Human occupation of northern Europe in MIS 13: Happisburgh Site 1 (Norfolk, UK) and its European context

The timing, environmental setting and archaeological signatures of an early human presence in northernEurope have been longstanding themes of Palaeolithic research. In the space of 20 years, the earliestrecord of human occupation in Britain has been pushed back from 500 ka (Boxgrove) to 700 ka (Pakefield)and then to >800 ka (Happisburgh Site 3). Other sites also contribute to this record of humanoccupation; a second locality at Happisburgh, referred to as Site 1, attests to human presence at around500 ka (MIS 13). This paper provides the first comprehensive account of research undertaken at HappisburghSite 1 since 2000. The early human landscape and depositional environment was that of a riverfloodplain, where an active river channel, in which a grey sand was deposited, was abandoned, forming afloodplain lake, with marginal marsh/swamp environments, which was infilled with organic mud. Thissuccession is sealed by Middle Pleistocene glacial deposits. An assemblage of 199 flint flakes, flake toolsand cores was recovered from the grey sand and organic mud. The evidence from Happisburgh Site 1 isplaced in the context of the wider British and European MIS 13 record. The growing evidence for asignificant dispersal of humans into northern Europe around 500 ka raises critical questions concerningthe environmental conditions under which this took place. We also consider the evolutionary andbehavioural changes in human populations that might have enabled the more widespread and persistentperiod of human presence in northern Europe at this time.</p

A multimodal molecular imaging approach targeting urokinase plasminogen activator receptor for the diagnosis, resection and surveillance of urothelial cell carcinoma

With a 5-year recurrence rate of 30-78%, urothelial cell carcinoma (UCC) rates amongst the highest of all solid malignancies. Consequently, after transurethral resection, patients are subjugated to life-long endoscopic surveillance. A multimodal near-infrared (NIR) fluorescence-based imaging strategy can improve diagnosis, resection and surveillance, hence increasing quality of life.Methods: Expression of urokinase plasminogen activator receptor (uPAR) and epithelial cell adhesion molecule (EpCAM) are determined on paraffin-embedded human UCC using immunohistochemistry and on UCC cell lines by flow cytometry. MNPR-101, a humanised monoclonal antibody targeting uPAR is conjugated to IRDye800CW and binding is validated in vitro using surface plasmon resonance and cell-based binding assays. In vivo NIR fluorescence and photoacoustic three-dimensional (3D) imaging are performed with subcutaneously growing human UM-UC-31uc2 cells in BALB/c-nude mice. The translational potential is confirmed in a metastasising UM-UC-31uc2 orthotopic mouse model. InfliximabIRDye800CW and rituximab-IRDye800CW are used as controls.Results: UCCs show prominent uPAR expression at the tumour-stroma interface and EpCAM on epithelial cells. uPAR and EpCAM are expressed by 6/7 and 4/7 UCC cell lines, respectively. In vitro, MNPR-101-IRDye800CW has a picomolar affinity for domain 2-3 of uPAR. In vivo fluorescence imaging with MNPR-101-IRDye800CW, specifically delineates both subcutaneous and orthotopic tumours with tumour-to-background ratios reaching as high as 6.8, differing significantly from controls (p < 0.0001). Photoacoustic 3D in depth imaging confirms the homogenous distribution of MNPR-101-IRDye800CW through the tumour.Conclusions: MNPR-101-IRDye800CW is suitable for multimodal imaging of UCC, awaiting clinical translation. (C) 2021 The Author(s). Published by Elsevier Ltd.Surgical oncolog

Displaced midshaft fractures of the clavicle: non-operative treatment versus plate fixation (Sleutel-TRIAL). A multicentre randomised controlled trial

