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The evidence on the role of Toll-like receptors (TLR) and their ligands in atherosclerosis development has been summarised. Bacterial lipopolysaccharides (LPS) could interact with TLR4 and induce macrophage transformation into foam cells, triggering atherosclerotic lesion development in the vascular wall. TLR4 mutations are associated with reduced atherosclerosis risk. Other microbial ligands and heat shock proteins could also induce atherosclerosis. A universal theory of atherogenesis is proposed, considering atherosclerosis induction and progression as an adverse effect of the interaction between exogenous and endogenous ligands and TLR.

Toll-like receptors (TLR) can interact with intestinal microflora under physiological steady-state conditions. This interaction is required for intestinal homeostasis. Activation of TLRs by ligands of commensal microflora is required for the protection against gut injury and associated mortality. The normoflora ligands induce the expression of proinflammation and anti-inflammation cytokines. The more active normoflora ligand is lipopolysaccharide (LPS).

In the article one of variants of checking the operability of relay equipment for railway automation is examined with the use of method of noise diagnostics (an identification of noise signals on the basis of using the moments of density of probability distribution for random noise signals).

Aim. To study mucous (parietal) gastroduodenal microflora in healthy persons, patients with ulcer and chronic gastritis, to develop diagnostic criteria and classification of gastroduodenal dysbacteriosis. Material and methods. Biopsy specimens were obtained from gastroduodenal mucosa of 134 patients with ulcer, 36 - with chronic gastritis and 28 healthy subjects. The mucous microflora agents were isolated microbiologically from biopsy specimens obtained from different compartments of the stomach and duodenum. The spectrum of their enzymatic activity and cytotoxic properties were determined. Results. Gastroduodenal mucous microflora of healthy subjects was represented with 1-2, less often with 3-4 cultures of 12 species, enzymatic activity spectrum of microorganisms was small, cytotoxicity was absent. In ulcer recurrence and exacerbation of chronic gastritis gastroduodenal zone showed dysbacteriosis characterized by overgrowth of mucous microflora (up to 22 species of microorganisms) with a wide spectrum of enzymatic activity and cytotoxic properties. The criteria of dysbacteriosis diagnosis and classification are proposed. Conclusion. The role of gastroduodenal mucous microflora in ulcer and gastritis course is specified. New approaches to effective treatment of gastroduodenal diseases may be developed with consideration of dysbacteriosis.

Обосновывается, что широкое распространение инфо-, генно-, когно- и нанотехнологий, виртуальной реальности, биологических компьютеров из молекул ДНК и т.п. и одновременное развитие глобального системного кризиса, охватившего все стороны жизни человеческого сообщества привели к тому, что обеспечить не только информационную безопасность, но и мир и безопасность разным странам, регионам, муниципальным образованиям и разным людям в многонациональном обществе в этих условиях не представляется возможным. Для определения условий дальнейшего развития, построения информационного общества и одновременно обеспечения мира и информационной безопасности использован новый методологический инструментарий, который позволилвыявить объективные причины возникновения глобального системного кризиса, найти пути выхода на бескризисный путь развития. Показана необходимость перехода к адекватной, не входящей в про- тиворечие с научно-техническими достижениями XXI века, модели жизнеустройства человеческого сообщества ДНҚ молекулаларынан биологиялық компьютерлерді, виртуалды қазіргі қолданысты, инфо-, генно-, когно- жəне нано-технологиялырының кең таратылуымен негізделеді жəне т.б. ақпараттық қауіпсіздігін ғана қамтамасыз етпейтін, адамдық қоғам өмірінің барлық жақтарын қамтитын, глобальді жүйелік дағдарыстың біртекті дамуы, бейбітшілік пен əртүрлі елдердің қауіпсіздігі, аймақтар мен муниципалды білім алудың жəне осы шарттардағы көп ұлттық қоғамдағы əртүрлі тұлғаларға мүмкіндік берілмейді. Болашақта даму шарттарын анықтау үшін ақпараттық қоғамның тұрғызылуы мен дүниежүзілік біртекті қамтамасыз етуге жəне ақпараттық қауіпсіздікті дамытудың дағдарыссыздыққа өту жолын табу мен жаһандандырудың жүйелік дағдарыстың пайда болу объективті себептерін ашып көрсетуге жаңа əдістемелік құралдары қолданылды. Адамдық қоғамның өмірлік құрылысының модельдері, XXI ғасырдың ғылыми-техникалық жетістіктерінің қайшылықтарына кірмейтін, сəйкестігіне керектілігі көрсетілген

