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1.
Genome Biol ; 20(1): 204, 2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31597575

RESUMO

Following publication of the original article [1], a typographical error in the formula for calculating di in the "Scans for local adaptation" subsection in the Method section, was identified. The correct formula should be.

2.
Cell ; 179(3): 729-735.e10, 2019 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-31495572

RESUMO

We report an ancient genome from the Indus Valley Civilization (IVC). The individual we sequenced fits as a mixture of people related to ancient Iranians (the largest component) and Southeast Asian hunter-gatherers, a unique profile that matches ancient DNA from 11 genetic outliers from sites in Iran and Turkmenistan in cultural communication with the IVC. These individuals had little if any Steppe pastoralist-derived ancestry, showing that it was not ubiquitous in northwest South Asia during the IVC as it is today. The Iranian-related ancestry in the IVC derives from a lineage leading to early Iranian farmers, herders, and hunter-gatherers before their ancestors separated, contradicting the hypothesis that the shared ancestry between early Iranians and South Asians reflects a large-scale spread of western Iranian farmers east. Instead, sampled ancient genomes from the Iranian plateau and IVC descend from different groups of hunter-gatherers who began farming without being connected by substantial movement of people.

3.
Nat Commun ; 10(1): 3670, 2019 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-31431628

RESUMO

Situated at over 5,000 meters above sea level in the Himalayan Mountains, Roopkund Lake is home to the scattered skeletal remains of several hundred individuals of unknown origin. We report genome-wide ancient DNA for 38 skeletons from Roopkund Lake, and find that they cluster into three distinct groups. A group of 23 individuals have ancestry that falls within the range of variation of present-day South Asians. A further 14 have ancestry typical of the eastern Mediterranean. We also identify one individual with Southeast Asian-related ancestry. Radiocarbon dating indicates that these remains were not deposited simultaneously. Instead, all of the individuals with South Asian-related ancestry date to ~800 CE (but with evidence of being deposited in more than one event), while all other individuals date to ~1800 CE. These differences are also reflected in stable isotope measurements, which reveal a distinct dietary profile for the two main groups.

4.
Science ; 365(6448)2019 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-31147405

RESUMO

How food production first entered eastern Africa ~5000 years ago and the extent to which people moved with livestock is unclear. We present genome-wide data from 41 individuals associated with Later Stone Age, Pastoral Neolithic (PN), and Iron Age contexts in what are now Kenya and Tanzania to examine the genetic impacts of the spreads of herding and farming. Our results support a multiphase model in which admixture between northeastern African-related peoples and eastern African foragers formed multiple pastoralist groups, including a genetically homogeneous PN cluster. Additional admixture with northeastern and western African-related groups occurred by the Iron Age. These findings support several movements of food producers while rejecting models of minimal admixture with foragers and of genetic differentiation between makers of distinct PN artifacts.

5.
Nature ; 570(7760): 236-240, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31168094

RESUMO

Much of the American Arctic was first settled 5,000 years ago, by groups of people known as Palaeo-Eskimos. They were subsequently joined and largely displaced around 1,000 years ago by ancestors of the present-day Inuit and Yup'ik1-3. The genetic relationship between Palaeo-Eskimos and Native American, Inuit, Yup'ik and Aleut populations remains uncertain4-6. Here we present genomic data for 48 ancient individuals from Chukotka, East Siberia, the Aleutian Islands, Alaska, and the Canadian Arctic. We co-analyse these data with data from present-day Alaskan Iñupiat and West Siberian populations and published genomes. Using methods based on rare-allele and haplotype sharing, as well as established techniques4,7-9, we show that Palaeo-Eskimo-related ancestry is ubiquitous among people who speak Na-Dene and Eskimo-Aleut languages. We develop a comprehensive model for the Holocene peopling events of Chukotka and North America, and show that Na-Dene-speaking peoples, people of the Aleutian Islands, and Yup'ik and Inuit across the Arctic region all share ancestry from a single Palaeo-Eskimo-related Siberian source.

