969 resultados para Wells, H. G. (Herbert George), 1866-1946.
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Mode of access: Internet.
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At head of title: G. Foucart et Adolphe Cattaui bey.
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Mode of access: Internet.
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Vol. 3 published by Bowes & Bowes, 1913.
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Mode of access: Internet.
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The financial crisis of 2007-2008 led to extraordinary government intervention in firms and markets. The scope and depth of government action rivaled that of the Great Depression. Many traded markets experienced dramatic declines in liquidity leading to the existence of conditions normally assumed to be promptly removed via the actions of profit seeking arbitrageurs. These extreme events motivate the three essays in this work. The first essay seeks and fails to find evidence of investor behavior consistent with the broad 'Too Big To Fail' policies enacted during the crisis by government agents. Only in limited circumstances, where government guarantees such as deposit insurance or U.S. Treasury lending lines already existed, did investors impart a premium to the debt security prices of firms under stress. The second essay introduces the Inflation Indexed Swap Basis (IIS Basis) in examining the large differences between cash and derivative markets based upon future U.S. inflation as measured by the Consumer Price Index (CPI). It reports the consistent positive value of this measure as well as the very large positive values it reached in the fourth quarter of 2008 after Lehman Brothers went bankrupt. It concludes that the IIS Basis continues to exist due to limitations in market liquidity and hedging alternatives. The third essay explores the methodology of performing debt based event studies utilizing credit default swaps (CDS). It provides practical implementation advice to researchers to address limited source data and/or small target firm sample size.
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Purpose: The recognition of breast cancer as a spectrum tumor in Lynch syndrome remains controversial. The aim of this study was to explore features of breast cancers arising in Lynch syndrome families. Experimental Design: This observational study involved 107 cases of breast cancer identified from the Colorectal Cancer Family Registry (Colon CFR) from 90 families in which (a) both breast and colon cancer co-occurred, (b) families met either modified Amsterdam criteria, or had at least one early-onset (<50 years) colorectal cancer, and (c) breast tissue was available within the biospecimen repository for mismatch repair (MMR) testing. Eligibility criteria for enrollment in the Colon CFR are available online. Breast cancers were reviewed by one pathologist. Tumor sections were stained for MLH1, PMS2, MSH2, and MSH6, and underwent microsatellite instability testing. Results: Breast cancer arose in 35 mutation carriers, and of these, 18 (51%) showed immunohistochemical absence of MMR protein corresponding to the MMR gene mutation segregating the family. MMR-deficient breast cancers were more likely to be poorly differentiated (P = 0.005) with a high mitotic index (P = 0.002), steroid hormone receptor–negative (estrogen receptor, P = 0.031; progesterone receptor, P = 0.022), and to have peritumoral lymphocytes (P = 0.015), confluent necrosis (P = 0.002), and growth in solid sheets (P < 0.001) similar to their colorectal counterparts. No difference in age of onset was noted between the MMR-deficient and MMR-intact groups. Conclusions: MMR deficiency was identified in 51% of breast cancers arising in known mutation carriers. Breast cancer therefore may represent a valid tissue option for the detection of MMR deficiency in which spectrum tumors are lacking
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The starting point for this presentation is that applicants provide a large surplus of information when submitting a NHMRC Project Grant proposal for funding. This is costly in their time, attracts high administration costs, makes the task appear daunting for peer reviewers and may reduce the quality of the peer review leading to less than perfect reliability in decision making. We are currently experimenting with alternate models to see whether similar reliability in funding outcomes are achieved at less cost. We will compare traditional NHMRC Grant Review Panels (GRPs) with panels that use less information and journal style panels. By way of background to this experimental work, we will show some results on current levels of reliability for GRPs, the costs incurred by all who participate in Project Grant selection, and the level of reliability acceptable to researchers. By experimenting in this way and building an evidence base for how research funding should be allocated, the NHMRC is showing international leadership in this important field.
