Northwest African Neolithic initiated by migrants from Iberia and Levant.

In northwestern Africa, lifestyle transitioned from foraging to food production around 7,400 years ago but what sparked that change remains unclear. Archaeological data support conflicting views: (1) that migrant European Neolithic farmers brought the new way of life to North Africa1-3 or (2) that local hunter-gatherers adopted technological innovations4,5. The latter view is also supported by archaeogenetic data6. Here we fill key chronological and archaeogenetic gaps for the Maghreb, from Epipalaeolithic to Middle Neolithic, by sequencing the genomes of nine individuals (to between 45.8- and 0.2-fold genome coverage). Notably, we trace 8,000 years of population continuity and isolation from the Upper Palaeolithic, via the Epipaleolithic, to some Maghrebi Neolithic farming groups. However, remains from the earliest Neolithic contexts showed mostly European Neolithic ancestry. We suggest that farming was introduced by European migrants and was then rapidly adopted by local groups. During the Middle Neolithic a new ancestry from the Levant appears in the Maghreb, coinciding with the arrival of pastoralism in the region, and all three ancestries blend together during the Late Neolithic. Our results show ancestry shifts in the Neolithization of northwestern Africa that probably mirrored a heterogeneous economic and cultural landscape, in a more multifaceted process than observed in other regions.

Assessing Definitions and Incentives Adopted for Innovation for Pharmaceutical Products in Five High-Income Countries: A Systematic Literature Review.

BACKGROUND: The concept of health care innovation varies across organizations and countries. Harmonizing the definitions of innovation can augment the discovery of new therapies, minimize costs, and streamline drug development and approval processes. A systematic literature review (SLR) was conducted to gather insights surrounding different elements of innovation in the USA, the UK, France, Germany, and Japan. The SLR identified studies that have defined innovation and captured the types of incentives provided to promote innovation. METHODS: The MEDLINE, Embase, and EconLit databases were searched via the OVID SP platform on October 22, 2020. A secondary desk search literature review was performed to identify additional information of interest in regional languages: French, German, and Japanese. All the relevant literature in English was screened using the Linguamatics natural language processing (NLP) tool, except for articles from EconLit, which were screened manually using structured search strategies. Articles that describe a definition of innovation or refer to a definition of innovation published were included. All full-text articles were reviewed manually, and two reviewers independently screened the full texts for eligibility. RESULTS: After screening, 90 articles were considered to meet the SLR objectives. The most common dimension of innovation identified was therapeutic benefit as a measure of innovation, followed by newness and novelty aspects of innovations. Incentives around exclusivities were found to be the most prevalent in the data set, followed by rewards and premiums. Among the different therapy areas, the largest number of innovations was targeted at oncology. CONCLUSIONS: This SLR highlights the lack of a unified definition of innovation among regulatory authorities and health technology assessment bodies in five countries, and variation in the types of incentives associated with innovation. The targeted countries cover different dimensions of definition and incentives of innovation at varying levels, with a few focused on specific therapy areas. Harmonization and consensus for innovation would be needed across countries because drug development is a global undertaking. This SLR envisages a more holistic approach to evaluation, wherein the value provided to patients and health systems is accounted for. The results of this SLR will help to promote broader discussion among different stakeholders and decision makers across countries to identify gaps in policies and develop sustainable strategies to promote innovation for pharmaceutical products.

Diffusion of innovations: a guiding framework for public health.

Exploring the behavior change process has been of interest and importance to public health professionals, to translate research into practice. Diffusion of innovations (DOI) model has been extensively applied in public health to examine the process by which innovation is passively communicated to individuals and groups. It builds on a staged model of awareness, persuasion, decision, implementation, and confirmation; and categorizes communities into innovators (2.5%), early adopters (13.5%), early majority (34%), late majority (34%) and laggards (16%). It reflects on the diversity of strategies to be applied for different cadres of the society to bring about a wholistic change. Nonetheless, DOI suffers from 'pro-innovation' and 'individual blame' bias, as it fails to account for the influence of societal, cultural, and extraneous factors affecting individual behavior change. The social networks theory (SNT) in contrast, explains behavior change based on social networks and their influences. It builds on the constructs of homophily, centralization, reciprocity, transitivity, and density; and fills the void in the DOI model. We suggest public health professionals to combine the constructs of DOI and SNT in rolling out behavior change interventions, to yield a comprehensive approach.

