Safety and efficacy of ledipasvir-sofosbuvir in black patients with hepatitis C virus infection: A retrospective analysis of phase 3 data.

UNLABELLED: Black patients chronically infected with genotype 1 hepatitis C virus (HCV) have historically had lower rates of response to interferon-based treatment than patients of other races. In the phase 3 ION program, the single-tablet regimen of the NS5A inhibitor ledipasvir and NS5B nucleotide polymerase inhibitor sofosbuvir was shown to be safe and highly effective in the general population. The aim of this study was to evaluate the safety and efficacy of ledipasvir/sofosbuvir in black patients using data from the three open-label ION clinical trials, which evaluated the safety and efficacy of 8, 12, and 24 weeks of ledipasvir/sofosbuvir with or without ribavirin for the treatment of treatment-naïve and treatment-experienced patients with genotype 1 HCV, including those with compensated cirrhosis. The primary endpoint was sustained virologic response at 12 weeks after the end of therapy (SVR12). For our analysis, rates of SVR12, treatment-emergent adverse events, and graded laboratory abnormalities were analyzed in black versus non-black patients. Of the 1949 patients evaluated, 308 (16%) were black. On average, black patients were older, had higher body mass index, were more likely to be IL28B non-CC, and had a lower serum alanine aminotransferase at baseline than non-black patients. Overall, 95% of black and 97% of non-black patients achieved SVR12. The rate of relapse was 3% in black patients as compared with 2% in non-black patients. The most common adverse events included fatigue, headache, nausea, and insomnia. The majority of adverse events occurred more frequently in the ribavirin-containing arms of the studies. No differences were observed in overall safety by race. CONCLUSION: A once-daily dosage of ledipasvir/sofosbuvir was similarly effective in black and non-black patients with genotype 1 HCV infection. The addition of ribavirin did not appear to increase SVR12 but was associated with higher rates of adverse events.

(Table 1) Downhole variation of potassium, apparent K-Ar age, and inert gas abundances at DSDP Holes 69-504B, 70-504B and 83-504B

Ne, Ar, Kr, Xe, and K2O were measured in representative samples of holocrystalline basalt from DSDP Hole 504B. No hiatus in inert gas abundance is recognized at the base of the "oxic" alteration zone and the extent rather than the nature of alteration appears to determine these abundances. When the inert gas abundances are separately plotted against K2O, two distinct trends of loss emerge, one for alteration involving K-gain, the other for K-loss. Apparent whole-rock K-Ar ages are anomalous in the upper 50 m of basement, and below 300 m sub-basement. In the intervening zone of basement, celadonization adds sufficient potassium and eliminates enough "primary" 40Ar early in the history of the basalts for "excess" 40Ar to become subordinate to radiogenic 40Ar in basalts showing potassium enrichment greater than 0.2%. Stratigraphically correct K-Ar ages are obtained, therefore, from K-enriched basalts of the oxic alteration zone.

Effects of a harmful algal bloom on the community ecology, movements and spatial distributions of fishes in a microtidal estuary

Harmful algal blooms can adversely affect fish communities, though their impacts are highly context-dependent and typically differ between fish species. Various approaches, comprising univariate and multivariate analyses and multimetric Fish Community Indices (FCI), were employed to characterise the perceived impacts of a Karlodinium veneficum bloom on the fish communities and ecological condition of the Swan Canning Estuary, Western Australia. The combined evidence suggests that a large proportion of the more mobile fish species in the offshore waters of the bloom-affected area relocated to other regions during the bloom. This was indicated by marked declines in mean species richness, catch rates and FCI scores in the bloom region but concomitant increases in these characteristics in more distal regions, and by pronounced and atypical shifts in the pattern of inter-regional similarities in fish community composition during the bloom. The lack of any significant changes among the nearshore fish communities revealed that bloom impacts were less severe there than in deeper, offshore waters. Nearshore habitats, which generally are in better ecological condition than adjacent offshore waters in this system, may provide refuges for fish during algal blooms and other perturbations, mirroring similar observations of fish avoidance responses to such stressors in estuaries worldwide.

