5 research outputs found
REÅ AVANJE JEDNOG PROBLEMA U ORGANSKOJ HEMIJI METODOM EKVIVALENTNIH JEDNAÄINA
U teorijskoj organskoj hemiji, zakoni molekulsko ā orbitalne teorije omoguÄuju da se odrede energetska stanja Ļ ā elektrona u konjugovanim (nezasiÄenim) jedinjenjima. Pri ovome energetski nivoi elektrona, dobijaju se razvijanjem odgovarajuÄe determinante koja se formira koristeÄi tri karakteristiÄne matrice po definiciji. Svakom jedinjenju, pri ovome pridružuje se odgovarajuÄi polinom, dok Äe energetski nivoi zavisiti od njegovih nula. Kod velike veÄine jedinjenja koja se susreÄu u teoriji i praksi, dobijeni polinom uvek ima bar jednu racionalnu nulu pa se problem reÅ”ava jednostavno metodom faktorizacije. Problem nastaje kada karakteristiÄni polinom nema ni jednu racionalnu nulu. U ovom sluÄaju moguÄa je primena gotovih matematiÄkih formula koje su meÄutim nepodesne za praktiÄnu upotrebu. Isto tako moguÄa je i primena numeriÄkih metoda, koje daju samo približno realno reÅ”enje koje nije pogodno za primenu s obzirom da se gotovo uvek traži taÄno realno reÅ”enje. UzimajuÄi u obzir predhodno, u radu biÄe dat predlog za reÅ”avanje gore navedenog problema na bazi formiranja ekvivalentnih jednaÄina preko odgovarajuÄih matematiÄkih transformacija, koje omoguÄuju da se na relativno jednostavan naÄin dobiju taÄno sve realne nule polinoma. U prikazanom radu, reÅ”avanje matematiÄkog problema biÄe ilustrovano na nekoliko karakteristiÄnih primera. TaÄnost dobijenih rezultata prema predloženoj metodi biÄe izvedena poreÄenjem sa približnim numeriÄkim reÅ”enjem koristeÄi odgovarajuÄi raÄunarski program, odnosno numeriÄke metode
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Cumulative, additive benefits of memantine-donepezil combination over component monotherapies in moderate to severe Alzheimerās dementia: a pooled area under the curve analysis
Introduction: Treatment in moderate or severe Alzheimerās disease (AD) often involves adding memantine to a cholinesterase-inhibitor (ChEI: donepezil, galantamine, rivastigmine). Evidence from six-month randomized trials and long-term observational studies supports superiority of memantine-ChEI combination to ChEI monotherapy. We utilized area-under-the-curve (AUC) analysis to assess six-month cumulative treatment efficacy of memantine-donepezil combination versus component monotherapies on individual clinical domains and on a composite index. Methods: Data were pooled from 1,408 individuals with moderate to severe AD from four six-month randomized trials of memantine monotherapy (n = 570) or add-on therapy (donepezil-only subset: n = 847). AUC changes from baseline on measures of cognition (SIB), function (ADCS-ADL19), behavior (NPI), global status (CIBIC-Plus), and a composite index (4D-CI: equally weighted composite of four domain measures) were calculated using the trapezoidal rule and evaluated via analysis of covariance (ANCOVA) (2-sided-Ī± = 0.05). AUC results were contrasted with visit-by-visit changes from baseline (āsnapshot analysisā), performed using a mixed-effects model with repeated measures (MMRM). Results: Over the entire six-month period, placebo-only treatment was associated with significant cumulative worsening on all outcomes. Memantine-donepezil combination showed significantly greater AUC improvements (point x week) on the SIB, NPI, and CIBIC-Plus than placebo-donepezil (SIB: 68.4 versus 32.0, P = 0.019; NPI: ā74.3 versus ā28.2, P = 0.003; CIBIC-Plus: ā2.5 versus 1.4, P = 0.006) and memantine-only monotherapies (SIB: 68.4 versus 12.0, P <0.001; NPI: ā74.3 versus ā7.4, P <0.001; CIBIC-Plus: ā2.5 versus 2.7, P <0.001), whereas these comparisons were not significant for the ADCS-ADL19 (memantine-donepezil (1.4) versus placebo-donepezil (ā0.9), P = 0.407; versus memantine-only (ā12.2), P = 0.310). Composite index analysis demonstrated significant cumulative advantages of memantine-donepezil combination (630.0) over placebo-donepezil (344.7, P <0.001) and memantine-only (152.1, P <0.001) treatments. Combining memantine and donepezil had an additive effect. Compared with AUC analysis, baseline-to-endpoint change-score analysis underestimated effects of combination therapy, monotherapies, or both. Conclusions: This large pooled area-under-the-curve analysis of randomized-trial data in moderate to severe AD provides ecologically valid support that adding memantine to stable donepezil results in overall clinical benefits that are additive compared with individual monotherapies, continue to accumulate through six-month treatment, and are at least 50% greater than those of monotherapies