In Global Health Research, Is It Legitimate To Stop Clinical Trials Early on Account of Their Opportunity Costs?

This debate examines the ethics of reallocating resources invested in existing trials of older products into new trials of more scientifically advanced products

A generative-oriented model-driven design environment for customizable video surveillance systems

To tackle the growing complexity and huge demand for tailored domestic video surveillance systems along with a high demanding time-to-market expectation, engineers at IVV Automação, LDAa are exploiting video surveillance domain as families of systems that can be developed following a pay-as-you-go fashion rather than developing an ex-nihilo new product. Several and different new functionalities are required for each new product’s hardware platforms (e.g., ranging from mobile phone, PDA to desktop PC) and operating systems (e.g., flavors of Linux, Windows and MAC OS X). Some of these functionalities have special economical constraints of development time and memory footprint. To better accommodate all the above listing requirements, a model-driven generative software development paradigm supported by mainstream tools is proposed to offer a significant leverage in hiding commonalities and configuring variabilities across families of video surveillance products while maintaining the new product quality.This work was funded through the Competitive Factors Operational Program COMPETE and through national funds though the Science and Technology Foundation - FCT, within the project: FCOMP-01-0124-FEDER-022674. This work was developed in cooperation with IVV Automation; all support and means provided by the company is acknowledged

Разработка тест-систем для полуколичественного выявления антител у свиней к вирусу гепатита Е в Республике Беларусь

Viral hepatitis E infection affects up to 80-100 % of domestic pigs worldwide and is characterized by high seroprevalence among domestic pigs in temperate climate countries. Epizootic monitoring of HEV infection is insufficient in the Republic of Belarus due to lack of the required number of available and inexpensive diagnostic ELISA kits with good sensitivity and specificity. In this regard, research on development of domestic ELISA kit for semi-quantitative detection of antibodies to hepatitis E virus in pigs with subsequent assessment of seroprevalence to HEV in pig population in the Republic of Belarus is relevant. The results of studies on development of enzyme-linked immunosorbent assay kit for semi-quantitative determination of class G immunoglobulins to HEV in pig blood serum using recombinant proteins, including immunodominant amino acid sequences corresponding to the ORF2 and ORF3 proteins of HEV genotype 3 are presented in the paper. The optimal concentration for sorption of ORF2 and ORF3 proteins has been determined, which is 2 μg/ml and 1 μg/ml, respectively. The diagnostic sensitivity of this test kit makes 94.8 %, and the diagnostic specificity makes 100 %. Coefficients of variation being the criterion for assessing the intra-serial and inter-serial reproducibility of this test kit, make 3.5 % and 12.4 %, respectively, which allows to obtain reproducible results and identify specific anti-HEV antibodies in all positive samples of pig blood serum. When studying 1235 pig sera samples from various pig farms of Brest, Vitebsk, Gomel, Grodno, Minsk and Mogilev regions, seroprevalence of anti-HEV antibodies has been determined in 168 or 13.6 % of animals. The described diagnostic method can be widely used in science and practice for the further study of seroprevalence of anti-HEV. Acknowledgments. The research was carried out as part of the Interstate program of innovation cooperation of States - participants of the CIS up to 2020, with the financial support of the Ministry of education and science of the Russian Federation, the project ID RFMEFI61316X0 061, and the State Committee for Science and Technology of the Republic of Belarus.Инфекция вирусного гепатита Е поражает до 80–100 % домашних свиней во всем мире и характеризуется высокой серопревалентностью среди поголовья домашних свиней в странах с умеренным климатом. В Республике Беларусь эпизоотический мониторинг ВГЕ-инфекции является недостаточным ввиду отсутствия необходимого количества доступных и недорогих диагностических ИФА тест-систем с хорошей чувствительностью и специфичностью. В этой связи проведение исследований по разработке отечественной тест-системы для полуколичественного выявления антител к вирусу гепатита Е у свиней с последующей оценкой серопревалентности к ВГЕ в популяции свиней в Республике Беларусь является актуальным. В статье представлены результаты исследований по разработке иммуноферментной тест-системы для полуколичественного определения иммуноглобулинов класса G к ВГЕ в сыворотке крови свиней с использованием рекомбинантных белков, включающих иммунодоминантные аминокислотные последовательности, соответствующие белкам ОRF2 и ОRF3 ВГЕ 3-го генотипа. Определена оптимальная концентрация для сорбции белков ОRF2 и ОRF3 – 2 и 1 мкг/мл соответственно. Диагностическая чувствительность данной тест-системы составляет 94,8 %, а диагностическая специфичность – 100 %. Коэффициенты вариации, являющиеся критерием оценки внутрисерийной и межсерийной воспроизводимости данной тест-системы, составляют 3,5 и 12,4 % соответственно, что позволяет получать воспроизводимые результаты и выявлять специфические антитела к ВГЕ во всех положительных образцах сывороток крови свиней. При исследовании 1235 проб сывороток свиней из разных свиноводческих хозяйств Брестской, Витебской, Гомельской, Гродненской, Минской и Могилевской областей антитела к антигенам вируса гепатита Е (ВГЕ) были обнаружены у 168, или у 13,6 % животных. Описанный метод диагностики может найти широкое применение для науки и практики с целью дальнейшего изучения серопревалентности анти-ВГЕ. Благодарности. Работа выполнена в рамках Межгосударственной программы инновационного сотрудничества государств – участников СНГ на период до 2020 года при финансовой поддержке Министерства образования и науки Российской Федерации, идентификатор проекта RFMEFI61316X0061, и Государственного комитета по науке и технологиям Республики Беларусь

