Search

In order to evaluate the percentage of weed cover in different cultivation techniques, a study was made of the population of weeds, in the production unit "Manuel Sánchez" of the Sugar Company "Argeo Martinez", Guantánamo, between April and July 2014, in the 1st shoot strain, variety C90-647, on a soil alluvial, compacted, from 24 days after the mechanized harvest. The percentage of coverage, wealth, dominance and species diversity were evaluated in five management techniques and three replications, as well as the economic valuation. The results showed that the coverage percentage varied indistinctly by treatment and remained below 1.4 % from 30 days until the study stage was concluded. The Margalef index was higher for the Deep Cultivation treatment 1.10 + 1.60 m, while the similarity index for all the combinations at 90 days after assembly showed imbalance of species between treatments with values lower than 0.5. The diversity of weeds showed that a total of 11 weed species inhabited the area with a predominance of the Poaceae; relative abundance was observed in five species with superiority of Cynodon dactylon revealing a gradual decrease in the Deep Cultivation treatment 1.10 + 1.60 m during the period. The lowest and highest cost for clean days, was for the treatments Unaltered coverage of crop residues and deep cultivation 1.10 + 1.60 m respectively.

Programmed cell death is an important part of tissue development, and traditionally it is considered that neuronal death is a stochastic process in response to neurotrophic factor deprivation. Here the authors show that for TrkC+ proprioreceptors, which neurons die is predetermined molecularly by how much TrkC is present, as well as by a gene expression signature.

Abstract Purpose To assess the incidence of BCR‐ABL kinase domain (KD) mutation detection and its prognostic significance in chronic phase chronic myeloid leukemia (CP‐CML) patients treated with tyrosine kinase inhibitors (TKIs). Patients and Methods We analyzed characteristics and outcome of 253 CP‐CML patients who had at least one mutation analysis performed using direct sequencing. Of them, 187 patients were early CP (ECP) and 66 were late CP late chronic phase (LCP) and 88% were treated with Imatinib as first‐line TKI. Results Overall, 80 (32%) patients harbored BCR‐ABL KD mutations. A BCR‐ABL KD mutation was identified in 57% of patients, who progressed to accelerated or blastic phases (AP‐BP), and 47%, 29%, 35%, 16% and 26% in patients in CP‐CML at the time of mutation analysis who lost a complete hematologic response, failed to achieve or loss of a prior complete cytogenetic and major molecular response, respectively. Overall survival and cumulative incidence of CML‐related death were significantly correlated with the disease phase whatever the absence or presence of a mutation was and for the latter the mutation subgroup (T315I vs P‐loop vs non‐T315I non‐P‐loop) (P

Abstract Background Eradication of minimal residual disease (MRD), at the end of Fludarabine-Cyclophosphamide-Rituximab (FCR) treatment, is a validated surrogate marker for progression-free and overall survival in chronic lymphocytic leukaemia. But such deep responses are also associated with severe immuno-depletion, leading to infections and the development of secondary cancers. Methods We assessed, blood MRD and normal immune cell levels at the end of treatment, in 162 first-line FCR patients, and analysed survival and adverse event. Results Multivariate Landmark analysis 3 months after FCR completion identified unmutated IGHV status (HR, 2.03, p = 0.043), the level of MRD reached (intermediate versus low, HR, 2.43, p = 0.002; high versus low, HR, 4.56, p = 0.002) and CD4 > 200/mm3 (HR, 3.30, p

The dioxide of sulfur in 2014 represented the second pollutant of more emission to the atmosphere for the fixed sources in Villa Clara, being the entities fuel oil consumers the responsible maxims. The objectives of this work have been to quantify the polluting load of the dioxide of sulfur emitted by the sources of the MINAG, to determine the percentage that represents these emissions of the total, for municipalities and consumption of fuel, to evaluate the quality of the air and to propose measures of reduction of the emission. The method applied was using direct mensuration with analyzers of gases and factors of emission of AP-42 of the Agency of Environmental Protection of the United States (EPA), the evaluation of the quality of the air was carried out through the moderation of the dispersion of the pollutant with the software ISC-AERMOD Version 3.15 of the EPA. The results show that the polluting load of the dioxide of sulfur was of 68 t, 80 % emitted in the municipality of Santo Domingo and 97 % to burn fuel oil. The quality of the air is acceptable, faulty and dreadful in near different areas to the emission sources. Applying the measures proposals, the energy efficiency can rise and to reduce the consumption of fuel to 3 % (38 t) and the emission in 1.8 t, favoring the costs of the entities and propitiating smaller deterioration of the quality of the air in the affected areas.