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Extrapulmonary small cell and small cell neuroendocrine tumors of unknown primary site are, in general, aggressive neoplasms with a short median survival. Like small cell lung cancer (SCLC), they often are responsive to chemotherapy and radiotherapy. Small cell lung cancer and well differentiated neuroendocrine carcinomas of the gastrointestinal tract and pancreas tend to express somatostatin receptors. These tumors may be localized in patients by scintigraphic imaging using radiolabeled somatostatin analogues. A patient with an anaplastic neuroendocrine small cell tumor arising on a background of multiple endocrine neoplasia type 1 syndrome is reported. The patient had a known large pancreatic gastrinoma and previously treated parathyroid adenopathy. At presentation, there was small cell cancer throughout the liver and skeleton. Imaging with a radiolabeled somatostatin analogue, 111In- pentetreotide (Mallinckrodt Medical B. V., Petten, Holland), revealed all sites of disease detected by routine biochemical and radiologic methods. After six cycles of chemotherapy with doxorubicin, cyclophosphamide, and etoposide, there was almost complete clearance of the metastatic disease. 111In-pentetreotide scintigraphy revealed uptake consistent with small areas of residual disease in the liver, the abdomen (in mesenteric lymph nodes), and posterior thorax (in a rib). The primary gastrinoma present before the onset of the anaplastic small cell cancer showed no evidence of response to the treatment. The patient remained well for 1 year and then relapsed with brain, lung, liver, and skeletal metastases. Despite an initial response to salvage radiotherapy and chemotherapy with carboplatin and dacarbazine, the patient died 6 months later.
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NHMRC Project Grants and ARC Discovery Grants are two of the major sources of funding for new ideas in Australian science. Many scientists rely on them for their job or the jobs of their staff. They are highly competitive with only around 1 in 5 applications winning funding. To increase the chances of winning funding, scientists spend a long time writing carefully crafted applications, generally at the sacrifice of their research output. And the pressures on the system and our scientists are only going to get worse.
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Competition for research funding is intense and the opinions of an expert peer reviewer can mean the difference between success and failure in securing funding. The allocation of expert peer reviewers is therefore vitally important and funding agencies strive to avoid using reviewers who have real or perceived conflicts of interest. This article examines the impact of including or excluding peer reviewers based on their conflicts of interest, and the final ranking of funding proposals. Two 7-person review panels assessed a sample of National Health and Medical Research Council (NHMRC) of Australia proposals in Basic Science or Public Health. Using a pre-post comparison, the proposals were first scored after the exclusion of reviewers with a high or medium conflict, and re-scored after the return of reviewers with medium conflicts. The main outcome measures are the agreements in ranks and funding success before and after excluding the medium conflicts. Including medium conflicts of interest had little impact on the ranks or funding success. The Bland–Altman 95% limits of agreement were ± 3.3 ranks and ± 3.4 ranks in the two panels which both assessed 36 proposals. Overall there were three proposals (4%) that had a reversed funding outcome after including medium conflicts. Relaxing the conflict of interest rules would increase the number of expert reviewers included in the panel discussions which could increase the quality of peer review and make it easier to find reviewers.
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Background Despite the widely recognised importance of sustainable health care systems, health services research remains generally underfunded in Australia. The Australian Centre for Health Services Innovation (AusHSI) is funding health services research in the state of Queensland. AusHSI has developed a streamlined protocol for applying and awarding funding using a short proposal and accelerated peer review. Method An observational study of proposals for four health services research funding rounds from May 2012 to November 2013. A short proposal of less than 1,200 words was submitted using a secure web-based portal. The primary outcome measures are: time spent preparing proposals; a simplified scoring of grant proposals (reject, revise or accept for interview) by a scientific review committee; and progressing from submission to funding outcomes within eight weeks. Proposals outside of health services research were deemed ineligible. Results There were 228 eligible proposals across 4 funding rounds: from 29% to 79% were shortlisted and 9% to 32% were accepted for interview. Success rates increased from 6% (in 2012) to 16% (in 2013) of eligible proposals. Applicants were notified of the outcomes within two weeks from the interview; which was a maximum of eight weeks after the submission deadline. Applicants spent 7 days on average preparing their proposal. Applicants with a ranking of reject or revise received written feedback and suggested improvements for their proposals, and resubmissions composed one third of the 2013 rounds. Conclusions The AusHSI funding scheme is a streamlined application process that has simplified the process of allocating health services research funding for both applicants and peer reviewers. The AusHSI process has minimised the time from submission to notification of funding outcomes.