Reenvisioning Traditional to Regenerative Therapeutic Advances in Managing Nonalcoholic Fatty Liver Disease in Diabetes Mellitus.

Reports indicate the increasing prevalence of liver disorders in diabetes mellitus (DM) patients. Clinically, it has also been revealed that the existence of nonalcoholic fatty liver disease (NAFLD) enhances the incidence of type 2 diabetes mellitus (T2DM), while T2DM exacerbates NAFLD to extremely severe forms of steatohepatitis, cirrhosis, and hepatocellular carcinoma. This implies the coexistence and bidirectional nature of NAFLD and T2DM, which function synergistically to drive adverse consequences in clinical practice. For treatment of such comorbid state, though the existing practices such as lifestyle management, traditional Chinese medicines (TCM), and pharmaceuticals have offered somewhat relief, the debate continues about the optimal therapeutic impacts. Recent developments in the field of tissue engineering have led to a renewed interest in novel biomaterial alternatives such as stem cells. This might be attributable to their differentiation potential towards hepatic and pancreatic lineage. These cellular therapies could be further complemented by platelet-derived biomaterials, TCM formulations, or any specific drug. Based on these abovementioned approaches, we aimed to comprehensively analyze various preclinical and clinical studies from traditional to regenerative therapeutic approaches in managing concomitant NAFLD and T2DM.

Surgery for Ventricular Tachycardia.

The treatment of drug-refractory chronic ventricular tachycardia (VT) has undergone a revolution over the last 50 years. We now have automatic implantable cardioverter defibrillator therapy with pace-terminating capabilities, and catheter ablation of VT has refined mapping and improved methods of lesion generation. Between 1980 and 1993, Houston Methodist Hospital became a leader in the diagnosis and surgical ablation of VT and other arrhythmias. This is a brief account of that period and some of the experiences and lessons that have led to significant advances used today.

Recent trends in natural polysaccharide based bioinks for multiscale 3D printing in tissue regeneration: A review.

Biofabrication by three-dimensional (3D) printing has been an attractive technology in harnessing the possibility to print anatomical shaped native tissues with controlled architecture and resolution. 3D printing offers the possibility to reproduce complex microarchitecture of native tissues by printing live cells in a layer by layer deposition to provide a biomimetic structural environment for tissue formation and host tissue integration. Plant based biomaterials derived from green and sustainable sources have represented to emulate native physicochemical and biological cues in order to direct specific cellular response and formation of new tissues through biomolecular recognition patterns. This comprehensive review aims to analyze and identify the most commonly used plant based bioinks for 3D printing applications. An overview on the role of different plant based biomaterial of terrestrial origin (Starch, Nanocellulose and Pectin) and marine origin (Ulvan, Alginate, Fucoidan, Agarose and Carrageenan) used for 3D printing applications are discussed elaborately. Furthermore, this review will also emphasis in the functional aspects of different 3D printers, appropriate printing material, merits and demerits of numerous plant based bioinks in developing 3D printed tissue-like constructs. Additionally, the underlying potential benefits, limitations and future perspectives of plant based bioinks for tissue engineering (TE) applications are also discussed.

Introduction to the EQIPD quality system.

While high risk of failure is an inherent part of developing innovative therapies, it can be reduced by adherence to evidence-based rigorous research practices. Supported through the European Union's Innovative Medicines Initiative, the EQIPD consortium has developed a novel preclinical research quality system that can be applied in both public and private sectors and is free for anyone to use. The EQIPD Quality System was designed to be suited to boost innovation by ensuring the generation of robust and reliable preclinical data while being lean, effective and not becoming a burden that could negatively impact the freedom to explore scientific questions. EQIPD defines research quality as the extent to which research data are fit for their intended use. Fitness, in this context, is defined by the stakeholders, who are the scientists directly involved in the research, but also their funders, sponsors, publishers, research tool manufacturers, and collaboration partners such as peers in a multi-site research project. The essence of the EQIPD Quality System is the set of 18 core requirements that can be addressed flexibly, according to user-specific needs and following a user-defined trajectory. The EQIPD Quality System proposes guidance on expectations for quality-related measures, defines criteria for adequate processes (i.e. performance standards) and provides examples of how such measures can be developed and implemented. However, it does not prescribe any pre-determined solutions. EQIPD has also developed tools (for optional use) to support users in implementing the system and assessment services for those research units that successfully implement the quality system and seek formal accreditation. Building upon the feedback from users and continuous improvement, a sustainable EQIPD Quality System will ultimately serve the entire community of scientists conducting non-regulated preclinical research, by helping them generate reliable data that are fit for their intended use.

