Neoadjuvant radiochemotherapy for locally advanced gastric cancer: a phase I-II study

Background: To study in a phase I-II trial the maximum tolerated dose, the toxicity, and the tolerance of adding radiotherapy to systemic chemotherapy administered preoperatively in patients with locoregionally advanced gastric adenocarcinoma. Patients and methods: Patients with adenocarcinoma of the stomach (T3-4Nany or TanyN+), performance status ≤1, normal hematological, hepatic and renal functions received two cycles of cisplatin 100 mg/m2 on day 1, 5-FU 800 mg/m2 on days 1 to 4 and leucovorin 60 mg b.i.d. on days 1 to 4 q3w, concomitantly with radiation therapy escalated in three dose tiers (31.2, 38.4 and 45.6 Gy). Results: Nineteen patients were accrued and 18 completed neoadjuvant therapy. Major toxicity consisted of grade 3/4 leucopenia and mucositis in 89% and 36% of the patients, respectively. Only one episode of febrile neutropenia was recorded. Dose level number 2 (38.4 Gy) with the chemotherapy given q4w is the recommended dose level. All patients were subsequently operated and no fatalities occurred. Pathological assessment showed one complete and eight partial responses. Two- and 3-year relapse-free survival rates were 57% and 50%, respectively. Only one patient relapsed locally. The peritoneum was the most frequent site of relapse. Conclusions: This neoadjuvant therapeutic program is relatively well tolerated, does not seem to increase the operative risk, and might increase the locoregional control of the disease. The frequency of peritoneal involvement in relapsing patients underscores the need for a more effective systemic treatmen

Movement of Artificial Bacterial Flagella in Heterogeneous Viscous Environments at the Microscale

Swimming microrobots have the potential to be used in medical applications such as targeted drug delivery. The challenges for navigating microrobots in the human body lie not only in the viscosity of body fluids but also in the existence of different types of fibers and cells such as blood cells or protein strands. This paper investigates artificial bacterial flagella (ABFs), which are helical microrobots actuated by an external magnetic field, in methyl cellulose solutions of different concentrations. It can be shown that the microrobots can be propelled in these gel-like heterogeneous solutions and successful swimming was demonstrated in solutions with a viscosity of more than 20 times that of water. Furthermore, results indicate that the existence of fibers can help ABFs swim more effectively, which agrees with previous experimental results reported for natural bacteria

Development and evolution of dentition pattern and tooth order in the Skates and Rays (Batoidea; Chondrichthyes)

Shark and ray (elasmobranch) dentitions are well known for their multiple generations of teeth, with isolated teeth being common in the fossil record. However, how the diverse dentitions characteristic of elasmobranchs form is still poorly understood. Data on the development and maintenance of the dental patterning in this major vertebrate group will allow comparisons to other morphologically diverse taxa, including the bony fishes, in order to identify shared pattern characters for the vertebrate dentition as a whole. Data is especially lacking from the Batoidea (skates and rays), hence our objective is to compile data on embryonic and adult batoid tooth development contributing to ordering of the dentition, from cleared and stained specimens and micro-CT scans, with 3D rendered models. We selected species (adult and embryonic) spanning phylogenetically significant batoid clades, such that our observations may raise questions about relationships within the batoids, particularly with respect to current molecular-based analyses. We include developmental data from embryos of recent model organisms Leucoraja erinacea and Raja clavata to evaluate the earliest establishment of the dentition. Characters of the batoid dentition investigated include alternate addition of teeth as offset successional tooth rows (versus single separate files), presence of a symphyseal initiator region (symphyseal tooth present, or absent, but with two parasymphyseal teeth) and a restriction to tooth addition along each jaw reducing the number of tooth families, relative to addition of successor teeth within each family. Our ultimate aim is to understand the shared characters of the batoids, and whether or not these dental characters are shared more broadly within elasmobranchs, by comparing these to dentitions in shark outgroups. These developmental morphological analyses will provide a solid basis to better understand dental evolution in these important vertebrate groups as well as the general plesiomorphic vertebrate dental condition

Unmanned aircraft systems as a new source of disturbance for wildlife: A systematic review.