6.
Am J Kidney Dis ; 74(3): 361-372, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31126666

RESUMO

RATIONALE & OBJECTIVE: There is debate on whether weight loss, a hallmark of frailty, signals higher risk for adverse outcomes among recipients of deceased donor kidney transplantation (DDKT). STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: Using national Organ Procurement and Transplantation Network data, we included all DDKT recipients in the United States between December 4, 2004, and December 3, 2014, who were adults (aged ≥ 18 years) when listed for DDKT. EXPOSURES: Relative pre-DDKT weight change as a continuous predictor and categorized as <5% weight change from listing to DDKT, ≥5% to <10% weight loss, ≥10% weight loss, ≥5% to <10% weight gain, and ≥10% weight gain. OUTCOMES: We examined 3 post-DDKT outcomes: (1) transplant hospitalization length of stay (LOS) in days, (2) all-cause graft failure, and (3) mortality. ANALYTIC APPROACH: Unadjusted fractional polynomial methods, multivariable log-gamma models, and multivariable Cox proportional hazards models. RESULTS: Among 94,465 recipients of DDKT, median pre-DDKT weight change was 0 (interquartile range, -3.5 to +3.9) kg. There were nonlinear unadjusted associations between relative pre-DDKT weight loss and longer transplant hospitalization LOS, higher all-cause graft loss, and higher mortality. Compared with recipients with <5% pre-DDKT weight change (n = 49,366; 52%), recipients who lost ≥10% of their listing weight (n = 10,614; 11%) had 0.66 (95% CI, 0.23-1.09) days longer average transplant hospitalization LOS (P = 0.003), 1.11-fold higher graft loss (adjusted HR [aHR], 1.11; 95% CI, 1.06-1.17; P < 0.001), and 1.18-fold higher mortality (aHR, 1.18; 95% CI, 1.11-1.25; P < 0.001) independent of recipient, donor, and transplant factors. Pre-DDKT dialysis exposure, listing body mass index category, and waiting time modified the association of pre-DDKT weight change with hospital LOS (interaction P < 0.10), but not with all-cause graft loss and mortality. LIMITATIONS: Unmeasured confounders and inability to identify volitional weight change. Also, the higher significance level set to increase the power of detecting interactions with the fixed sample size may have resulted in increased risk for type 1 error. CONCLUSIONS: DDKT recipients with ≥10% pre-DDKT weight loss are at increased risk for adverse outcomes and may benefit from augmented support post-DDKT.

7.
Nat Ecol Evol ; 3(6): 986-987, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31068681

RESUMO

In the version of this Article originally published, there were errors in the colour ordering of the legend in Fig. 5b, and in the positions of the target and surrogate populations in Fig. 5c. This has now been corrected. The conclusions of the study are in no way affected. The errors have been corrected in the HTML and PDF versions of the article.

8.
Artigo em Inglês | MEDLINE | ID: mdl-31056357

RESUMO

OBJECTIVE: The study objective was to determine whether targeted therapy to optimize cerebral oxygenation is associated with improved neurocognitive and perioperative outcomes. METHODS: In a prospective trial, intraoperative cerebral oximetry monitoring using bilateral forehead probes was performed in cardiac surgical patients who were randomly assigned to an intervention group in which episodes of cerebral oxygen desaturation (<60% for >60 consecutive seconds at either probe) triggered an intervention protocol or a control group in which the cerebral oximetry data were hidden from the clinical team, and no intervention protocol was applied. Cognitive testing was performed preoperatively and at postoperative months 3 and 6; domains studied were response speed, processing speed, attention, and memory. Perioperative outcomes studied were death, hospital length of stay, intensive care unit length of stay, postoperative day of extubation, time on mechanical ventilation, intensive care unit delirium, Sequential Organ Failure Assessment on intensive care unit admission, and intensive care unit blood transfusion. RESULTS: Group mean memory change scores were significantly better in the intervention group at 6 months (0.60 [standard error, 0.30] vs -0.17 [standard error, 0.33], adjusted P = .008). However, presence, duration, and severity of cerebral desaturation were not associated with cognitive change scores. Perioperative outcomes did not differ between the intervention and control groups. CONCLUSIONS: Targeted therapy to optimize cerebral oxygenation was associated with better memory outcome in a group of cardiac surgical patients. Some aspects of the protocol other than desaturation duration and severity contributed to the observed neuroprotective effect.

