In the past decade, the early Acheulean before 1 Mya has been a focus of active research. Acheulean lithic assemblages have been shown to extend back to ∼1.75 Mya, and considerable advances in core ...reduction technologies are seen by 1.5 to 1.4 Mya. Here we report a bifacially flaked bone fragment (maximum dimension ∼13 cm) of a hippopotamus femur from the ∼1.4 Mya sediments of the Konso Formation in southern Ethiopia. The large number of flake scars and their distribution pattern, together with the high frequency of cone fractures, indicate anthropogenic flaking into handaxe-like form. Use-wear analyses show quasi-continuous alternate microflake scars, wear polish, edge rounding, and striae patches along an ∼5-cm-long edge toward the handaxe tip. The striae run predominantly oblique to the edge, with some perpendicular, on both the cortical and inner faces. The combined evidence is consistent with the use of this bone artifact in longitudinal motions, such as in cutting and/or sawing. This bone handaxe is the oldest known extensively flaked example from the Early Pleistocene. Despite scarcity of well-shaped bone tools, its presence at Konso shows that sophisticated flaking was practiced by ∼1.4 Mya, not only on a range of lithic materials, but also occasionally on bone, thus expanding the documented technological repertoire of African Early Pleistocene Homo.
Nonalcoholic fatty liver disease (NAFLD) is an increasingly common condition, affecting up to 25% of the population worldwide. NAFLD has been linked to several conditions, including hepatic ...inflammation, fibrosis, and hepatocellular carcinoma (HCC), however the role of NAFLD in cholangitis and the development of cholangiocellular carcinoma (CCC) remains poorly understood. This study investigated whether a high‐fat diet (HFD) promotes cholangitis and the development of CCC in mice. We used liver‐specific E‐cadherin gene (CDH1) knockout mice, CDH1∆Liv, which develop spontaneous inflammation in the portal areas along with periductal onion skin‐like fibrosis, similar to that of primary sclerosing cholangitis (PSC). An HFD or normal diet (ND) was fed to CDH1∆Liv mice for 7 mo. In addition, CDH1∆Liv mice were crossed with LSL‐KrasG12D mice, fed an HFD, and assessed in terms of liver tumor development. The extent of cholangitis and number of bile ductules significantly increased in mice fed an HFD compared with ND‐administered CDH1∆Liv mice. The numbers of Sox9 and CD44‐positive stem cell‐like cells were significantly increased in HFD mice. LSL‐KrasG12D /CDH1∆Liv HFD mice exhibited increased aggressiveness along with the development of numerous HCC and CCC, whereas LSL‐KrasG12D/CDH1∆Liv ND mice showed several macroscopic tumors with both HCC and CCC components. In conclusion, NAFLD exacerbates cholangitis and promotes the development of both HCC and CCC in mice.
Cdh1 deletion in cholangiocytes develops spontaneous cholangitis and ductular reaction. The extent of cholangitis and ductular reaction is increased in mice with NAFLD. Additional Kras mutation develops cholangiocellular tumors in mice with Cdh1 deleted cholangiocytes and NAFLD promotes development of cholangiocellular tumors.
Recent theoretical progress potentially refutes past claims that paleodemographic estimations are flawed by statistical problems, including age mimicry and sample bias due to differential ...preservation. The life expectancy at age 15 of the Jomon period prehistoric populace in Japan was initially estimated to have been ∼16 years while a more recent analysis suggested 31.5 years. In this study, we provide alternative results based on a new methodology. The material comprises 234 mandibular canines from Jomon period skeletal remains and a reference sample of 363 mandibular canines of recent‐modern Japanese. Dental pulp reduction is used as the age‐indicator, which because of tooth durability is presumed to minimize the effect of differential preservation. Maximum likelihood estimation, which theoretically avoids age mimicry, was applied. Our methods also adjusted for the known pulp volume reduction rate among recent‐modern Japanese to provide a better fit for observations in the Jomon period sample. Without adjustment for the known rate in pulp volume reduction, estimates of Jomon life expectancy at age 15 were dubiously long. However, when the rate was adjusted, the estimate results in a value that falls within the range of modern hunter‐gatherers, with significantly better fit to the observations. The rate‐adjusted result of 32.2 years more likely represents the true life expectancy of the Jomon people at age 15, than the result without adjustment. Considering ∼7% rate of antemortem loss of the mandibular canine observed in our Jomon period sample, actual life expectancy at age 15 may have been as high as ∼35.3 years.
