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Hepatocellular carcinoma (HCC) is recognized to have a strong tendency for vascular invasion. However, right atrial (RA) involvement is uncommon. It has been principally described as a fortuitous discovery during oncology follow-up or as an autopsy finding of patients with known HCC. We present a case of a patient whose initial HCC presentation was an RA mass found during a dyspnea investigation. Thereby, on the basis of this new finding, clinicians should consider HCC in their differential diagnosis when discovering an RA mass. Résumé: Le carcinome hépatocellulaire (CHC) est fortement associé à une invasion vasculaire. Une atteinte auriculaire droite est toutefois peu fréquente. Elle a principalement été décrite comme une découverte fortuite lors d'un examen de suivi en oncologie ou à l'autopsie chez des patients qui avaient reçu un diagnostic de CHC. Nous vous présentons le cas d'un patient dont le CHC s'est présenté initialement sous forme de masse au niveau de l'oreillette droite lors d'un examen mené en raison d'une dyspnée. Compte tenu de cette observation, les cliniciens doivent envisager un diagnostic différentiel de CHC lorsqu'une masse est découverte au niveau de l'oreillette droite.

Abstract Background Biochemical and hematological parameters are important tools for assessing the physiological profile of vital organs, and can be recorded to create reference values used for clinical diagnosis of diseases. Many research laboratories lack the means to establish their own set of reference parameters for use in their research, and while there are articles in the literature that discuss laboratory parameters for healthy BALB/c mice, few studies address the evaluation of these parameters in pathological situations, such as in mice inoculated with Ehrlich tumor. Method BALB/c‐FMABC mice previously inoculated with Ehrlich tumor were maintained under appropriate conditions. Blood samples were taken for analysis of hematological parameters using automated and semi‐automated equipment to create a set of the animal welfare parameters for evaluation. Result Results were obtained for all the hematological parameters for all groups analyzed. These showed: statistically significant differences between the initial and final tumor weight; comparable initial tumour volume and weight; an increase in leukocytes in the 7‐day group with a characteristic predominance of lymphocytes and neutrophils; statistically significant changes in RDW in the 21‐day group and in the welfare parameters in the 28‐day group. Conclusion The study successfully defined and established reference values for hematological and welfare parameters for all groups analyzed.

The Co-catalysed hydroformylation of olefins produces selectively linear but not branched aldehydes. Here, the authors show that microporous MOFs increase the olefins density in the pores beyond neat conditions allowing high branched selectivity through kinetic modulation when added to a liquid phase hydroformylation mixture.

Mesoscale oceanic eddies have a visible signature on sea surface temperature (SST) satellite images, portraying diverse patterns of coherent vortices, temperature gradients, and swirling filaments. However, learning the regularities of such signatures defines a challenging pattern recognition task, due to their complex structure but also to the cloud coverage which can corrupt a large fraction of the image. We introduce a novel deep learning approach to classify sea temperature eddy signatures, even if they are corrupted by strong cloud coverage. A large dataset of SST image patches is automatically retained and used to train a CNN-based classifier. Classification is performed with very high accuracy on coherent eddy signatures and is robust to a high level of cloud coverage, surpassing human expert efficiency on this task. This methodology can serve to validate and correct detections on satellite altimetry, the standard method used until now to track mesoscale eddies.

Abstract Background Administering anti-vascular endothelial growth factor (anti-VEGF) by intraocular injection has been shown to have a safe systemic profile. Nevertheless, incidents of acute kidney injury following anti-VEGF injection have been reported. We assessed the long-term effect of multiple intravitreal anti-VEGF injections on measures of renal function in patients with diabetes including rate of change of estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (ACR). Methods A retrospective review of patients receiving diabetic macular oedema (DMO) treatment was undertaken. Serum creatinine, ACR, number of intravitreal anti-VEGF injections and clinical characteristics were collected from electronic healthcare records (EHR). A co-efficient of eGFR and ACR change with time was calculated over a mean duration of 2.6 years. Regression modelling was used to assess variation in the number of anti-VEGF injections and change in eGFR and ACR. Results The EHR of 85 patients with DMO (59% male, 78% type 2 diabetes mellitus [T2DM]) were reviewed. On average, 26.8 intravitreal anti-VEGF injections were given per patient over a mean duration of 31 months. No association between increasing number of anti-VEGF injections and rate of eGFR decline (beta = 0.04, 95% confidence intervals [CI]: − 0.02, 0.09; p = 0.22) or ACR change over time (beta = 0.02, CI: − 0.19, 0.23; p = 0.86) was detected, following adjustment for hypertension, cerebrovascular disease, T2DM, and medications taken. Conclusion Our data suggests regular long-term intravitreal VEGF inhibition does not significantly alter the rate of change in eGFR and/or ACR with increasing number of treatment injections.