Contains fulltext : 96826.pdf (publisher's version ) (Open Access)BACKGROUND: The traditional view that the vast majority of midshaft clavicular fractures heal with good functional outcomes following non-operative treatment may be no longer valid for all midshaft clavicular fractures. Recent studies have presented a relatively high incidence of non-union and identified speciic limitations of the shoulder function in subgroups of patients with these injuries. AIM: A prospective, multicentre randomised controlled trial (RCT) will be conducted in 21 hospitals in the Netherlands, comparing fracture consolidation and shoulder function after either non-operative treatment with a sling or a plate fixation. METHODS/DESIGN: A total of 350 patients will be included, between 18 and 60 years of age, with a dislocated midshaft clavicular fracture. The primary outcome is the incidence of non-union, which will be determined with standardised X-rays (Antero-Posterior and 30 degrees caudocephalad view). Secondary outcome will be the functional outcome, measured using the Constant Score. Strength of the shoulder muscles will be measured with a handheld dynamometer (MicroFET2). Furthermore, the health-related Quality of Life score (ShortForm-36) and the Disabilities of Arm, Shoulder and Hand (DASH) Outcome Measure will be monitored as subjective parameters. Data on complications, bone union, cosmetic aspects and use of painkillers will be collected with follow-up questionnaires. The follow-up time will be two years. All patients will be monitored at regular intervals over the subsequent twelve months (two and six weeks, three months and one year). After two years an interview by telephone and a written survey will be performed to evaluate the two-year functional and mechanical outcomes. All data will be analysed on an intention-to-treat basis, using univariate and multivariate analyses. DISCUSSION: This trial will provide level-1 evidence for the comparison of consolidation and functional outcome between two standardised treatment options for dislocated midshaft clavicular fractures. The gathered data may support the development of a clinical guideline for treatment of clavicular fractures. TRIAL REGISTRATION: Netherlands National Trial Register NTR2399

ICDP workshop on the Lake Tanganyika Scientific Drilling Project: a late Miocene–present record of climate, rifting, and ecosystem evolution from the world's oldest tropical lake

The Neogene and Quaternary are characterized by enormous changes in global climate and environments, including global cooling and the establishment of northern high-latitude glaciers. These changes reshaped global ecosystems, including the emergence of tropical dry forests and savannahs that are found in Africa today, which in turn may have influenced the evolution of humans and their ancestors. However, despite decades of research we lack long, continuous, well-resolved records of tropical climate, ecosystem changes, and surface processes necessary to understand their interactions and influences on evolutionary processes. Lake Tanganyika, Africa, contains the most continuous, long continental climate record from the mid-Miocene (∼10 Ma) to the present anywhere in the tropics and has long been recognized as a top-priority site for scientific drilling. The lake is surrounded by the Miombo woodlands, part of the largest dry tropical biome on Earth. Lake Tanganyika also harbors incredibly diverse endemic biota and an entirely unexplored deep microbial biosphere, and it provides textbook examples of rift segmentation, fault behavior, and associated surface processes. To evaluate the interdisciplinary scientific opportunities that an ICDP drilling program at Lake Tanganyika could offer, more than 70 scientists representing 12 countries and a variety of scientific disciplines met in Dar es Salaam, Tanzania, in June 2019. The team developed key research objectives in basin evolution, source-to-sink sedimentology, organismal evolution, geomicrobiology, paleoclimatology, paleolimnology, terrestrial paleoecology, paleoanthropology, and geochronology to be addressed through scientific drilling on Lake Tanganyika. They also identified drilling targets and strategies, logistical challenges, and education and capacity building programs to be carried out through the project. Participants concluded that a drilling program at Lake Tanganyika would produce the first continuous Miocene–present record from the tropics, transforming our understanding of global environmental change, the environmental context of human origins in Africa, and providing a detailed window into the dynamics, tempo and mode of biological diversification and adaptive radiations.© Author(s) 2020. This open access article is distributed under the Creative Commons Attribution 4.0 License

The first Miocene fossils from coastal woodlands in the southern East African Rift