9.
Artigo em Inglês | MEDLINE | ID: mdl-31053860

RESUMO

PURPOSE: Several factors lead to medication non-adherence after hospital discharge. Hospitals and pharmacies have implemented bedside medication delivery (BMD) programs for patients, in an attempt to reduce barriers and improve medication adherence. Here, we provide a critical review of the literature on these programs. DATA SOURCES: We conducted a literature search on BMD programs in PubMed, Google Scholar, Scopus and a general Google search using these keywords: 'medication delivery bedside', 'discharge medication delivery', 'meds to bedside' and 'meds to beds'. STUDY SELECTION: We identified 10 reports and include data from all reports. DATA EXTRACTION: Data on study characteristics and settings were extracted along with four outcomes: medication error, patient satisfaction, 30-day hospital readmission and visits to the emergency department. RESULTS OF DATA SYNTHESIS: Of the 10 reports, only 4 were peer-reviewed publications; others were reported in the lay press. Outcomes were reported in both qualitative and quantitative terms. Less than half of reports provided quantitative data on 30-day readmission and patient satisfaction. Others suggested qualitative improvement in these outcomes but did not provide data or specific details. None reported outcomes of their programs beyond 30 days. CONCLUSION: We highlight the need for increased use of optimal program design and more rigorous evaluations of the impact of BMD programs. We also provide guidelines on the types of evaluations that are likely needed and encourage improved reporting.

10.
Nat Ecol Evol ; 3(6): 966-976, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31036896

RESUMO

The indigenous populations of inner Eurasia-a huge geographic region covering the central Eurasian steppe and the northern Eurasian taiga and tundra-harbour tremendous diversity in their genes, cultures and languages. In this study, we report novel genome-wide data for 763 individuals from Armenia, Georgia, Kazakhstan, Moldova, Mongolia, Russia, Tajikistan, Ukraine and Uzbekistan. We furthermore report additional damage-reduced genome-wide data of two previously published individuals from the Eneolithic Botai culture in Kazakhstan (~5,400 BP). We find that present-day inner Eurasian populations are structured into three distinct admixture clines stretching between various western and eastern Eurasian ancestries, mirroring geography. The Botai and more recent ancient genomes from Siberia show a decrease in contributions from so-called 'ancient North Eurasian' ancestry over time, which is detectable only in the northern-most 'forest-tundra' cline. The intermediate 'steppe-forest' cline descends from the Late Bronze Age steppe ancestries, while the 'southern steppe' cline further to the south shows a strong West/South Asian influence. Ancient genomes suggest a northward spread of the southern steppe cline in Central Asia during the first millennium BC. Finally, the genetic structure of Caucasus populations highlights a role of the Caucasus Mountains as a barrier to gene flow and suggests a post-Neolithic gene flow into North Caucasus populations from the steppe.


Assuntos
Grupo com Ancestrais do Continente Asiático , Fluxo Gênico , Geografia , Humanos , Federação Russa
11.
Genome Biol ; 20(1): 82, 2019 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-31023338

RESUMO

BACKGROUND: Africa is the origin of modern humans within the past 300 thousand years. To infer the complex demographic history of African populations and adaptation to diverse environments, we sequenced the genomes of 92 individuals from 44 indigenous African populations. RESULTS: Genetic structure analyses indicate that among Africans, genetic ancestry is largely partitioned by geography and language, though we observe mixed ancestry in many individuals, consistent with both short- and long-range migration events followed by admixture. Phylogenetic analysis indicates that the San genetic lineage is basal to all modern human lineages. The San and Niger-Congo, Afroasiatic, and Nilo-Saharan lineages were substantially diverged by 160 kya (thousand years ago). In contrast, the San and Central African rainforest hunter-gatherer (CRHG), Hadza hunter-gatherer, and Sandawe hunter-gatherer lineages were diverged by ~ 120-100 kya. Niger-Congo, Nilo-Saharan, and Afroasiatic lineages diverged more recently by ~ 54-16 kya. Eastern and western CRHG lineages diverged by ~ 50-31 kya, and the western CRHG lineages diverged by ~ 18-12 kya. The San and CRHG populations maintained the largest effective population size compared to other populations prior to 60 kya. Further, we observed signatures of positive selection at genes involved in muscle development, bone synthesis, reproduction, immune function, energy metabolism, and cell signaling, which may contribute to local adaptation of African populations. CONCLUSIONS: We observe high levels of genomic variation between ethnically diverse Africans which is largely correlated with geography and language. Our study indicates ancient population substructure and local adaptation of Africans.