Abstract Background Orphan medicines show some characteristics that hinder the evaluation of their clinical added value. The often low level of evidence available for orphan drugs, together with a high budget impact and an incremental cost-effectiveness ratio many times higher than drugs used for non-orphan diseases, represent challenges in their appraisal and effective access to clinical use. In order to explore how to handle these hurdles, the Catalan Health Service (CatSalut) began an initiative on a multidimensional assessment of drugs value during the appraisal process. Reflective multicriteria decision analysis (MCDA) using analytical methods was chosen, since it may help to standardise and contextualize all the relevant data related with the drug that could contribute to a decision. The aim of the study was to determine whether the implementation of reflective MCDA methodology could support the decision-making process about orphan medicines in the context of CatSalut. Methods The assessment and decision-making process for orphan drugs in the Programa d’Harmonització Farmacoterapeutica (PHF) of CatSalut was prioritized to test the implementation of the reflective MCDA both a qualitative and quantitatively. A staged approach was used with the following main steps: selection and structuration of quantitative criteria (Core Model) and qualitative criteria (Contextual Tool), framework scoring and assessment of three orphan drug case studies. This proof-of-concept would grant a continued refinement of the methodology and, if and when validated, its potential integration to other therapeutic areas of the PHF. Results The final framework was composed by 10 quantitative criteria (Core Model) and 4 qualitative criteria (Contextual Tool) according to the PHF goals being the most important criteria “disease severity”, “unmet need”, “comparative effectiveness” and “comparative safety /tolerability”. The matrix developed for the case studies served as a guide for the selection of the essential information that the decision-makers were expected to include in a framework. The reflective discussion was considered the most relevant phase of the approach to support inputs for health decision-making processes reflecting both drug value and place in therapy. Conclusions The study showed that reflective MCDA methodology could be implemented to complement the decision-making process in CatSalut, as an aid to determine the clinical added value for orphan medicines. MCDA provided transparency and a structured discussion during the committee meetings, thus increasing transparency and predictability of the relevant items supporting the agreements adopted on orphan drugs access.

Resumen: Antecedentes: La hiperpotasemia constituye un importante desequilibrio electrolítico en la enfermedad renal crónica (ERC). Los inhibidores del sistema renina-angiotensina-aldosterona (iSRAA) tienen propiedades beneficiosas cardiorrenales, aunque son causa importante de hiperpotasemia. Objetivo: Examinar la prevalencia de la hiperpotasemia en la ERC, identificar factores asociados a su aparición y la relación entre hiperpotasemia y mortalidad. Pacientes y métodos: Estudio observacional retrospectivo en pacientes con ERC en el período 1971-2017. La población se categorizó en 3 grupos: grupo 1, pacientes con ERC sin tratamiento renal sustitutivo; grupo 2, pacientes en hemodiálisis, y grupo 3, pacientes en diálisis peritoneal continua ambulatoria. Resultados: Se evaluó a 2.629 pacientes. La prevalencia observada en los distintos grupos fue del 9,6, el 16,4 y el 10,6%, respectivamente. Los factores de riesgo relacionados con la aparición de hiperpotasemia en el grupo de ERC fueron la tasa de filtrado glomerular (FG) (p < 0,001), la creatinina plasmática (p < 0,001), el sodio plasmático (p < 0,001), la hemoglobina (p = 0,028), la presión arterial diastólica (p = 0,012), la ingesta de inhibidores de la enzima de conversión de la angiotensina o antagonistas de receptores de angiotensina ii (p = 0,008), el tratamiento con metformina (p < 0,001) y la diabetes (p = 0,045). El tratamiento con iSRAA incrementó de forma relevante la hiperpotasemia a medida que disminuía el FG, así como en pacientes con diabetes o insuficiencia cardiaca. Conclusiones: La hiperpotasemia es una alteración metabólica frecuente en pacientes con ERC que aumenta en presencia de fármacos con propiedades beneficiosas cardiorrenales (iSRAA), por lo que en muchos casos los pacientes pierden el beneficio asociado a estos fármacos. Nuevos compuestos no absorbibles de reciente aparición, que se unen al potasio en el tracto gastrointestinal potenciando su excreción fecal, manteniendo el beneficio cardiorrenal de los iSRAA, pudieran ser relevantes en la evolución de los pacientes con ERC. Abstract: Background: Hyperkalaemia is a significant electrolyte imbalance in chronic kidney disease (CKD). Renin-angiotensin-aldosterone system inhibitors (RAASi) have beneficial cardio-renal properties, although they can often cause hyperkalaemia. Objective: To examine the prevalence of hyperkalaemia in CKD, identify factors associated with its appearance and the relationship between hyperkalaemia and mortality. Patients and methods: Retrospective observational study on patients with CKD in the period 1971-2017. The population was categorised into 3 groups: Group 1, patients with CKD without renal replacement therapy; Group 2, patients on haemodialysis; and Group 3, patients on continuous ambulatory peritoneal dialysis. Results: A total of 2,629 patients were evaluated. The prevalence observed in the different groups was: 9.6%, 16.4% and 10.6%, respectively. Risk factors related to the appearance of hyperkalaemia in the CKD group were glomerular filtration rate (GFR) (P

