Direct Dates and mtDNA of Late Pleistocene Human Skeletons from South America: A Comment on Chatters et al. (2014)

In a recent paper in the journal Science (2014, Vol. 344, pp. 750–754), J. Chatters et al. present a new early human skeleton from the Yucatan, Mexico, considering it in the context of eight other early “Paleoamerican” individuals—all from North America—that previously yielded ancient genetic evidence and/or direct radiocarbon ages. Despite including the archaeological site of Monte Verde II, Chile, in their discussion, we were alarmed that the authors otherwise ignored the South American record, presenting a map with the southern continent being devoid of PaleoAmerican human remains. We felt it important to remind our colleagues that South America has produced numerous directly dated human skeletal remains that are as old as the ones cited by Chatters et al. for North America, and that several of these have actually yielded mitochondrial (mt) DNA. Significant implications can be derived from this radiocarbon, bioanthropological, and mtDNA dataset, especially considering the antiquity of the earliest human populations and process of peopling of the New World.Facultad de Ciencias Naturales y Muse

Arrival of Paleo-Indians to the Southern Cone of South America: New Clues from Mitogenomes

With analyses of entire mitogenomes, studies of Native American mitochondrial DNA (mtDNA) variation have entered the final phase of phylogenetic refinement: the dissection of the founding haplogroups into clades that arose in America during and after human arrival and spread. Ages and geographic distributions of these clades could provide novel clues on the colonization processes of the different regions of the double continent. As for the Southern Cone of South America, this approach has recently allowed the identification of two local clades (D1g and D1j) whose age estimates agree with the dating of the earliest archaeological sites in South America, indicating that Paleo-Indians might have reached that region from Beringia in less than 2000 years. In this study, we sequenced 46 mitogenomes belonging to two additional clades, termed B2i2 (former B2l) and C1b13, which were recently identified on the basis of mtDNA control-region data and whose geographical distributions appear to be restricted to Chile and Argentina. We confirm that their mutational motifs most likely arose in the Southern Cone region. However, the age estimate for B2i2 and C1b13 (11–13,000 years) appears to be younger than those of other local clades. The difference could reflect the different evolutionary origins of the distinct South American-specific sub-haplogroups, with some being already present, at different times and locations, at the very front of the expansion wave in South America, and others originating later in situ, when the tribalization process had already begun. A delayed origin of a few thousand years in one of the locally derived populations, possibly in the central part of Chile, would have limited the geographical and ethnic diffusion of B2i2 and explain the present-day occurrence that appears to be mainly confined to the Tehuelche and Araucanian-speaking grou

An alternative model for the early peopling of Southern South America revealed by analyses of three mitochondrial DNA haplogroups

After several years of research, there is now a consensus that America was populated from Asia through Beringia, probably at the end of the Pleistocene. But many details such as the timing, route(s), and origin of the first settlers remain uncertain. In the last decade genetic evidence has taken on a major role in elucidating the peopling of the Americas. To study the early peopling of South America, we sequenced the control region of mitochondrial DNA from 300 individuals belonging to indigenous populations of Chile and Argentina, and also obtained seven complete mitochondrial DNA sequences. We identified two novel mtDNA monophyletic clades, preliminarily designated B2l and C1b13, which together with the recently described D1g sub-haplogroup have locally high frequencies and are basically restricted to populations from the extreme south of South America. The estimated ages of D1g and B2l, about ∼ 15,000 years BP, together with their similar population dynamics and the high haplotype diversity shown by the networks, suggests that they probably appeared soon after the arrival of the first settlers and agrees with the dating of the earliest archaeological sites in South America (Monte Verde, Chile, 14,500 BP). One further sub-haplogroup, D4h3a5, appears to be restricted to Fuegian-Patagonian populations and reinforces our hypothesis of the continuity of the current Patagonian populations with the initial founders. Our results indicate that the extant native populations inhabiting South Chile and Argentina are a group which had a common origin, and suggest a population break between the extreme south of South America and the more northern part of the continent. Thus the early colonization process was not just an expansion from north to south, but also included movements across the Andes.Instituto Multidisciplinario de Biología Celula

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

PANC Study (Pancreatitis: A National Cohort Study): national cohort study examining the first 30 days from presentation of acute pancreatitis in the UK