Abstract Predation and mortality are often difficult to estimate in the ocean, which hampers the management and conservation of marine fishes. We used data from pop-up satellite archival tags to investigate the ocean predation and mortality of adult Atlantic salmon (Salmo salar) released from 12 rivers flowing into the North Atlantic Ocean. Data from 156 tagged fish revealed 22 definite predation events (14%) and 38 undetermined mortalities (24%). Endothermic fish were the most common predators (n = 13), with most of these predation events occurring in the Gulf of St. Lawrence and from the Bay of Biscay to the Irish Shelf. Predation by marine mammals, most likely large deep-diving toothed whales (n = 5), and large ectothermic fish (n = 4) were less frequent. Both the estimated predation rates (ZP) and total mortality rates (ZM) where higher for Atlantic salmon from Canada, Ireland, and Spain (ZP = 0.60–1.32 y−1, ZM = 1.73–3.08 y−1) than from Denmark and Norway (ZP = 0–0.13 y−1, ZM = 0.19–1.03 y−1). This geographical variation in ocean mortality correlates with ongoing population declines, which are more profound for southern populations, indicating that low ocean survival of adults may act as an additional stressor to already vulnerable populations.

Aspidasept (Pep19-2.5) and its derivative Pep19-4LF (“Aspidasept II”) are anti-infective and anti-inflammatory synthetic polypeptides currently in development for application against a variety of moderate to severe bacterial infections that could lead to systemic inflammation, as in the case of severe sepsis and septic shock, as well as application to non-systemic diseases in the case of skin and soft tissue infections (SSTI). In the present study, Aspidasept and Aspidasept II and their part structures were analysed with respect to their toxic behavior in different established models against a variety of relevant cells, and in electrophysiological experiments targeting the hERG channel according to ICH S7B. Furthermore, the effects in mouse models of neurobiological behavior and the local lymph node according to OECD test guideline 429 were investigated, as well as a rat model of repeated dose toxicology according to ICH M3. The data provide conclusive information about potential toxic effects, thus specifying a therapeutic window for the application of the peptides. Therefore, these data allow us to define Aspidasept concentrations for their use in clinical studies as parenteral application.

Given their safety and efficiency in protecting protein integrity, polysorbates (PSs) have been the most widely used excipients for the stabilization of protein therapeutics for years. In recent decades, however, there have been numerous reports about visible or sub-visible particles in PS-containing biotherapeutic products, which is a major quality concern for parenteral drugs. Alternative excipients that are safe for parenteral administration, efficient in protecting different protein drugs against various stress conditions, effective in protein stabilization in high-concentrated liquid formulations, stable under the storage conditions for the duration of the product’s shelf-life, and compatible with other formulation components and the primary packaging are highly sought after. The aim of this paper is to review potential alternative excipients from different families, including surfactants, carbohydrate- and amino acid-based excipients, synthetic amphiphilic polymers, and ionic liquids that enable protein stabilization. For each category, important characteristics such as the ability to stabilize proteins against thermal and mechanical stresses, current knowledge related to the safety profile for parenteral administration, potential interactions with other formulation components, and primary packaging are debated. Based on the provided information and the detailed discussion thereof, this paper may pave the way for the identification or development of efficient excipients for biotherapeutic protein stabilization.

The performance of a desalination membrane depends on a specific pore size suitable for both water permeability and salt rejection. To increase membrane permeability, the applied pressure should be increased, which creates the need to improve membrane stability. In this research article, a molecular dynamics (MD) simulation was performed using ReaxFF module from Amsterdam Modeling suite (AMS) software to simulate water desalination efficiency using a single and multi-layer graphene membrane. The graphene membrane with different pore sizes and a multi-layer graphene membrane with descending pore size in each layer were designed and studied under different pressures. The stability of the membrane was checked using Material Studio 2019 by studying the dynamics summary. The single-layer graphene membrane was evaluated under pressures ranging from 100 to 500 MPa, with the salt rejection ranging from 95% to 82% with a water permeability of 0.347 × 10−9 to 2.94 × 10−9 (mm.g.cm−2s−1.bar−1), respectively. Almost 100% salt rejection was achieved for the multi-layer graphene membrane. This study successfully demonstrated the design and optimization of graphene membrane performance without functionalization.

One of the pathological hallmarks of Alzheimer’s disease (AD) is the formation of amyloid-β plaques. Since acetylcholinesterase (AChE) promotes the formation of such plaques, the inhibition of this enzyme could slow down the progression of amyloid-β aggregation, hence being complementary to the palliative treatment of cholinergic decline. Antiaggregation assays performed for apigenin and quercetin, which are polyphenolic compounds that exhibit inhibitory properties against the formation of amyloid plaques, reveal distinct inhibitory effects of these compounds on Aβ40 aggregation in the presence and absence of AChE. Furthermore, the analysis of the amyloid fibers formed in the presence of these flavonoids suggests that the Aβ40 aggregates present different quaternary structures, viz., smaller molecular assemblies are generated. In agreement with a noncompetitive inhibition of AChE, molecular modeling studies indicate that these effects may be due to the binding of apigenin and quercetin at the peripheral binding site of AChE. Since apigenin and quercetin can also reduce the generation of reactive oxygen species, the data achieved suggest that multitarget catechol-type compounds may be used for the simultaneous treatment of various biological hallmarks of AD.

