A 39,600-year-old leather punch board from Canyars, Gavà, Spain

Puncture alignments are found on Palaeolithic carvings, pendants, and other fully shaped These marks were interpreted as abstract decorations, system of notations, and features and animal depictions. Here, we create an experimental framework for the analysis and human-made punctures and apply it to a highly intriguing, punctured bone fragment found at Early Upper Palaeolithic coastal site from Catalonia, Spain. Changes of tool and variation in the and orientation of punctures are consistent with the interpretation of this object as the earliest- work punch board recording six episodes of hide pricking, one of which was to produce a linear results indicate that Aurignacian hunters-gatherers used this technology to produce leather tailored clothes well before the introduction of bone eyed needles in Europe 15,000 years later

Atrophic non-union with severe osteolysis of the radius in a healthy child: successful rescue surgery. Management with fibular allograft and autograft growth factors in a paediatric patient

Background. Forearm fractures are the most frequent fractures in children and adolescents and they are more common in males than in females. In the last 20 years the increase of surgical indications have resulted in more complications, among them the non-unions, considered extremely rare and severe in children, have increased in incidence. We report a successful treatment of misdiagnosed forearm atrophic non-union with severe osteolysis using fibula allograft and autograft growth factors in a previously healthy 4-year-old child. Clinical case. A 4 year-old boy presented to our hospital with massive bone loss and a negative bone biopsy for Gorham-Stout Syndrome, he also showed reactive bone tissue with abnormal vascularity, necrotic osteocartilaginous fragments and giant mononucleated cells. Other lab tests did not show any modifications, so all the causes of paediatric osteolysis were ruled out. He had already undergone a few surgeries on that fracture and we performed others before achieving a good result, obtained with an autologous fibula graft with medullary growth factors stabilized with Kirschner wire. At the follow up 28 months later, the patient showed total consolidation of the initial area of non- union, no neurovascular deficit and no joint deficiency. Discussion. Non-union in paediatric patients is rare and therefore difficult to treat and diagnose. Since all of our tests ruled out the main causes of paediatric non-union, we managed the case with strategies usually applied to adult patients, carefully respecting the growth plates. Conclusion. Although this is a single-case report, it underlines the importance of early diagnosis, the difficulty to rule out some pediatric causes of bone loss and the complicances of a wrong diagnosis/treatment. It also shows that the use of allograft bone and autograft growth factors in a pediatric patient, who has undergone multiple surgeries, can lead to excellent result

An audiovisual corpus of guided tours in cultural sites : data collection protocols in the CHROME project

Creating interfaces for cultural heritage access is considered a fundamental research field because of the many beneficial effects it has on society. In this era of significant advances towards natural interaction with machines and deeper understanding of social communication nuances, it is important to investigate the communicative strategies human experts adopt when delivering contents to the visitors of cultural sites, as this allows the creation of a strong theoretical background for the development of efficient conversational agents. In this work, we present the data collection and annotation protocols adopted for the ongoing creation of the reference material to be used in the Cultural Heritage Resources Orienting Multimodal Experiences (CHROME) project to accomplish that goa

Status of faecal pollution in ports: A basin-wide investigation in the Adriatic Sea

Ports are subject to a variety of anthropogenic impacts, and there is mounting evidence of faecal contamination through several routes. Yet, little is known about pollution in ports by faecal indicator bacteria (FIB). FIB spatio-temporal dynamics were assessed in 12 ports of the Adriatic Sea, a semi-enclosed basin under strong anthropogenic pressure, and their relationships with environmental variables were explored to gain insight into pollution sources. FIB were abundant in ports, often more so than in adjacent areas ; their abundance patterns were related to salinity, oxygen, and nutrient levels. In addition, a molecular method, quantitative (q)PCR, was used to quantify FIB. qPCR enabled faster FIB determination and water quality monitoring that culture-based methods. These data provide robust baseline evidence of faecal contamination in ports and can be used to improve the management of routine port activities (dredging and ballast water exchange), having potential to spread pathogens in the sea

Optimized EGFR blockade strategies in <i>EGFR</i> addicted gastroesophageal adenocarcinomas

Purpose: Gastric and gastroesophageal adenocarcinomas represent the third leading cause of cancer mortality worldwide. Despite significant therapeutic improvement, the outcome of patients with advanced gastroesophageal adenocarcinoma is poor. Randomized clinical trials failed to show a significant survival benefit in molecularly unselected patients with advanced gastroesophageal adenocarcinoma treated with anti-EGFR agents.Experimental Design: We performed analyses on four cohorts: IRCC (570 patients), Foundation Medicine, Inc. (9,397 patients), COG (214 patients), and the Fondazione IRCCS Istituto Nazionale dei Tumori (206 patients). Preclinical trials were conducted in patient-derived xenografts (PDX).Results: The analysis of different gastroesophageal adenocarcinoma patient cohorts suggests that EGFR amplification drives aggressive behavior and poor prognosis. We also observed that EGFR inhibitors are active in patients with EGFR copy-number gain and that coamplification of other receptor tyrosine kinases or KRAS is associated with worse response. Preclinical trials performed on EGFR-amplified gastroesophageal adenocarcinoma PDX models revealed that the combination of an EGFR mAb and an EGFR tyrosine kinase inhibitor (TKI) was more effective than each monotherapy and resulted in a deeper and durable response. In a highly EGFR-amplified nonresponding PDX, where resistance to EGFR drugs was due to inactivation of the TSC2 tumor suppressor, cotreatment with the mTOR inhibitor everolimus restored sensitivity to EGFR inhibition.Conclusions: This study underscores EGFR as a potential therapeutic target in gastric cancer and identifies the combination of an EGFR TKI and a mAb as an effective therapeutic approach. Finally, it recognizes mTOR pathway activation as a novel mechanism of primary resistance that can be overcome by the combination of EGFR and mTOR inhibitors