Effects of a harmful algal bloom on the community ecology, movements and spatial distributions of fishes in a microtidal estuary

Harmful algal blooms can adversely affect fish communities, though their impacts are highly context-dependent and typically differ between fish species. Various approaches, comprising univariate and multivariate analyses and multimetric Fish Community Indices (FCI), were employed to characterise the perceived impacts of a Karlodinium veneficum bloom on the fish communities and ecological condition of the Swan Canning Estuary, Western Australia. The combined evidence suggests that a large proportion of the more mobile fish species in the offshore waters of the bloom-affected area relocated to other regions during the bloom. This was indicated by marked declines in mean species richness, catch rates and FCI scores in the bloom region but concomitant increases in these characteristics in more distal regions, and by pronounced and atypical shifts in the pattern of inter-regional similarities in fish community composition during the bloom. The lack of any significant changes among the nearshore fish communities revealed that bloom impacts were less severe there than in deeper, offshore waters. Nearshore habitats, which generally are in better ecological condition than adjacent offshore waters in this system, may provide refuges for fish during algal blooms and other perturbations, mirroring similar observations of fish avoidance responses to such stressors in estuaries worldwide.

The hypoxia that developed in a microtidal estuary following an extreme storm produced dramatic changes in the benthos

Runoff from an extreme storm on 22 March 2010 led, during the next 3 months, to the formation of a pronounced halocline and underlying hypoxia in the upper reaches of the microtidal Swan–Canning Estuary. Benthic macroinvertebrates were sampled between January 2010 and October 2011 at five sites along 10 km of this region. By mid-April, the number of species, total density, Simpson’s evenness index and taxonomic distinctness had declined markedly, crustaceans had disappeared and the densities of annelids and molluscs had declined slightly. These faunal attributes (except Simpson’s index) and species composition did not recover until after the end of the hypoxia. The survival of annelids and loss of crustaceans in this period reflects different sensitivities of these taxa to severe environmental stress. The results emphasise that microtidal estuaries with long residence times are highly vulnerable to the effects of environmental perturbations, particularly during warmer periods of the year.

The hypoxia that developed in a microtidal estuary following an extreme storm produced dramatic changes in the benthos

Runoff from an extreme storm on 22 March 2010 led, during the next 3 months, to the formation of a pronounced halocline and underlying hypoxia in the upper reaches of the microtidal Swan–Canning Estuary. Benthic macroinvertebrates were sampled between January 2010 and October 2011 at five sites along 10 km of this region. By mid-April, the number of species, total density, Simpson’s evenness index and taxonomic distinctness had declined markedly, crustaceans had disappeared and the densities of annelids and molluscs had declined slightly. These faunal attributes (except Simpson’s index) and species composition did not recover until after the end of the hypoxia. The survival of annelids and loss of crustaceans in this period reflects different sensitivities of these taxa to severe environmental stress. The results emphasise that microtidal estuaries with long residence times are highly vulnerable to the effects of environmental perturbations, particularly during warmer periods of the year.

Clustering in non-parametric multivariate analyses.

Non-parametric multivariate analyses of complex ecological datasets are widely used. Following appropriate pre-treatment of the data inter-sample resemblances are calculated using appropriate measures. Ordination and clustering derived from these resemblances are used to visualise relationships among samples (or variables). Hierarchical agglomerative clustering with group-average (UPGMA) linkage is often the clustering method chosen. Using an example dataset of zooplankton densities from the Bristol Channel and Severn Estuary, UK, a range of existing and new clustering methods are applied and the results compared. Although the examples focus on analysis of samples, the methods may also be applied to species analysis. Dendrograms derived by hierarchical clustering are compared using cophenetic correlations, which are also used to determine optimum  in flexible beta clustering. A plot of cophenetic correlation against original dissimilarities reveals that a tree may be a poor representation of the full multivariate information. UNCTREE is an unconstrained binary divisive clustering algorithm in which values of the ANOSIM R statistic are used to determine (binary) splits in the data, to form a dendrogram. A form of flat clustering, k-R clustering, uses a combination of ANOSIM R and Similarity Profiles (SIMPROF) analyses to determine the optimum value of k, the number of groups into which samples should be clustered, and the sample membership of the groups. Robust outcomes from the application of such a range of differing techniques to the same resemblance matrix, as here, result in greater confidence in the validity of a clustering approach.

Clustering in non-parametric multivariate analyses.

Non-parametric multivariate analyses of complex ecological datasets are widely used. Following appropriate pre-treatment of the data inter-sample resemblances are calculated using appropriate measures. Ordination and clustering derived from these resemblances are used to visualise relationships among samples (or variables). Hierarchical agglomerative clustering with group-average (UPGMA) linkage is often the clustering method chosen. Using an example dataset of zooplankton densities from the Bristol Channel and Severn Estuary, UK, a range of existing and new clustering methods are applied and the results compared. Although the examples focus on analysis of samples, the methods may also be applied to species analysis. Dendrograms derived by hierarchical clustering are compared using cophenetic correlations, which are also used to determine optimum  in flexible beta clustering. A plot of cophenetic correlation against original dissimilarities reveals that a tree may be a poor representation of the full multivariate information. UNCTREE is an unconstrained binary divisive clustering algorithm in which values of the ANOSIM R statistic are used to determine (binary) splits in the data, to form a dendrogram. A form of flat clustering, k-R clustering, uses a combination of ANOSIM R and Similarity Profiles (SIMPROF) analyses to determine the optimum value of k, the number of groups into which samples should be clustered, and the sample membership of the groups. Robust outcomes from the application of such a range of differing techniques to the same resemblance matrix, as here, result in greater confidence in the validity of a clustering approach.

Positronium collisions with rare-gas atoms

We calculate elastic scattering of positronium (Ps) by the Xe atom using the recently developed pseudopotential method (Fabrikant and Gribakin 2014 Phys. Rev. A 90 052717) and review general features of Ps scattering from heavier rare-gas atoms: Ar, Kr and Xe. The total scattering cross section is dominated by two contributions: elastic scattering and Ps ionization (break-up). To calculate the Ps ionization cross sections we use the binary-encounter method for Ps collisions with an atomic target. Our results for the ionization cross section agree well with previous calculations carried out in the impulse approximation. Our total Ps–Xe cross section, when plotted as a function of the projectile velocity, exhibits similarity with the electron-Xe cross section for the collision velocities higher than 0.8 a.u., and agrees very well with the measurements at Ps velocities above 0.5 a.u.

Reactions of atomic and molecular ions with acetone, 1,1,1- trifluoroacetone, and hexafluoroacetone: An investigation of the effects of molecular structure on the dynamics and kinetics of ion-molecule reactions

A selected ion flow tube study of the reactions of a series of gas-phase atomic cations (S⁺, Xe⁺, O⁺, Kr⁺, N⁺, Ar⁺ and Ne⁺) and molecular ions (SF _n⁺ (n = 1-5), CF_n⁺ (n = 1-3), CF₂Cl⁺, H₃O⁺, NO⁺, N ₂O⁺, CO₂⁺, CO⁺, and N₂⁺) spanning a large range of recombination energies (6.3-21.6 eV), with acetone, 1,1,1-trifluoroacetone, and hexafluoroacetone has been undertaken with the objective of exploring the nature of the reaction ion chemistry as the methyl groups in acetone are substituted for CF₃. The reaction rate coefficients and product ion branching ratios for all 66 reactions, measured at 298 K, are reported. The experimental reaction rate coefficients are compared to theoretically calculated collisional values. Several distinct reaction processes were observed among the large number of reactions studied, including charge transfer (non-dissociative and dissociative), abstraction, ion-molecule associations and, in the case of the reactions involving the reagent ion H₃O⁺, proton transfer. 

Digital Humanities Research Through Design

Humanities Computing gave rise to the Digital Humanities, which brought considerations of a wider scope of the digital turn to humanities research. Increasingly, the area is understood to include the field of design, exemplified by definitions that describe the Digital Humanities as a “generative enterprise”. We suggest that design contributes not only to the making of digital artefacts. Design practiced with the aim to generate new knowledge constitues a research method. Design research contributes to the Digital Humanities expertise in addressing complex problems and methods for making the knowledge that is generated during a design process explicit.

Microstructures layering, mechanisms in the middle waters of the Persian Gulf

Layered structures, known as micro structures in marine environments are common features of which their formation mechanisms are first reviewed. Some methods of measuring such features based on the measurements and theories are presented for the Persian Gulf. This includes determination of layers with temperature inversion (TI) associated with double diffusive convection (DDC). The relevant associated parameters are estimated from ROPME CTD data for late winter and early summer of 1992. Only in certain parts temperature inversion and DDC are observed which seem to produce layered structures. Observations show that the places with TI and DDC are mainly confined to the frontal regions where the water entering the Persian Gulf and water exiting it meet, nearly along the axis of the Gulf. TI and DDC is mainly observer in the northern bound of the front. Typical density ratio for regions with TI and DDC is 0.7 to 0.2 and the mean depth is at about 37 ± 3 m for the Persian Gulf. TI and DDC are also found in the outflow from the Persian Gulf to the Oman Gulf which is found to be at a depth of about 250 m. Horizontal addiction and reduction of solar heating seem to be the main reasons in producing layers with TI and DDC. It is also found that the regime of DDC in the Persian Gulf is more diffusive and the flow associated with intrusion layers with TI is non-isopycnal (more unstable). However for the Oman sea both diffusive and finger regime are observed and the flow is inferred to be isopycnal (more stable statically). Typical heat and salt fluxes due to DDC are found to be 6 W/m2 and 0.36 W/m2 respectively. Effective salinity diffusivity, Ks and heat diffusivity, Kr have been estimated for the places with DDC in the Persian Gulf and Oman Gulf (Ks=1.1 *10-7 m2/s, KT= 1.88*10-6 m2/s). Their values are within the values obtained by others. The buoyancy frequency for the Persian Gulf with typical mean value of 0.05s-1 is much higher than these of the free Oceans. Such large values of N (typically 0.05 s-1) indicate that processes such as tide can produce strong internal waves which may be another factor in producing layered structures. This requires separate study.

Ku metodzie integralnej w teologii fundamentalnej. Sposoby konstruowania interdyscyplinarnych działań w poszukiwaniu locorum theologicorum. Zastosowanie i weryfikacja na przykładzie życia i twórczości Simone Weil

Niniejsza praca powstała z rozpoznanej potrzeby projektowania nowych ujęć poznawczych w teologii obejmujących, w tym samym stopniu, odniesienia do dziedzin teologicznych, jak i innych nauk. Podjęto próbę skonstruowania procedur badawczych, które mogą stać się punktem wyjścia ku stworzeniu pełnej metody integralnej w teologii fundamentalnej. Stąd tytuł pracy Ku metodzie integralnej w teologii fundamentalnej. Budowanie nowych zasad aktywności badawczej związane jest zawsze z etapem konstrukcyjnym i etapem weryfikacyjnym przygotowanych narzędzi, co zostało wyartykułowane w podtytułach: Sposoby konstruowania interdyscyplinarnych działań w poszukiwaniu »locorum theologicorum«. Zastosowanie i weryfikacja na przykładzie życia i twórczości Simone Weil. Tym samym praca jest dwuczęściowa. Celem pierwszej części jest przedstawienie, w jaki sposób konstruować poszukiwania nowych locorum theologicorum. Druga część pracy ma charakter weryfikacyjny. Opracowane narzędzia badawcze zostały zastosowane do odpowiedzi na pytanie: Na ile życie i twórczość francuskiej myślicielki, Simone Weil, może stać się źródłem dla tworzonych współcześnie opinii teologicznych? W przedstawianej pracy powiązano, dość ściśle, konstruowanie integralnego ujęcia badawczego z poszukiwaniem nowych czy reinterpretacją już rozeznanych miejsc teologicznych. Główny cel pracy związany jest z opisywaniem działań, które uprawdopodobniają otrzymanie nowych treści. Przyjęty sposób działania to wyjaśnianie, nie mające statusu pełnej prawdziwości logicznej; jednak jest ono procedurą, która pozwala w pewnym stopniu obiektywizować subiektywne dane płynące z otaczającej nas rzeczywistości. Pozwoliło to na kompetentne poruszanie się w przestrzeni zdań uznanych za prawdziwe zarówno w ramach teologii, jak i innych nauk. Dlatego w tej pracy skupiono się na przedstawieniu procedur poszukiwań, weryfikacji i możliwego zastosowania w badaniach naukowych współczesnych miejsc teologicznych. Ważniejszy jest sposób otrzymywania określonych wyników, a wynik tychże działań doceniony jest dopiero na etapie weryfikacyjnym skonstruowanych narzędzi badawczych. W części pierwszej pracy skupiono się na tworzeniu ogólnych zasad myślenia w ramach teologii fundamentalnej. Konstruowanie narzędzi badawczych rozpoczęto od rozeznania i przedstawienia najgłębszych fundamentów, korzeni zastosowanych procedur poprzez opis zasad opracowywania i przygotowywania działań operacyjnych. Określenie tych zasad związane jest z wprowadzeniem nowego sposobu ujmowania problematyki badawczej poprzez tak zwane myślenie modelowe. Pozwala ono na włączenie w proces uzasadniania otrzymanych wyników, oprócz dowodzenia i tłumaczenia, również tak zwanego wyjaśniania, poprzez zataczanie coraz wyższych kręgów po metodycznej spirali, której osią jest odniesienie do Bożego Objawienia odczytanego we wspólnocie Kościoła. Dzięki temu otrzymano śmiałą hipotezę, w której uwzględniono w tym samym stopniu Objawienie Boga, jak i adresata tegoż, z jego pełnym osadzeniem w rzeczywistościach ziemskich. Holistyczne, w ramach tworzonego modelu, ujmowanie problematyki pozwoliło również na ukazywanie ciągle nowych aspektów tworzonej metody integralnej. Opracowane zostały zasady konstruowania modelu ujmowania rzeczywistości Objawienia w aspekcie przedmiotowym. Jako podstawę działań przyjęto istniejącą już w teologii fundamentalnej metodę historiozbawczą. Przechodząc do systematycznej prezentacji, jako odniesienia graniczne tworzonego modelu «przestrzeni eklezjalnej» wprowadzono ujęcia teologiczne św. Ireneusza z Lyonu i św. Justyna Męczennika. Konstruując narzędzia pozwalające na ujęcia podmiotowe treści przeżyć odbiorcy Objawienia jako odniesienia graniczne wprowadzono koncepcje Umberto Eco, Geralda O’Collinsa i Paula Ricoeura. Pozwalają one na modelowe ujęcie ludzkich przeżyć jako «dzieła otwartego». W etapie czwartym podjęto próbę ustalenia zasad wzajemnego przenikania się ujęć przedmiotowych i podmiotowych problematyki badawczej, by stworzyć ujęcie integralne w opracowywaniu treści teologicznych. Powstały model «wzajemnych oddziaływań» okazał się przydatnym narzędziem w ocenie teologicznego potencjału interdyscyplinarnych oddziaływań pomiędzy teologią fundamentalną a treściami innych nauk. Pozwolił on doprecyzować warunki możliwości przyjęcia jakiejś ludzkiej aktywności jako locus theologicus z zachowaniem odpowiedniej relacji do Objawienia odczytanego we wspólnocie Kościoła z możliwym do osiągnięcia stopniem obiektywizacji. W cześć drugiej pracy realizuje się konieczną w naukach weryfikację opracowanych narzędzi badawczych i uwiarygodnienia działań operacyjnych poprzez zastosowanie do analizy konkretnego przypadku, którym jest życie i twórczość Simone Weil. Praca w tej części również została podzielona na etapy według aspektowego ujęcia umożliwiającego różne punkty widzenia tego samego przedmiotu badawczego. Ponieważ opracowane modele teoretyczne tworzą ramy dla nowej twórczości badacza, kolejne etapy weryfikacyjne są dalszym ciągiem budowania sposobów ujęcia ukonkretnionej tematyki. Życie i twórczość Simone Weil zostały przedstawione w czterech perspektywach badawczych. Pierwsza z nich jest ujęciem z punktu widzenia relacji «dzieło – autor dzieła», kolejna wprowadza dodatkowe odniesienia związane z relacją «dzieło – odbiorca dzieła». Trzeci aspekt skupia się na możliwych do odczytania z twórczości Simone Weil, treściach teologicznych na bazie relacji «dzieło – badacz dzieła». Najpłodniejszym badawczo okazało się odniesienie «dzieła», któremu na imię Simone Weil ku wymiarowi eschatologicznemu chrześcijaństwa. Opracowana metoda i przedstawione warunki weryfikacyjne ustalające kryteria w uznaniu jej przemyśleń i koncepcji jako locus theologicus ukazały się jako niezwykle przydatne.

Quiralidade, superfície de energia potencial e dinâmica de complexos envolvendo H2O2 + gases nobres

Tese (doutorado)—Universidade de Brasília, Instituto de Física, 2015.