Why is repositioning public health innovation towards a social paradigm necessary? A reflection on the field of public health through the examples of Ebola and Covid-19.

Health innovations are generally oriented on a techno-economic vision. In this perspective, technologies are seen as an end in themselves, and there is no arrangement between the technical and the social values of innovation. This vision prevails in sanitary crises, in which management is carried out based on the search for punctual, reactive, and technical solutions to remedy a specific problem without a systemic/holistic, sustainable, or proactive approach. This paper attempts to contribute to the literature on the epistemological orientation of innovations in the field of public health. Taking the Covid-19 and Ebola crises as examples, the primary objective is to show how innovation in health is oriented towards a techno-economic paradigm. Second, we propose a repositioning of public health innovation towards a social paradigm that will put more emphasis on the interaction between social and health dimensions in the perspective of social change. We will conclude by highlighting the roles that public health could play in allowing innovations to have more social value, especially during sanitary crises.

Using Technology to Promote Patient Engagement in Nutrition Care: A Feasibility Study.

Empowering patients to participate in nutrition care during hospitalisation may improve their dietary intakes and associated outcomes. This study tested the acceptability and feasibility of a technology-based intervention to engage hospital patients in nutrition care at a tertiary teaching hospital in Australia. The hospital used an electronic foodservice system (EFS), by which patients ordered meals via bedside computers. Adults at nutritional risk received the nutrition technology (NUTRI-TEC) intervention, involving nutrition assessment, education on nutrition requirements and training on using the EFS to enter food intakes and monitor nutrition goals. Acceptability was assessed using patient satisfaction and engagement surveys. Feasibility was assessed by evaluating the intervention delivery/fidelity and patient recruitment/retention. Patients' dietary intakes were observed daily to indicate the intervention's effects and assess the accuracy of the patient-recorded intakes. Descriptive and inferential statistics were used to analyse the data. Of the 71 patients recruited, 49 completed the study (55% male; median (IQR) age 71 (65-78) years; length of stay 10 (7-14) days). Patient satisfaction with NUTRI-TEC was high. Intervention delivery and fidelity targets were met but recruitment (≥50%) and retention (≥75%) targets were not; only 31% of patients agreed to participate and 69% completed the study (mostly due to unexpected/early discharge). Patient- and researcher-recorded dietary intakes correlated strongly, indicating patients can record food intakes accurately using technology. This study highlights the important role technology is likely to play in facilitating patient engagement and improving care during hospitalisation.

Most important advances in preventive cardiology during this past decade: Viewpoint from the American Society for Preventive Cardiology.

The rapidly expanding field of preventive cardiology has brought with it several major advances in the past decade. Changes in guidelines for cholesterol mangement focusing on the identification of "statin eligible groups" and removal of actual low-density lipoprotein cholesterol (LDL-C) targets, in particular, as well as lower targets for blood pressure in updated hypertension guidelines, have made a major impact on healthcare. The availability of the sodium glucose transport protein-2 (SGLT2) inhibitors and glucagon-like peptide -1 receptor antagonists (GLP1-RA) for managing diabetes have shifted our focus in diabetes care beyond glucose lowering to addressing cardiovascular risk reduction. While many prior trials of fish oil therapy have failed to show benefit, the recent Reduction of Cardiovascular Events With EPA - Intervention Trial (REDUCE-IT) testing the efficacy of icosapent ethyl has shown dramatic benefit in further addressing residual atherosclerotic cardiovascular disease (ASCVD) risk beyond statin therapy not only in those with known ASCVD, but also in diabetic patients with multiple risk factors. The past decade also ushered in confirmation of the inflammation hypothesis of atherosclerosis with the Canakinumab Anti-Inflammatory Thrombosis Outcomes Study (CANTOS) using canakinumab, despite the fact the therapy was not approved by the Food and Drug Administration (FDA) for cardiovascular risk reduction. Also, to improve our understanding of heart disease in women, the emergence of novel concepts of ischemia or myocardial infarction in those with normal or nonobstructive atherosclerotic disease has been a major advance. Moreover, the past decade brought the emergence of proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibody therapy and the cardiovascular risk reduction benefits seen in the Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk (FOURIER) and Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab (ODYSSEY OUTCOMES) trials, providing further evidence-based therapy for additional reduction of ASCVD risk beyond statin therapy. The PCSK9 monoclonal antibodies have facilitated the attainment of LDL-C levels never previously thought possible. Finally with the mRNA interference therapy inclisiran in development, we may soon have a "vaccine-like" approach for addressing dyslipidemia and atherosclerosis.