The Miocene was a key time in the evolution of African ecosystems witnessing the origin of the African apes and the isolation of eastern coastal forests through an expanding arid corridor. Until recently, however, Miocene sites from the southeastern regions of the continent were unknown. Here, we report the first Miocene fossil teeth from the shoulders of the Urema Rift in Gorongosa National Park, Mozambique. We provide the first 1) radiometric ages of the Mazamba Formation, 2) reconstructions of paleovegetation in the region based on pedogenic carbonates and fossil wood, and 3) descriptions of fossil teeth. Gorongosa is unique in the East African Rift in combining marine invertebrates, marine vertebrates, reptiles, terrestrial mammals, and fossil woods in coastal paleoenvironments. The Gorongosa fossil sites offer the first evidence of woodlands and forests on the coastal margins of southeastern Africa during the Miocene, and an exceptional assemblage of fossils including new species

On the variability of the Dmanisi mandibles.

The description of a new skull (D4500) from the Dmanisi site (Republic of Georgia) has reopened the debate about the morphological variability within the genus Homo. The new skull fits with a mandible (D2600) often referred as 'big' or 'enigmatic' because of its differences with the other Dmanisi mandibles (D211 and D2735). In this report we present a comparative study of the variability of the Dmanisi mandibles under a different perspective, as we focus in morphological aspects related to growth and development. We have followed the notion of modularity and phenotypic integration in order to understand the architectural differences observed within the sample. Our study reveals remarkable shape differences between D2600 and the other two mandibles, that are established early in the ontogeny (during childhood or even before) and that do not depend on size or sexual dimorphism. In addition, D2600 exhibits a mosaic of primitive and derived features regarding the Homo clade, which is absent in D211 and D2735. This mosaic expression is related to the location of the features and can be explained under the concept of modularity. Our study would support the possibility of two different paleodemes represented at the Dmanisi site. This hypothesis has been previously rejected on the basis that all the individuals were constrained in the same stratigraphic and taphonomic settings. However, our revision of the complex Dmanisi stratigraphy suggests that the accumulation could cover an undetermined period of time. Even if "short" in geological terms, the hominin accumulation was not necessarily synchronic. In the same line we discard that the differences between D2600 and the small mandibles are consequence of wear-related dentoalveolar remodeling. In addition, dental wear pattern of D2600 could suggest an adaptation to a different ecological niche than the other Dmanisi individuals

Climate-driven lacustrine dynamics from the Early Pleistocene Lorenyang Lake, Turkana Basin, Kenya

International audienceTwo stratigraphic records from Kaitio in West Turkana, Kenya, span 1.87 - 1.34 Ma, and document environmentalcharacter and variability through a critical interval for human evolution and cultural development. The WTK13core collected by the Hominin Sites and Paleolakes Drilling Project (HSPDP) recovered 216 m of sediment at95% recovery. A parallel outcrop record of 180 m was investigated in exposures along the Kaitio laga close to thedrill site. Six tephrostratigraphic markers, the Chari, Lokapetamoi, 22Q-3, Etirr, Ebei and KBS Tuffs are presentin the outcrop and/or core. These were characterized by single-shard geochemical analysis, and provide links tothe well-established tephrochronology of the Turkana Basin. Magnetic polarity stratigraphy of the two recordsdocuments the top of the Olduvai Subchron (C2N) at 1.78 Ma.The lithostratigraphic record, bolstered by magnetic susceptibility and sedimentary facies characterization, demonstratesa first-order transition from a deeper lacustrine system to a dynamic lake margin setting, followed by deltaprogradation. Facies analysis reveals repeated fluctuations of lake level at Milankovitch and sub-Milankovitchscales. Core-outcrop correlation allows detailed comparisons between diagenetically-prone outcrop samples andmore pristine samples from the deep core. The excellent preservation of the core sediments makes it possible toobtain critical climate records of organic biomarkers, pollen, phytoliths and other proxies.This detailed archive of environmental variability is closely linked to the rich paleontological and archaeologicaldiscoveries from nearby sites and around the Turkana Basi