790 research outputs found
Preoperative systemic inflammation predicts postoperative infectious complications in patients undergoing curative resection for colorectal cancer
The presence of systemic inflammation before surgery, as evidenced by the glasgow prognostic score (mGPS), predicts poor long-term survival in colorectal cancer. The aim was to examine the relationship between the preoperative mGPS and the development of postoperative complications in patients undergoing potentially curative resection for colorectal cancer. Patients (n=455) who underwent potentially curative resections between 2003 and 2007 were assessed consecutively, and details were recorded in a database. The majority of patients presented for elective surgery (85%) were over the age of 65 years (70%), were male (58%), were deprived (53%), and had TNM stage I/II disease (61%), had preoperative haemoglobin (56%), white cell count (87%) and mGPS 0 (58%) in the normal range. After surgery, 86 (19%) patients developed a postoperative complication; 70 (81%) of which were infectious complications. On multivariate analysis, peritoneal soiling (P<0.01), elevated preoperative white cell count (P<0.05) and mGPS (P<0.01) were independently associated with increased risk of developing a postoperative infection. In elective patients, only the mGPS (OR=1.75, 95% CI=1.17-2.63, P=0.007) was significantly associated with increased risk of developing a postoperative infection. Preoperative elevated mGPS predicts increased postoperative infectious complications in patients undergoing potentially curative resection for colorectal cancer
Why Some Interfaces Cannot be Sharp
A central goal of modern materials physics and nanoscience is control of
materials and their interfaces to atomic dimensions. For interfaces between
polar and non-polar layers, this goal is thwarted by a polar catastrophe that
forces an interfacial reconstruction. In traditional semiconductors this
reconstruction is achieved by an atomic disordering and stoichiometry change at
the interface, but in multivalent oxides a new option is available: if the
electrons can move, the atoms don`t have to. Using atomic-scale electron energy
loss spectroscopy we find that there is a fundamental asymmetry between
ionically and electronically compensated interfaces, both in interfacial
sharpness and carrier density. This suggests a general strategy to design sharp
interfaces, remove interfacial screening charges, control the band offset, and
hence dramatically improving the performance of oxide devices.Comment: 12 pages of text, 6 figure
Lessons learned and lessons missed: impact of the coronavirus disease 2019 (COVID-19) pandemic on all-cause mortality in 40 industrialised countries and US states prior to mass vaccination [version 2; peer review: 2 approved]
Background: Industrialised countries had varied responses to the COVID-19 pandemic, which may lead to different death tolls from COVID-19 and other diseases. Methods: We applied an ensemble of 16 Bayesian probabilistic models to vital statistics data to estimate the number of weekly deaths if the pandemic had not occurred for 40 industrialised countries and US states from mid-February 2020 through mid-February 2021. We subtracted these estimates from the actual number of deaths to calculate the impacts of the pandemic on all-cause mortality. Results: Over this year, there were 1,410,300 (95% credible interval 1,267,600-1,579,200) excess deaths in these countries, equivalent to a 15% (14-17) increase, and 141 (127-158) additional deaths per 100,000 people. In Iceland, Australia and New Zealand, mortality was lower than would be expected in the absence of the pandemic, while South Korea and Norway experienced no detectable change. The USA, Czechia, Slovakia and Poland experienced >20% higher mortality. Within the USA, Hawaii experienced no detectable change in mortality and Maine a 5% increase, contrasting with New Jersey, Arizona, Mississippi, Texas, California, Louisiana and New York which experienced >25% higher mortality. Mid-February to the end of May 2020 accounted for over half of excess deaths in Scotland, Spain, England and Wales, Canada, Sweden, Belgium, the Netherlands and Cyprus, whereas mid-September 2020 to mid-February 2021 accounted for >90% of excess deaths in Bulgaria, Croatia, Czechia, Hungary, Latvia, Montenegro, Poland, Slovakia and Slovenia. In USA, excess deaths in the northeast were driven mainly by the first wave, in southern and southwestern states by the summer wave, and in the northern plains by the post-September period. Conclusions: Prior to widespread vaccine-acquired immunity, minimising the overall death toll of the pandemic requires policies and non-pharmaceutical interventions that delay and reduce infections, effective treatments for infected patients, and mechanisms to continue routine health care
Synthesized grain size distribution in the interstellar medium
We examine a synthetic way of constructing the grain size distribution in the
interstellar medium (ISM). First we formulate a synthetic grain size
distribution composed of three grain size distributions processed with the
following mechanisms that govern the grain size distribution in the Milky Way:
(i) grain growth by accretion and coagulation in dense clouds, (ii) supernova
shock destruction by sputtering in diffuse ISM, and (iii) shattering driven by
turbulence in diffuse ISM. Then, we examine if the observational grain size
distribution in the Milky Way (called MRN) is successfully synthesized or not.
