeholder perspectives. We commit to adhering to these guidelines and expect they will promote a high ethical standard in DNA research on human remains going forward. In this Perspective, a group representing a range of stakeholders makes the case for a set of five proposed globally applicable ethical guidelines for ancient human DNA research.

RT-PCR/MALDI-TOF mass spectrometry-based detection of SARS-CoV-2 in saliva specimens.

Abstract: As severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infections continue, there is a substantial need for cost-effective and large-scale testing that utilizes specimens that can be readily collected from both symptomatic and asymptomatic individuals in various community settings. Although multiple diagnostic methods utilize nasopharyngeal specimens, saliva specimens represent an attractive alternative as they can rapidly and safely be collected from different populations. While saliva has been described as an acceptable clinical matrix for the detection of SARS-CoV-2, evaluations of analytic performance across platforms for this specimen type are limited. Here, we used a novel sensitive RT-PCR/MALDI-TOF mass spectrometry-based assay (Agena MassARRAY®) to detect SARS-CoV-2 in saliva specimens. The platform demonstrated high diagnostic sensitivity and specificity when compared to matched patient upper respiratory specimens. We also evaluated the analytical sensitivity of the platform and determined the limit of detection of the assay to be 1562.5 copies/ml. Furthermore, across the five individual target components of this assay, there was a range in analytic sensitivities for each target with the N2 target being the most sensitive. Overall, this system also demonstrated comparable performance when compared to the detection of SARS-CoV-2 RNA in saliva by the cobas® 6800/8800 SARS-CoV-2 real-time RT-PCR Test (Roche). Together, we demonstrate that saliva represents an appropriate matrix for SARS-CoV-2 detection on the novel Agena system as well as on a conventional real-time RT-PCR assay. We conclude that the MassARRAY® system is a sensitive and reliable platform for SARS-CoV-2 detection in saliva, offering scalable throughput in a large variety of clinical laboratory settings.

The return of the Beaker Folk? : Rethinking migration and population change in British prehistory

Abstract: Recent aDNA analysis has demonstrated that the centuries surrounding the arrival of the Beaker Complex in Britain witnessed a massive turnover in the genetic make-up of the population Here we consider the archaeological implications of this finding, and propose two hypotheses - Beaker Colonisation and Steppe Drift - that might help us understand the underlying social processes, and propose directions for future research

A minimally destructive protocol for DNA extraction from ancient teeth.

Abstract: Ancient DNA sampling methods-although optimized for efficient DNA extraction-are destructive, relying on drilling or cutting and powdering (parts of) bones and teeth As the field of ancient DNA has grown, so have concerns about the impact of destructive sampling of the skeletal remains from which ancient DNA is obtained Due to a particularly high concentration of endogenous DNA, the cementum of tooth roots is often targeted for ancient DNA sampling, but destructive sampling methods of the cementum often result in the loss of at least one entire root Here, we present a minimally destructive method for extracting ancient DNA from dental cementum present on the surface of tooth roots This method does not require destructive drilling or grinding, and, following extraction, the tooth remains safe to handle and suitable for most morphological studies, as well as other biochemical studies, such as radiocarbon dating We extracted and sequenced ancient DNA from 30 teeth (and nine corresponding petrous bones) using this minimally destructive extraction method in addition to a typical tooth sampling method We find that the minimally destructive method can provide ancient DNA that is of comparable quality to extracts produced from teeth that have undergone destructive sampling processes Further, we find that a rigorous cleaning of the tooth surface combining diluted bleach and UV light irradiation seems sufficient to minimize external contaminants usually removed through the physical removal of a superficial layer when sampling through regular powdering methods

Blood Donation and COVID-19: Reconsidering the 3-Month Deferral Policy for Gay, Bisexual, Transgender, and Other Men Who Have Sex With Men.

Abstract: In April 2020, in light of COVID-19-related blood shortages, the US Food and Drug Administration (FDA) reduced the deferral period for men who have sex with men (MSM) from its previous duration of 1 year to 3 months.Although originally born out of necessity, the decades-old restrictions on MSM donors have been mitigated by significant advancements in HIV screening, treatment, and public education. The severity of the ongoing COVID-19 pandemic-and the urgent need for safe blood products to respond to such crises-demands an immediate reconsideration of the 3-month deferral policy for MSM.We review historical HIV testing and transmission evidence, discuss the ethical ramifications of the current deferral period, and examine the issue of noncompliance with donor deferral rules. We also propose an eligibility screening format that involves an individual risk-based screening protocol and, unlike current FDA guidelines, does not effectively exclude donors on the basis of gender identity or sexual orientation. Our policy proposal would allow historically marginalized community members to participate with dignity in the blood donation process without compromising blood donation and transfusion safety outcomes.