Abstract Recent discoveries of Homo floresiensis and H. luzonensis raise questions regarding how extreme body size reduction occurred in some extinct Homo species in insular environments. Previous ...investigations at Mata Menge, Flores Island, Indonesia, suggested that the early Middle Pleistocene ancestors of H. floresiensis had even smaller jaws and teeth. Here, we report additional hominin fossils from the same deposits at Mata Menge. An adult humerus is estimated to be 9 − 16% shorter and thinner than the type specimen of H. floresiensis dated to ~60,000 years ago, and is smaller than any other Plio-Pleistocene adult hominin humeri hitherto reported. The newly recovered teeth are both exceptionally small; one of them bears closer morphological similarities to early Javanese H. erectus . The H. floresiensis lineage most likely evolved from early Asian H. erectus and was a long-lasting lineage on Flores with markedly diminutive body size since at least ~700,000 years ago.
Background
The eradication rate of vonoprazan‐based first‐line triple therapy (combined with clarithromycin and amoxicillin) (V‐AC) was reported to be 97.6% in patients with clarithromycin ...(CAM)‐susceptible Helicobacter pylori in a phase III study, whereas our real‐world, prospective, multicenter cohort study yielded an eradication rate <90%.
Objective
To validate the eradication rate of V‐AC using CAM‐susceptible testing in a multicenter, prospective, randomized trial.
Methods
We included 147 treatment‐naïve H. pylori‐positive patients 41 with CAM‐resistant infections and 106 with CAM‐susceptible infections. The CAM‐susceptible group patients were randomized to either the V‐AC group (vonoprazan 20 mg bid, amoxicillin 750 mg bid, and clarithromycin 200 or 400 mg bid) or PPI‐AC group (lansoprazole 30 mg, rabeprazole 10 mg, or esomeprazole 20 mg bid; amoxicillin 750 mg bid; and clarithromycin 200 or 400 mg bid). All CAM‐resistant H. pylori were eradicated by V‐AC, as measured by the urea breath test around 8 weeks after eradication. Safety was evaluated by patient questionnaires.
Results
The intention‐to‐treat and per‐protocol eradication rates of V‐AC in the CAM‐susceptible H. pylori‐infected patients were 87.3% (95% confidence interval 75.5%‐94.7%) and 88.9% (77.4%‐95.8%). The respective eradication rates of PPI‐AC were 76.5% (62.5%‐87.2%) and 86.7% (73.2%‐94.9%). No significant difference was observed between the V‐AC and PPI‐AC regimes in terms of the intention‐to‐treat (P = .21) or per‐protocol (P = .77) analyses. The questionnaire scores did not differ significantly between the groups. Both the intention‐to‐treat and per‐protocol eradication rates of V‐AC in the CAM‐resistant patients were 82.9% (67.9%‐92.8%).
Conclusion
The eradication rate of V‐AC treatment in the CAM‐susceptible H. pylori‐infected patients was <90%, as was that by PPI‐AC, thus V‐AC is not ideal regimen in CAM‐susceptible H. pylori. However, the 82.9% eradication rate of V‐AC in the CAM‐resistant infections may indicate the potential of V‐AC with modified dose, dosing interval, and treatment duration. (UMIN000016337).
Accurate characterization of sexual dimorphism is crucial in evolutionary biology because of its significance in understanding present and past adaptations involving reproductive and resource use ...strategies of species. However, inferring dimorphism in fossil assemblages is difficult, particularly with relatively low dimorphism. Commonly used methods of estimating dimorphism levels in fossils include the mean method, the binomial dimorphism index, and the coefficient of variation method. These methods have been reported to overestimate low levels of dimorphism, which is problematic when investigating issues such as canine size dimorphism in primates and its relation to reproductive strategies. Here, we introduce the posterior density peak (pdPeak) method that utilizes the Bayesian inference to provide posterior probability densities of dimorphism levels and within-sex variance. The highest posterior density point is termed the pdPeak. We investigated performance of the pdPeak method and made comparisons with the above-mentioned conventional methods via 1) computer-generated samples simulating a range of conditions and 2) application to canine crown-diameter datasets of extant known-sex anthropoids. Results showed that the pdPeak method is capable of unbiased estimates in a broader range of dimorphism levels than the other methods and uniquely provides reliable interval estimates. Although attention is required to its underestimation tendency when some of the distributional assumptions are violated, we demonstrate that the pdPeak method enables a more accurate dimorphism estimate at lower dimorphism levels than previously possible, which is important to illuminating human evolution.
Objectives
The bony labyrinth of the inner ear has special relevance when tracking phenotypic evolution because it is often well preserved in fossil and modern primates. Here we track the evolution ...of the bony labyrinth of anthropoid primates during the Mio−Plio−Pleistocene—the time period that gave rise to the extant great apes and humans.