In recent years, markers research has focused on the structural components of cartilage matrix. Specifically, a second generation of degradation markers has been developed against type II collagen neoepitopes generated by specific enzymes. A particular effort has been made to measure the degradation of minor collagens III and X of the cartilage matrix. However, because clinical data, including longitudinal controlled studies, are very scarce, it remains unclear whether they will be useful as an alternative to or in combination with current more established collagen biological markers to assess patients with osteoarthritis (OA). In addition, new approaches using high-throughput technologies allowed to detect new types of markers and improve the knowledge about the metabolic changes linked to OA. The relative advances coming from phenotype research are a first attempt to classify the heterogeneity of OA, and several markers could improve the phenotype characterization. These phenotypes could improve the selection of patients in clinical trials limiting the size of the studies by selecting patients with OA characteristics corresponding to the metabolic pathway targeted by the molecules evaluated. In addition, the inclusion of rapid progressors only in clinical trials would facilitate the demonstration of efficacy of the investigative drug to reduce joint degradation. The combination of selective biochemical markers appears as a promising and cost-effective approach to fulfill this unmet clinical need. Among the various potential roles of biomarkers in OA, their ability to monitor drug efficacy is probably one of the most important, in association with clinical and imaging parameters. Biochemical markers have the unique property to detect changes in joint tissue metabolism within a few weeks.

Objective To describe patient characteristics and healthcare costs associated with uveitic macular oedema (UME) in US clinical practices from a commercial payer’s perspective.Methods and analysis The IBM MarketScan Commercial Subset (1 October 2015–31 March 2020) was used to identify patients with non-infectious uveitis (NIU), with or without UME. Patients with UME at any time were further classified into subgroups of patients who received a UME diagnosis during the study period and those who received a UME diagnosis and local steroid injection (LSI) during the study period. Demographic and clinical characteristics, NIU-related treatments and healthcare costs were described for each cohort and subgroup during the most recent 12 months of continuous health plan enrolment. Healthcare costs were also described by vision status among all patients with NIU.Results A total of 36 322 patients with NIU were identified, of whom 3 301 (9.1%) had UME and 33 021 (90.9%) had no UME. Patients with UME more frequently received NIU-related treatment compared with those without UME (64.6% vs 45.0%), particularly LSI treatment (12.5% vs 0.7%). Mean total all-cause healthcare costs per-patient-per-year (PPPY) were higher among patients with UME ($19 851) than patients without UME ($16 188) and were especially high among those with bilateral UME ($24 162). Further, vision loss was more commonly observed in those with UME versus those without UME (5.7% vs 2.2%) and a trend of increasing healthcare costs with increasing vision loss was observed.Conclusion NIU is associated with substantial clinical and economic burden, particularly when UME is present.

The consumption of processed foods is increasingly widespread and could have an impact on diet quality and health. Understanding the factors influencing people’s eating habits is useful for assessing such impact. There are limited data on the consumption patterns of processed foods and associated factors influencing the dietary patterns in Singapore. This cross-sectional study based on a food frequency questionnaire aimed to examine how the consumption of processed foods among 2079 Singapore residents aged 18 to 89 years varies with sociodemographic factors. The analysis of the consumption by processed food groups showed that the studied factors, i.e., age, gender, ethnicity, housing and health status, all contributed to differences in processed food consumption to varying extents, with ethnicity being the key factor driving the variation. Such differences were also confirmed to a limited degree by determining another measure of consumption, i.e., a processed food variety score. The findings in this study could inform further work in relation to dietary risks.

El famoso globo terráqueo de Martin Behaim, concebidú y realizado en Nuremberg en 1492, no es el único testigo medieval de esta forma particular de representación de la Tierra. Al examinar los primeros testimonios, nos damos cuenta de que la función y el contenido de estos globos cambian significativamente: dejan de ilustrar los efectos de los fenómenos celestiales y se limitan a la representación de la superficie de la Tierra. De ahí las preguntas: ¿cómo y por qué pasamos de la representación bidimensional de los mappae mundi a la tridimensional en el siglo XV? ¿Y cómo y por qué se produjo el cambio de contenido en las representaciones tridimensionales? La adaptación de la imagen ptolemaica a la forma particular de un globo, y su enriquecimiento con datos de viajes por tierra en Asia y exploraciones marítimas en África han surgido antes de Behaim en círculos germánicos que siguen siendo poco conocidos.

Objectives We evaluated whether implementation of lockdown orders in South Africa affected ambulatory clinic visitation in rural Kwa-Zulu Natal (KZN).Design Observational cohortSetting Data were analysed from 11 primary healthcare clinics in northern KZN.Participants A total of 46 523 individuals made 89 476 clinic visits during the observation period.Exposure of interest We conducted an interrupted time series analysis to estimate changes in clinic visitation with a focus on transitions from the prelockdown to the level 5, 4 and 3 lockdown periods.Outcome measures Daily clinic visitation at ambulatory clinics. In stratified analyses, we assessed visitation for the following subcategories: child health, perinatal care and family planning, HIV services, non-communicable diseases and by age and sex strata.Results We found no change in total clinic visits/clinic/day at the time of implementation of the level 5 lockdown (change from 90.3 to 84.6 mean visits/clinic/day, 95% CI −16.5 to 3.1), or at the transitions to less stringent level 4 and 3 lockdown levels. We did detect a >50% reduction in child healthcare visits at the start of the level 5 lockdown from 11.9 to 4.7 visits/day (−7.1 visits/clinic/day, 95% CI −8.9 to 5.3), both for children aged

