Biosimilars: An update on clinical trials (review of published and ongoing studies)

Biosimilars represent a new trend in the treatment of many immune-mediated inflammatory diseases. Regulatory requirements for approval of biosimilars are different from those of originators and rely mostly on the evidence generated from bioequivalence studies and in particular from RCTs. Our goal in this review was to search for relevant studies from randomized controlled trials on the biosimilars adalimumab, etanercept, infliximab and ustekinumab compared with their reference medication (publication in Medline) and ongoing studies in clinical trial registries. For infliximab biosimilars, we found data on patients with ankylosing spondylitis rheumatoid arthritis indicating no clinically relevant differences regarding efficacy and safety, as well as data on inflammatory bowel diseases and psoriasis. In addition, three registered studies of adalimumab biosimilars and just one study of an etanercept biosimilar were being carried out in patients with psoriasis. Ongoing studies on adalimumab, etanercept, and infliximab biosimilars in patients with rheumatoid arthritis were also identified. The conclusion seems to be that there are only 4 clinical trials on psoriasis (3 for the adalimumab biosimilar and 1 for etanercept biosimilar) and 1 clinical trial for Pso, CD, UC, RA, and AS (with the Infliximab biosimilar). Thus, the real and unique advantage of biosimilars is the low price derived from the special design studies despite the high technology used in fabrication process. Although not all ongoing biosimilar trials may have been registered, the present situation in terms of registered trials is quite unsatisfactory and provision of further clinical data and inclusion of patients in patient registries will be crucial.  </p

A Corporate Model of Similitude for SMEs Reunion into a Corporation, Viewed from the Angle of Physical Thought, and Its Complex Economic and Social Impact

In order to exceed the circularity of formal economic thinking, the authors of the present paper favour the models of thinking specific to physics, which are also constructed statistically and mathematically, in an attempt to find an answer to the reunion of similar small and medium enterprises (SMEs), into multinational corporations. A model based on the theory of similitude is thus made use of, born from the very essence of physics, and having an economic and social destination and a complex impact. The physical models intended for economic systems are expressed as systems of partial differential equations, and the result becomes a new vision of reality. This paper details an original model based on physical similitude for SME amalgamation under the name of multinational corporations. After an introduction to the physical theory of similitude, the first section describes the physics model because of the reunion of similar SMEs. The real birth of some corporations in Serbia forms the content of the second section; the economic and social phenomena relating to the generation of such corporations, and the corporate social responsibility are emphasized. The idea of social complexity and its impact as the fifth dimension of a modern multinational corporation conclude the paper.physical model, small and medium enterprise (SME), multinational corporation (MNE), corporate social responsibility (CSR), economic and social complexity

A Corporate Model of Similitude for SMEs Reunion into a Corporation, Viewed from the Angle of Physical Thought, and Its Complex Economic and Social Impact

In order to exceed the circularity of formal economic thinking, the authors of the present paper favour the models of thinking specific to physics, which are also constructed statistically and mathematically, in an attempt to find an answer to the reunion of similar small and medium enterprises (SMEs), into multinational corporations. A model based on the theory of similitude is thus made use of, born from the very essence of physics, and having an economic and social destination and a complex impact. The physical models intended for economic systems are expressed as systems of partial differential equations, and the result becomes a new vision of reality. This paper details an original model based on physical similitude for SME amalgamation under the name of multinational corporations. After an introduction to the physical theory of similitude, the first section describes the physics model because of the reunion of similar SMEs. The real birth of some corporations in Serbia forms the content of the second section; the economic and social phenomena relating to the generation of such corporations, and the corporate social responsibility are emphasized. The idea of social complexity and its impact as the fifth dimension of a modern multinational corporation conclude the paper

Наличие субъективных признаков усталости в группе подростков, обучающихся в Лицее информатики г. Яссы

Universitatea de Medicină şi Farmacie Iaşi, Liceul de Informatică Iaşi, Conferinţa știinţifico-practică naţională cu participare internaţională Sănătatea ocupaţională: probleme și realizări prima ediţie 5-7 iunie 2014Computer asctivity is very tiring because it intensely requires eyesight and nervous system’s focus. The study was done on a group of 48 students from the Computer Science Highschoool. We have studied the presence of subjective signs of fatigue and the number of hours spent on the computer. Most students spend 2-3 hours (45,83%) or even 4-6 hours (20,83%) on the computer. Cephalalgia is present in 43,75% of the questionned students, and optic pains are admitted by 45,83% of the questioned students, the calculated differences according to grade being statistically insignificant for a p< 0,01 (Gl – 1, χ² – 9,65), whichguides us to a worsening of the fatigues phenomenon for the XI-th grade. The diagnosed eyesight uneasiness are present in 29,16% of the questionned students. The activity on the computer is very demanding and will become more demanding when it willl be a professional activity.Работа на компьютере очень утомительна, потому что сопровождается перенапряжением зрения и процессами концентрации нервной системы. Исследование было проведено на группе из 48 учащихся лицея информатики. Были изучено наличие субъективных признаков усталости и количество часов, проведенных перед компьютером. Большинство учеников проводят перед компьютером 2-3 часа (45,83%) или даже 4-6 часов (20,83%). Головная боль была отмечена у 43,75% анкетированных учащихся, глазные боли были отмечены у 45,83% опрошенных учеников, установлены достоверные отличия в зависимости от класса, р <0,01 (GL – 1 , χ ² – 9,65 ), что свидетельствует об усилении утомления у учеников XI-го класса. Нарушения зрения были выявлены у 29,16% опрошенных. Работа на компьютере является напряженной и это напряжение будет усиливается по мере того, как она станет профессиональной деятельностью

Status Report 2006

The European Union is implementing challenging commitments to reduce greenhouse gas emissions by 8% in accord with the Kyoto protocol, and has established ambitious targets for renewable energies and energy end-use efficiency in its White Paper: Energy for the Future: Renewable Sources of Energy. In the past decade, renewable energy technologies have made significant progress in terms of performance, cost and reliability, thanks to vigorous research, development, demonstration and market introduction programmes at European, national and also regional level. Developments primarily rooted in environmental concerns are now penetrating all societal decision making and have led to a new, dynamic, and exponentially growing industry. Three major drivers are determining today’s socio-economic framework for the impressive renewables’ industrial and market developments. First, successful application of legally binding feed-in tariffs; secondly, liberalisation of the electricity market, and thus new possibilities for decentralisation of power generation. Third, and in the medium term, there is the undisputed need for massive re-powering the larger part of Europe’s generation capacity. This will incur generally higher electricity costs, which reflect somewhat better the real costs (incl. externalities) of all the different energy technologies. Thus a more favourable market situation for sustainable technology choices will evolve, e.g. for massive renewable power generation. While technology development has been a key driver in the progress of renewables, first examples of significant penetration would have been impossible without appropriate, supporting policies including instruments such as introduction targets, carbon taxes, elimination of non-technical barriers, internalisation of external costs of energy, and harmonisation of market rules. The efficient end-use of energy is a parallel area where modern technology, policies, better public conscience of the issues and market forces, like the utilities’ interest to exploit the potentials for avoidance of new transmission and generation capacity, have combined to achieve significant results. New integrated marketing concepts, like energy service companies, have been very successful lately, and organisationally break ground for the implementation of sharper physical efficiency concepts as well. This is of particular strategic importance for the New Member States of the EU, as the use of energy, including electricity, in these countries is still significantly less efficient than in the old Member States. The aim of this Status Report is to provide relevant, validated and independent information on renewable energy and the efficient end-use of electricity to decision makers and the public.JRC.H.8-Renewable energie

Part One: Extracellular Vesicles as Valuable Players in Diabetic Cardiovascular Diseases

