Two-step algorithm for the automated analysis of fluorescent microscopy data in biomedical applications

© 2017 IEEE. Measurement automation is essential in various biomedical and biotechnological applications become increasingly important with their intensification and wide utilization. Estimation of both pro- and eukaryotic cells subpopulations in different cultures, samples and tissues, including differentiation of live and dead bacterial cells, stem cells in eukaryotic cell culture and so on are essential in multiple biomedical and biotechnological applications. Fluorescent microscopy is a widely used methodology to obtain the above estimates. Wide utilization of biotechnologies increases the importance of automatic microscopic image processing tools design aiming at both qualitative and quantitative assessment of cells sub-populations. Existing methods are mostly based either on cell detection and counting or on the statistical analysis of image areas with similar staining. However, these methods exhibit known drawbacks including their inapplicability to the communities of cells adherent to each other and to external surfaces with biofilms being a prominent example. Another limitation of standard image processing tools in their high level of automation limiting the ability of the operator to adjust the algorithm parameters to particular microscopic imaging conditions as well as to specific features of the studied cells subpopulations. Here we present a two-step algorithm including preliminary adjustment of its parameters to the imaging conditions based on several representative images from the studied cohort in the first step and fully automated analysis of a large series of images with fixed algorithm parameters in the second step. Out results indicate that the suggested methodology is barely sensitive to the decision threshold value that allows to reduce the parameterization of the algorithm

Locoregional and systemic therapy for hepatocellular carcinoma

The management of hepatocellular carcinoma (HCC) remains challenging due to late presentation and the presence of accompanying liver dysfunction. As such, most patients are not eligible for curative resection and liver transplant. Management in this scenario depends on a number of factors including hepatic function, tumor burden, patency of hepatic vasculature and patients' functional status. Based on these, patients can be offered catheter based intra-arterial therapy for intermediate stage disease and in more advanced disease, sorafenib. Given recent data, regorafenib is now an option following failure of sorafenib. Catheter directed intra-arterial therapy takes advantage of tumor hypervascularity and the unique dual blood supply of the liver, as hepatic tumors receive arterial perfusion via the hepatic artery while the rest of the liver is supplied by the portal vein. This allows selective embolization and delivery of chemotherapeutic agents to the tumor. Compared to best supportive care, intra-arterial therapy offers a survival benefit in intermediate stage HCC and is the recommended approach for treatment. None of the catheter based approaches; including bland embolization, conventional trans-arterial chemoembolization (cTACE), drug eluting bead trans-arterial chemoembolization (DEB-TACE) or trans-arterial radioembolization (TARE) offers a clear advantage over the other, although DEB-TACE may be characterized by less systemic toxicity. All of these approaches are contraindicated in patients with portal vein thrombosis (PVT). On the other hand, intra-arterial, radio embolization, with Yttrium-90 (Y90) can be offered to patients with PVT. The place of this modality in management of HCC is still being investigated. The role of sorafenib in advanced HCC is not in doubt, as until recently, it was the only systemic therapy approved for the management in this setting. This is despite multiple trials evaluating other agents. The addition of sorafenib to catheter-based therapy in intermediate stage disease has also failed to show any benefit. The modest survival benefit with sorafenib and the failure of other targeted agents suggest that it is important to look beyond inhibition of angiogenesis in advanced HCC. Identification of key drivers and mediators of HCC remains paramount for successful drug development. In line with this, it is refreshing that the excitement that has followed developments in cancer immunotherapy is finding its way to HCC with early trials of anti-PD1 monoclonal antibodies showing sufficient activity that phase III trials are now ongoing for Pembrolizumab and Nivolumab in advanced HCC. Future drug development efforts will focus on defining the feasibility of combining different treatment approaches targeting multiple important modulators of HCC

Life threatening hemobilia after endoscopic retrograde cholangiopancreatography (ERCP)

Arterial vascular complication from endoscopic retrograde cholangiopancreatography (ERCP) is exceedingly rare. This report describes a life threatening hemobilia, from a pseudoaneurysm of the right hepatic artery (RHA), which occurred post ERCP. The pseudoaneurysm and the active bleed were diagnosed by selective angiography of the RHA, and successfully treated with stenting