Abstract Background Acute pancreatitis is a common, yet complex, emergency surgical presentation. Multiple guidelines exist and management can vary significantly. The aim of this first UK, multicentre, prospective cohort study was to assess the variation in management of acute pancreatitis to guide resource planning and optimize treatment. Methods All patients aged greater than or equal to 18 years presenting with acute pancreatitis, as per the Atlanta criteria, from March to April 2021 were eligible for inclusion and followed up for 30 days. Anonymized data were uploaded to a secure electronic database in line with local governance approvals. Results A total of 113 hospitals contributed data on 2580 patients, with an equal sex distribution and a mean age of 57 years. The aetiology was gallstones in 50.6 per cent, with idiopathic the next most common (22.4 per cent). In addition to the 7.6 per cent with a diagnosis of chronic pancreatitis, 20.1 per cent of patients had a previous episode of acute pancreatitis. One in 20 patients were classed as having severe pancreatitis, as per the Atlanta criteria. The overall mortality rate was 2.3 per cent at 30 days, but rose to one in three in the severe group. Predictors of death included male sex, increased age, and frailty; previous acute pancreatitis and gallstones as aetiologies were protective. Smoking status and body mass index did not affect death. Conclusion Most patients presenting with acute pancreatitis have a mild, self-limiting disease. Rates of patients with idiopathic pancreatitis are high. Recurrent attacks of pancreatitis are common, but are likely to have reduced risk of death on subsequent admissions. </jats:sec

Antiquity of mtDNA lineage D1g from the southern cone of South America supports pre Clovis migration

The southern cone of South America has been an important source of information regarding the early peopling of the Americas. The discovery of the Monte Verde site was revolutionary; it led to wide acceptance of the pre-Clovis hypothesis and its corollary, the coastal migration route. Although numerous additional pre-Clovis sites have been reported in South America, debate continues about the timing of the earliest human migration. Perhaps because of the paucity of very early sites in North America, researchers there are increasingly focused on the genomic evidence. The mitochondrial subhaplogroup D1g described in 2012 and found in Amerindian populations of southern Chile and Argentina, represents today as Monte Verde did before, an interesting paradox that has not yet received much attention. The age calculated for D1g, between 25,000 and 19,000 cal yr BP is extremely old for a South American mitochondrial subhaplogroup. The anomalous age of this haplogroup does not fit the currently accepted framework for the other mtDNA haplogroups in the Americas. In this article I compare D1g old age with those from other published D phylogenies, using the rho calculation methodology in order to test the reliability of this older age estimate. Might this lineage be evidence for an early pre-Clovis migration

Análisis de ADNmt de 4 poblaciones rurales de la isla de Chiloé sugiere la presencia de los descendientes de una etnia extinta, los Chonos

El archipiélago de Chiloé (41º44´S - 43º45´S) ubicado en el sur de Chile, fue en el pasado un importante corredor poblacional, estando actualmente habitado por los descendientes de varios grupos indígenas. Históricamente, el archipiélago de Chiloé estuvo habitado por dos etnias con modo de subsistencia marcadamente diferentes, los Chonos, canoeros nómades que habitaron los archipiélagos al sur de la Isla grande de Chiloé hasta la Península de Taitao y los Huilliches, horticultores que habitaron principalmente Chiloé continental y la Isla Grande. Además, culturalmente, los Huilliches han sido asociados a la etnia Mapuche mientras que a los Chonos se les vincula con poblaciones de canoeros fuego-patagónicos como los Kaweskar y Yamanas. En base a las frecuencias de haplogrupos mitocondriales, las poblaciones rurales de la isla han sido asociadas tanto con poblaciones Huilliches como Yamanas. En este trabajo se obtuvieron y analizaron las secuencias de la región Hipervariable I, II y III del ADN mitocondrial de 4 poblaciones rurales de Chiloé provenientes de las localidades de Carelmapu (n=41), Quetalmahue (n=41), Laitec (n=42) y Detif (n=17). Se realizaron los siguientes análisis con el fin de examinar y esclarecer las relaciones filogeográficas de estos grupos y su relación étnica: Dendograma neighbor-joining (MEGA 4.0); redes de haplotipos (Network 4.5); distribución mismatch (DnaSP 5.0); cálculos de índices de diversidad molecular, Fst y Amova, en los dos últimos se comparó con secuencias de Huilliches, Yamanas y Kaweskar (Arlequin 3.01). Los resultados obtenidos de Amova y Fst conglomeran a las poblaciones en estudio en dos grupos bien diferenciados. Por un lado tenemos a los individuos de Carelmapu, Quetalmahue y Detif, relacionados con la población Huilliche. Laitec, por el contrario, muestra una relación más cercana con poblaciones de canoeros Fuego-patagónicos que con Huilliches, a pesar de la importante distancia geográfica con los primeros. Además, las distribuciones mismatch para los haplogrupos C y D muestran diferencias entre Laitec y Carelmapu, Quetalmahue y Detif, sugiriendo una historia demográfica distinta. Todo esto, sumado a la evidencia etnohistórica de reubicación de los últimos grupos de Chonos por Misiones Jesuitas en la época de la colonia, sugiere que los habitantes de Laitec podrían corresponder a descendientes de los Chonos, hoy considerados extintos.Simposio: Estructura poblacional y diversidad filética de linajes maternos en poblaciones del Cono SurFinanciamiento: FONDECYT 11060442, Beca CONICYT, Instituto de Ecología y Biodiversidad ICM P05-002, PFB 023Financing: FONDECYT 11060442, Beca CONICYT, Instituto de Ecología y Biodiversidad ICM P05-002, PFB 023Financiamento: FONDECYT 11060442, Beca CONICYT, Instituto de Ecología y Biodiversidad ICM P05-002, PFB 023Asociación de Antropología Biológica de la República Argentin

