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Locus Coeruleus (LC) is the main noradrenergic nucleus of the brain, which is involved in many physiological functions including cognition; its impairment may be crucial in the neurobiology of a variety of brain diseases. Locus Coeruleus-Magnetic Resonance Imaging (LC-MRI) allows to identify in vivo LC in humans. Thus, a variety of research teams have been using LC-MRI to estimate LC integrity in normal aging and in patients affected by neurodegenerative disorders, where LC integrity my work as a biomarker. A number of variations between LC-MRI studies exist, concerning post-acquisition analysis and whether this had been performed within MRI native space or in ad hoc -built MRI template space. Moreover, the reproducibility and reliability of this tool is still to be explored. Therefore, in the present study, we analyzed a group of neurologically healthy, cognitively intact elderly subjects, using both a native space- and a template space-based LC-MRI analysis. We found a good inter-method agreement, particularly considering the LC Contrast Ratio. The template space-based approach provided a higher spatial resolution, lower operator-dependency, and allowed the analysis of LC topography. Our ad hoc -developed LC template showed LC morphological data that were in line with templates published very recently. Remarkably, present data significantly overlapped with a recently published LC “metaMask”, that had been obtained by averaging the results of a variety of previous LC-MRI studies. Thus, such a template space-based approach may pave the way to a standardized LC-MRI analysis and to be used in future clinic–anatomical correlations.

The aim of the paper was to evaluate dry and wet periods in selected climatic stations in eastern Slovakia using the drought indices. We evaluated drought occurrence using the following indexes: standardized precipitation index (SPI), streamflow drought index (SDI), drought reconnaissance index (RDI) and standardized evapotranspiration index (SPEI) in a 12-month step over the period 1960-2015. The evaluation of the results showed alternation of wet and dry periods. The result of the work is identification of the dry and wet years according the separate indexes during the evaluated period.

One of the most important aspects of climate change is the time distribution of precipitation and its historical changes. In this study, trend analysis of annual precipitation, daily maxims and days without precipitation in three precipitation stations in eastern Slovakia is presented. These are stations Poprad, Košice, and Kamenica nad Cirochou. Individual trends are compared and evaluated. Significant positive trend was observed in maximum daily precipitation in Kamenica nad Cirochou station and in total annual precipitation in Poprad station. Moderate positive trend was observed in maximum daily precipitation in Poprad station and number of days without precipitation in Kamenica nad Cirochou station. No trends were observed in Kosice station.

The study of hydrological risk assessment is performed with the goal to reduce impacts of droughts and floods. Drought is the most complex but least understood of all natural hazards. It is broadly defined as \"severe water shortage\". Floods cause huge but mainly material damages. Mentioned natural hazards cause loss of life, human and animal suffering and damage to economy and environment. The present study area is prone to extreme climate events such as drought and flood. The objective of this study was to investigate precipitation trends in the chosen climatic stations in Libya and Slovakia. Annual and monthly precipitation trends were detected by the Mann-Kendall statistical test. Significant negative trends of annual precipitation were found in four out of seventeen analyzed rainfall gauging stations in Libya. Significant positive trends of annual precipitation were found in six out of twenty analyzed rainfall gauging stations in Slovakia. November and August were observed to have decreasing trends in Libya and March in Slovakia. All other months displayed increasing trends in precipitation. The results show a trend towards drier conditions in Libya and an increase of moisture in Slovakia.

The paper presents a drought characterization for Slovakia based on the standardized precipitation index at the time scale of three months (SPI3) applied to the precipitation records at 491 Slovakian rain gauges over a considerable span (33 years). After a drought spatial regionalization, using Principal Component Analysis (PCA), the kernel occurrence rate estimation method coupled with bootstrap confidence band was applied to characterize the yearly drought occurrence rates in each one of the regions given by the PCA, aiming at identifying trends in the frequency of the droughts. The study also includes examples of surfaces of precipitation thresholds that can be easily and reliably utilized to recognize and monitor the drought occurrences at the early stages of their development. Those surfaces were obtained by reverting to the original precipitation field the values of the SPI that represent drought limits.

When extreme and non-extreme physical events, such as drought, can affect elements of human systems in an adverse manner, it assumes the characteristic of a hazard. Droughts are the most complex but least understood of all natural hazards. It is broadly defined as a \"severe water shortage\". The objective of this paper was to investigate the number of days without precipitation during 30 years in chosen climatic stations in the eastern Slovakia. The results of the research proved that the occurrence of a drought in Slovakia is rare although periods longer than 30 days without precipitation were detected. This research may be helpful as one of the documents for water management practice, for example, for proposals of water harvesting in the country, the designing of other water structures or agricultural practices in the study area. The study of drought assessment is performed with the main goal of reducing negative impacts of droughts.

The paper focuses on assessing the effects of floods on selected components of the environment in the Hornád river basin: the impact of floods on population, water conditions, soil, fauna, flora and their habitats, structure and use of land and landscape, protected areas and their protection zones, the territorial system of ecological stability, urban complexes and land use, cultural and historical heritage, cultural values of an intangible nature, and archaeological and paleontological sites and important geological localities. The assessment was performed using the risk analysis method. The risk index was calculated by summing the products of probabilities and consequences for each impact of flooding on the components of the environment, and the total value of the risk index is 5.5 (average risk). The hazard index was determined by quantification of industrial sources of pollution in the river basin: each source of pollution was assigned a point score; the total hazard is represented by the sum of the points for these sources of pollution, and is equal to 19. The total risk index is then represented by the product of the risk and hazard indices, i.e. 104.5. This value indicates a low level of flood damage risk in the Hornád river basin.