Association between COVID-19 diagnosis and presenting chief complaint from New York City triage data.

Abstract: Background and aim New York City (NYC) is an epicenter of the COVID-19 pandemic in the United States. Proper triage of patients with possible COVID-19 via chief complaint is critical but not fully optimized. This study aimed to investigate the association between presentation by chief complaints and COVID-19 status. Methods We retrospectively analyzed adult emergency department (ED) patient visits from five different NYC hospital campuses from March 1, 2020 to May 13, 2020 of patients who underwent nasopharyngeal COVID-19 RT-PCR testing. The positive and negative COVID-19 cohorts were then assessed for different chief complaints obtained from structured triage data. Sub-analysis was performed for patients older than 65 and within chief complaints with high mortality. Results Of 11,992 ED patient visits who received COVID-19 testing, 6524/11992 (54.4%) were COVID-19 positive. 73.5% of fever, 67.7% of shortness of breath, and 65% of cough had COVID-19, but others included 57.5% of weakness/fall/altered mental status, 55.5% of glycemic control, and 51.4% of gastrointestinal symptoms. In patients over 65, 76.7% of diarrhea, 73.7% of fatigue, and 69.3% of weakness had COVID-19. 45.5% of dehydration, 40.5% of altered mental status, 27% of fall, and 24.6% of hyperglycemia patients experienced mortality. Conclusion A novel high risk COVID-19 patient population was identified from chief complaint data, which is different from current suggested CDC guidelines, and may help triage systems to better isolate COVID-19 patients. Older patients with COVID-19 infection presented with more atypical complaints warranting special consideration. COVID-19 was associated with higher mortality in a unique group of complaints also warranting special consideration.

Genomic transformation and social organization during the Copper Age-Bronze Age transition in southern Iberia.

Abstract: This work was supported by the Max Planck Society (V.V.-M. and W.H.); European Research Council (ERC) grant 771234—PALEoRIDER (W.H.); Spanish Ministry of Economy, Industry and Competitiveness project HAR2017-85962-P (C.O., C.R.-H., M.I.F., E.C.B., C.V.-F., V.L., R.M., and R.R.); AGAUR 2017SGR1044 (C.O., C.R.-H., M.I.F., E.C.B., C.V.-F., V.L., R.M., and R.R.); ICREA Academia program (R.R.); John Templeton Foundation grant 61220 (D.R.); and Paul Allen Family Foundation (D.R.). D.R. is an Investigator of the Howard Hughes Medical Institute.

Social stratification without genetic differentiation at the site of Kulubnarti in Christian Period Nubia

Abstract: Nubia has been a corridor for the movement of goods, culture, and people between sub-Saharan Africa, Egypt, and West Eurasia since prehistory, but little is known about the genetic landscape of the region prior to the influence of the Islamic migrations that began in the late 1st millennium CE. We report genome-wide data for 66 individuals from the site of Kulubnarti ([~]650-1000 CE), increasing the number of ancient individuals with genome-level data from the Nile Valley from three to 69. Our results shed light on the genetic ancestry of a Christian Period group and help to address a long-standing question about the relationships among people buried in two neighboring cemeteries who show skeletal evidence of differences in morbidity and mortality that are broadly suggestive of differences in social status. We find that the Kulubnarti Nubians were admixed with [~]43% Nilotic-related ancestry on average (individual proportions varied between [~]36-54%) and the remaining ancestry reflecting a West Eurasian-related gene pool likely introduced into Nubia through Egypt, but ultimately deriving from an ancestry pool like that found in the Bronze and Iron Age Levant. The admixed ancestry at Kulubnarti reflects interactions between genetically-distinct people in northeast Africa spanning almost a millennium, with West Eurasian ancestry disproportionately associated with females, highlighting the impact of female mobility in this region. We find no significant differences in ancestry among individuals from the two plausibly socially-stratified cemeteries at Kulubnarti, supporting hypotheses that the groups may have been socially divided but were not genetically distinct. We identify seven pairs of inter-cemetery relatives as close as second-degree, suggesting that any social divisions at Kulubnarti did not prevent mixing between groups. Present-day Nubians are not directly descended from the Christian Period people from Kulubnarti without additional admixture, attesting to the dynamic history of interaction that continues to shape the cultural and genetic landscape of Nubia.