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Background The Global Burden of Disease, Injuries, and Risk Factor study 2013 (GBD 2013) is the first of a series of annual updates of the GBD. Risk factor quantification, particularly of modifiable risk factors, can help to identify emerging threats to population health and opportunities for prevention. The GBD 2013 provides a timely opportunity to update the comparative risk assessment with new data for exposure, relative risks, and evidence on the appropriate counterfactual risk distribution. Methods Attributable deaths, years of life lost, years lived with disability, and disability-adjusted life-years (DALYs) have been estimated for 79 risks or clusters of risks using the GBD 2010 methods. Risk–outcome pairs meeting explicit evidence criteria were assessed for 188 countries for the period 1990–2013 by age and sex using three inputs: risk exposure, relative risks, and the theoretical minimum risk exposure level (TMREL). Risks are organised into a hierarchy with blocks of behavioural, environmental and occupational, and metabolic risks at the first level of the hierarchy. The next level in the hierarchy includes nine clusters of related risks and two individual risks, with more detail provided at levels 3 and 4 of the hierarchy. Compared with GBD 2010, six new risk factors have been added: handwashing practices, occupational exposure to trichloroethylene, childhood wasting, childhood stunting, unsafe sex, and low glomerular filtration rate. For most risks, data for exposure were synthesised with a Bayesian meta-regression method, DisMod-MR 2.0, or spatial-temporal Gaussian process regression. Relative risks were based on meta-regressions of published cohort and intervention studies. Attributable burden for clusters of risks and all risks combined took into account evidence on the mediation of some risks such as high body-mass index (BMI) through other risks such as high systolic blood pressure and high cholesterol. Findings All risks combined account for 57·2% (95% uncertainty interval [UI] 55·8–58·5) of deaths and 41·6% (40·1–43·0) of DALYs. Risks quantified account for 87·9% (86·5–89·3) of cardiovascular disease DALYs, ranging to a low of 0% for neonatal disorders and neglected tropical diseases and malaria. In terms of global DALYs in 2013, six risks or clusters of risks each caused more than 5% of DALYs: dietary risks accounting for 11·3 million deaths and 241·4 million DALYs, high systolic blood pressure for 10·4 million deaths and 208·1 million DALYs, child and maternal malnutrition for 1·7 million deaths and 176·9 million DALYs, tobacco smoke for 6·1 million deaths and 143·5 million DALYs, air pollution for 5·5 million deaths and 141·5 million DALYs, and high BMI for 4·4 million deaths and 134·0 million DALYs. Risk factor patterns vary across regions and countries and with time. In sub-Saharan Africa, the leading risk factors are child and maternal malnutrition, unsafe sex, and unsafe water, sanitation, and handwashing. In women, in nearly all countries in the Americas, north Africa, and the Middle East, and in many other high-income countries, high BMI is the leading risk factor, with high systolic blood pressure as the leading risk in most of Central and Eastern Europe and south and east Asia. For men, high systolic blood pressure or tobacco use are the leading risks in nearly all high-income countries, in north Africa and the Middle East, Europe, and Asia. For men and women, unsafe sex is the leading risk in a corridor from Kenya to South Africa. Interpretation Behavioural, environmental and occupational, and metabolic risks can explain half of global mortality and more than one-third of global DALYs providing many opportunities for prevention. Of the larger risks, the attributable burden of high BMI has increased in the past 23 years. In view of the prominence of behavioural risk factors, behavioural and social science research on interventions for these risks should be strengthened. Many prevention and primary care policy options are available now to act on key risks.
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The normal-mode solution to the problem of acoustic wave propagation in an isovelocity ocean with a wavy surface is considered. The surface wave amplitude is assumed to be small compared to the acoustic wavelength, and the method of multiple scales is employed to study the interaction between normal-mode acoustic waves and the surface waves. A nonresonant interaction causes small fluctuations of the amplitude and phase of the acoustic wave at a rate dependent on the frequency of the surface wave. Backscatter occurs if the wavenumber of the surface wave is larger than that of the acoustic wave. The interaction becomes resonant if appropriate phase-matching conditions are satisfied. In this case, two acoustic normal modes get coupled, resulting in a large-scale periodic exchange of energy from one mode to another.
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The crystal structure of TANDEM (des-N-tetramethyltriostin A), a synthetic analogue of the quinoxaline antibiotic triostin A, has been determined independently at -135 and 7 'C and refined to R values of 0.088 and 0.147, respectively. The molecule has approximate 2-fold symmetry, with the quinoxaline chromophores and the disulfide cross-bridge projecting from opposite sides of the peptide ring. The quinoxaline groups are nearly parallel to each other and separated by about 6.5 A. The peptide backbone resembles a distorted antiparallel 13 ribbon joined by intramolecular hydrogen bonds N-H(LVal)--O(L-Ala). At low temperatures, the TANDEM molecule is surrounded by a regular first- and second-order hydration sphere containing 14 independent water molecules. At room temperature, only the first-order hydration shell is maintained. Calculations of the interplanar separation of the quinoxaline groups as a function of their orientation with respect to the peptide ring support the viability of TANDEM to intercalate bifunctionally into DNA.