Polyelectrolytes are water-soluble polymers having repeat units carrying electrolyte groups. As polyionic molecules having like charge units, they are self-repelling with a rod-like conformation in solution. Inkjet applications of polyelectrolytes include particle dispersing, surface modification, and multilayer structures. This work investigates the physical properties of low molecular weight sodium polyacrylate (NaPA) and poly-diallyl dimethyl ammonium chloride (polyDADMAC) polyelectrolyte solutions in the water–ethanol mixture in relation to their behavior in inkjet deposition. In rotational rheometry measurements, the solutions are found to behave in a Newtonian fashion once the effects of experimental artifacts are taken into account. The range of NaPA concentrations that could be studied was limited to 1 wt./wt. % by the poor solubility of NaPA in the presence of ethanol, and at these concentrations, the addition of NaPA to the solvent did not have a significant effect on the jetting behavior. PolyDADMAC had good solubility, and concentrations up to 10 wt./wt. % were studied and jetted successfully. While an increase in polyelectrolyte concentration resulted in a slow increase in ink viscosity, this was not found to have a significant effect on the required jetting voltage or maximum stable jetting frequency, though drop detachment and satellite droplet formation times were found to increase. As a practical limitation of polyDADMAC inks, solvent evaporation was found to lead to idle nozzles becoming non-jetting, with the allowed idle time decreasing rapidly as ink polyDADMAC concentration increased. This non-jetting behavior is likely due to residence time at the nozzle exit leading to the local surface tension and/or viscosity increase, differing from the bulk ink properties.

In this study, BiOCl based nanocomposites were used as photocatalytic membranes for a simulated study on water desalination in reverse osmosis membrane systems. Through molecular dynamic simulation, the molecular structure of BiOCl, BiOCl/Ag2S and BiOCl/Bi2O3 heterojunctions were designed and their electronic properties, mechanical properties, and membrane performance for water desalination were evaluated for the first time. The molecular structure was created, and a geometry optimization task was used to optimize it. Material Studio 2019 CASTEP was used for simulation of the electronic and mechanical properties and water desalination was performed by ReaxFF software under pressures between 0 and 250 MPa. The novel BiOCl based nanocomposites showed improved electronic and mechanical properties and, most importantly, improvements in salt rejection and water permeability as compared to well-known materials such as graphene and MoS2. BiOCl and BiOCl/Ag2S had a bandgap around two, which is the ideal bandgap for semiconductor photocatalysts. A salt rejection of 98% was achieved under an applied pressure of 10 MPa. Salt rejection was higher for BiOCl/Bi2O3, while water permeability was higher for BiOCl/Ag2S. The monolayer BiOCl was unstable under pressures higher than 50 MPa, but the mechanical stability of BiOCl/Ag2S increased twofold and increased fourfold for BiOCl/Bi2O3, which is even higher than MoS2. However, between the three nanocomposites, BiOCl/Ag2S was found to be the most ideal photocatalytic nanocomposite membrane.

A copper alloy phalera discovered during the excavation of a Roman villa at Bulgnéville (Vosges), with openwork decoration of crested newts (Triturus cristatus), is alomost identical to another phalera, found some sixty years ago on the surface of a field on the site of the small Roman town of Vorganium (Kerilien at Plounéventer, Finistère). Similar artefacts have also been found in Belgium, Austria and Hungary. Such phaleras, with their characteristic ternary animal decoration, attached to horse harnesses, are dated to the late second or early third century and attest to the continuity of aesthetic traditions rooted in the native cultural background during the Roman period.

The aim of this study was obtain a semi skim milk enriched with sacha inchi oil (Plukenetia volubilis L.), with sensory acceptability and a suitable storage container. The raw materials used were: fresh semi skim milk of creole cow and virgin sacha inchi oil. The content of polyunsaturated fatty acids raised from 2.8% to 3.0; 3.2% and 3.4% according to the treatment. It was evaluated the sensory microbiological properties of the semi skim milk during its storage period of 30 days. The packaging material used were high density polyethylene container and glass container. The best formulation for semi skim milk was the correspond to 3% of fatty acids stored in glass container which obtained values of: Taste 2.2; Color 2.1; Texture 2.2 and Appearance 2.2 on a maximum of 5.0 units. It is concluded that the production of semi skim milk enriched with fatty acids of sacha inchi is feasible.

This paper argues against a common misunderstanding of Foucault's work. Even after the release of his lectures at the Collège de France, which ran throughout the 1970s until his death in 1984, he is still often taken to have made an "ethical" turn toward the end of his life. As opposed to his genealogies of power published in the 1970s, which are relentlessly suspicious of claims of individual agency, his final monographs focus on the ethical self-formation of free individuals. I suggest that this basic misinterpretation makes possible interpretations of Foucault's work as being sympathetic to neoliberal government, by linking the ethical turn to a "liberal" or "neoliberal" turn in his thought. I present a case against the ethical turn by arguing that Foucault's main focus, throughout the 1970s and 1980s, is a concern for the ways in which we become obligated by truth.