Background: Hyperkalaemia is a significant electrolyte imbalance in chronic kidney disease (CKD). Renin–angiotensin–aldosterone system inhibitors (RAASi) have beneficial cardio-renal properties, although they can often cause hyperkalaemia. Objective: To examine the prevalence of hyperkalaemia in CKD, identify factors associated with its appearance and the relationship between hyperkalaemia and mortality. Patients and methods: Retrospective observational study on patients with CKD in the period 1971–2017. The population was categorised into 3 groups: Group 1, patients with CKD without renal replacement therapy; Group 2, patients on haemodialysis; and Group 3, patients on continuous ambulatory peritoneal dialysis. Results: A total of 2629 patients were evaluated. The prevalence observed in the different groups was: 9.6%, 16.4% and 10.6%, respectively. Risk factors related to the appearance of hyperkalaemia in the CKD group were glomerular filtration rate (GFR) (p

This oceanographic dataset was gathered during the TIC-MOC cruise, which was designed to characterize the dynamics of the Brazil-Malvinas Confluence. The cruise was carried on board the R/V Hespérides, with departure from Ushuaia and arrival to Salvador de Bahía. A total of 66 conductivity-temperature-depth (CTD) stations were completed between 8 and 22 March 2015, offshore from the continental platform and within 45°S-35°S and 61°W-50°W. At each station, water samples were collected, which were used to calibrate the CTD salinity-oxygen sensors and to determine inorganic nutrient concentrations, and the horizontal current was measured. Along its track, the vessel recorded surface temperature and salinity, as well as the horizontal flow down to about 700 m. Lastly, eight position-transmitting drifters were launched and two profiling floats were deployed and later recovered.

Background: In 2016-2017, 68 women in Southern Vietnam had RT-PCR confirmed Zika virus (ZIKV) infection during pregnancy. We report here the outcomes of the pregnancies and the virological analyses related to this outbreak. Methods: We collected clinical and epidemiological information from the women who were enrolled in the study. Medical records related to the pregnancy in 2016–2017 were retrieved for those who were not able to be enrolled in the study. Children born to women with ZIKV infection during pregnancy were also enrolled. Serum samples were evaluated for presence of ZIKV antibodies. Phylogenetic analyses were performed on Zika virus genomes sequenced from the 2016–2017 serum samples. Findings: Of the 68 pregnancies, 58 were livebirths and 10 were medically terminated. Four of the medical records from cases of fetal demise were able to be retrieved, of which one was consistent with congenital ZIKV infection. Of the 58 women with a livebirth, 21 participated in the follow-up investigation. All but two women had serologic evidence of ZIKV infection. Of the 21 children included in the study (mean age: 30.3 months), 3 had microcephaly at birth. No other clinical abnormalities were reported and no differences in neurodevelopment were observed compared to a control group. Phylogenetic analysis revealed a clade within the ZIKV Asian lineage and branch at the root of samples from the 2013–2014 French Polynesian outbreak. The prM S139N mutation was not observed. Interpretation: We have been able to demonstrate a clade within the ZIKV Asian lineage implicated in adverse pregnancy outcomes in Southern Vietnam. Funding: INCEPTION project (PIA/ANR-16-CONV-0005) and a grant received from BNP Paribas Simplidon.