Assuntos
Adaptação Biológica , Grupo com Ancestrais do Continente Africano/genética , Evolução Biológica , Filogenia , Densidade Demográfica , África , Genoma Humano , Migração Humana , Humanos , Filogeografia
12.
Trends Genet ; 35(5): 319-329, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30954285

RESUMO

Paleogenomics, also known as genome-wide ancient DNA analysis, is transforming our understanding of the human past, but has been much less intensively used to understand the history of other species. However, paleogenomic studies of non-human animals and plants have the potential to address an equally rich range of evolutionary, paleoecological, paleoenvironmental, and archaeological research questions. Three recent case studies of cave bears, horses, and maize provide examples of the ways that paleogenomics can be used to examine potential causes of extinctions and dynamic processes of domestication. Much more research in these areas is needed, and we conclude by highlighting key future directions.

13.
Nat Ecol Evol ; 3(5): 765-771, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30988490

RESUMO

The roles of migration, admixture and acculturation in the European transition to farming have been debated for over 100 years. Genome-wide ancient DNA studies indicate predominantly Aegean ancestry for continental Neolithic farmers, but also variable admixture with local Mesolithic hunter-gatherers. Neolithic cultures first appear in Britain circa 4000 BC, a millennium after they appeared in adjacent areas of continental Europe. The pattern and process of this delayed British Neolithic transition remain unclear. We assembled genome-wide data from 6 Mesolithic and 67 Neolithic individuals found in Britain, dating 8500-2500 BC. Our analyses reveal persistent genetic affinities between Mesolithic British and Western European hunter-gatherers. We find overwhelming support for agriculture being introduced to Britain by incoming continental farmers, with small, geographically structured levels of hunter-gatherer ancestry. Unlike other European Neolithic populations, we detect no resurgence of hunter-gatherer ancestry at any time during the Neolithic in Britain. Genetic affinities with Iberian Neolithic individuals indicate that British Neolithic people were mostly descended from Aegean farmers who followed the Mediterranean route of dispersal. We also infer considerable variation in pigmentation levels in Europe by circa 6000 BC.


Assuntos
DNA Antigo , Genoma , Europa (Continente) , Humanos , Dinâmica Populacional , Reino Unido
14.
Elife ; 82019 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-30895926

RESUMO

Genetic predictions of height differ among human populations and these differences have been interpreted as evidence of polygenic adaptation. These differences were first detected using SNPs genome-wide significantly associated with height, and shown to grow stronger when large numbers of sub-significant SNPs were included, leading to excitement about the prospect of analyzing large fractions of the genome to detect polygenic adaptation for multiple traits. Previous studies of height have been based on SNP effect size measurements in the GIANT Consortium meta-analysis. Here we repeat the analyses in the UK Biobank, a much more homogeneously designed study. We show that polygenic adaptation signals based on large numbers of SNPs below genome-wide significance are extremely sensitive to biases due to uncorrected population stratification. More generally, our results imply that typical constructions of polygenic scores are sensitive to population stratification and that population-level differences should be interpreted with caution. Editorial note: This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that all the issues have been addressed (see decision letter).

15.
Nat Commun ; 10(1): 590, 2019 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-30713341

RESUMO

Archaeogenetic studies have described the formation of Eurasian 'steppe ancestry' as a mixture of Eastern and Caucasus hunter-gatherers. However, it remains unclear when and where this ancestry arose and whether it was related to a horizon of cultural innovations in the 4th millennium BCE that subsequently facilitated the advance of pastoral societies in Eurasia. Here we generated genome-wide SNP data from 45 prehistoric individuals along a 3000-year temporal transect in the North Caucasus. We observe a genetic separation between the groups of the Caucasus and those of the adjacent steppe. The northern Caucasus groups are genetically similar to contemporaneous populations south of it, suggesting human movement across the mountain range during the Bronze Age. The steppe groups from Yamnaya and subsequent pastoralist cultures show evidence for previously undetected farmer-related ancestry from different contact zones, while Steppe Maykop individuals harbour additional Upper Palaeolithic Siberian and Native American related ancestry.

17.
Nat Commun ; 9(1): 3913, 2018 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-30237547

RESUMO

In the original version of this Article, references in the format 'First author et al.' were inappropriately deleted. These errors have been corrected in the PDF and HTML versions of the Article.