Despite an array of preventive global public health interventions, SARS-CoV-2 has continued to spread significantly, infecting millions of people across the globe weekly. Newer variants of interest and concern have continued to emerge, placing the need for policymakers to rethink prevention strategies to end the pandemic. The approval of SARS-CoV-2 vaccines for public health use in December 2020 was seen as a significant development towards pandemic control and possibly ending the pandemic. However, breakthrough infections have continued to be observed among the ‘fully vaccinated’, and the duration and sustainability of vaccine-induced immunity has remained a topical public health discourse. In the absence of accurate public health communication, the breakthrough infections and waning immunity concepts have potential to further compound vaccine hesitancy. With this viewpoint, we discuss breakthrough SARS-CoV-2 infections, waning immunity, the need for COVID-19 booster shots, vaccine inequities, and the need to address vaccine hesitancy adequately to propel global vaccination programs forward.

INSPIRE-SAT 7 is a French 2-Unit CubeSat (11.5 × 11.5 × 22.7 cm) primarily designed for Earth and Sun observation. INSPIRE-SAT 7 is one of the missions of the International Satellite Program in Research and Education (INSPIRE). Twice the size of a 4 × 4 Rubik’s Cube and weighing about 3 kg, INSPIRE-SAT 7 will be deployed in Low Earth Orbit (LEO) in 2023 to join its sister satellite, UVSQ-SAT. INSPIRE-SAT 7 represents one of the in-orbit demonstrators needed to test how two Earth observation CubeSats in orbit can be utilized to set up a satellite constellation. This new scientific and technological pathfinder CubeSat mission (INSPIRE-SAT 7) uses a multitude of miniaturized sensors on all sides of the CubeSat to measure the Earth’s energy budget components at the top-of-the-atmosphere for climate change studies. INSPIRE-SAT 7 contains also a High-Frequency (HF) payload that will receive HF signals from a ground-based HF transmitter to probe the ionosphere for space weather studies. Finally, this CubeSat is equipped with several technological demonstrators (total solar irradiance sensors, UV sensors to measure solar spectral irradiance, a new Light Fidelity (Li-Fi) wireless communication system, a new versatile telecommunication system suitable for CubeSat). After introducing the objectives of the INSPIRE-SAT 7 mission, we present the satellite definition and the mission concept of operations. We also briefly show the observations made by the UVSQ-SAT CubeSat, and assess how two CubeSats in orbit could improve the information content of their Earth’s energy budget measurements. We conclude by reporting on the potential of future missions enabled by CubeSat constellations.

The sustained increase in atmospheric [CO2] over the past two centuries has brought a series of global challenges in plant-environment interactions. However, genetic mechanisms in botanical adaption and feedback to environmental alteration remain elusive. Here we collected and analysed transcriptome sequencing data from leaf tissues of maize Zea mays conditioned under high [CO2] stress for 0, 7 or 14 d. A total of 1390 genes, either up- or down-regulated, differed significantly in these conditions. Gene Ontology (GO) enrichment terms and KEGG metabolism pathways included protein phosphorylation, protein ubiquitination, oxidation-reduction, plant organ development, cellular response to endogenous response and MAPK signaling. We also identified three densely connected gene clusters: TCP/PYE, WRKYs and MYC/JAZ from significant DEGs. In conclusion, we provided a genetic database for biologists in botany, agronomy and ecology to further investigate the molecular machinery by which C4-plants respond to elevated atmospheric [CO2] and accompanying global climate change.

UV and ambient light-induced modifications and related degradation of therapeutic proteins are observed during manufacturing and storage. Therefore, to ensure product quality, protein formulations need to be analyzed with respect to photo-degradation processes and eventually protected from light exposure. This task usually demands the application and combination of various analytical methods. This review addresses analytical aspects of investigating photo-oxidation products and related mediators such as reactive oxygen species generated via UV and ambient light with well-established and novel techniques.

Abstract Milk production in dairy cow udders is a complex and dynamic physiological process that has resisted explanatory modelling thus far. The current standard model, Wood’s model, is empirical in nature, represents yield in daily terms, and was published in 1967. Here, we have developed a dynamic and integrated explanatory model that describes milk yield at the scale of the milking session. Our approach allowed us to formally represent and mathematically relate biological features of known relevance while accounting for stochasticity and conditional elements in the form of explicit hypotheses, which could then be tested and validated using real-life data. Using an explanatory mathematical and biological model to explore a physiological process and pinpoint potential problems (i.e., “problem finding”), it is possible to filter out unimportant variables that can be ignored, retaining only those essential to generating the most realistic model possible. Such modelling efforts are multidisciplinary by necessity. It is also helpful downstream because model results can be compared with observed data, via parameter estimation using maximum likelihood and statistical testing using model residuals. The process in its entirety yields a coherent, robust, and thus repeatable, model.

