25 research outputs found

    The 4^4He(e,ep)(e,e'p) Cross Section at Large Missing Energy

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    The (e,ep)(e,e'p) reaction on 4He^{4}{He} nuclei was studied in kinematics designed to emphasize effects of nuclear short-range correlations. The measured cross sections display a peak in the kinematical regions where two-nucleon processes are expected to dominate. Theoretical models incorporating short-range correlation effects agree reasonably with the data.Comment: 4 pages LaTeX, using espcrc1.sty and wrapfig.sty (included), two figures. Talk presented by J. Templon at the 15th Int. Conf. on Few-Body Problems in Physics, Groningen, The Netherlands, 22-26 July, 199

    Towards liver-directed gene therapy: Retrovirus-mediated gene transfer into human hepatocytes

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    Liver-directed gene therapy is being considered in the treatment of inherited metabolic diseases. One approach we are considering is the transplantation of autologous hepatocytes that have been genetically modified with recombinant retroviruses ex vivo. We describe, in this report, techniques for isolating human hepatocytes and efficiently transducing recombinant genes into primary cultures. Hepatocytes were isolated from tissue of four different donors, plated in primary culture, and exposed to recombinant retroviruses expressing either the LacZ reporter gene or the cDNA for rabbit LDL receptor. The efficiency of gene transfer under optimal conditions, as determined by Southern blot analysis, varied from a maximum of one proviral copy per cell to a minimum of 0.1 proviral copy per cell. Cytochemical assays were used to detect expression of the recombinant derived proteins, E. coli β-galactosidase and rabbit LDL receptor. Hepatocytes transduced with the LDL receptor gene expressed levels of receptor protein that exceeded the normal endogenous levels. The ability to isolate and genetically modify human hepatocytes, as described in this report, is an important step towards the development of liver-directed gene therapies in humans.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45540/1/11188_2005_Article_BF01233625.pd

    Global surveillance of cancer survival 1995-2009: analysis of individual data for 25,676,887 patients from 279 population-based registries in 67 countries (CONCORD-2)

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    BACKGROUND: Worldwide data for cancer survival are scarce. We aimed to initiate worldwide surveillance of cancer survival by central analysis of population-based registry data, as a metric of the effectiveness of health systems, and to inform global policy on cancer control. METHODS: Individual tumour records were submitted by 279 population-based cancer registries in 67 countries for 25·7 million adults (age 15-99 years) and 75,000 children (age 0-14 years) diagnosed with cancer during 1995-2009 and followed up to Dec 31, 2009, or later. We looked at cancers of the stomach, colon, rectum, liver, lung, breast (women), cervix, ovary, and prostate in adults, and adult and childhood leukaemia. Standardised quality control procedures were applied; errors were corrected by the registry concerned. We estimated 5-year net survival, adjusted for background mortality in every country or region by age (single year), sex, and calendar year, and by race or ethnic origin in some countries. Estimates were age-standardised with the International Cancer Survival Standard weights. FINDINGS: 5-year survival from colon, rectal, and breast cancers has increased steadily in most developed countries. For patients diagnosed during 2005-09, survival for colon and rectal cancer reached 60% or more in 22 countries around the world; for breast cancer, 5-year survival rose to 85% or higher in 17 countries worldwide. Liver and lung cancer remain lethal in all nations: for both cancers, 5-year survival is below 20% everywhere in Europe, in the range 15-19% in North America, and as low as 7-9% in Mongolia and Thailand. Striking rises in 5-year survival from prostate cancer have occurred in many countries: survival rose by 10-20% between 1995-99 and 2005-09 in 22 countries in South America, Asia, and Europe, but survival still varies widely around the world, from less than 60% in Bulgaria and Thailand to 95% or more in Brazil, Puerto Rico, and the USA. For cervical cancer, national estimates of 5-year survival range from less than 50% to more than 70%; regional variations are much wider, and improvements between 1995-99 and 2005-09 have generally been slight. For women diagnosed with ovarian cancer in 2005-09, 5-year survival was 40% or higher only in Ecuador, the USA, and 17 countries in Asia and Europe. 5-year survival for stomach cancer in 2005-09 was high (54-58%) in Japan and South Korea, compared with less than 40% in other countries. By contrast, 5-year survival from adult leukaemia in Japan and South Korea (18-23%) is lower than in most other countries. 5-year survival from childhood acute lymphoblastic leukaemia is less than 60% in several countries, but as high as 90% in Canada and four European countries, which suggests major deficiencies in the management of a largely curable disease. INTERPRETATION: International comparison of survival trends reveals very wide differences that are likely to be attributable to differences in access to early diagnosis and optimum treatment. Continuous worldwide surveillance of cancer survival should become an indispensable source of information for cancer patients and researchers and a stimulus for politicians to improve health policy and health-care systems

    Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

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    Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

    Whole-genome sequencing reveals host factors underlying critical COVID-19

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    Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

    Inclusive (p,3He) reactions on 59Co and 197Au at incident energies of 120, 160, and 200 MeV

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    Measurements of inclusive (p,3He) reactions on 59Co and 197Au at incident energies of 120, 160, and 200 MeV are compared with calculations based on a statistical multistep direct reaction theory. The angular range extends from 10° to 160° and emission energies exceeding 30 MeV were studied. It is found that the multistep contributions are dominant for all but the highest outgoing energies. This is in qualitative agreement with previous results for the inclusive (p,α) reaction at the same incident energies and targets.Articl

    Inclusive (p,α) reactions on 27Al, 59Co, and 197Au at incident energies of 120, 160, and 200 MeV

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    Measurements of inclusive (p,α) reactions on 27Al, 59Co, and 197Au at incident energies between 120 and 200 MeV are compared with the trend expected from systematics and also with calculations based on a statistical multistep direct reaction theory. Although reasonable agreement is obtained between the experimental angular distributions and the predictions of the parametrized systematics at various emission energies, significant discrepancies are nevertheless observed. Calculations with the quantum-mechanical multistep formulation confirm that the higher-step contributions are more important at these incident energies than found in a previous study at lower projectile energies.Articl

    Bulk Metallic Glass Multiscale Tooling for Molding of Polymers with Micro to Nano Features : A Review

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    There is a growing demand for single-use disposable polymer devices with features at submicron scales. This requires resilient tooling which can be patterned to scales of the order of hundreds of nanometers. The requisite topology can be imparted to silicon, but it is too brittle to be of use in a die to mold thousands of plastic parts. The polycrystalline nature of tool steel means that it cannot be patterned with submicron detail. Some bulk amorphous alloys have the requisite mechanical properties to be viable as materials for such dies, and can be patterned—e.g., via embossing as a supercooled liquid into MEMS silicon or using focused ion beam (FIB)—with submicron features which may persevere over many thousands of molding cycles. The composition of the amorphous alloy must be carefully selected to suit the particular molding application (polymer/process). The state-of-the-art methodology is presented, along with results of our recent experimental investigations.Deposited by bulk import5/11/2013. SB
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