Análisis de ADNmt de 4 poblaciones rurales de la isla de Chiloé sugiere la presencia de los descendientes de una etnia extinta, los Chonos

El archipiélago de Chiloé (41º44´S - 43º45´S) ubicado en el sur de Chile, fue en el pasado un importante corredor poblacional, estando actualmente habitado por los descendientes de varios grupos indígenas. Históricamente, el archipiélago de Chiloé estuvo habitado por dos etnias con modo de subsistencia marcadamente diferentes, los Chonos, canoeros nómades que habitaron los archipiélagos al sur de la Isla grande de Chiloé hasta la Península de Taitao y los Huilliches, horticultores que habitaron principalmente Chiloé continental y la Isla Grande. Además, culturalmente, los Huilliches han sido asociados a la etnia Mapuche mientras que a los Chonos se les vincula con poblaciones de canoeros fuego-patagónicos como los Kaweskar y Yamanas. En base a las frecuencias de haplogrupos mitocondriales, las poblaciones rurales de la isla han sido asociadas tanto con poblaciones Huilliches como Yamanas. En este trabajo se obtuvieron y analizaron las secuencias de la región Hipervariable I, II y III del ADN mitocondrial de 4 poblaciones rurales de Chiloé provenientes de las localidades de Carelmapu (n=41), Quetalmahue (n=41), Laitec (n=42) y Detif (n=17). Se realizaron los siguientes análisis con el fin de examinar y esclarecer las relaciones filogeográficas de estos grupos y su relación étnica: Dendograma neighbor-joining (MEGA 4.0); redes de haplotipos (Network 4.5); distribución mismatch (DnaSP 5.0); cálculos de índices de diversidad molecular, Fst y Amova, en los dos últimos se comparó con secuencias de Huilliches, Yamanas y Kaweskar (Arlequin 3.01). Los resultados obtenidos de Amova y Fst conglomeran a las poblaciones en estudio en dos grupos bien diferenciados. Por un lado tenemos a los individuos de Carelmapu, Quetalmahue y Detif, relacionados con la población Huilliche. Laitec, por el contrario, muestra una relación más cercana con poblaciones de canoeros Fuego-patagónicos que con Huilliches, a pesar de la importante distancia geográfica con los primeros. Además, las distribuciones mismatch para los haplogrupos C y D muestran diferencias entre Laitec y Carelmapu, Quetalmahue y Detif, sugiriendo una historia demográfica distinta. Todo esto, sumado a la evidencia etnohistórica de reubicación de los últimos grupos de Chonos por Misiones Jesuitas en la época de la colonia, sugiere que los habitantes de Laitec podrían corresponder a descendientes de los Chonos, hoy considerados extintos.Simposio: Estructura poblacional y diversidad filética de linajes maternos en poblaciones del Cono SurFinanciamiento: FONDECYT 11060442, Beca CONICYT, Instituto de Ecología y Biodiversidad ICM P05-002, PFB 023Financing: FONDECYT 11060442, Beca CONICYT, Instituto de Ecología y Biodiversidad ICM P05-002, PFB 023Financiamento: FONDECYT 11060442, Beca CONICYT, Instituto de Ecología y Biodiversidad ICM P05-002, PFB 023Asociación de Antropología Biológica de la República Argentin