Use of mathematical derivatives (time-domain differentiation) on chromatographic data to enhance the detection and quantification of an unknown 'rider' peak

Two samples of an anticancer prodrug, AQ4N, were submitted for HPLC assay and showed an unidentified impurity that eluted as a 'rider' on the tail of the main peak. Mathematical derivatization of the chromatograms offered several advantages over conventional skimmed integration. A combination of the second derivative amplitude and simple linear regression gave a novel method for estimating the true peak area of the impurity peak. All the calculation steps were carried out using a widely available spreadsheet program. (C) 2003 Elsevier B.V. All rights reserved

Introduction to the special issue on neural networks in financial engineering

There are several phases that an emerging field goes through before it reaches maturity, and computational finance is no exception. There is usually a trigger for the birth of the field. In our case, new techniques such as neural networks, significant progress in computing technology, and the need for results that rely on more realistic assumptions inspired new researchers to revisit the traditional problems of finance, problems that have often been tackled by introducing simplifying assumptions in the past. The result has been a wealth of new approaches to these time-honored problems, with significant improvements in many cases

Three-body monopole corrections to the realistic interactions

It is shown that a very simple three-body monopole term can solve practically all the spectroscopic problems--in the $p$, $sd$ and $pf$ shells--that were hitherto assumed to need drastic revisions of the realistic potentials.Comment: 4 pages, 5figure

Information scraps: how and why information eludes our personal information management tools

In this paper we describe information scraps -- a class of personal information whose content is scribbled on Post-it notes, scrawled on corners of random sheets of paper, buried inside the bodies of e-mail messages sent to ourselves, or typed haphazardly into text files. Information scraps hold our great ideas, sketches, notes, reminders, driving directions, and even our poetry. We define information scraps to be the body of personal information that is held outside of its natural or We have much still to learn about these loose forms of information capture. Why are they so often held outside of our traditional PIM locations and instead on Post-its or in text files? Why must we sometimes go around our traditional PIM applications to hold on to our scraps, such as by e-mailing ourselves? What are information scraps' role in the larger space of personal information management, and what do they uniquely offer that we find so appealing? If these unorganized bits truly indicate the failure of our PIM tools, how might we begin to build better tools? We have pursued these questions by undertaking a study of 27 knowledge workers. In our findings we describe information scraps from several angles: their content, their location, and the factors that lead to their use, which we identify as ease of capture, flexibility of content and organization, and avilability at the time of need. We also consider the personal emotive responses around scrap management. We present a set of design considerations that we have derived from the analysis of our study results. We present our work on an application platform, jourknow, to test some of these design and usability findings

Explosivity : an unusual challenge in drug development

There remains an urgent global need for new drugs to combat diseases such as malaria, tuberculosis and cancer, as well as overcoming increasing antibiotic resistance. Chemists are moving into ‘new chemical space’ for drug design (1,2) and with this comes the possibility of traditional (and stable) ‘carbon-carbon’ bond structures being replaced by more ‘exotic’ bonding arrangements. While the implication of this on pharmaceutical stability can often be mitigated by suitable formulation and storage strategies, we came across an unusual case of chemical stability: the possibility that the drug was an explosive! By pushing drug designing into uncharted chemical space it could be argued that the possibility of finding explosive molecules of pharmaceutical interest will increase

The Birmingham Boron Neutron Capture Therapy (BNCT) project : developments towards selective internal particle therapy

This paper will review progress on two aspects of the Birmingham BNCT project. Firstly on evaluation of the effects of high and low LET radiations when delivered simultaneously, and secondly on attempts to optimise delivery of the boron carrier compound BPA through pharmacokinetic studies. Simultaneous or non-simultaneous irradiations of V79 cells with alpha-particle and X-ray irradiations were performed. Alpha doses of 2 and 2.5 Gy were chosen and the impact on survival when delivered separately or simultaneously with variable doses of X-rays was evaluated. The pharmacokinetics of the delivery of a new formulation of BPA (BPA-mannitol) are being investigated in brain tumour patients through a study with 2 × 2 design featuring intravenous and intracarotid artery infusion of BPA, with or without a mannitol bolus. On the combined effect of low and high LET radiations, a synergistic effect was observed when alpha and X-ray doses are delivered simultaneously. The effect is only present at the 2.5 Gy alpha dose and is a very substantial effect on both the shape of the survival curve and the level of cell killing. This indicates that the alpha component may have the effect of inhibiting the repair of damage from the low LET radiation dose delivered simultaneously. On the pharmacokinetics of BPA, data on the first three cohorts indicate that bioavailability of BPA in brain ECF is increased substantially through the addition of a mannitol bolus, as well as by the use of intracarotid artery route of infusion. In both cases, for some patients the levels after infusion approach those seen in blood, whereas the ECF levels for intravenous infusion without mannitol are typically less than 10% of the blood values

Life table analysis of Diaphorina citri (Hemiptera: Psyllidae) infesting sweet orange (Citrus sinensis) in São Paulo