Previous research in India has identified urbanisation, human mobility and population demographics as key variables associated with higher district level COVID-19 incidence. However, the spatiotemporal dynamics of mobility patterns in rural and urban areas in India, in conjunction with other drivers of COVID-19 transmission, have not been fully investigated. We explored travel networks within India during two pandemic waves using aggregated and anonymized weekly human movement datasets obtained from Google, and quantified changes in mobility before and during the pandemic compared with the mean baseline mobility for the 8-week time period at the beginning of 2020. We fit Bayesian spatiotemporal hierarchical models coupled with distributed lag non-linear models (DLNM) within the integrated nested Laplace approximate (INLA) package in R to examine the lag-response associations of drivers of COVID-19 transmission in urban, suburban, and rural districts in India during two pandemic waves in 2020-2021. Model results demonstrate that recovery of mobility to 99% that of pre-pandemic levels was associated with an increase in relative risk of COVID-19 transmission during the Delta wave of transmission. This increased mobility, coupled with reduced stringency in public intervention policy and the emergence of the Delta variant, were the main contributors to the high COVID-19 transmission peak in India in April 2021. During both pandemic waves in India, reduction in human mobility, higher stringency of interventions, and climate factors (temperature and precipitation) had 2-week lag-response impacts on the R t of COVID-19 transmission, with variations in drivers of COVID-19 transmission observed across urban, rural and suburban areas. With the increased likelihood of emergent novel infections and disease outbreaks under a changing global climate, providing a framework for understanding the lagged impact of spatiotemporal drivers of infection transmission will be crucial for informing interventions.

"Leaving no one behind" is the fundamental objective of the 2030 Agenda for Sustainable Development. Latin America and the Caribbean is marked by social inequalities, whilst its total population is projected to increase to almost 760 million by 2050. In this context, contemporary and spatially detailed datasets that accurately capture the distribution of residential population are critical to appropriately inform and support environmental, health, and developmental applications at subnational levels. Existing datasets are under-utilised by governments due to the non-alignment with their own statistics. Therefore, official statistics at the finest level of administrative units available have been implemented to construct an open-access repository of high-resolution gridded population datasets for 40 countries in Latin American and the Caribbean. These datasets are detailed here, alongside the 'top-down' approach and methods to generate and validate them. Population distribution datasets for each country were created at a resolution of 3 arc-seconds (approximately 100 m at the equator), and are all available from the WorldPop Data Repository., (© 2023. The Author(s).)

Diastrophic dysplasia (DTD) is an uncommon pathology which falls under the group of skeletal dysplasias with its first symptoms observed from birth. The pathology is often featured by short stature and abnormally short extremities (also known as short-limbed dwarfism); the osseous structures of the body (bones and joints) are characterized through defective development in many body regions. More than 300 genes were reported to be involved in DTD etiology with autosomal recessive, autosomal dominant and X-linked manner. We describe clinical case of a 42-year-old woman from the west of Ukraine with diastrophic dysplasia and two pathogenic variants c.1020_1022del (p.Val341del) and c.1957T>A (p.Cys653Ser) identified in SLC26A2 gene. SLC26A2-related diastrophic dysplasia was confirmed based on the presence of pathogenic variants in SLC26A2 , which is associated with autosomal recessive forms of skeletal dysplasia, combined with phenotypic symptoms and radiographic findings., (© 2022 Bondarenko M. et al., published by Sciendo.)

This study uses computational design to explore the performance of a novel electro-membrane microfluidic diode consisting of physically conjugated nanoporous and micro-perforated ion-exchange layers. Previously, such structures have been demonstrated to exhibit asymmetric electroosmosis, but the model was unrealistic in several important respects. This numerical study investigates two quantitative measures of performance (linear velocity of net flow and efficiency) as functions of such principal system parameters as perforation size and spacing, the thickness of the nanoporous layer and the zeta potential of the pore surface. All of these dependencies exhibit pronounced maxima, which is of interest for future practical applications. The calculated linear velocities of net flows are in the range of several tens of liters per square meter per hour at realistically applied voltages. The system performance somewhat declines when the perforation size is increased from 2 µm to 128 µm (with a parallel increase of the inter-perforation spacing) but remains quite decent even for the largest perforation size. Such perforations should be relatively easy to generate using inexpensive equipment.

