Sobre la paleobiología de Hippopotamus antiquus Desmarest,1822: ¿Un megaherbívoro acuático sin análogos vivientes?

Los hipopótamos se encuentran representados hoy día por dos especies africanas, Hippopotamus amphibius, el hipopótamo común, de vida semiacuática, y Choeropsis liberiensis, el hipopótamo pigmeo, de hábitos más terrestres (Boisserie, 2005). Los hipopótamos comunes se desenvuelven en zonas de aguas tranquilas y someras, que abandonan durante la noche para pacer vegetación terrestre (Nowak 1999). Por ello, sus poblaciones experimentan una mortalidad acusada durante las sequías prolongadas, debido a la escasez de pastos en las inmediaciones de las pozas de barro a las que se ven confinados (Eltringham, 1999). Los hipopótamos no nadan, se desplazan caminando por el fondo de los ríos y lagos; por ello, sus huesos, cortos y robustos, presentan la cavidad medular rellena de tejido esponjoso, para regular su flotabilidad. Por sus condiciones ecológicas de alta dependencia del medio acuático y al no soportar temperaturas frías extremas, los hipopótamos resultan excelentes indicadores climáticos y ecológicos, mostrando una estrecha relación con los homininos donde ambos coexisten. Hippopotamus antiquus es una especie extinta con un amplio registro en los yacimientos del Villafranquiense superior y el Galeriense de Europa y Asia occidental. En el Pleistoceno inferior de África y en el Corredor Levantino (yacimiento de ‘Ubeidiya, Israel) se ha documentado la presencia de H. gorgops, especie hermana (si no la misma) de la forma registrada en Eurasia. La cronología de la llegada a Europa de H. antiquus, procedente del continente austral, es una cuestión muy debatida. Algunas referencias sitúan la especie en Italia en torno a unos 2,0 Ma, como en Coste San Giacomo (Bellucci et al. 2012), pero su presencia en las paleomastocenosis europeas no se normaliza hasta una cronología próxima a 1,6-1,5 Ma, con un buen registro en el yacimiento de Venta Micena en Orce y en la mayor parte de las tafocenosis europeas posteriores hasta la base del Pleistoceno medio (vg., Barranco León, Fuente Nueva 3, Cal Guardiola e Incarcal en España; Colle Curti, Figline e Isernia La Pineta en Italia; Ravin de Voulgarakis en Grecia; o Untermassfeld en Alemania). Aunque el género de vida de H. antiquus se presume en la literatura como similar al del hipopótamo moderno, el estudio de su anatomía y los análisis biogeoquímicos de los restos óseos de Venta Micena revelan características que lo diferencian de esta especie en cuanto a su mayor dependencia del medio acuático y su alimentación. Así, concretamente, el estudio isotópico de los mamíferos del parque nacional del Amboseli (Kenia) y de Venta Micena muestra valores de 15N singularmente altos para el colágeno de H. antiquus en comparación a los de los restantes ungulados de la tafocenosis, mientras que para H. amphibius son similares a los de otros herbívoros de Amboseli. Esta diferencia es interpretable como evidencia de la alimentación de la especie extinta sobre macrófitos acuáticos en un lago relativamente salino, en vez de pacer de noche vegetación terrestre en las riberas de lagos y ríos, como ocurre en la especie actual. De hecho, un análisis reciente de la vegetación actual de un par de lagunas saladas de la provincia de Málaga (García-Aguilar et al. 2015) ha mostrado diferencias importantes en los valores de 15N entre su vegetación acuática (8,85 a 13,48‰) y las plantas herbáceas de la llanura circundante (-0,42 a 1,78‰). La anatomía esquelética de H. antiquus es congruente con esta inferencia paleobiológica. Por ejemplo, sus órbitas oculares y sus narinas se encuentran particularmente elevadas en comparación a las de H. amphibius y el paladar es proporcionalmente más estrecho y alargado, todo lo cual sugiere unos hábitos más acuáticos, aunque podría deberse también en parte a efectos alométricos. Por otra parte, los segmentos distales de las extremidades se encuentran acortados en la especie extinta respecto a la moderna. Así, el cociente entre las longitudes de los huesos largos en H. antiquus y H. amphibius es mayor en el estilópodo (húmero: 126%, fémur: 125%) que en el zeugópodo (radio: 119%, tibia: 114%) y, a su vez, vuelve a descender en el autópodo (mc3: 109%, mt3: 106%). Finalmente, la masa corporal media estimada para H. antiquus usando ecuaciones de regresión lineal ajustadas en ungulados a partir de la anchura de los cuatro huesos largos principales (húmero, fémur, radioulna y tibia), 3163 kg, es 2,14 veces mayor que la calculada para H. amphibius con dichas ecuaciones, 1476 kg, valor similar a la masa real de la especie (1.475 kg en los machos y 1.360 kg en las hembras; Nowak 1999).Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

A comparison of the taphonomic attributes of quarries VM3 and VM4 of the Early Pleistocene site of Venta Micena (Baza Basin, SE Spain)