Исследование взаимной динамики стохастических нормально распределенных процессов при аддитивной амплитудной расстройке между ними

The joint analysis of several signals is essential for better understanding of the principles underlying the complex systems dynamics. We consider three methods for estimating the stability of the relative dynamics of two surrogate processes. The first one is based on calculation of the phase synchronization coefficient S and the second one on estimation of the cross-conditional entropy CE. The third approach uses the average value of the coherence function of the two processes - the coherence coefficient C. We study the sensitivity of these methods in relation to the amplitude randomization between test processes. All methods are applied to analyze two types of normally distributed random stochastic processes, with either short-term correlations characterized by finite correlation time or long-term correlations with theoretically infinite correlation time characterized by Hurst exponents. In our research, we generate two copies of the surrogate process with either short-term or long-term correlations. Then we attribute the additive white noise to one of these copies at first with the uniform distribution and then with the Gaussian distribution and the same variance. Next, we calculate the coefficients that characterize the mutual behavior of the two test processes and estimate their statistical characteristics. It is found that the sensitivity of all methods to Gaussian additive noise is higher than that of uniform one. We show that processes with long-term correlation react more actively to the additive amplitude noise then processes with short-term correlation. The influence of Hurst exponent value for the processes with long-term correlation is expressed for the coefficients S and C. The influence of correlation time is demonstrated for the coefficients S and СЕ. Our results may be useful in investigations of the mutual dynamics of two processes belonging to the considered types. Функционирование сложных систем возможно характеризовать совместными статистическими характеристиками порождаемых этими системами сигналов. Рассмотрены три подхода к оцениванию стабильности взаимного поведения двух тестовых процессов. Первый подход основан на расчете коэф­фициента фазовой синхронизации (КФС) между процессами. Второй метод базируется на определении взаимной условной энтропии (ВУЭ) процессов. Согласно третьему методу для оценивания стабильности взаимной динамики процессов используется среднее значение функции когерентности (ФК). Исследована чувствительность указанных методов к аддитивной амплитудной расстройке между процессами. Рас­ смотрены два типа процессов: с кратковременной зависимостью и заданным временем корреляции (ВК) и с долговременной зависимостью, определяемой значением показателя Херста. В исследованиях генерирова­лись две копии процесса с известными корреляционными свойствами. Затем в одну из копий вносилась ад­дитивная амплитудная помеха с независимыми отсчетами, подчиняющимися равномерному или нормаль­ ному распределению с одинаковой дисперсией. Для каждого типа помехи и каждого значения ее интенсив­ности оценивались статистические характеристики КФС, ВУЭ и ФК. Выявлено, что чувствительность рассмотренных методов к нормально распределенной расстройке выше, чем к равномерной. При этом процессы с долговременной зависимостью активнее реагируют на аддитивную амплитудную расстройку, чем процессы с кратковременной зависимостью. Влияние показателя Херста для процессов с долговременной зависимостью выражено для КФС и ФК. ВК процессов с кратковременной зависимостью влияет на КФС и ВУЭ. Полученные результаты позволяют обоснованно выбрать необходимый метод анализа взаимной динамики процессов, принадлежащий к рассмотренным в настоящей статье типам.

Исследование методов оценивания стабильности взаимного поведения стохастических процессов

The sensitivity of some methods for estimating the mutual dynamic stability of stochastic processes with given correlative properties was studied in relation to the phase detuning between the processes. Two classes of normally distributed random stochastic processes are considered: the processes with short-term correlation and the processes with a long-term correlation, characterized by the specified Hurst coefficients.На примере тестовых процессов с заданными корреляционными свойствами исследована чувствительность методов оценивания стабильности взаимной динамики стохастических процессов к фазовой расстройке между ними. Рассмотрены два класса нормально распределенных стохастических случайных процессов: процессы с кратковременной зависимостью и процессы с долговременной зависимостью, характеризующиеся заданным показателем Херста