Abstract Background Malaria accounts for the largest portion of healthcare demand in Angola. A pillar of malaria control in Angola is the appropriate management of malaria illness, including testing of suspect cases with rapid diagnostic tests (RDTs) and treatment of confirmed cases with artemisinin-based combination therapy (ACT). Periodic systematic evaluations of malaria case management are recommended to measure health facility readiness and adherence to national case management guidelines. Methods Cross-sectional health facility surveys were performed in low-transmission Huambo and high-transmission Uíge Provinces in early 2016. In each province, 45 health facilities were randomly selected from among all public health facilities stratified by level of care. Survey teams performed inventories of malaria commodities and conducted exit interviews and re-examinations, including RDT testing, of a random selection of all patients completing outpatient consultations. Key health facility readiness and case management indicators were calculated adjusting for the cluster sampling design and utilization. Results Availability of RDTs or microscopy on the day of the survey was 71% (54–83) in Huambo and 85% (67–94) in Uíge. At least one unit dose pack of one formulation of an ACT (usually artemether–lumefantrine) was available in 83% (66–92) of health facilities in Huambo and 79% (61–90) of health facilities in Uíge. Testing rates of suspect malaria cases in Huambo were 30% (23–38) versus 69% (53–81) in Uíge. Overall, 28% (13–49) of patients with uncomplicated malaria, as determined during the re-examination, were appropriately treated with an ACT with the correct dose in Huambo, compared to 60% (42–75) in Uíge. Incorrect case management of suspect malaria cases was associated with lack of healthcare worker training in Huambo and ACT stock-outs in Uíge. Conclusions The results reveal important differences between provinces. Despite similar availability of testing and ACT, testing and treatment rates were lower in Huambo compared to Uíge. A majority of true malaria cases seeking care in health facilities in Huambo were not appropriately treated with anti-malarials, highlighting the importance of continued training and supervision of healthcare workers in malaria case management, particularly in areas with decreased malaria transmission.

Review

INTRODUCTION: Several studies have shown that older people have a higher risk of exposure to viral hepatitis B and C than younger people. This study aimed to determine the seroprevalence of hepatitis B and C and their associated factors in people aged 45+ years old in Burera, a rural district of Rwanda. METHODS: a cross sectional study was conducted from July to December 2017 during a mass campaign of hepatitis B (HBV) and hepatitis C (HCV) screening and vaccination of eligible populations against HBV in Burera District. Blood samples were collected and hepatitis B surface antigen (HBsAg) and an antibody against hepatitis C (Anti-HCV) were detected using an Enzyme-Linked Immuno-Sorbent Assay (ELISA). The associated factors were identified using a structured questionnaire and the data was analyzed using SPSS software. RESULTS: of the 374 people included in this study, 53.2% were females. The median age was 56 years old with an interquartile range (IQR) of 50 - 63 years old. The prevalence of HBV and HCV infection was 6.4% and 9.4%, respectively, with 0.3% co-infection rate. Age, social economic level, history of blood transfusion, history of never using a condom, as well as a history of injury with a used sharp material were significantly associated with HCV infection. CONCLUSION: the study showed a high seroprevalence of both HBV and HCV in Burera´s elderly population aged 45+ years. Several factors associated with HBV and HCV in this study could be prevented through education and improved hygiene.

The discovery of therapeutic monoclonal antibodies (mAbs) primarily focuses on their biological activity favoring the selection of highly potent drug candidates. These candidates, however, may have physical or chemical attributes that lead to unfavorable chemistry, manufacturing, and control (CMC) properties, such as low product titers, conformational and colloidal instabilities, or poor solubility, which can hamper or even prevent development and manufacturing. Hence, there is an urgent need to consider the developability of mAb candidates during lead identification and optimization. This work provides a comprehensive proof of concept study for the significantly improved developability of a mAb variant that was optimized with the help of sophisticated in silico tools relative to its difficult-to-develop parental counterpart. Interestingly, a single amino acid substitution in the variable domain of the light chain resulted in a three-fold increased product titer after stable expression in Chinese hamster ovary cells. Microscopic investigations revealed that wild type mAb-producing cells displayed potential antibody inclusions, while the in silico optimized variant-producing cells showed a rescued phenotype. Notably, the drug substance of the in silico optimized variant contained substantially reduced levels of aggregates and fragments after downstream process purification. Finally, formulation studies unraveled a significantly enhanced colloidal stability of the in silico optimized variant while its folding stability and potency were maintained. This study emphasizes that implementation of bioinformatics early in lead generation and optimization of biotherapeutics reduces failures during subsequent development activities and supports the reduction of project timelines and resources.