A unified genealogy of modern and ancient genomes

Abstract: The sequencing of modern and ancient genomes from around the world has revolutionised our understanding of human history and evolution1,2. However, the general problem of how best to characterise the full complexity of ancestral relationships from the totality of human genomic variation remains unsolved. Patterns of variation in each data set are typically analysed independently, and often using parametric models or data reduction techniques that cannot capture the full complexity of human ancestry3,4. Moreover, variation in sequencing technology5,6, data quality7 and in silico processing8,9, coupled with complexities of data scale10, limit the ability to integrate data sources. Here, we introduce a non-parametric approach to inferring human genealogical history that overcomes many of these challenges and enables us to build the largest genealogy of both modern and ancient humans yet constructed. The genealogy provides a lossless and compact representation of multiple datasets, addresses the challenges of missing and erroneous data, and benefits from using ancient samples to constrain and date relationships. Using simulations and empirical analyses, we demonstrate the power of the method to recover relationships between individuals and populations, as well as to identify descendants of ancient samples. Finally, we show how applying a simple non-parametric estimator of ancestor geographical location to the inferred genealogy recapitulates key events in human history. Our results demonstrate that whole-genome genealogies are a powerful means of synthesising genetic data and provide rich insights into human evolution.

Indian genetic heritage in Southeast Asian populations

Abstract: The great ethnolinguistic diversity found today in mainland Southeast Asia (MSEA) reflects multiple migration waves of people in the past. Deeply divergent East Eurasian hunter-gatherers were the first anatomically modern human population known to migrate to the region. Agriculturalists from South China migrated to the region and admixed with the local hunter-gatherers during the Neolithic period. During the Bronze and Iron Ages, the genetic makeup of people in MSEA changed again, indicating an additional influx of populations from South China. Maritime trading between MSEA and India was established at the latest 300 BCE, and the formation of early states in Southeast Asia during the first millennium CE was strongly influenced by Indian culture, and this cultural influence is still prominent today. Several ancient Indian-influenced states were located in present-day Thailand, and various populations in the country are likely to be descendants of people from those states. To systematically explore Indian genetic heritage in MSEA, we generated genome-wide SNP data (the HumanOrigins array) for 119 present-day individuals belonging to 10 ethnic groups from Thailand and co-analyzed them with published data from MSEA using the PCA, ADMIXTURE, f3-statistics, qpAdm, and qpGraph methods. We found South Asian low-level admixture in various MSEA populations which are probably descendants of people from the ancient Indian-influenced states, but failed to find a South Asian genetic component in present-day hunter-gatherer groups and relatively isolated groups from highlands in Northern Thailand. Our results also support close genetic affinity between Kra-Dai-speaking (also known as Tai-Kadai) and Austronesian-speaking populations, which fits a linguistic hypothesis suggesting cladality of the two language families. Author Summary Mainland Southeast Asia is a region with great ethnolinguistic diversity and complex population history. We studied genetic population history of present-day mainland Southeast Asian populations using genome-wide SNP data (the HumanOrigins array). We generated new data for 10 present-day ethnic groups from Thailand, which we further combined with published data from mainland and island Southeast Asians and worldwide populations. We revealed South Asian genetic admixture in various mainland Southeast Asian ethnic groups which are highly influenced by Indian culture, but failed to find it in groups who remained culturally isolated until recently. Our finding suggests that a massive migration of Indian people in the past was responsible for the spread of Indian culture in mainland Southeast Asia. We also found support for a close genetic affinity between Kra-Dai- and Austronesianspeaking populations, which fits a linguistic hypothesis suggesting cladality of the two language families.