Исследование методов оценивания стабильности взаимного поведения стохастических процессов

The sensitivity of some methods for estimating the mutual dynamic stability of stochastic processes with given correlative properties was studied in relation to the phase detuning between the processes. Two classes of normally distributed random stochastic processes are considered: the processes with short-term correlation and the processes with a long-term correlation, characterized by the specified Hurst coefficients.На примере тестовых процессов с заданными корреляционными свойствами исследована чувствительность методов оценивания стабильности взаимной динамики стохастических процессов к фазовой расстройке между ними. Рассмотрены два класса нормально распределенных стохастических случайных процессов: процессы с кратковременной зависимостью и процессы с долговременной зависимостью, характеризующиеся заданным показателем Херста

The impact of Grey Heron (Ardea cinerea L.) colony on soil biogeochemistry and vegetation: a natural long-term in situ experiment in a planted pine forest

Increased anthropogenic pressure including intensification of agricultural activities leads to long-term decline of natural biotopes, with planted forests often considered as promising compensatory response, although reduced biodiversity and ecosystem stability represent their common drawbacks. Here we present a complex investigation of the impact of a large Grey Heron (Ardea cinerea L.) colony on soil biogeochemistry and vegetation in a planted Scots pine forest representing a natural in situ experiment on an engineered ecosystem. After settling around 2006, the colony expanded for 15 years, leading to the intensive deposition of nutrients with feces, food remains and feather thereby considerably altering the local soil biogeochemistry. Thus, lower pH levels around 4.5, 10- and 2-fold higher concentrations of phosphorous and nitrogen, as well as 1.2-fold discrepancies in K, Li, Mn, Zn and Co., respectively, compared to the surrounding control forest area could be observed. Unaltered total organic carbon (Corg) suggests repressed vegetation, as also reflected in the vegetation indices obtained by remote sensing. Moreover, reduced soil microbial diversity with considerable alternations in the relative abundance of Proteobacteria, Firmicutes, Acidobacteriota, Actinobacteriota, Verrucomicrobiota, Gemmatimonadota, Chujaibacter, Rhodanobacter, and Bacillus has been detected. The above alterations to the ecosystem also affected climate stress resilience of the trees indicated by their limited recovery from the major 2010 drought stress, in marked contrast to the surrounding forest (p = 3∙10−5). The complex interplay between geographical, geochemical, microbiological and dendrological characteristics, as well as their manifestation in the vegetation indices is explicitly reflected in the Bayesian network model. Using the Bayesian inference approach, we have confirmed the predictability of biodiversity patterns and trees growth dynamics given the concentrations of keynote soil biogeochemical alternations with correlations R > 0.8 between observations and predictions, indicating the capability of risk assessment that could be further employed for an informed forest management

Ассоциации полиморфных вариантов rs2305619 и rs3816527 гена пентраксина-3 (PTX3) с особенностями клинического течения и исходов у пациентов с гипертрофической кардиомиопатией: результаты 11-летнего наблюдения.