Understanding the fine scale and subnational spatial distribution of reproductive, maternal, newborn, child, and adolescent health and development indicators is crucial for targeting and increasing the efficiency of resources for public health and development planning. National governments are committed to improve the lives of their people, lift the population out of poverty and to achieve the Sustainable Development Goals. We created an open access collection of high resolution gridded and district level health and development datasets of India using mainly the 2015-16 National Family Health Survey (NFHS-4) data, and provide estimates at higher granularity than what is available in NFHS-4, to support policies with spatially detailed data. Bayesian methods for the construction of 5 km × 5 km high resolution maps were applied for a set of indicators where the data allowed (36 datasets), while for some other indicators, only district level data were produced. All data were summarised using the India district administrative boundaries. In total, 138 high resolution and district level datasets for 28 indicators were produced and made openly available., (© 2023. The Author(s).)

In this work, we demonstrate that cutting diamond crystals with a laser (532 nm wavelength, 0.5 mJ energy, 200 ns pulse duration at 15 kHz) produced a ≲20 nm thick surface layer with magnetic order at room temperature. We measured the magnetic moment of five natural and six CVD diamond crystals of different sizes, nitrogen contents and surface orientations with a SQUID magnetometer. A robust ferromagnetic response at 300 K was observed only for crystals that were cut with the laser along the (100) surface orientation. The magnetic signals were much weaker for the (110) and negligible for the (111) orientations. We attribute the magnetic order to the disordered graphite layer produced by the laser at the diamond surface. The ferromagnetic signal vanished after chemical etching or after moderate temperature annealing. The obtained results indicate that laser treatment of diamond may pave the way to create ferromagnetic spots at its surface.

Public and school holidays have important impacts on population mobility and dynamics across multiple spatial and temporal scales, subsequently affecting the transmission dynamics of infectious diseases and many socioeconomic activities. However, worldwide data on public and school holidays for understanding their changes across regions and years have not been assembled into a single, open-source and multitemporal dataset. To address this gap, an open access archive of data on public and school holidays in 2010-2019 across the globe at daily, weekly, and monthly timescales was constructed. Airline passenger volumes across 90 countries from 2010 to 2018 were also assembled to illustrate the usage of the holiday data for understanding the changing spatiotemporal patterns of population movements., (© 2022. The Author(s).)

The transport of ions and water in nanopores is of interest for a number of natural and technological processes. Due to their practically identical long straight cylindrical pores, nanoporous track-etched membranes are suitable materials for investigation of its mechanisms. This communication reports on simultaneous measurements of osmotic pressure and salt diffusion with a 24 nm pore track-etched membrane. Due to the use of dilute electrolyte solutions (1-4 mM KCl and LiCl), this pore size was commensurate with the Debye screening length. Advanced interpretation of experimental results using a full version of the space-charge model has revealed that osmotic pressure and salt diffusion can be quantitatively correlated with electrostatic interactions of ions with charged nanopore walls. The surface-charge density is shown to increase with electrolyte concentration in agreement with the mechanism of deprotonation of weakly acidic surface groups. Moreover, a lack of significant surface-charge dependence on the kind of cation (K + or Li + ) demonstrates that binding of salt counterions does not play a major role in this system.

This study is devoted to the development of a methodological approach to mathematical analysis and data interpretation of blood serum phosphorescence intensity in cancer patients for determining the pathological states and differential diagnostics of oncological process stages. The purpose of the study is blood serum phosphorescence research in patients with colorectal cancer (CRC) and stomach adenocarcinoma (SAC) and determination of the ultraweak luminescence role for diagnostics of the disease, determining its stages, control of pathogenetic therapy efficiency and forecast of recovery. The values of phosphorescence intensity of blood serum films in patients with CRC and SAC are significantly higher than the corresponding values for the control group. Contrary to the absolute intensity, the relative intensity increase compared to the control group is much more informative for oncoprocess diagnostics, since it exhibits three times increase even at the first stage of tumoral process. Serum phosphorescence intensity continues to increase with progressing of the disease. As the result of our study, the relative intensity increase compared to the first stage can be recommended as an informative indicator for differential diagnostics of oncological process stages. As a conclusion, determination of blood serum phosphorescence intensity can be considered as a sensitive and specific diagnostic method in oncology. With a correct methodological approach to data processing and interpretation, this method can be used in clinical practice for determining the oncopathological states, differential diagnostics of oncoprocess stages and diagnostics of precancer changes, which precede tumoral process development.