The site of Venta Micena (Guadix-Baza Depression, SE Spain), a rich Fossil-Lagerstätten of late Early Pleistocene age (1.6-1.5 Ma), preserves a diverse assemblage of large mammals. Up to date, >24,000 skeletal remains have been unearthed from the surface excavated (~400 m2) in the two main quarries of the site, VM3 and VM4, which represents a density of fossils of >60/m2. Although this density is not homogeneously recorded across the 80-120 cm thick VM stratum, which outcrops over ~2.5 km, it suggests that tens of millions of fossils were preserved in the micritic limestones of this lithological unit. VM3 has been interpreted as a den of the giant hyena Pachycrocuta brevirostris in the plain that surrounded the Baza paleolake. Taphonomic analyses showed that the hyenas: (i) scavenged the prey hunted by the hypercarnivores, sabertoothed felids and wild dogs; (ii) transported the remains to their communal den as whole carcasses or selected anatomical parts; and (iii) fractured the skeletal parts according to their marrow contents and mineral density, which resulted in well-defined consumption sequences. In the case of VM4, an excavation quarry ~350 m distant from VM3, preliminary taphonomic analyses of the assemblage showed several differences, including: (i) a higher frequency of elements in anatomical connection than in VM3; (ii) a lower proportion of bones tooth-marked by carnivores (5.5%) compared with their frequency in VM3 (29.4%); (iii) a lower proportion of remains with salivary and gastric alterations (0.06% in both cases) than in VM3 (0.34% and 0.15%, respectively); and (iv) a less advanced degree of weathering (90.8% of bones show weathering stage 0 in VM4 compared to 75.9% in VM3).ICAZ Taphonomy Working Group, CSIC, MNCN Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tec

Deciphering the record of hyaenic activity in the Early Pleistocene site of Fuente Nueva-3 (Baza Basin, SE Spain)

FN3 is an open air site, dated ~1.4 Ma. Their archaeological levels preserve evidences of human presence, consisting in lithic artefacts and cuts and percussion marks on bones. The lithic remains are associated with abundant macromammals bones with a very wide size range, from proboscideans to small mustelids. Carnivores are represented, mainly, by isolated teeth, bellowing to canids, ursids, felids and hyaenids, and their activity is recorded by the presence of different tooth marks types. However, there exists an important difference in the carnivore record between the levels, consisting in the presence of more than 200 coprolites in the Upper Level, whereas in the Lower Level these elements are practically absent. For the identification of the defecating organism, different analyses have been performed. The morphological study evidences the presence of the seven shape-types of pellets, although the most common morphologies are round, oval and disk. The colour of hyena faeces is also very characteristic, colour analysis of FN3 coprolites shows a predominance of whitish and very pale brown tonalities. To determine the composition, the samples were studied by XRD, XRF and SEM. The results have revealed that the coprolites mostly consist of calcium phosphate. These data are consistent with the expected composition of faeces in an organism that ingests a large amount of bones, in addition, macroscopic observation of the coprolites surface evidence the presence of numerous fragments of digested bones within them. All these features allow us to adscribe the FN3 coprolites to the hyaena Pachycrocuta brevirostris, species of which several teeth have been found at this site.This record manifests a great difference between both archaeological levels, showing in the Upper Level a scenario were hominin and hyaenids coexisted and competed for food resources, whereas in the Lower Level hyaenas were practically absent, and the main modifying agent was early Homo.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Sharing food with hyenas: a latrine of Pachycrocuta brevirostris in the Early Pleistocene assemblage of Fuente Nueva-3 (Orce, Baza Basin, SE Spain)

The Early Pleistocene archeological site of Fuente Nueva-3 (FN3) preserves some of the oldest evidence of hominin presence in Western Europe, including a huge assemblage of Oldowan tools and evidence of butchering and marrow processing of large mammal bones. Moreover, there is also evidence of the regular presence of carnivores at the site, including a small proportion of bones that show tooth marks, the majority of which can be attributed to the giant, short-faced hyena Pachycrocuta brevirostris, and there are 220 coprolites, most of them from the Upper Archeological Level. In order to identify the defecating agent, we analyze here the coprolites and compare them with other specimens from the literature and with scats from zoo spotted hyenas (Crocuta crocuta). The morphology, color, size, and chemical composition of the FN3 coprolites allow us to attribute them to the hyena P. brevirostris, which is also represented at the site by fossil specimens. In addition, we evaluate the origin of the accumulation of coprolites and discuss on the role played by the scavenging hyenas in the accumulation and modification of the bone remains unearthed at the site, which allows evaluating the contribution of the giant hyena to this Early Pleistocene site. Finally, based on the lithology of layer 5 of the Upper Archeological Level, fine sands and clays deposited in a salt-lake environment, we hypothesize that this layer may have acted as a quicksand where large-sized animals like elephants were trapped and their carcasses lured scavenging carnivores.Depto. de Geodinámica, Estratigrafía y PaleontologíaFac. de Ciencias GeológicasTRUEJunta de AndalucíaGeneralitat de CatalunyaMinisterio de Ciencia e InnovaciónComunidad de Madridpu

Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)

Improved risk stratification of patients with atrial fibrillation: an integrated GARFIELD-AF tool for the prediction of mortality, stroke and bleed in patients with and without anticoagulation.