The objective of this study was to determine the association of polymorphic variants rs2305619 and rs3816527 of the PTX3 gene with clinical profile and outcomes in hypertrophic cardiomyopathy (HCM) patients.Methods and materials. The study population consisted of 153 patients ≥18 years old with a confirmed diagnosis of HCM. The control group included 200 healthy donors. Duration of follow-up was 11 years (2008–2019 yrs.). The study design included a new model for determining variants of the clinical profile and outcomes of HCM. Polymorphic variants rs2305619 and rs3816527 of the PTX3 gene were genotyped by polymerase chain reaction.Results. The mortality rate in patients ≥18 years old with 1, 2 and 3 adverse pathways of HCM progression was significantly higher, compared with those without adverse pathways (р<0.001). A combination of chronic heart failure (CHF) with midrange and reduced LVEF (<49 %) with 1, 2 and 3 adverse pathways in HCM patients occurred more frequently, compared with those who had CHF with preserved LVEF (≥50 %) (odds ratio (OR) = 0.168, 95 % confidence interval (CI) =0.068–0.412, р<0.001). The genetic testing showed no significant differences in genotype and allele frequencies of polymorphic variants rs2305619 and rs3816527 of the PTX3 gene in patients with HCM and control groups. It was found a tendency for increase in GG genotype frequency (p<0.068) and significant increase in G allele frequency of rs2305619 of the PTX3 gene in HCM patients ≥18 years old and CHF with mid-range and reduced LVEF (<49 %) (A:G, OR=0.521, 95 % CI=0.301–0.902, p<0.019). HCM patients (age – 63 [58; 75] years) and type 2 diabetes mellitus demonstrated high prevalence in AG and GG genotypes (p<0.008) and G allele frequencies of rs2305619 of the PTX3 gene (A:G, OR =1.952, 95 % CI=1.076–3.542, p<0.026).Conclusions. HCM progression along 1 and more adverse pathways in patients ≥18 years old has been characterized with adverse outcome. G allele of rs2305619 of the PTX3 gene is associated with CHF with mid-range and reduced LVEF (<49 %) in HCM patients ≥18 years old. The associations of G allele and AG and GG genotypes of rs2305619 of the PTX3 gene with diabetes type 2 are observed in elderly HCM patients.Цель – изучить ассоциации полиморфных вариантов rs2305619 и rs3816527 гена пентраксина-3 (PTX3) с особенностями клинического течения и исходов у пациентов с гипертрофической кардиомиопатией (ГКМП).Методы и материалы. В исследование (2008–2019) включены 153 пациента в возрасте ≥18 лет с подтвержденным диагнозом ГКМП. Группу контроля составили 200 практически здоровых человек. Дизайн исследования включал в себя новую модель определения вариантов клинического течения и исходов ГКМП. Полиморфные варианты rs2305619 и rs3816527 гена PTX3 были идентифицированы методом полимеразной цепной реакции.Результаты. У пациентов с ГКМП в возрасте ≥18 лет при наличии одного, двух и трех путей прогрессирования заболевания смертность за 11 лет значимо превышала аналогичный показатель у пациентов с малосимптомным течением (р<0,001). Хроническая сердечная недостаточность (ХСН) со средней и сниженной фракцией выброса левого желудочка (ФВ ЛЖ) (<49 %) значимо чаще сочеталась с наличием одного, двух и трех путей прогрессирования заболевания, по сравнению с ХСН с сохраненной ФВ ЛЖ (≥50 %) (ОШ=0,168, 95 % ДИ=0,068–0,412, р<0,001). Значимых различий в распределении генотипов и аллелей полиморфных вариантов rs2305619 и rs3816527 гена PTX3 у больных ГКМП и контрольной группе получено не было. Аллель G rs2305619 гена PTX3 определялся достоверно чаще у пациентов с ГКМП и ХСН со средней и сниженной ФВ ЛЖ (<49 %), по сравнению с сохраненной ФВ ЛЖ (≥50 %) (A:G, ОШ=0,521, 95 % ДИ=0,301–0,902, p<0,019). Была определена тенденция к преобладанию генотипа GG rs2305619 гена PTX3 при наличии ХСН со средней и сниженной ФВ ЛЖ (<49 %) (p<0,068). У пациентов с ГКМП и сахарным диабетом (СД) II типа (возраст – 63 [58; 75] года) статистически значимо преобладали генотипы AG и GG (p<0,008) и аллель G rs2305619 гена PTX3 (A:G, ОШ =1,952, 95 % ДИ=1,076–3,542, p<0,026)

Service delays in strongly linked network communities

We analyze aggregated traffic dynamics obtained from strongly linked network communities. Our results based on two empirical data traces from university campus networks indicate that neglecting the statistical links between traffic patterns generated by individual network nodes leads to the drastic underestimation of both waiting and sojourn times. We also show that similar effects can be observed in simulated traffic patterns obtained by agent based modeling. Moreover, we suggest several indices that could be used to quantify the links between nodes and show their relation with the queuing system performance indicators