High-quality population-based cancer recurrence data are scarcely available, mainly due to complexity and cost of registration. For the first time in Belgium, we developed a tool to estimate distant recurrence after a breast cancer diagnosis at the population level, based on real-world cancer registration and administrative data. Data on distant cancer recurrence (including progression) from patients diagnosed with breast cancer between 2009-2014 were collected from medical files at 9 Belgian centers to train, test and externally validate an algorithm (i.e., gold standard). Distant recurrence was defined as the occurrence of distant metastases between 120 days and within 10 years after the primary diagnosis, with follow-up until December 31, 2018. Data from the gold standard were linked to population-based data from the Belgian Cancer Registry (BCR) and administrative data sources. Potential features to detect recurrences in administrative data were defined based on expert opinion from breast oncologists, and subsequently selected using bootstrap aggregation. Based on the selected features, classification and regression tree (CART) analysis was performed to construct an algorithm for classifying patients as having a distant recurrence or not. A total of 2507 patients were included of whom 216 had a distant recurrence in the clinical data set. The performance of the algorithm showed sensitivity of 79.5% (95% CI 68.8-87.8%), positive predictive value (PPV) of 79.5% (95% CI 68.8-87.8%), and accuracy of 96.7% (95% CI 95.4-97.7%). The external validation resulted in a sensitivity of 84.1% (95% CI 74.4-91.3%), PPV of 84.1% (95% CI 74.4-91.3%), and an accuracy of 96.8% (95% CI 95.4-97.9%). Our algorithm detected distant breast cancer recurrences with an overall good accuracy of 96.8% for patients with breast cancer, as observed in the first multi-centric external validation exercise.

The RAS2val19 allele, which renders the cAMP–PKA pathway constitutively active and decreases the replicative life-span of yeast cells, is demonstrated to increase production of reactive oxygen species (ROS) and to elevate oxidative protein damage. Mito chondrial respiration in the mutant is locked in a non-phosphorylating mode prone to generate ROS but this phenotype is not linked to a constitutively active PKA pathway. In contrast, providing RAS2val19 cells with the mammalian uncoupling protein UCP1 restores phosphorylating respiration and reduces ROS levels, but does not correct for PKA-dependent defects. Thus, the RAS2val19 allele acts like a double-edged sword with respect to oxidation management: (i) it diminishes expression of STRE element genes required for oxidative stress defenses in a PKA-dependent fashion, and (ii) it affects endogenous ROS production and the respiratory state in a PKA-independent way. The effect of the oncogenic RAS allele on the replicative life-span is primarily asserted via the PKA-dependent pathway since Pde2p, but not UCP1, overproduction suppressed premature aging of the RAS2val19 mutant.

Background Niemann-Pick disease type C (NP-C) is a rare neurovisceral disease characterised by progressive neurological degeneration, where the rate of neurological disease progression varies depending on age at neurological onset. We report longitudinal data on functional disease progression and safety observations in patients in the international NPC Registry who received continuous treatment with miglustat. Methods The NPC Registry is a prospective observational cohort of NP-C patients. Enrolled patients who received ≥1 year of continuous miglustat therapy (for ≥90 % of the observation period, with no single treatment interruption >28 days) were included in this analysis. Disability was measured using a scale rating the four domains, ambulation, manipulation, language and swallowing from 0 (normal) to 1 (worst). Neurological disease progression was analysed in all patients based on: 1) annual progression rates between enrolment and last follow up, and; 2) categorical analysis with patients categorised as ‘improved/stable’ if ≥3/4 domain scores were lower/unchanged, and as ‘progressed’ if <3 scores were lower/unchanged between enrolment and last follow-up visit. Results In total, 283 patients were enrolled from 28 centers in 13 European countries, Canada and Australia between September 2009 and October 2013; 92 patients received continuous miglustat therapy. The mean (SD) miglustat exposure during the observation period (enrolment to last follow-up) was 2.0 (0.7) years. Among 84 evaluable patients, 9 (11 %) had early-infantile (<2 years), 27 (32 %) had late-infantile (2 to <6 years), 30 (36 %) had juvenile (6 to <15 years) and 18 (21 %) had adolescent/adult (≥15 years) onset of neurological manifestations. The mean (95%CI) composite disability score among all patients was 0.37 (0.32,0.42) at enrolment and 0.44 (0.38,0.50) at last follow-up visit, and the mean annual progression rate was 0.038 (0.018,0.059). Progression of composite disability scores appeared highest among patients with neurological onset during infancy or childhood and lowest in those with adolescent/adult-onset. Overall, 59/86 evaluable patients (69 %) were categorized as improved/stable and the proportion of improved/stable patients increased with age at neurological onset. Safety findings were consistent with previous data. Conclusions Disability status was improved/stable in the majority of patients who received continuous miglustat therapy for an average period of 2 years.