OBJECTIVES: To provide an accurate, web-based tool for stratifying patients with atrial fibrillation to facilitate decisions on the potential benefits/risks of anticoagulation, based on mortality, stroke and bleeding risks. DESIGN: The new tool was developed, using stepwise regression, for all and then applied to lower risk patients. C-statistics were compared with CHA2DS2-VASc using 30-fold cross-validation to control for overfitting. External validation was undertaken in an independent dataset, Outcome Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF). PARTICIPANTS: Data from 39 898 patients enrolled in the prospective GARFIELD-AF registry provided the basis for deriving and validating an integrated risk tool to predict stroke risk, mortality and bleeding risk. RESULTS: The discriminatory value of the GARFIELD-AF risk model was superior to CHA2DS2-VASc for patients with or without anticoagulation. C-statistics (95% CI) for all-cause mortality, ischaemic stroke/systemic embolism and haemorrhagic stroke/major bleeding (treated patients) were: 0.77 (0.76 to 0.78), 0.69 (0.67 to 0.71) and 0.66 (0.62 to 0.69), respectively, for the GARFIELD-AF risk models, and 0.66 (0.64-0.67), 0.64 (0.61-0.66) and 0.64 (0.61-0.68), respectively, for CHA2DS2-VASc (or HAS-BLED for bleeding). In very low to low risk patients (CHA2DS2-VASc 0 or 1 (men) and 1 or 2 (women)), the CHA2DS2-VASc and HAS-BLED (for bleeding) scores offered weak discriminatory value for mortality, stroke/systemic embolism and major bleeding. C-statistics for the GARFIELD-AF risk tool were 0.69 (0.64 to 0.75), 0.65 (0.56 to 0.73) and 0.60 (0.47 to 0.73) for each end point, respectively, versus 0.50 (0.45 to 0.55), 0.59 (0.50 to 0.67) and 0.55 (0.53 to 0.56) for CHA2DS2-VASc (or HAS-BLED for bleeding). Upon validation in the ORBIT-AF population, C-statistics showed that the GARFIELD-AF risk tool was effective for predicting 1-year all-cause mortality using the full and simplified model for all-cause mortality: C-statistics 0.75 (0.73 to 0.77) and 0.75 (0.73 to 0.77), respectively, and for predicting for any stroke or systemic embolism over 1 year, C-statistics 0.68 (0.62 to 0.74). CONCLUSIONS: Performance of the GARFIELD-AF risk tool was superior to CHA2DS2-VASc in predicting stroke and mortality and superior to HAS-BLED for bleeding, overall and in lower risk patients. The GARFIELD-AF tool has the potential for incorporation in routine electronic systems, and for the first time, permits simultaneous evaluation of ischaemic stroke, mortality and bleeding risks. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier for GARFIELD-AF (NCT01090362) and for ORBIT-AF (NCT01165710)

Two-year outcomes of patients with newly diagnosed atrial fibrillation: results from GARFIELD-AF.

AIMS: The relationship between outcomes and time after diagnosis for patients with non-valvular atrial fibrillation (NVAF) is poorly defined, especially beyond the first year. METHODS AND RESULTS: GARFIELD-AF is an ongoing, global observational study of adults with newly diagnosed NVAF. Two-year outcomes of 17 162 patients prospectively enrolled in GARFIELD-AF were analysed in light of baseline characteristics, risk profiles for stroke/systemic embolism (SE), and antithrombotic therapy. The mean (standard deviation) age was 69.8 (11.4) years, 43.8% were women, and the mean CHA2DS2-VASc score was 3.3 (1.6); 60.8% of patients were prescribed anticoagulant therapy with/without antiplatelet (AP) therapy, 27.4% AP monotherapy, and 11.8% no antithrombotic therapy. At 2-year follow-up, all-cause mortality, stroke/SE, and major bleeding had occurred at a rate (95% confidence interval) of 3.83 (3.62; 4.05), 1.25 (1.13; 1.38), and 0.70 (0.62; 0.81) per 100 person-years, respectively. Rates for all three major events were highest during the first 4 months. Congestive heart failure, acute coronary syndromes, sudden/unwitnessed death, malignancy, respiratory failure, and infection/sepsis accounted for 65% of all known causes of death and strokes for <10%. Anticoagulant treatment was associated with a 35% lower risk of death. CONCLUSION: The most frequent of the three major outcome measures was death, whose most common causes are not known to be significantly influenced by anticoagulation. This suggests that a more comprehensive approach to the management of NVAF may be needed to improve outcome. This could include, in addition to anticoagulation, interventions targeting modifiable, cause-specific risk factors for death. CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

Elective cancer surgery in COVID-19-free surgical pathways during the SARS-CoV-2 pandemic: An international, multicenter, comparative cohort study

PURPOSE As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19–free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19–free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19–free surgical pathways. Patients who underwent surgery within COVID-19–free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19–free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score–matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19–free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION Within available resources, dedicated COVID-19–free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks