44 research outputs found
Characterization and comparability of biosimilars: A filgrastim case of study and regulatory perspectives for Latin America
Background: Developing countries have an estimate of ten times more
approved biosimilars than developed countries. This disparity demands
the need of an objective regulation that incorporates health policies
according to the technological and economical capabilities of each
country. One of the challenges lies on the establishment of
comparability principles based on a physicochemical and biological
characterization that should determine the extent of additional
non-clinical and clinical studies. This is particularly relevant for
licensed biosimilars in developing countries, which have an extensive
clinical experience since their approval as generics, in some cases
more than a decade. To exemplify the current status of biosimilars in
Mexico, a characterization exercise was conducted on licensed
filgrastim biosimilars using pharmacopeial and extended
characterization methodologies. Results: Most of the evaluated products
complied with the pharmacopeial criteria and showed comparability in
their Critical Quality Attributes (CQAs) towards the reference product.
These results were expected in accordance with their equivalent
performance during their licensing as generics. Accordingly, a rational
approval and registration renewal scheme for biosimilars is proposed,
that considers the proper identification of CQAs and its thoroughly
evaluation using selected techniques. Conclusions: This approach
provides support to diminish uncertainty of exhibiting different
pharmacological profiles and narrows or even avoids the necessity of
comparative clinical studies. Ultimately, this proposal is intended to
improve the accessibility to high quality biosimilars in Latin America
and other developing countries
Two-pion Bose-Einstein correlations in central Pb-Pb collisions at = 2.76 TeV
The first measurement of two-pion Bose-Einstein correlations in central Pb-Pb
collisions at TeV at the Large Hadron Collider is
presented. We observe a growing trend with energy now not only for the
longitudinal and the outward but also for the sideward pion source radius. The
pion homogeneity volume and the decoupling time are significantly larger than
those measured at RHIC.Comment: 17 pages, 5 captioned figures, 1 table, authors from page 12,
published version, figures at
http://aliceinfo.cern.ch/ArtSubmission/node/388
Suppression of charged particle production at large transverse momentum in central Pb-Pb collisions at TeV
Inclusive transverse momentum spectra of primary charged particles in Pb-Pb
collisions at = 2.76 TeV have been measured by the ALICE
Collaboration at the LHC. The data are presented for central and peripheral
collisions, corresponding to 0-5% and 70-80% of the hadronic Pb-Pb cross
section. The measured charged particle spectra in and GeV/ are compared to the expectation in pp collisions at the same
, scaled by the number of underlying nucleon-nucleon
collisions. The comparison is expressed in terms of the nuclear modification
factor . The result indicates only weak medium effects ( 0.7) in peripheral collisions. In central collisions,
reaches a minimum of about 0.14 at -7GeV/ and increases
significantly at larger . The measured suppression of high- particles is stronger than that observed at lower collision energies,
indicating that a very dense medium is formed in central Pb-Pb collisions at
the LHC.Comment: 15 pages, 5 captioned figures, 3 tables, authors from page 10,
published version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/98
Palaeoecological data indicates land-use changes across Europe linked to spatial heterogeneity in mortality during the Black Death pandemic
The Black Death (1347–1352 CE) is the most renowned pandemic in human history, believed by many to have killed half of Europe’s population. However, despite advances in ancient DNA research that conclusively identified the pandemic’s causative agent (bacterium Yersinia pestis), our knowledge of the Black Death remains limited, based primarily on qualitative remarks in medieval written sources available for some areas of Western Europe. Here, we remedy this situation by applying a pioneering new approach, ‘big data palaeoecology’, which, starting from palynological data, evaluates the scale of the Black Death’s mortality on a regional scale across Europe. We collected pollen data on landscape change from 261 radiocarbon-dated coring sites (lakes and wetlands) located across 19 modern-day European countries. We used two independent methods of analysis to evaluate whether the changes we see in the landscape at the time of the Black Death agree with the hypothesis that a large portion of the population, upwards of half, died within a few years in the 21 historical regions we studied. While we can confirm that the Black Death had a devastating impact in some regions, we found that it had negligible or no impact in others. These inter-regional differences in the Black Death’s mortality across Europe demonstrate the significance of cultural, ecological, economic, societal and climatic factors that mediated the dissemination and impact of the disease. The complex interplay of these factors, along with the historical ecology of plague, should be a focus of future research on historical pandemics
Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study
Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research
PSEUDALBIORIX, A NEW GENUS OF IDEORONCIDAE (PSEUDOSCORPIONES, NEOBISIOIDEA) FROM CENTRAL AMERICA
Volume: 34Start Page: 610End Page: 62
Whole organ, venation and epidermal cell morphological variations are correlated in the leaves of **Arabidopsis** mutants
Technological developments for pumped-hydro energy storage
Today, everything seems to indicate that pumped hydro energy storage (PHES) is experiencing a second, or even third, youth (Fayolle and Lafon, 2008). Main drivers of such reemergence are mostly related with concerns on climate change and depletion of fossil fuels, which have been transposed into international agreements, regional directives, and national and local regulations (UN, 1998; EC, 2009). As a consequence of these concerns and associated regulations, there has been a strong deployment of renewable energy (REN) technologies, which is still ongoing. Amongst all REN sources, wind seems to be at present the one with the largest economically feasible potential (Lu et al., 2009), but also with the highest variability (Wan, 2005; Taulan et al., 2009; Paradinas et al., 2012), and the most difficult to predict (Greaves et al., 2009; Hodge et al., 2012). In this context, PHES \u201creemerges\u201d as an excellent means to integrate wind power into the electric power system, not only because of its maturity and technically proven flexibility, but also because of its significant remaining potential (EURELECTRIC, 2011; IEA, Technology Roadmap, 2012; Lacal Ar\ue1ntegui et al., 2012). Within this new role, special attention is given to variable speed PHES (Schwery and Kunz, 2009; EPRI, 2013; HEA, 2013) and hydraulic short-circuit operation (Taulan et al., 2009; Lippold et al. 2012). The objective of this report is to describe some current trends and future challenges on PHES in relation with its role in REN integration, with special emphasis on mechanical aspects of hydraulic machinery, power electronics devices used for variable speed operation, and utilities\u2019 operation strategies both in liberalized and centralized markets contexts. The remainder of this document is organized as follows. In Chapter 1, after a brief introduction and historical background, the new generation of PHES is presented with particular focus on those equipped with variable-speed technology. Typical configurations of pumped-storage hydropower plants (PSHPs) are also briefly described, discussing their capability for providing grid support services, such as load-frequency regulation, inertia and short-circuit power. Chapter 2 focuses on reversible pumpturbines, discussing their operating limits and presenting the state-of art of the research on their unstable behavior. In chapter 3, the operating principle and some basic aspects of the electrical machines most widely used in PSPHs are described. In chapter 4, power electronics devices typically used in PSHPs for both start-up in pumping mode and variable speed operation are described in detail, along with some recent developments on variable speed drives. In chapter 5, utilities\u2019 operation strategies are reviewed in detail, and some future challenges to make the best possible use of PHES assets according to their new role are identified