РЕЗУЛЬТАТЫ ИСПОЛЬЗОВАНИЯ СОФОСБУВИРА В КОМБИНАЦИИ С ЛЕДИПАСВИРОМ ИЛИ ДАКЛАТАСВИРОМ ДЛЯ ЛЕЧЕНИЯ ХРОНИЧЕСКОГО ГЕПАТИТА С В РЕСПУБЛИКЕ БЕЛАРУСЬ

To evaluate the efficacy of therapy with sofosbuvir in combination with ledipasvir or daclatasvir, the results of treatment of 299 patients with chronic hepatitis C, including 128 non-responders to combined interferon plus ribavirin therapy, who have prognostically unfavorable single nucleotide polymorphisms 39743165T> G (rs8099917) and 39738787C> T (rs12979860) of interleukin-28B gene, were analyzed. 57 people had liver cirrhosis. 80,9% (242) had genotype 1 of hepatitis C virus, 5% (15) – genotype 2, 13,7% (41) – genotype 3, and 0,4% (1) – genotype 4.All 299 patients, who adhered to the recommendations of the European Association for the Study of the Liver 2016 and the American Association for the Study of the Liver Disease 2017, achieved a sustained virologic response 12 weeks after the end of therapy. The clinical case of treatment failure, associated with the lack of confirmation of the elimination of hepatitis C virus by means of highly sensitive polymerase chain reaction methods and with the later identified amino acid substitution in position Y93H of NS5A (resistance to NS5A inhibitors), is shown.It is necessary to carry out monitoring of effectiveness of therapy only by means of highly sensitive polymerase chain reaction (from 10 ME/ml). If the virus elimination delays in patients with advanced stages of liver fibrosis it is needed to use the prolonged schemes of treatment. Repeated treatment of patients with existence of a mutation of Y93H requires the use of new NS5A inhibitors or combined drugs.С целью оценки эффективности терапии препаратами софосбувир в комбинации с ледипасвиром или даклатасвиром были проанализированы исходы лечения 299 пациентов с хроническим гепатитом С, включая 128 ранее неудачно пролеченных интерферонами и рибавирином, а также имеющих прогностически неблагоприятные однонуклеотидные полиморфизмы 39743165T>G (rs8099917) и 39738787C>T (rs12979860) гена интерлейкин-28В. У 57 пациентов был диагностирован цирроз печени, 128 пациентов были ранее неудачно пролечены интерферонами и рибавирином. У 80,9% (242) был первый генотип вируса, у 5% (15) – второй, у 13,7% (41) – третий, у 0,4% (1) – четвертый.В результате исследования было отмечено, что все 299 пациентов, которые придерживались рекомендаций European Association for the Study of the Liver 2015, 2016 и American Association for the Study of the Liver Disease 2017, достигли устойчивого вирусологического ответа через 12 недель после окончания терапии. Приведен клинический случай неудачного лечения, связанный с отсутствием подтверждения элиминации вируса гепатита С при помощи высокочувствительных методов полимеразной цепной реакции и с позднее выявленной аминокислотной заменой в позиции Y93H NS5A (резистентность к ингибиторам NS5A).Мониторинг эффективности терапии необходимо проводить только при помощи высокочувствительных методик полимеразной цепной реакции (от 10 МЕ/мл) и при задержке элиминации вируса у пациентов с продвинутыми стадиями фиброза печени использовать пролонгированные схемы лечения. Для повторного лечения пациентов с наличием мутации Y93Н необходимы новые препараты ингибиторов NS5A или комбинированных препаратов.