The German health care Innovation Fund - An incentive for innovations to promote the integration of health care.

PURPOSE: Many health systems face challenges such as rising costs and lacking quality, both of which can be addressed by improving the integration of different health care sectors and professions. The purpose of this viewpoint is to present the German health care Innovation Fund (IF) initiated by the Federal Government to support the development and diffusion of integrated health care. DESIGN/METHODOLOGY/APPROACH: This article describes the design and rationale of the IF in detail and provides first insights into its limitations, acceptance and implementation by relevant stakeholders. FINDINGS: In its first period, the IF offered € 1.2 billion as start-up funding for model implementation and evaluation over a period of four years (2016-2019). This period was recently extended to a second round until 2024, offering € 200 million a year as from 2020. The IF is triggering the support of relevant insurers for the development of new integrated care models. In addition, strict evaluation requirements have led to a large number of health service research projects which assess structural and process improvements and thus enable evidence-based policy decisions. ORIGINALITY/VALUE: This article is the first of its kind to present the German IF to the international readership. The IF is a political initiative through which to foster innovations and promote integrated health care.

Digital Health and the Care of the Patient With Arrhythmia: What Every Electrophysiologist Needs to Know.

The field of cardiac electrophysiology has been on the cutting edge of advanced digital technologies for many years. More recently, medical device development through traditional clinical trials has been supplemented by direct to consumer products with advancement of wearables and health care apps. The rapid growth of innovation along with the mega-data generated has created challenges and opportunities. This review summarizes the regulatory landscape, applications to clinical practice, opportunities for virtual clinical trials, the use of artificial intelligence to streamline and interpret data, and integration into the electronic medical records and medical practice. Preparation of the new generation of physicians, guidance and promotion by professional societies, and advancement of research in the interpretation and application of big data and the impact of digital technologies on health outcomes will help to advance the adoption and the future of digital health care.

Artificial intelligence: a disruptive tool for a smarter medicine.

OBJECTIVE: Although highly successful, the medical R&D model is failing at improving people's health due to a series of flaws and defects inherent to the model itself. A new collective intelligence, incorporating human and artificial intelligence (AI) could overcome these obstacles. Because AI will play a key role in this new collective intelligence, it is necessary that those involved in healthcare have a general knowledge of how these technologies work. With this comprehensive review, we intend to provide it. MATERIALS AND METHODS: A broad-ranging search has been undertaken on institutional and non-institutional websites in order to identify relevant papers, comments and reports. RESULTS: We firstly describe the flaws and defects of the current R&D biomedical model and how the generation of a new collective intelligence will result in a better and wiser medicine through a truly personalized and holistic approach. We, then, discuss the new forms of data collection and data processing and the different types of artificial learning and their specific algorithms. Finally, we review the current uses and applications of AI in the biomedical field and how these can be expanded, as well as the limitations and challenges of applying these new technologies in the medical field. CONCLUSIONS: This colossal common effort based on a new collective intelligence will exponentially improve the quality of medical research, resulting in a radical change for the better in the healthcare model. AI, without replacing us, is here to help us achieve the ambitious goal set by the WHO in the Alma Ata declaration of 1978: "Health for All".

[Melting-Pain Therapy for difficult mental health patients]. / L'activité Melting-pain therapy pour les malades mentaux difficiles.

The nurses in the unit for difficult patients at Cadillac hospital have developed an innovative art therapy concept: Melting-Pain Therapy. In this workshop patients produce a collective piece of art created through participants' individual sessions with a nurse. These patients are exclusively men, suffering mainly from schizophrenia, who have been or who are potentially dangerous. The photographs accompanying this article show some examples of these art brut creations.