18.
BMC Med Inform Decis Mak ; 18(Suppl 3): 79, 2018 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-30255805

RESUMO

BACKGROUND: Worldwide, over 14% of individuals hospitalized for psychiatric reasons have readmissions to hospitals within 30 days after discharge. Predicting patients at risk and leveraging accelerated interventions can reduce the rates of early readmission, a negative clinical outcome (i.e., a treatment failure) that affects the quality of life of patient. To implement individualized interventions, it is necessary to predict those individuals at highest risk for 30-day readmission. In this study, our aim was to conduct a data-driven investigation to find the pharmacological factors influencing 30-day all-cause, intra- and interdepartmental readmissions after an index psychiatric admission, using the compendium of prescription data (prescriptome) from electronic medical records (EMR). METHODS: The data scientists in the project received a deidentified database from the Mount Sinai Data Warehouse, which was used to perform all analyses. Data was stored in a secured MySQL database, normalized and indexed using a unique hexadecimal identifier associated with the data for psychiatric illness visits. We used Bayesian logistic regression models to evaluate the association of prescription data with 30-day readmission risk. We constructed individual models and compiled results after adjusting for covariates, including drug exposure, age, and gender. We also performed digital comorbidity survey using EMR data combined with the estimation of shared genetic architecture using genomic annotations to disease phenotypes. RESULTS: Using an automated, data-driven approach, we identified prescription medications, side effects (primary side effects), and drug-drug interaction-induced side effects (secondary side effects) associated with readmission risk in a cohort of 1275 patients using prescriptome analytics. In our study, we identified 28 drugs associated with risk for readmission among psychiatric patients. Based on prescription data, Pravastatin had the highest risk of readmission (OR = 13.10; 95% CI (2.82, 60.8)). We also identified enrichment of primary side effects (n = 4006) and secondary side effects (n = 36) induced by prescription drugs in the subset of readmitted patients (n = 89) compared to the non-readmitted subgroup (n = 1186). Digital comorbidity analyses and shared genetic analyses further reveals that cardiovascular disease and psychiatric conditions are comorbid and share functional gene modules (cardiomyopathy and anxiety disorder: shared genes (n = 37; P = 1.06815E-06)). CONCLUSIONS: Large scale prescriptome data is now available from EMRs and accessible for analytics that could improve healthcare outcomes. Such analyses could also drive hypothesis and data-driven research. In this study, we explored the utility of prescriptome data to identify factors driving readmission in a psychiatric cohort. Converging digital health data from EMRs and systems biology investigations reveal a subset of patient populations that have significant comorbidities with cardiovascular diseases are more likely to be readmitted. Further, the genetic architecture of psychiatric illness also suggests overlap with cardiovascular diseases. In summary, assessment of medications, side effects, and drug-drug interactions in a clinical setting as well as genomic information using a data mining approach could help to find factors that could help to lower readmission rates in patients with mental illness.

19.
Cureus ; 10(7): e2903, 2018 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-30197844

RESUMO

Familial dysalbuminemic hyperthyroxinemia (FDH) is the most common cause of the inherited increase of serum thyroxine in Caucasians. This disorder occurs due to a missense mutation in the human serum albumin, resulting in an increased affinity of thyroxine to the binding sites on the human serum albumin (HSA) molecule. HSA is a carrier protein of thyroid hormones and only 10% of thyroxine (T4) is bound to human serum albumin, 75% is bound to thyroxine-binding globulin, 15% to transthyretin, and 0.03% is free. The disorder is characterized by a greater elevation of serum thyroxine than triiodothyronine (T3). The high serum concentration of T4 is due to the modification of a binding site located in the N-terminal half of HSA (in subdomain IIA). Arg218 or Arg222 gets replaced with smaller amino acids, such as histidine, proline, or serine, due to missense mutation; this reduces the steric hindrances in the binding site and creates a high-affinity binding site for thyroxine. We herein report a case of FDH with a characteristically elevated total T4 and normal free T4 (measured by equilibrium dialysis).

20.
Sci Adv ; 4(8): eaat5473, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30101195

RESUMO

Some recent academic and popular literature implies that the problem of the colonization of the Americas has been largely resolved in favor of one specific model: a Pacific coastal migration, dependent on high marine productivity, from the Bering Strait to South America, thousands of years before Clovis, the earliest widespread cultural manifestation south of the glacial ice. Speculations on maritime adaptations and typological links (stemmed points) across thousands of kilometers have also been advanced. A review of the current genetic, archeological, and paleoecological evidence indicates that ancestral Native American population expansion occurred after 16,000 years ago, consistent with the archeological record, particularly with the earliest securely dated sites after ~15,000 years ago. These data are largely consistent with either an inland (ice-free corridor) or Pacific coastal routes (or both), but neither can be rejected at present. Systematic archeological and paleoecological investigations, informed by geomorphology, are required to test each hypothesis.

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