Background: Cystic and alveolar echinococcosis (CE and AE) are neglected tropical diseases caused by Echinococcus granulosus sensu lato and E. multilocularis, and are emerging zoonoses in Kyrgyzstan. In this country, the spatial distribution of CE and AE surgical incidence in 2014-2016 showed marked heterogeneity across communities, suggesting the presence of ecological determinants underlying CE and AE distributions., Methodology/principal Findings: For this reason, in this study we assessed potential associations between community-level confirmed primary CE (no.=2359) or AE (no.=546) cases in 2014-2016 in Kyrgyzstan and environmental and climatic variables derived from satellite-remote sensing datasets using conditional autoregressive models. We also mapped CE and AE relative risk. The number of AE cases was negatively associated with 10-year lag mean annual temperature. Although this time lag should not be considered as an exact measurement but with associated uncertainty, it is consistent with the estimated 10-15-year latency following AE infection. No associations were detected for CE. We also identified several communities at risk for CE or AE where no disease cases were reported in the study period., Conclusions/significance: Our findings support the hypothesis that CE is linked to an anthropogenic cycle and is less affected by environmental risk factors compared to AE, which is believed to result from spillover from a wild life cycle. As CE was not affected by factors we investigated, hence control should not have a geographical focus. In contrast, AE risk areas identified in this study without reported AE cases should be targeted for active disease surveillance in humans. This active surveillance would confirm or exclude AE transmission which might not be reported with the present passive surveillance system. These areas should also be targeted for ecological investigations in the animal hosts., Competing Interests: The authors have declared that no competing interests exist.

Despite recent advances in deciphering cancer drug resistance mechanisms, relapse is a widely observed phenomenon in advanced cancers, mainly due to intratumor clonal heterogeneity. How tumor clones progress and impact each other remains elusive. In this study, we developed 2D and 3D non-small cell lung cancer co-culture systems and defined a phenomenological mathematical model to better understand clone dynamics. Our results demonstrated that the drug-sensitive clones inhibit the proliferation of the drug-resistant ones under untreated conditions. Model predictions and their experimental in vitro and in vivo validations indicated that a metronomic schedule leads to a better regulation of tumor cell heterogeneity over time than a maximum-tolerated dose schedule, while achieving control of tumor progression. We finally showed that drug-sensitive and -resistant clones exhibited different metabolic statuses that could be involved in controlling the intratumor heterogeneity dynamics. Our data suggested that the glycolytic activity of drug-sensitive clones could play a major role in inhibiting the drug-resistant clone proliferation. Altogether, these computational and experimental approaches provide foundations for using metronomic therapy to control drug-sensitive and -resistant clone balance and highlight the potential of targeting cell metabolism to manage intratumor heterogeneity.

Top-down population modelling has gained applied prominence in public health, planning, and sustainability applications at the global scale. These top-down population modelling methods often rely on remote-sensing (RS) derived representation of the built-environment and settlements as key predictive covariates. While these RS-derived data, which are global in extent, have become more advanced and more available, gaps in spatial and temporal coverage remain. These gaps have prompted the interpolation of the built-environment and settlements, but the utility of such interpolated data in further population modelling applications has garnered little research. Thus, our objective was to determine the utility of modelled built-settlement extents in a top-down population modelling application. Here we take modelled global built-settlement extents between 2000 and 2012, created using a spatio-temporal disaggregation of observed settlement growth. We then demonstrate the applied utility of such annually modelled settlement data within the application of annually modelling population, using random forest informed dasymetric disaggregations, across 172 countries and a 13-year period. We demonstrate that the modelled built-settlement data are consistently the 2nd most important covariate in predicting population density, behind annual lights at night, across the globe and across the study period. Further, we demonstrate that this modelled built-settlement data often provides more information than current annually available RS-derived data and last observed built-settlement extents., Competing Interests: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of the data; in the writing of the manuscript, or in the decision to publish the results.Table 1List of countries modelled. Countries are given by their ISO standard 3-letter code.Table 1RegionCountries (ISO 3 Code)East Asia & the PacificASM AUS BRN CHN FJI FSM GUM HKG IDN JPN KHM KIR KOR LAO MMR MNG MNP MYS NCL NZL PHL PNG PRK PYF SGP SLB THA TLS TUV TWN VNM VUT WSMEuropeALB ARM AUT AZE BEL BGR BIH BLR CHE CYP CZE DEU DNK ESP EST FIN FRA FRO GBR GEO GRC HRV HUN IRL ISL ITA KOS LTU LUX LVA MDA MKD MLT NLD NOR POL PRT ROU RUS SRB SVK SVN SWE TUR UKRLatin America & the CaribbeanABW ARG BOL BRA CHL COL CRI CUB CUW DOM ECU GTM GUY HND HTI MEX MTQ NIC PAN PER PRI PRY SLV SUR URY VENSouth AsiaAFG BGD BTN IND LKA MDV NPL PAKSub-Saharan AfricaAGO BDI BEN BFA CAF CIV CMR COD ETH GAB GHA GIN GMB GNB KEN LBR LSO MDG MLI MOZ MRT MUS MWI NAM NER NGA RWA SEN SLE SOM SWZ SYC TCD TGO TZA UGA ZAF ZMB ZWEWest Asia & Northern AfricaDZA EGY IRN IRQ ISR JOR KAZ KGZ LBN MAR OMN QAT SAU SDN SSD SYR TJK TUN YEMTable 2List of countries excluded from analysis and corresponding reason for exclusionTable 2Countries ExcludedReason for ExclusionAntarcticaNot modelled at allUnited States of AmericaResource limitsAnguilla; Aland Islands; Andorra; United Arab Emirates;Antigua and Barbuda; Bonaire, Sint Eustatius, and Saba; Bahrain; Bahamas; Saint Barthelemy; Belize; Bermuda; Barbados; Botswana; Republic of Congo; Cook Islands; Comoros; Cape Verde; Cayman Islands; Djibouti; Dominica; Eritrea;Western Sahara; Falkland Islands; Guernsey; Gibraltar; Guadeloupe; Equatorial Guinea; Grenada; French Guiana;Isle of Man; Jamaica; Saint Kitts and Nevis; Kuwait; Libya;Saint Lucia; Lichtenstein; Macao; Saint Martin (French portion); Monaco; Marshall Islands; Montenegro; Montserrat; Mayotte; New Caledonia; Norfolk Island; Niue; Nauru; Pitcairn Islands; Palau; Palestine; Reunion; Saint Helena;Svalbard and Jan Mayen Islands; San Marino;Saint Pierre and Miquelon; Sao Tome and Principe;Sint Maarten (Dutch portion); Seychelles;Turks and Caicos Islands; Tokelau; Turkmenistan; Tonga; Trinidad and Tobago; Vatican City;Saint Vincent and the Grenadines; British Virgin Islands;Virgin Islands (U.S.); Wallis and FutunaRegional parameterization of BSGM and or population model, (© 2020 The Author(s).)

Mapping urban features/human built-settlement extents at the annual time step has a wide variety of applications in demography, public health, sustainable development, and many other fields. Recently, while more multitemporal urban features/human built-settlement datasets have become available, issues still exist in remotely-sensed imagery due to spatial and temporal coverage, adverse atmospheric conditions, and expenses involved in producing such datasets. Remotely-sensed annual time-series of urban/built-settlement extents therefore do not yet exist and cover more than specific local areas or city-based regions. Moreover, while a few high-resolution global datasets of urban/built-settlement extents exist for key years, the observed date often deviates many years from the assigned one. These challenges make it difficult to increase temporal coverage while maintaining high fidelity in the spatial resolution. Here we describe an interpolative and flexible modelling framework for producing annual built-settlement extents. We use a combined technique of random forest and spatio-temporal dasymetric modelling with open source subnational data to produce annual 100 m × 100 m resolution binary built-settlement datasets in four test countries located in varying environmental and developmental contexts for test periods of five-year gaps. We find that in the majority of years, across all study areas, the model correctly identified between 85 and 99% of pixels that transition to built-settlement. Additionally, with few exceptions, the model substantially out performed a model that gave every pixel equal chance of transitioning to built-settlement in each year. This modelling framework shows strong promise for filling gaps in cross-sectional urban features/built-settlement datasets derived from remotely-sensed imagery, provides a base upon which to create urban future/built-settlement extent projections, and enables further exploration of the relationships between urban/built-settlement area and population dynamics., (© 2019 The Authors.)

Ion passage through ion-exchange membranes is vital in electrodialysis desalination, batteries and fuel cells, and water splitting. Simplified models of ion transport through such membranes frequently assume complete exclusion of co-ions (ions with the same sign of charge as the fixed charge in the membrane) from the membrane. However, a second assumption of constant counterion electrochemical potentials across the membrane leads to simple analytical expressions for ion fluxes and transmembrane potentials. Moreover, linear corrections to account for a small membrane electrical resistance yield analytical expressions with a wider applicability. For bi-ionic potential measurements and current-induced concentration polarization at low salt concentrations, these analytical solutions match the fluxes and potentials obtained numerically without the limiting assumptions. This gives confidence in both the limiting assumptions (under appropriate conditions) and the numerical solutions. At low ion concentrations, the analytical solutions may enable rapid characterization of membrane coatings or boundary layers in solution, and such boundary layers are important in many applications of ion-exchange membranes. In fact, the assumption of complete co-ion exclusion is sometimes more limiting than the constraint of constant electrochemical potentials of counterions across the membrane. Remarkably, this limiting case readily yields the ion accumulation and depletion regions above "ion-exchange patches" that reside beneath a solution with an applied electric field. Such regions are important for sample preconcentration in microfluidic devices.

Multi-temporal, globally consistent, high-resolution human population datasets provide consistent and comparable population distributions in support of mapping sub-national heterogeneities in health, wealth, and resource access, and monitoring change in these over time. The production of more reliable and spatially detailed population datasets is increasingly necessary due to the importance of improving metrics at sub-national and multi-temporal scales. This is in support of measurement and monitoring of UN Sustainable Development Goals and related agendas. In response to these agendas, a method has been developed to assemble and harmonise a unique, open access, archive of geospatial datasets. Datasets are provided as global, annual time series, where pertinent at the timescale of population analyses and where data is available, for use in the construction of population distribution layers. The archive includes sub-national census-based population estimates, matched to a geospatial layer denoting administrative unit boundaries, and a number of co-registered gridded geospatial factors that correlate strongly with population presence and density. Here, we describe these harmonised datasets and their limitations, along with the production workflow. Further, we demonstrate applications of the archive by producing multi-temporal gridded population outputs for Africa and using these to derive health and development metrics. The geospatial archive is available at https://doi.org/10.5258/SOTON/WP00650., (© 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group and Science Press on behalf of the International Society for Digital Earth, supported by the CASEarth Strategic Priority Research Programme.)

Tracking spatiotemporal changes in GHG emissions is key to successful implementation of the United Nations Framework Convention on Climate Change (UNFCCC). And while emission inventories often provide a robust tool to track emission trends at the country level, subnational emission estimates are often not reported or reports vary in robustness as the estimates are often dependent on the spatial modeling approach and ancillary data used to disaggregate the emission inventories. Assessing the errors and uncertainties of the subnational emission estimates is fundamentally challenging due to the lack of physical measurements at the subnational level. To begin addressing the current performance of modeled gridded CO 2 emissions, this study compares two common proxies used to disaggregate CO 2 emission estimates. We use a known gridded CO 2 model based on satellite-observed nighttime light (NTL) data (Open Source Data Inventory for Anthropogenic CO 2 , ODIAC) and a gridded population dataset driven by a set of ancillary geospatial data. We examine the association at multiple spatial scales of these two datasets for three countries in Southeast Asia: Vietnam, Cambodia and Laos and characterize the spatiotemporal similarities and differences for 2000, 2005, and 2010. We specifically highlight areas of potential uncertainty in the ODIAC model, which relies on the single use of NTL data for disaggregation of the non-point emissions estimates. Results show, over time, how a NTL-based emissions disaggregation tends to concentrate CO 2 estimates in different ways than population-based estimates at the subnational level. We discuss important considerations in the disconnect between the two modeled datasets and argue that the spatial differences between data products can be useful to identify areas affected by the errors and uncertainties associated with the NTL-based downscaling in a region with uneven urbanization rates., (© 2019 The Author(s).)