An integrative skeletal and paleogenomic analysis of prehistoric stature variation suggests relatively reduced health for early European farmers

Abstract: Human culture, biology, and health were shaped dramatically by the onset of agriculture ~12,000 years before present (BP). Subsistence shifts from hunting and gathering to agriculture are hypothesized to have resulted in increased individual fitness and population growth as evidenced by archaeological and population genomic data alongside a simultaneous decline in physiological health as inferred from paleopathological analyses and stature reconstructions of skeletal remains. A key component of the health decline inference is that relatively shorter statures observed for early farmers may (at least partly) reflect higher childhood disease burdens and poorer nutrition. However, while such stresses can indeed result in growth stunting, height is also highly heritable, and substantial inter-individual variation in the height genetic component within a population is typical. Moreover, extensive migration and gene flow were characteristics of multiple agricultural transitions worldwide. Here, we consider both osteological and ancient DNA data from the same prehistoric individuals to comprehensively study the trajectory of human stature variation as a proxy for health across a transition to agriculture. Specifically, we compared ‘predicted’ genetic contributions to height from paleogenomic data and ‘achieved’ adult osteological height estimated from long bone measurements on a per-individual basis for n=160 ancient Europeans from sites spanning the Upper Paleolithic to the Iron Age (~38,000-2,400 BP). We found that individuals from the Neolithic were shorter than expected (given their individual polygenic height scores) by an average of −4.47 cm relative to individuals from the Upper Paleolithic and Mesolithic (P=0.016). The average osteological vs. expected stature then increased relative to the Neolithic over the Copper (+2.67 cm, P=0.052), Bronze (+3.33 cm, P=0.032), and Iron Ages (+3.95 cm, P=0.094). These results were partly attenuated when we accounted for genome-wide genetic ancestry variation in our sample (which we note is partly duplicative with the individual polygenic score information). For example, in this secondary analysis Neolithic individuals were −3.48 cm shorter than expected on average relative to individuals from the Upper Paleolithic and Mesolithic (P=0.056). We also incorporated observations of paleopathological indicators of non-specific stress that can persist from childhood to adulthood in skeletal remains (linear enamel hypoplasia, cribra orbitalia, and porotic hyperostosis) into our model. Overall, our work highlights the potential of integrating disparate datasets to explore proxies of health in prehistory.

Genome-wide analysis of nearly all the victims of a 6200 year old massacre

Abstract: Paleogenomic and bioanthropological studies of ancient massacres have highlighted sites where the victims were male and plausibly died all in battle, or were executed members of the same family as might be expected from a killing intentionally directed at subsets of a community, or where the massacred individuals were plausibly members of a migrant community in conflict with previously established groups, or where there was evidence that the killing was part of a religious ritual. Here we provide evidence of killing on a massive scale in prehistory that was not directed to a specific family, based on genome-wide ancient DNA for 38 of the 41 documented victims of a 6,200 year old massacre in Potocani, Croatia and combining our results with bioanthropological data. We highlight three results: (i) the majority of individuals were unrelated and instead were a sample of what was clearly a large farming population, (ii) the ancestry of the individuals was homogenous which makes it unlikely that the massacre was linked to the arrival of new genetic ancestry, and (iii) there were approximately equal numbers of males and females. Combined with the bioanthropological evidence that the victims were of a wide range of ages, these results show that large-scale indiscriminate killing is a horror that is not just a feature of the modern and historic periods, but was also a significant process in pre-state societies.

Genetic landscape of Gullah African Americans.

Abstract: Objectives Gullah African Americans are descendants of formerly enslaved Africans living in the Sea Islands along the coast of the southeastern U.S., from North Carolina to Florida. Their relatively high numbers and geographic isolation were conducive to the development and preservation of a unique culture that retains deep African features. Although historical evidence supports a West-Central African ancestry for the Gullah, linguistic and cultural evidence of a connection to Sierra Leone has led to the suggestion of this country/region as their ancestral home. This study sought to elucidate the genetic structure and ancestry of the Gullah. Materials and methods We leveraged whole-genome genotype data from Gullah, African Americans from Jackson, Mississippi, African populations from Sierra Leone, and population reference panels from Africa and Europe to infer population structure, ancestry proportions, and global estimates of admixture. Results Relative to non-Gullah African Americans from the Southeast US, the Gullah exhibited higher mean African ancestry, lower European admixture, a similarly small Native American contribution, and increased male-biased European admixture. A slightly tighter bottleneck in the Gullah 13 generations ago suggests a largely shared demographic history with non-Gullah African Americans. Despite a slightly higher relatedness to populations from Sierra Leone, our data demonstrate that the Gullah are genetically related to many West African populations. Discussion This study confirms that subtle differences in African American population structure exist at finer regional levels. Such observations can help to inform medical genetics research in African Americans, and guide the interpretation of genetic data used by African Americans seeking to explore ancestral identities.