The use of small Unmanned Aircraft Systems (UAS; also known as "drones") for professional and personal-leisure use is increasing enormously. UAS operate at low altitudes (<500 m) and in any terrain, thus they are susceptible to interact with local fauna, generating a new type of anthropogenic disturbance that has not been systematically evaluated. To address this gap, we performed a review of the existent literature about animals' responses to UAS flights and conducted a pooled analysis of the data to determine the probability and intensity of the disturbance, and to identify the factors influencing animals' reactions towards the small aircraft. We found that wildlife reactions depended on both the UAS attributes (flight pattern, engine type and size of aircraft) and the characteristics of animals themselves (type of animal, life-history stage and level of aggregation). Target-oriented flight patterns, larger UAS sizes, and fuel-powered (noisier) engines evoked the strongest reactions in wildlife. Animals during the non-breeding period and in large groups were more likely to show behavioral reactions to UAS, and birds are more prone to react than other taxa. We discuss the implications of these results in the context of wildlife disturbance and suggest guidelines for conservationists, users and manufacturers to minimize the impact of UAS. In addition, we propose that the legal framework needs to be adapted so that appropriate actions can be undertaken when wildlife is negatively affected by these emergent practices

Meeting Report: Aging Research and Drug Discovery

Aging is the single largest risk factor for most chronic diseases, and thus possesses large socioeconomic interest to continuously aging societies. Consequently, the field of aging research is expanding alongside a growing focus from the industry and investors in aging research. This year's 8th Annual Aging Research and Drug Discovery ARDD) meeting was organized as a hybrid meeting from August 30th to September 3rd 2021 with more than 130 attendees participating on-site at the Ceremonial Hall at University of Copenhagen, Denmark, and 1800 engaging online. The conference comprised of presentations from 75 speakers focusing on new research in topics including mechanisms of aging and how these can be modulated as well as the use of AI and new standards of practices within aging research. This year, a longevity workshop was included to build stronger connections with the clinical community

The Sail-Backed Reptile Ctenosauriscus from the Latest Early Triassic of Germany and the Timing and Biogeography of the Early Archosaur Radiation

Background Archosaurs (birds, crocodilians and their extinct relatives including dinosaurs) dominated Mesozoic continental ecosystems from the Late Triassic onwards, and still form a major component of modern ecosystems (>10,000 species). The earliest diverse archosaur faunal assemblages are known from the Middle Triassic (c. 244 Ma), implying that the archosaur radiation began in the Early Triassic (252.3–247.2 Ma). Understanding of this radiation is currently limited by the poor early fossil record of the group in terms of skeletal remains. Methodology/Principal Findings We redescribe the anatomy and stratigraphic position of the type specimen of Ctenosauriscus koeneni (Huene), a sail-backed reptile from the Early Triassic (late Olenekian) Solling Formation of northern Germany that potentially represents the oldest known archosaur. We critically discuss previous biomechanical work on the ‘sail’ of Ctenosauriscus, which is formed by a series of elongated neural spines. In addition, we describe Ctenosauriscus-like postcranial material from the earliest Middle Triassic (early Anisian) Röt Formation of Waldhaus, southwestern Germany. Finally, we review the spatial and temporal distribution of the earliest archosaur fossils and their implications for understanding the dynamics of the archosaur radiation. Conclusions/Significance Comprehensive numerical phylogenetic analyses demonstrate that both Ctenosauriscus and the Waldhaus taxon are members of a monophyletic grouping of poposauroid archosaurs, Ctenosauriscidae, characterised by greatly elongated neural spines in the posterior cervical to anterior caudal vertebrae. The earliest archosaurs, including Ctenosauriscus, appear in the body fossil record just prior to the Olenekian/Anisian boundary (c. 248 Ma), less than 5 million years after the Permian–Triassic mass extinction. These earliest archosaur assemblages are dominated by ctenosauriscids, which were broadly distributed across northern Pangea and which appear to have been the first global radiation of archosaurs

Private Enforcement, Corruption, and Antitrust Design

Recent adoption of competition laws across the globe has highlighted the importance of institutional considerations for antitrust effectiveness and the need for comparative institutional analyses of antitrust that extend beyond matters of substantive law. Contributing to the resulting nascent research agenda, we examine how the rationale for enabling versus precluding private antitrust enforcement as one salient choice in antitrust design depends on whether antitrust enforcement is corruption-free or plagued by corruption. Contingent on the nature of adjudicatory bias, bribery either discourages private antitrust lawsuits or incentivizes firms to engage in frivolous litigation. Corruption expectedly reduces the effectiveness of antitrust enforcement at deterring antitrust violations. Yet private antitrust enforcement as a complement to public enforcement can be social welfare-enhancing even in the presence of corruption. Under some circumstances, corruption actually increases the relative social desirability of private antitrust enforcement. Our analysis highlights that the appropriate design of antitrust institutions is context-specific