Materials and Methods
We use geometric morphometrics to analyze labyrinthine morphology in a wide range of extant and fossil anthropoids, including New World and Old World monkeys, apes, and humans; fossil taxa are represented by Aegyptopithecus, Microcolobus, Epipliopithecus, Nacholapithecus, Oreopithecus, Ardipithecus, Australopithecus, and Homo.
Results
Our results show that the morphology of the anthropoid bony labyrinth conveys a statistically significant phylogenetic signal especially at the family level. The bony labyrinthine morphology of anthropoids is also in part associated with size, but does not cluster by locomotor adaptations. The Miocene apes examined here, regardless of inferred locomotor behaviors, show labyrinthine morphologies distinct from modern great apes.
Discussion
Our results suggest that labyrinthine variation contains mixed signals and alternative explanations need to be explored, such as random genetic drift and neutral phenotypic evolution, as well as developmental constraints. The observed pattern in fossil and extant hominoids also suggests that an additional factor, for example, prenatal brain development, could have potentially had a larger role in the evolutionary modification of the bony labyrinth than hitherto recognized.
Aim: This was a prospective, multicenter, single-arm intervention, against historical controls, study of the efficacy of a vonoprazan-based 7-day triple regimen with metronidazole (VPZ-AMPC-MNZ) as a ...first-line therapy for eradicating clarithromycin-resistant Helicobacter pylori (H. pylori). Methods: We enrolled 35 patients positive for clarithromycin-resistant H. pylori, as assessed by culture, without a history of eradication. These 35 patients were prospectively eradicated with VPZ-AMPC-MNZ. As historical controls, we also assessed 98 patients with clarithromycin-resistant H. pylori from our prior prospective studies, who achieved H. pylori eradication with a 7-day triple regimen including clarithromycin (VPZ-AMPC-CAM). A preplanned analysis was performed as a superiority study against the historical controls (VPZ-AMPC-MNZ compared to VPZ-AMPC-CAM). In each regimen, vonoprazan was used at 20 mg bid, amoxicillin at 750 mg bid, metronidazole at 250 mg bid, and clarithromycin at 200 mg or 400 mg bid for 7 days. We assessed the outcome of eradication therapy using a 13C-urea breath test or H. pylori stool antigen test. We evaluated safety using patient questionnaires. Results: The intention-to-treat (ITT) and per-protocol (PP) eradication rates of VPZ-AMPC-MNZ were both 100% (95% confidence interval (95% CI) 90.0–100%, n = 35). The eradication rates of VPZ-AMPC-CAM were 76.5% (95% CI 66.9–84.5%, n = 98) in the ITT analysis and 77.3% (95% CI 67.7–85.2%, n = 97) in the PP analysis. The eradication rate of VPZ-AMPC-MNZ was significantly higher than that of VPZ-AMPC-CAM in both the ITT (p = 0.00052) and PP (p = 0.00095) analyses. Conclusions: The findings suggest that 7-day VPZ-AMPC-MNZ was superior to 7-day VPZ-AMPC-CAM as a first-line regimen for eradicating clarithromycin-resistant H. pylori. We suggest VPZ-AMPC-MNZ as the standard first-line regimen for eradication of clarithromycin-resistant H. pylori in Japan.
The palaeobiological record of 12 million to 7 million years ago (Ma) is crucial to the elucidation of African ape and human origins, but few fossil assemblages of this period have been reported from ...sub-Saharan Africa. Since the 1970s, the Chorora Formation, Ethiopia, has been widely considered to contain ~10.5 million year (Myr) old mammalian fossils. More recently, Chororapithecus abyssinicus, a probable primitive member of the gorilla clade, was discovered from the formation. Here we report new field observations and geochemical, magnetostratigraphic and radioisotopic results that securely place the Chorora Formation sediments to between ~9 and ~7 Ma. The C. abyssinicus fossils are ~8.0 Myr old, forming a revised age constraint of the human-gorilla split. Other Chorora fossils range in age from ~8.5 to 7 Ma and comprise the first sub-Saharan mammalian assemblage that spans this period. These fossils suggest indigenous African evolution of multiple mammalian lineages/groups between 10 and 7 Ma, including a possible ancestral-descendent relationship between the ~9.8 Myr old Nakalipithecus nakayamai and C. abyssinicus. The new chronology and fossils suggest that faunal provinciality between eastern Africa and Eurasia had intensified by ~9 Ma, with decreased faunal interchange thereafter. The Chorora evidence supports the hypothesis of in situ African evolution of the Gorilla-Pan-human clade, and is concordant with the deeper divergence estimates of humans and great apes based on lower mutation rates of ~0.5 × 10(-9) per site per year (refs 13 - 15).
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