A Multi‐Phase Quality Improvement Initiative for the Treatment of Active Delirium in Older Persons

Abstract: Background/objectives The Hospital Elder Life Program emerged 20 years ago as the reference model for delirium prevention in hospitalized older patients. However, implementation has been achieved at only 200 hospitals worldwide over the last 20 years. Among the barriers to implementation for some institutions is an unwillingness of hospital administration to assume the costs associated with implementing programs that service all hospitalized older patients at risk for delirium. Facing such a situation, we implemented a unique and self-evolving model of care of older hospitalized patients who had already developed delirium. Design Hypothesis testing was carried out using a pretest-posttest design on program administrative data. Setting Mount Sinai Hospital, New York, NY, a tertiary-care teaching facility. PARTICIPANTS A total of 9,214 consecutively admitted older patients to non-intensive care (ICU) inpatient units over a 5.5-year period, regardless of the suspected presence of delirium or risk status for developing delirium. Intervention A delirium intervention program targeting patients in whom delirium has already developed, with a modified delirium team supported by extensive workflow automation with custom tools in our electronic medical records system. Measurements Length of stay (LOS) for delirious and non-delirious patients on units where this program was piloted. Benzodiazepine, opiate, and antipsychotic use on the same units. Results There was a significant drop in LOS by 1.98 days (95% confidence interval = .24-3.71), a decrease in the average morphine dose equivalents administered from .38 mg to .21 mg per patient hospital day, diazepam dose equivalents from .22 mg to .15 mg per patient hospital day, and quetiapine administered from .17 mg to .14 mg per patient hospital day for delirious patients on the program pilot units. Conclusion Elements of our unique active delirium treatment program may provide some direction to other program developers working on improving the care of older hospitalized delirious patients. However, the supporting evidence presented is limited, and a more rigorous prospective study is needed.

MUST-Plus: A Machine Learning Classifier That Improves Malnutrition Screening in Acute Care Facilities.

Abstract: Malnutrition among hospital patients, a frequent, yet under-diagnosed problem is associated with adverse impact on patient outcome and health care costs. Development of highly accurate malnutrition...

Cosmopolitanism at the Roman Danubian Frontier, Slavic Migrations, and the Genomic Formation of Modern Balkan Peoples

Abstract: The Roman Empire expanded through the Mediterranean shores and brought human mobility and cosmopolitanism across this inland sea to an unprecedented scale. However, if this was also common at the Empire frontiers remains undetermined. The Balkans and Danube River were of strategic importance for the Romans acting as an East-West connection and as a defense line against “barbarian” tribes. We generated genome-wide data from 70 ancient individuals from present-day Serbia dated to the first millennium CE; including Viminacium, capital of Moesia Superior province. Our analyses reveal large scale-movements from Anatolia during Imperial rule, similar to the pattern observed in Rome, and cases of individual mobility from as far as East Africa. Between ∼250-500 CE, we detect gene-flow from Central/Northern Europe harboring admixtures of Iron Age steppe groups. Tenth-century CE individuals harbored North-Eastern European-related ancestry likely associated to Slavic-speakers, which contributed >20% of the ancestry of today’s Balkan people.

Synergistic effect of hypoalbuminaemia and hypotension in predicting in-hospital mortality and intensive care admission: a retrospective cohort study.

Abstract: Objective Hypoalbuminaemia is an important prognostic factor. It may be associated with poor nutritional states, chronic heart and kidney disease, long-standing infection and cancer. Hypotension is a hallmark of circulatory failure. We evaluated hypoalbuminaemia and hypotension synergism as predictor of in-hospital mortality and intensive care unit (ICU) admission. Design We retrospectively analysed emergency department (ED) visits from January 2011 to December 2019. Setting Data were retrieved from five Mount Sinai health system hospitals, New York. Participants We included consecutive ED patients ≥18 years with albumin measurements. Primary and secondary outcome measures Clinical outcomes were in-hospital mortality and ICU admission. The rates of these outcomes were stratified by systolic blood pressure (SBP) ( Results The cohort included 402 123 ED arrivals (27.9% of total adult ED visits). The rates of in-hospital mortality, ICU admission and overall admission were 1.7%, 8.4% and 47.1%, respectively. For SBP Conclusion Co-occurrence of hypotension and hypoalbuminaemia is associated with poor hospital outcomes.