Discovery of new drugs for cancer treatment is an expensive and time-consuming process and the percentage of drugs reaching the clinic remains quite low.Drug repositioning refers to the identification and development of new uses for existing drugs and represents an alternative drug development strategy.In this work, we evaluated the antitumor effect of metronomic treatment with a combination of two repositioned drugs, metformin and propranolol, in triple negative breast cancer models.By in vitro studies with five different breast cancer derived cells, we observed that combined treatment decreased proliferation (P < 0.001), mitochondrial activity (P < 0.001), migration (P < 0.001) and invasion (P < 0.001). In vivo studies in immunocompetent mice confirmed the potential of this combination in reducing tumor growth (P < 0.001) and preventing metastasis (P < 0.05).Taken together our results suggest that metformin plus propranolol combined treatment might be beneficial for triple negative breast cancer control, with no symptoms of toxicity.

Reverse osmosis and nanofiltration (NF) employ composite membranes whose ultrathin barrier layers are significantly more permeable to water than to salts. Although solution-diffusion models of salt transport through barrier layers typically assume ubiquitous electroneutrality, in the case of ultrathin selective skins and low ion partition coefficients, space-charge regions may occupy a significant fraction of the membrane barrier layer. This work investigates the implications of these deviations from electroneutrality on salt transport. Both immobile external surface charge and unequal cation and anion solvation energies in the barrier layer lead to regions with excess mobile charge, and the size of these regions increases with decreasing values of either feed concentrations or ion partition coefficients. Moreover, the low concentration of the more excluded ion in the space-charge region can greatly increase resistance to salt transport to enhance salt rejection during NF. These effects are especially pronounced for membranes with a fixed external surface charge density whose sign is the same as that of the more excluded ion in a salt. Because of the space-charge regions, the barrier-layer resistance to salt transport initially rises rapidly with increasing barrier thickness and then plateaus or even declines within a certain thickness range. This trend in resistance implies that thin, defect-free barrier layers will exhibit higher salt rejections than thicker layers during NF at a fixed transmembrane pressure. Deviations from electroneutrality are consistent with both changes in NF salt rejections that occur upon changing the sign of the membrane fixed external surface charge, and CaCl2 rejections that in some cases may first decrease, then increase and then decrease again with increasing CaCl2 concentrations in NF feed solutions.

Venous thromboembolism (VTE) is a serious disease that is often neglected, and effective and safe antithrombotic treatments are a public health priority. New antithrombotics such as rivaroxaban, apixaban, betrixaban, edoxaban, darexaban, TAK-442, LY517717, eribaxaban, otamixaban are being developed to overcome current therapeutic limitations. The new oral anticoagulants and parenteral otamixaban are under evaluation in clinical trials for VTE treatment, for VTE prevention in orthopedic surgery, for stroke prevention in patients with atrial fibrillation and for cardiovascular event prevention in patients with acute coronary syndrome. These antithrombotic agents directly and selectively inhibit factor Xa, and do not require coagulation monitoring and dose adjustment. Several of these drugs have shown promising results and have the potential to either replace or act as alternatives to traditional anticoagulants (heparins, vitamin K antagonists).

Objective: The Estimating Ambulation Capacity by History-Questionnaire (EACH-Q) and the Walking Impairment Questionnaire (WIQ) are used to estimate maximal walking distance (MWD). The EACH-Q and WIQ included 4 and 14 items respectively, among which one item dealing with running capacity. We hypothesised that this item was of little interest in patients with claudication., Design: The WIQ and EACH-Q were self-completed and corrected before a constant load (3.2 km h(-1); 10% slope) treadmill tests, maximised to 15 min., Patients: 371 patients (298 males/73 females, 62.9 ± 11.2 years)., Methods: The number of errors (duplicate, absent or paradoxical answers to one item) and correlation of questionnaire scores with MWD on treadmill were calculated, before and after skipping the answer to the running item., Results: The proportion of questionnaires with errors was 27% with the EACH-Q and 48% with the WIQ. Two-hundred and twenty-one (59.6%) and 245 (66%) out of 371 patients reported to be unable to run, for the EACH-Q and WIQ, respectively. The rate of errors was reduced by 15% for the EACH-Q (p < 0.05) when skipping the running item for scoring. The correlation coefficients between the MWD and the questionnaire scores were 0.449 and 0.485 for the EACH-Q and were 0.571 and 0.572 for the WIQ, before and after skipping the running item, respectively., Conclusion: Most of our patients reported to be unable to run and skipping the running item reduce the rate of errors in self-completing the questionnaires without impairing the correlation of questionnaire scores with treadmill results. It is likely that the running item could be removed from the WIQ and EACH-Q questionnaires., (Copyright © 2012 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.)