Wykorzystanie mniszka lekarskiego (Taraxacum officinale) do oceny antropogenicznego zanieczyszczenia środowiska metalami toksycznymi

The common dandelion (Taraxacum officinale) is a widely distributed plant, not only geographically but also in terms of diverse, often extremely polluted habitats. It is therefore potentially an ideal plant to study accumulation of anthropogenic pollution. The aim of the study was to determine the suitability of common dandelion to assess the environmental contamination of Cd, Cr, Cu, Fe, Mn, Ni, Pb, Ti, Zn, V. The plants were collected from sites initially identified as significantly polluted as well as habitats presumably hardly contaminated. Analyses were made using inductively coupled plasma optical emission spectrometry (ICP OES) in argon, following decomposition of the organic matrix of samples using a mixture of 65% HNO3 and 30% H2O2 in a microwave digestion system. Elevated levels of Cd, Cr, Cu, Fe, Ni and Ti were found both in the leaves and roots of dandelion collected from more polluted sites. The results show that the common dandelion can be a good bio-indicator of environmental contamination for these elements. For the other studied metals, the results were not so unequivocal. In the case of Cd, Cr, Mn, and Ni, statistically significant correlation was found in the concentrations of these elements between the dry matter of leaves and roots.Mniszek pospolity (Taraxacum officinale) jest rośliną bardzo rozpowszechnioną nie tylko geograficznie, lecz także pod względem różnorodności siedlisk, często niezwykle silnie zanieczyszczonych. Jest zatem rośliną potencjalnie idealną do badań nad kumulacją zanieczyszczeń antropogenicznych. Celem badań było ustalenie przydatności mniszka pospolitego do oceny skażenia środowiska naturalnego Cd, Cr, Cu, Fe, Mn, Ni, Pb, Ti, Zn, V. Rośliny pobrano z miejsc wstępnie uznanych za znacznie skażone oraz z siedlisk przypuszczalnie mało zanieczyszczonych. Analizy wykonano metodą spektrometrii emisyjnej ze wzbudzeniem w indukcyjnie sprzężonej plazmie argonowej (ICP OES), po dekompozycji osnowy organicznej próbek mieszaniną 65% HNO3 i 30% H2O2 w mineralizatorze mikrofalowym. Zarówno w liściach, jak i w korzeniach mniszka pobranego z miejsc bardziej zanieczyszczanych stwierdzono podwyższony poziom Cd, Cr, Cu, Fe, Ni i Ti. Uzyskane wyniki wskazują, że mniszek pospolity może być dobrym bioindykatorem skażenia środowiska tymi pierwiastkami. W odniesieniu do pozostałych badanych metali wyniki nie okazały się tak jednoznaczne. W przypadku Cd, Cr, Mn, i Ni wykazano występowanie statystycznie istotnych korelacji między zawartością tych pierwiastków w suchej masie liści i korzeni

Four different Phytophthora species that are able to infect Scots pine seedlings in laboratory conditions

To investigate susceptibility of young Scots pine seedlings to four Phytophthora species: Phytophthora cactorum, Phytophthora cambivora, Phytophthora plurivora and Phytophthora pini; seven-day-old seedlings of Scots pine (15 seedlings per experiment) were infected using agar plugs of the respective species. Control group also consisted of 15 seedlings and was inoculated with sterile agar plugs. Results unambiguously show that after 4.5 days, all seedlings show clear signs of infection and display severe symptoms of tissue damage and necrosis. Moreover, three and two seedlings in the P. cactorum and P. cambivora infected seedlings groups, respectively, collapsed. The length of largest necrosis measured 13.4±3.90 mm and was caused by P. cactorum. To rule out any putative contamination or infection by secondary pathogens, re-isolations of pathogens from infection sites were performed and were positive in 100% of plated pieces of infected seedlings. All re-isolations were, however, negative in the case of the control group. Detailed microscopic analyses of infected tissues of young seedlings confirmed the presence of numerous Phytophthora species inside and on the surface of infected seedlings. Therefore, our results suggest Phytophthora spp. and mainly P. cactorum and P. cambivora as aggressive pathogens of Scots pine seedlings and highlight a putative involvement of these species in the damping off of young Scots pine seedlings frequently observed in forest nurseries

Four different Phytophthora species that are able to infect Scots pine seedlings in laboratory conditions

To investigate susceptibility of young Scots pine seedlings to four Phytophthora species: Phytophthora cactorum, Phytophthora cambivora, Phytophthora plurivora and Phytophthora pini; seven-day-old seedlings of Scots pine (15 seedlings per experiment) were infected using agar plugs of the respective species. Control group also consisted of 15 seedlings and was inoculated with sterile agar plugs. Results unambiguously show that after 4.5 days, all seedlings show clear signs of infection and display severe symptoms of tissue damage and necrosis. Moreover, three and two seedlings in the P. cactorum and P. cambivora infected seedlings groups, respectively, collapsed. The length of largest necrosis measured 13.4±3.90 mm and was caused by P. cactorum. To rule out any putative contamination or infection by secondary pathogens, re-isolations of pathogens from infection sites were performed and were positive in 100% of plated pieces of infected seedlings. All re-isolations were, however, negative in the case of the control group. Detailed microscopic analyses of infected tissues of young seedlings confirmed the presence of numerous Phytophthora species inside and on the surface of infected seedlings. Therefore, our results suggest Phytophthora spp. and mainly P. cactorum and P. cambivora as aggressive pathogens of Scots pine seedlings and highlight a putative involvement of these species in the damping off of young Scots pine seedlings frequently observed in forest nurseries