BackgroundHyperlipidemia and hypertension are modifiable risk factors for Alzheimer's disease and related dementias (ADRD). Approximately 25% of adults over age 65 use both antihypertensives (AHTs) and statins for these conditions. While a growing body of evidence found statins and AHTs are independently associated with lower ADRD risk, no evidence exists on simultaneous use for different drug class combinations and ADRD risk. Our primary objective was to compare ADRD risk associated with concurrent use of different combinations of statins and antihypertensives.MethodsIn a retrospective cohort study (2007-2014), we analyzed 694,672 Medicare beneficiaries in the United States (2,017,786 person-years) who concurrently used both statins and AHTs. Using logistic regression adjusting for age, socioeconomic status and comorbidities, we quantified incident ADRD diagnosis associated with concurrent use of different statin molecules (atorvastatin, pravastatin, rosuvastatin, and simvastatin) and AHT drug classes (two renin-angiotensin system (RAS)-acting AHTs, angiotensin converting enzyme inhibitors (ACEIs) or angiotensin-II receptor blockers (ARBs), vs non-RAS-acting AHTs).FindingsPravastatin or rosuvastatin combined with RAS-acting AHTs reduce risk of ADRD relative to any statin combined with non-RAS-acting AHTs: ACEI+pravastatin odds ratio (OR) = 0.942 (CI: 0.899-0.986, p = 0.011), ACEI+rosuvastatin OR = 0.841 (CI: 0.794-0.892, pConclusionAmong older Americans, use of pravastatin and rosuvastatin to treat hyperlipidemia is less common than use of simvastatin and atorvastatin, however, in combination with RAS-acting AHTs, particularly ARBs, they may be more effective at reducing risk of ADRD. The number of Americans with ADRD may be reduced with drug treatments for vascular health that also confer effects on ADRD.

Tethys Platform is an open source framework for developing web-based applications for Earth Observation data. Our experience shows that Tethys significantly lowers the barrier for cloud-based app development, simplifies the process of accessing scalable distributed cloud computing resources and leverages additional software for data and computationally intensive modeling. The Tethys software development kit allows users to create web apps for visualizing, analyzing, and modeling Earth Observation data. Tethys platform provides a collaborative environment for scientists to develop and deploy several Earth Observation web applications across multiple Tethys portals. We work in partnership with leading regional organizations world-wide to help developing countries use information provided by earth-observing satellites and geospatial technologies for managing climate risks and land use. This paper highlights the several Tethys portals and web applications that were developed as part of this effort. Implementation of the Tethys framework has significantly improved the Application Readiness Level metric for several NASA projects and the potential impact of Tethys to replicate and scale other applied science programs.

Objective We sought to determine patients’ informational needs for post-treatment surveillance and elicit clinicians’ and patient advocates’ (ie, stakeholders) opinions regarding what patients should know about post-treatment surveillance in the USA.Design A mixed-methods study, using semi-structured interviews followed by a survey study.Setting Participants for the interviews were from two large academic medical centres and a safety-net hospital. The stakeholders were recruited from attendees at the Alliance for Clinical Trials in Oncology Network Spring 2016 meeting.Participants Participants for the in-depth interviews were purposively sampled. Eligible patients were 6 months to 5 years post curative resection for colorectal cancer and were fluent in English. Participants for the anonymous survey were stakeholders.Main outcome(s) and measure(s) The main outcome was patients’ with colorectal cancer informational needs for post-treatment surveillance, using an interview guide. The second outcome was the importance of the identified informational needs using an anonymous survey.Results Of the 67 patients approached, 31 were interviewed (response rate=46%), the majority were between 1 and 3 years post-treatment (81%) and diagnosed at stage III (74%). Despite a desire to monitor for cancer recurrence, patients had little understanding of the concept of post-treatment surveillance, equating surveillance with screening and a belief that if a recurrence was found early there would be a higher likelihood of cure. The survey suggested that clinicians (n=38) and patient advocates (n=11) had some differing opinions regarding what patients should know about surveillance to be active in decisions. For example, compared with clinicians, patient advocates felt that patients should know recurrence treatment options (100% vs 58%) and likelihood for cure following recurrence treatment (100% vs 38%).Conclusions The results of this exploratory mixed-methods study suggest that novel educational interventions targeting both patients and clinicians are needed to address the informational needs for post-treatment surveillance of colorectal cancer.

Many species are capable of facultative migration, but the relative roles of extrinsic vs. intrinsic factors in generating diverse migratory tactics remain unclear. Here we explore the proximate drivers of facultative migration in brown trout in an experimental laboratory setting. The effects of reduced food, as a putative environmental cue, were examined in two populations: one that exhibits high rates of anadromy (sea-migration) in nature, and one that does not exhibit anadromy in nature. Juveniles derived from wild-caught parents were reared for 2 years under four environmental treatments: low food in years 1 and 2 (Low-Low); high food in years 1 and 2 (High-High), low food in year 1 and high in year 2 (Low-High), and vice versa (High-Low). Food restriction had a significant effect on migratory tactics, with the frequency of smolts (juveniles choosing migration) highest in the Low-Low treatment in both populations. No individuals became smolts in the High-High treatment, and intermediate smolting rates were observed in the Low-High and High-Low treatments. Higher overall smolting rates in the naturally anadromous population suggested an inherited component to anadromy/migration decisions, but both populations showed variability in migratory tactics. Importantly, some fish from the naturally non-anadromous population became smolts in the experiment, implying the capacity for migration was lying “dormant,” but they exhibited lower hypo-osmoregulatory function than smolts from the naturally anadromous population. Tactic frequencies in the naturally anadromous population were more affected by food in the 2nd year, while food in the 1st year appeared more important for the naturally non-anadromous population. Migratory tactics were also related to sex, but underpinned in both sexes by growth in key periods, size, and energetic state. Collectively these results reveal how migration decisions are shaped by a complex interplay between extrinsic and intrinsic factors, informing our ability to predict how facultatively migratory populations will respond to environmental change.