An ecological life table for eggs and nymphs of Diaphorina citri Kuwayama (Hemiptera: Psyllidae) was constructed with data obtained from orange orchards (Citrus sinensis Osbeck) in 2 regions of the State of São Paulo, over 4 generations in the period from XI-2006 to V-2007, comprising spring, summer, and fall seasons. Young growing shoots with D. citri eggs present were identifed, and live individuals were counted until adult emergence. No predatory arthropods were observed in association with D. citri eggs and nymphs during the study. The mean parasitism of fourth- and ffth-instar nymphs by Tamarixia radiata Waterston (Hymenoptera: Eulophidae) was 2.3%. The durations of the egg–adult period were similar among the 4 generations, ranging from 18.0 to 24.7 d (at mean temperatures ranging from 21.6 to 26.0 °C) and followed the temperature requirement models obtained in the laboratory for D. citri. However, survival from the egg to the adult stage for the same period varied considerably from 1.7 to 21.4%; the highest mortalities were observed in the egg and small nymphal (frst- to thirdinstar) stages, which were considered to be key phases for population growth of the pest.Uma tabela de vida ecológica foi construída para ovos e ninfas de Diaphorina citri Kuwayama (Hemiptera: Psyllidae) com dados obtidos em pomares de laranja (Citrus sinensis Osbeck) em 2 regiões do estado de São Paulo, com 4 gerações, no período de novembro de 2006 a maio de 2007, compreendendo as estações de primavera, verão e outono. Ramos jovens em crescimento com a presença de ovos de D. citri foram identificados e os indivíduos vivos foram contados até a emergência dos adultos. Nenhum predador foi observado associado a ovos e ninfas de D. citri durante o estudo. A taxa média de parasitismo de ninfas de quarto e quinto ínstares por Tamarixia radiata Waterson (Hymenoptera: Eulophidae) foi de 2.3%. A duração do período de ovo a adulto foi semelhante entre as quatro gerações, variando de 18.0 a 24.7 dias (com temperaturas médias de 21.6 a 26.0 °C) e seguiram os modelos de exigencias térmicas obtidas em laboratório para D. citri. Todavia, a sobrevivencia de ovo até o estágio adulto variou consideravelmente para o mesmo período, de 1.7 a 21.4%, sendo que as maiores mortalidades foram observadas nos estágios de ovos e ninfas pequenas (de primeiro a terceiro ínstares), as quais foram consideradas fases chaves para o crescimento populacional desta praga.info:eu-repo/semantics/publishedVersio

Removing exogenous information using pedigree data

Management of certain populations requires the preservation of its pure genetic background. When, for different reasons, undesired alleles are introduced, the original genetic conformation must be recovered. The present study tested, through computer simulations, the power of recovery (the ability for removing the foreign information) from genealogical data. Simulated scenarios comprised different numbers of exogenous individuals taking partofthe founder population anddifferent numbers of unmanaged generations before the removal program started. Strategies were based on variables arising from classical pedigree analyses such as founders? contribution and partial coancestry. The ef?ciency of the different strategies was measured as the proportion of native genetic information remaining in the population. Consequences on the inbreeding and coancestry levels of the population were also evaluated. Minimisation of the exogenous founders? contributions was the most powerful method, removing the largest amount of genetic information in just one generation.However, as a side effect, it led to the highest values of inbreeding. Scenarios with a large amount of initial exogenous alleles (i.e. high percentage of non native founders), or many generations of mixing became very dif?cult to recover, pointing out the importance of being careful about introgression events in populatio

The validity of using ICD-9 codes and pharmacy records to identify patients with chronic obstructive pulmonary disease

Background: Administrative data is often used to identify patients with chronic obstructive pulmonary disease (COPD), yet the validity of this approach is unclear. We sought to develop a predictive model utilizing administrative data to accurately identify patients with COPD. Methods: Sequential logistic regression models were constructed using 9573 patients with postbronchodilator spirometry at two Veterans Affairs medical centers (2003-2007). COPD was defined as: 1) FEV1/FVC <0.70, and 2) FEV1/FVC < lower limits of normal. Model inputs included age, outpatient or inpatient COPD-related ICD-9 codes, and the number of metered does inhalers (MDI) prescribed over the one year prior to and one year post spirometry. Model performance was assessed using standard criteria. Results: 4564 of 9573 patients (47.7%) had an FEV1/FVC < 0.70. The presence of ≥1 outpatient COPD visit had a sensitivity of 76% and specificity of 67%; the AUC was 0.75 (95% CI 0.74-0.76). Adding the use of albuterol MDI increased the AUC of this model to 0.76 (95% CI 0.75-0.77) while the addition of ipratropium bromide MDI increased the AUC to 0.77 (95% CI 0.76-0.78). The best performing model included: ≥6 albuterol MDI, ≥3 ipratropium MDI, ≥1 outpatient ICD-9 code, ≥1 inpatient ICD-9 code, and age, achieving an AUC of 0.79 (95% CI 0.78-0.80). Conclusion: Commonly used definitions of COPD in observational studies misclassify the majority of patients as having COPD. Using multiple diagnostic codes in combination with pharmacy data improves the ability to accurately identify patients with COPD.Department of Veterans Affairs, Health Services Research and Development (DHA), American Lung Association (CI- 51755-N) awarded to DHA, the American Thoracic Society Fellow Career Development AwardPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/84155/1/Cooke - ICD9 validity in COPD.pd