Extracellular vesicles (EVs) are particles released in the extracellular space from all cell types in physiological and pathological conditions and emerge as a new way of cell-cell communication by transferring their biological contents into target cells. The levels and composition of circulating EVs differ from a normal condition to a pathological one, making them real circulating biomarkers. EVs have a very complex contribution in both health and disease, most likely in relationship between diabetes and cardiovascular disease. The involvement of EVs to the development of cardiovascular complications in diabetes remains an open discussion for therapists. Circulating EVs may offer a continuous access path to circulating information on the disease state and a new perspective in finding a correct diagnosis, in estimating a prognosis and also in applying an effective therapy. Besides their role as biomarkers and targets for therapy, EVs can be exploited as biological tools in influencing the different processes affected in diabetic cardiovascular diseases. This chapter will summarize the current knowledge about EVs as biological vectors modulating diabetic cardiovascular diseases, including atherosclerosis, coronary artery disease, and peripheral arterial disease. Finally, we will point out EVs’ considerable value as clinical biomarkers, therapeutic targets, and potential biomedical tools for the discovery of effective therapy in diabetic cardiovascular diseases

Part Two: Extracellular Vesicles as a Risk Factor in Neurodegenerative Diseases

Extracellular vesicles (EVs) involved in the intercellular communication hold cell-specific cargos that contain proteins, various species of RNA and lipids. EVs are emerging as powerful tools for diagnosis and therapy in most diseases but little is known about their role in central nervous system (CNS) physiology or disease. Considering the extraordinary intricated cytoarchitecture of the brain, the implication of EVs in its pathophysiology is difficult to establish. Blood circulating EVs derived from local or distant vascular cells or EVs released from brain into the cerebrospinal fluid (CSF) may influence the brain activity. EVs released in the blood stream from various tissues may influence the brain by passing through the blood-brain barrier (BBB) or through choroid plexus. Since the choroid plexus has also a clearance role, it might be possible that EVs carrying brain abnormal proteins to pass into the blood can be detected. Thus, considering that EVs are specialized cargos bearing combined signals between cells, they might be an interesting therapy target in the future for both regulating neurogenesis and abnormal protein clearance. We present here data gathered about EVs that may influence the CNS functionality and be involved in most common neurodegenerative diseases

Measurement of the top quark forward-backward production asymmetry and the anomalous chromoelectric and chromomagnetic moments in pp collisions at √s = 13 TeV

Abstract The parton-level top quark (t) forward-backward asymmetry and the anomalous chromoelectric (d̂ t) and chromomagnetic (μ̂ t) moments have been measured using LHC pp collisions at a center-of-mass energy of 13 TeV, collected in the CMS detector in a data sample corresponding to an integrated luminosity of 35.9 fb−1. The linearized variable AFB(1) is used to approximate the asymmetry. Candidate t t ¯ events decaying to a muon or electron and jets in final states with low and high Lorentz boosts are selected and reconstructed using a fit of the kinematic distributions of the decay products to those expected for t t ¯ final states. The values found for the parameters are AFB(1)=0.048−0.087+0.095(stat)−0.029+0.020(syst),μ̂t=−0.024−0.009+0.013(stat)−0.011+0.016(syst), and a limit is placed on the magnitude of | d̂ t| &lt; 0.03 at 95% confidence level. [Figure not available: see fulltext.

Search for Physics beyond the Standard Model in Events with Overlapping Photons and Jets

Results are reported from a search for new particles that decay into a photon and two gluons, in events with jets. Novel jet substructure techniques are developed that allow photons to be identified in an environment densely populated with hadrons. The analyzed proton-proton collision data were collected by the CMS experiment at the LHC, in 2016 at root s = 13 TeV, and correspond to an integrated luminosity of 35.9 fb(-1). The spectra of total transverse hadronic energy of candidate events are examined for deviations from the standard model predictions. No statistically significant excess is observed over the expected background. The first cross section limits on new physics processes resulting in such events are set. The results are interpreted as upper limits on the rate of gluino pair production, utilizing a simplified stealth supersymmetry model. The excluded gluino masses extend up to 1.7 TeV, for a neutralino mass of 200 GeV and exceed previous mass constraints set by analyses targeting events with isolated photons.Peer reviewe