Developing an Institute for Health Care Delivery Science: successes, challenges, and solutions in the first five years

Abstract: Medical knowledge is increasing at an exponential rate. At the same time, unexplained variations in practice and patient outcomes and unacceptable rates of medical errors and inefficiencies in health care delivery have emerged. Our Institute for Health Care Delivery Science (I-HDS) began in 2014 as a novel platform to conduct multidisciplinary healthcare delivery research. We followed ten strategies to develop a successful institute with excellence in methodology and strong understanding of the value of team science. Our work was organized around five hubs: 1) Quality/Process Improvement and Systematic Review, 2) Comparative Effectiveness Research, Pragmatic Clinical Trials, and Predictive Analytics, 3) Health Economics and Decision Modeling, 4) Qualitative, Survey, and Mixed Methods, and 5) Training and Mentoring. In the first 5 years of the I-HDS, we have identified opportunities for change in clinical practice through research using our health system’s electronic health record (EHR) data, and designed programs to educate clinicians in the value of research to improve patient care and recognize efficiencies in processes. Testing the value of several model interventions has guided prioritization of evidence-based quality improvements. Some of the changes in practice have already been embedded in the EHR workflow successfully. Development and sustainability of the I-HDS has been fostered by a mix of internal and external funding, including philanthropic foundations. Challenges remain due to the highly competitive funding environment and changes needed to adapt the EHR to healthcare delivery research. Further stakeholder engagement and culture change working with hospital leadership and I-HDS core and affiliate members continues.

A Simple Free-Text-like Method for Extracting Semi-Structured Data from Electronic Health Records: Exemplified in Prediction of In-Hospital Mortality

Abstract: The Epic electronic health record (EHR) is a commonly used EHR in the United States. This EHR contain large semi-structured “flowsheet” fields. Flowsheet fields lack a well-defined data dictionary and are unique to each site. We evaluated a simple free-text-like method to extract these data. As a use case, we demonstrate this method in predicting mortality during emergency department (ED) triage. We retrieved demographic and clinical data for ED visits from the Epic EHR (1/2014–12/2018). Data included structured, semi-structured flowsheet records and free-text notes. The study outcome was in-hospital death within 48 h. Most of the data were coded using a free-text-like Bag-of-Words (BoW) approach. Two machine-learning models were trained: gradient boosting and logistic regression. Term frequency-inverse document frequency was employed in the logistic regression model (LR-tf-idf). An ensemble of LR-tf-idf and gradient boosting was evaluated. Models were trained on years 2014–2017 and tested on year 2018. Among 412,859 visits, the 48-h mortality rate was 0.2%. LR-tf-idf showed AUC 0.98 (95% CI: 0.98–0.99). Gradient boosting showed AUC 0.97 (95% CI: 0.96–0.99). An ensemble of both showed AUC 0.99 (95% CI: 0.98–0.99). In conclusion, a free-text-like approach can be useful for extracting knowledge from large amounts of complex semi-structured EHR data.

Comparison of SARS-CoV-2 detection in Saliva by real-time RT-PCR and RT-PCR/MALDI-TOF Methods

Abstract: The coronavirus disease 2019 (COVID-19) pandemic has accelerated the need for rapid implementation of diagnostic assays for detection of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in respiratory specimens. While multiple molecular methods utilize nasopharyngeal specimens, supply chain constraints and need for easier and safer specimen collection warrant alternative specimen types, particularly saliva. Although saliva has been found to be a comparable clinical matrix for detection of SARS-CoV-2, evaluations of diagnostic and analytic performance across platforms for this specimen type are limited. Here, we compared two methods for SARS-CoV-2 detection in saliva: the Roche cobas® 6800/8800 SARS-CoV-2 real-time RT-PCR Test and the Agena Biosciences MassARRAY® SARS-CoV-2 Panel/MassARRAY® System. Overall, both systems had high agreement with one another, and both demonstrated high diagnostic sensitivity and specificity when compared to matched patient upper respiratory specimens. We also evaluated the analytical sensitivity of each platform and determined the limit of detection of the Roche assay was four times lower than that of Agena for saliva specimens (390.6 v. 1,562.5 copies/mL). Furthermore, across individual target components of each assay, T2 and N2 targets had the lowest limits of detection for each platform, respectively. Together, we demonstrate that saliva represents an appropriate specimen for SARS-CoV-2 detection in two technologies that have high agreement and differ in analytical sensitivities overall and across individual component targets. The addition of saliva as an acceptable specimen and understanding the sensitivity for testing on these platforms can further inform public health measures for screening and detection to combat the COVID-19 pandemic.