UltraViolet & infrared Sensors at high Quantum efficiency onboard a small SATellite (UVSQ-SAT) is a small satellite at the CubeSat standard, whose development began as one of the missions in the International Satellite Program in Research and Education (INSPIRE) consortium in 2017. UVSQ-SAT is an educational, technological and scientific pathfinder CubeSat mission dedicated to the observation of the Earth and the Sun. It was imagined, designed, produced and tested by LATMOS in collaboration with its academic and industrial partners, and the French-speaking radioamateur community. About the size of a Rubik’s Cube and weighing about 2 kg, this satellite was put in orbit in January 2021 by the SpaceX Falcon 9 launch vehicle. After briefly introducing the UVSQ-SAT mission, this paper will present the importance of measuring the Earth’s radiation budget and its energy imbalance and the scientific objectives related to its various components. Finally, the first in-orbit observations will be shown (maps of the solar radiation reflected by the Earth and of the outgoing longwave radiation at the top of the atmosphere during February 2021). UVSQ-SAT is one of the few CubeSats worldwide with a scientific goal related to climate studies. It represents a research in remote sensing technologies for Climate observation and monitoring.

Electron-electron interactions in many-body systems may manifest themselves through the fractional quantum Hall effect. Here, the authors perform transport measurements in bilayer graphene, and observe particle-hole symmetric fractional quantum Hall states in theN=2 Landau level.

This study examined whether the good or bad outcomes associated with mastery-approach (MAP) and performance-approach (PAP) goals depend on the extent to which they are motivated by autonomous or controlled motivation. A sample of 515 undergraduate students who participated in sport completed measures of achievement goals, motivation of achievement goals, perceived goal attainment, sport satisfaction, and both positive and negative affect. Results of moderated regression analyses revealed that the positive relations of both MAP and PAP goals with perceived goal attainment were stronger for athletes pursuing these goals with high level of autonomous goal motivation. Also, the positive relations between PAP goals and both sport satisfaction and positive affect were stronger at high levels of autonomous goal motivation and controlled goal motivation. The shape of all these significant interactions was consistent with tenets of Self-Determination Theory as controlled goal motivation was negatively associated with positive affect and sport satisfaction and positively associated with negative affect. Overall, these findings demonstrated the importance of considering goal motivation in order to better understand the conditions under which achievement goals are associated with better experiential and performance outcomes in the lives of sport participants.

In this paper, we analyze the problem of generating fluent English utterances from tabular data, focusing on the development of a sequence-to-sequence neural model which shows two major features: the ability to read and generate character-wise, and the ability to switch between generating and copying characters from the input: an essential feature when inputs contain rare words like proper names, telephone numbers, or foreign words. Working with characters instead of words is a challenge that can bring problems such as increasing the difficulty of the training phase and a bigger error probability during inference. Nevertheless, our work shows that these issues can be solved and efforts are repaid by the creation of a fully end-to-end system, whose inputs and outputs are not constrained to be part of a predefined vocabulary, like in word-based models. Furthermore, our copying technique is integrated with an innovative shift mechanism, which enhances the ability to produce outputs directly from inputs. We assess performance on the E2E dataset, the benchmark used for the E2E NLG challenge, and on a modified version of it, created to highlight the rare word copying capabilities of our model. The results demonstrate clear improvements over the baseline and promising performance compared to recent techniques in the literature.

In previous investigations, it was shown that the melting, as well as crystallization behavior of polyamide 12, could be manipulated by adjusting the particle size distribution of calcium carbonate as a functional filler. It was demonstrated that the melt properties of this compound show a significant dependency on the filler volume-based particle size. As finer and narrower the calcium carbonate particles in the polymer matrix become, the less influence the filler has on the melting properties, influencing the melt flow less significantly than the same surface amount of broad size distribution coarse calcium carbonate filler particles. However, due to increased nucleation, the crystallization behavior on cooling showed a markedly more rapid onset in the case of fine sub-micrometer filler particle size. To control further and optimize the thermal response properties of a filling compound for improved properties in additive manufacturing processing through selective laser sintering, the possibility to combine precisely defined particle size distributions has been studied, thereby combining the benefits of each particle size range within the chosen material size distribution contributes to the matrix. The melt flow at 190 °C, the melting speed, melting and crystallization point as well as crystallization time at 170 °C were analyzed. The thermal and flow properties of a polyamide 12 matrix can potentially be optimized with a combination of a precise amount of coarse and fine calcium carbonate filler. The improvements were exemplified using a twin-screw extruder for compounding, indicating the potential for optimizing functionally filled polymer in additive manufacturing.