We find that the three components actually synthesize the MRN grain size
distribution in the sense that the deficiency of small grains by (i) and (ii)
is compensated by the production of small grains by (iii). The fraction of each
{contribution} to the total grain processing of (i), (ii), and (iii) (i.e., the
relative importance of the three {contributions} to all grain processing
mechanisms) is 30-50%, 20-40%, and 10-40%, respectively. We also show that the
Milky Way extinction curve is reproduced with the synthetic grain size
distributions.Comment: 10 pages, 6 figures, accepted for publication in Earth, Planets, and
Spac
Understanding the response to Covid-19 - Exploring options for a resilient social and economic recovery in Scotland’s rural and island communities
Influenza nucleoprotein delivered with aluminium salts protects mice from an influenza virus that expresses an altered nucleoprotein sequence
Influenza virus poses a difficult challenge for protective immunity. This virus is adept at altering its surface proteins, the proteins that are the targets of neutralizing antibody. Consequently, each year a new vaccine must be developed to combat the current recirculating strains. A universal influenza vaccine that primes specific memory cells that recognise conserved parts of the virus could prove to be effective against both annual influenza variants and newly emergent potentially pandemic strains. Such a vaccine will have to contain a safe and effective adjuvant that can be used in individuals of all ages. We examine protection from viral challenge in mice vaccinated with the nucleoprotein from the PR8 strain of influenza A, a protein that is highly conserved across viral subtypes. Vaccination with nucleoprotein delivered with a universally used and safe adjuvant, composed of insoluble aluminium salts, provides protection against viruses that either express the same or an altered version of nucleoprotein. This protection correlated with the presence of nucleoprotein specific CD8 T cells in the lungs of infected animals at early time points after infection. In contrast, immunization with NP delivered with alum and the detoxified LPS adjuvant, monophosphoryl lipid A, provided some protection to the homologous viral strain but no protection against infection by influenza expressing a variant nucleoprotein. Together, these data point towards a vaccine solution for all influenza A subtypes
The Dynamical Structure and Evolution of Giant Molecular Clouds
Giant molecular clouds (GMCs) are the sites of star formation in the Galaxy. Many of their properties can be understood in terms of a model in which the GMCs and the star-forming clumps within them are in approximate pressure equilibrium, with turbulent motions treated as a separate pressure component
CRISPR-Cas9 In Vivo Gene Editing for Transthyretin Amyloidosis
BACKGROUND:
Transthyretin amyloidosis, also called ATTR amyloidosis, is a life-threatening disease characterized by progressive accumulation of misfolded transthyretin (TTR) protein in tissues, predominantly the nerves and heart. NTLA-2001 is an in vivo gene-editing therapeutic agent that is designed to treat ATTR amyloidosis by reducing the concentration of TTR in serum. It is based on the clustered regularly interspaced short palindromic repeats and associated Cas9 endonuclease (CRISPR-Cas9) system and comprises a lipid nanoparticle encapsulating messenger RNA for Cas9 protein and a single guide RNA targeting TTR.
METHODS:
After conducting preclinical in vitro and in vivo studies, we evaluated the safety and pharmacodynamic effects of single escalating doses of NTLA-2001 in six patients with hereditary ATTR amyloidosis with polyneuropathy, three in each of the two initial dose groups (0.1 mg per kilogram and 0.3 mg per kilogram), within an ongoing phase 1 clinical study.
RESULTS:
Preclinical studies showed durable knockout of TTR after a single dose. Serial assessments of safety during the first 28 days after infusion in patients revealed few adverse events, and those that did occur were mild in grade. Dose-dependent pharmacodynamic effects were observed. At day 28, the mean reduction from baseline in serum TTR protein concentration was 52% (range, 47 to 56) in the group that received a dose of 0.1 mg per kilogram and was 87% (range, 80 to 96) in the group that received a dose of 0.3 mg per kilogram.
CONCLUSIONS:
In a small group of patients with hereditary ATTR amyloidosis with polyneuropathy, administration of NTLA-2001 was associated with only mild adverse events and led to decreases in serum TTR protein concentrations through targeted knockout of TTR. (Funded by Intellia Therapeutics and Regeneron Pharmaceuticals; ClinicalTrials.gov number, NCT04601051. opens in new tab.
Formation of Supermassive Black Holes
Evidence shows that massive black holes reside in most local galaxies.
Studies have also established a number of relations between the MBH mass and
properties of the host galaxy such as bulge mass and velocity dispersion. These
results suggest that central MBHs, while much less massive than the host (~
0.1%), are linked to the evolution of galactic structure. In hierarchical
cosmologies, a single big galaxy today can be traced back to the stage when it
was split up in hundreds of smaller components. Did MBH seeds form with the
same efficiency in small proto-galaxies, or did their formation had to await
the buildup of substantial galaxies with deeper potential wells? I briefly
review here some of the physical processes that are conducive to the evolution
of the massive black hole population. I will discuss black hole formation
processes for `seed' black holes that are likely to place at early cosmic
epochs, and possible observational tests of these scenarios.Comment: To appear in The Astronomy and Astrophysics Review. The final
publication is available at http://www.springerlink.co
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