Towards a European Health Research and Innovation Cloud (HRIC)

The European Union (EU) initiative on the Digital Transformation of Health and Care (Digicare) aims to provide the conditions necessary for building a secure, flexible, and decentralized digital health infrastructure. Creating a European Health Research and Innovation Cloud (HRIC) within this environment should enable data sharing and analysis for health research across the EU, in compliance with data protection legislation while preserving the full trust of the participants. Such a HRIC should learn from and build on existing data infrastructures, integrate best practices, and focus on the concrete needs of the community in terms of technologies, governance, management, regulation, and ethics requirements. Here, we describe the vision and expected benefits of digital data sharing in health research activities and present a roadmap that fosters the opportunities while answering the challenges of implementing a HRIC. For this, we put forward five specific recommendations and action points to ensure that a European HRIC: i) is built on established standards and guidelines, providing cloud technologies through an open and decentralized infrastructure; ii) is developed and certified to the highest standards of interoperability and data security that can be trusted by all stakeholders; iii) is supported by a robust ethical and legal framework that is compliant with the EU General Data Protection Regulation (GDPR); iv) establishes a proper environment for the training of new generations of data and medical scientists; and v) stimulates research and innovation in transnational collaborations through public and private initiatives and partnerships funded by the EU through Horizon 2020 and Horizon Europe

Withdrawal of mechanical ventilation in amyotrophic lateral sclerosis patients: a multicenter Italian survey

Background: Law 219/2017 was approved in Italy in December 2017, after a years-long debate on the autonomy of healthcare choices. This Law, for the first time in Italian legislation, guarantees the patient's right to request for withdrawal of life-sustaining treatments, including mechanical ventilation (MV). Objective: To investigate the current status of MV withdrawal in amyotrophic lateral sclerosis (ALS) patients in Italy and to assess the impact of Law 219/2017 on this practice. Methods: We conducted a Web-based survey, addressed to Italian neurologists with expertise in ALS care, and members of the Motor Neuron Disease Study Group of the Italian Society of Neurology. Results: Out of 40 ALS Italian centers, 34 (85.0%) responded to the survey. Law 219/2017 was followed by an increasing trend in MV withdrawals, and a significant increase of neurologists involved in this procedure (p 0.004). However, variations across Italian ALS centers were observed, regarding the inconsistent involvement of community health services and palliative care (PC) services, and the intervention and composition of the multidisciplinary team. Conclusions: Law 219/2017 has had a positive impact on the practice of MV withdrawal in ALS patients in Italy. The recent growing public attention on end-of-life care choices, along with the cultural and social changes in Italy, requires further regulatory frameworks that strengthen tools for self-determination, increased investment of resources in community and PC health services, and practical recommendations and guidelines for health workers involved

Contrasting styles of (U)HP rock exhumation along the Cenozoic Adria-Europe plate boundary (Western Alps, Calabria, Corsica)

Since the first discovery of ultrahigh pressure (UHP) rocks 30 years ago in the Western Alps, the mechanisms for exhumation of (U)HP terranes worldwide are still debated. In the western Mediterranean, the presently accepted model of synconvergent exhumation (e.g., the channel-flow model) is in conflict with parts of the geologic record. We synthesize regional geologic data and present alternative exhumation mechanisms that consider the role of divergence within subduction zones. These mechanisms, i.e., (i) the motion of the upper plate away from the trench and (ii) the rollback of the lower plate, are discussed in detail with particular reference to the Cenozoic Adria-Europe plate boundary, and along three different transects (Western Alps, Calabria-Sardinia, and Corsica-Northern Apennines). In the Western Alps, (U)HP rocks were exhumed from the greatest depth at the rear of the accretionary wedge during motion of the upper plate away from the trench. Exhumation was extremely fast, and associated with very low geothermal gradients. In Calabria, HP rocks were exhumed from shallower depths and at lower rates during rollback of the Adriatic plate, with repeated exhumation pulses progressively younging toward the foreland. Both mechanisms were active to create boundary divergence along the Corsica-Northern Apennines transect, where European southeastward subduction was progressively replaced along strike by Adriatic northwestward subduction. The tectonic scenario depicted for the Western Alps trench during Eocene exhumation of (U)HP rocks correlates well with present-day eastern Papua New Guinea, which is presented as a modern analog of the Paleogene Adria-Europe plate boundary

Agreement and its Multimodal Communication in Debates: A Qualitative Analysis

The paper defines the notion of agreement from a cognitive point of view and analyses types of agreement signals in TV debates. Agreement is defined as a relation of identity, similarity or congruence between the opinions of two or more persons, by contrasting it with confirmation and admission, and the connected notions of proposal, assessment and opinion are overviewed. Research is then presented on the multimodal signals of agreement in debates from the Canal 9 and the AMI corpora; different ways to express agreement are singled out in extensive discourse, single words and body signals, and analysed through an annotation scheme of multimodal data. Different types of agreement are illustrated, including true, indirect and apparent agreement.