BackgroundIndividuals with diabetes need regular support to help them manage their diabetes on their own, ideally delivered via mechanisms that they already use, such as their mobile phones. One reason for the modest effectiveness of prior technology-based interventions may be that the patient perspective has been insufficiently incorporated. ObjectiveThis study aims to understand patients’ preferences for mobile health (mHealth) technology and how that technology can be integrated into patients’ routines, especially with regard to medication use. MethodsWe conducted semistructured qualitative individual interviews with patients with type 2 diabetes from an urban health care system to elicit and explore their perspectives on diabetes medication–taking behaviors, daily patterns of using mobile technology, use of mHealth technology for diabetes care, acceptability of text messages to support medication adherence, and preferred framing of information within text messages to support diabetes care. The interviews were digitally recorded and transcribed. The data were analyzed using codes developed by the study team to generate themes, with representative quotations selected as illustrations. ResultsWe conducted interviews with 20 participants, of whom 12 (60%) were female and 9 (45%) were White; in addition, the participants’ mean glycated hemoglobin A1c control was 7.8 (SD 1.1). Overall, 5 key themes were identified: patients try to incorporate cues into their routines to help them with consistent medication taking; many patients leverage some form of technology as a cue to support adherence to medication taking and diabetes self-management behaviors; patients value simplicity and integration of technology solutions used for diabetes care, managing medications, and communicating with health care providers; some patients express reluctance to rely on mobile technology for these diabetes care behaviors; and patients believe they prefer positively framed communication, but communication preferences are highly individualized. ConclusionsThe participants expressed some hesitation about using mobile technology in supporting diabetes self-management but have largely incorporated it or are open to incorporating it as a cue to make medication taking more automatic and less burdensome. When using technology to support diabetes self-management, participants exhibited individualized preferences, but overall, they preferred simple and positively framed communication. mHealth interventions may be improved by focusing on integrating them easily into daily routines and increasing the customization of content.

Summary: Many SARS-CoV-2-infected individuals remain asymptomatic. Little is known about the extent and quality of their antiviral humoral response. Here, we analyze antibody functions in 52 asymptomatic infected individuals, 119 mildly symptomatic, and 21 hospitalized patients with COVID-19. We measure anti-spike immunoglobulin G (IgG), IgA, and IgM levels with the S-Flow assay and map IgG-targeted epitopes with a Luminex assay. We also evaluate neutralization, complement deposition, and antibody-dependent cellular cytotoxicity (ADCC) using replication-competent SARS-CoV-2 or reporter cell systems. We show that COVID-19 sera mediate complement deposition and kill infected cells by ADCC. Sera from asymptomatic individuals neutralize the virus, activate ADCC, and trigger complement deposition. Antibody levels and functions are lower in asymptomatic individuals than they are in symptomatic cases. Antibody functions are correlated, regardless of disease severity. Longitudinal samplings show that antibody functions follow similar kinetics of induction and contraction. Overall, asymptomatic SARS-CoV-2 infection elicits polyfunctional antibodies neutralizing the virus and targeting infected cells.

Objectives We aimed to review SARS-CoV-2 seroprevalence studies conducted in Europe to understand how they may be used to inform ongoing control strategies for COVID-19.Design Scoping review of peer-reviewed publications and manuscripts on preprint servers from January 2020 to 15 September 2020.Primary measure Seroprevalence estimate (and lower and upper CIs). For studies conducted across a country or territory, we used the seroprevalence estimate and the upper and lower CIs and compared them to the total number of reported infections to calculate the ratio of reported to expected infections.Results We identified 23 population-based seroprevalence studies conducted in Europe. Among 12 general population studies, seroprevalence ranged from 0.42% among residual clinical samples in Greece to 13.6% in an area of high transmission in Gangelt, Germany. Of the eight studies in blood donors, seroprevalence ranged from 0.91% in North-Western Germany to 23.3% in a high-transmission area in Lombardy region, Italy. In three studies which recruited individuals through employment, seroprevalence ranged from 0.5% among factory workers in Frankfurt, Germany, to 10.2% among university employees in Milan, Italy. In comparison to nationally reported cases, the extent of infection, as derived from these seroprevalence estimates, is manyfold higher and largely heterogeneous.Conclusion Exposure to the virus in Europe has not reached a level of infection that would prevent further circulation of the virus. Effective vaccine candidates are urgently required to deliver the level of immunity in the population.

BackgroundWe developed a self-assessment and participatory web-based triage app to assess the trends of the COVID-19 pandemic in France in March 2020. ObjectiveWe compared daily large-scale RT–PCR test results to monitor recent reports of anosmia through a web-based app to assess the dynamics of emergency department visits, hospitalizations, and intensive care unit (ICU) admissions among individuals with COVID-19 in France. MethodsBetween March 21 and November 18, 2020, users of the maladiecoronavirus.fr self-triage app were asked questions about COVID-19 symptoms. Data on daily hospitalizations, large-scale positive results on RT–PCR tests, emergency department visits, and ICU admission of individuals with COVID-19 were compared to data on daily reports of anosmia on the app. ResultsAs of November 18, 2020, recent anosmia was reported 575,214 times from among approximately 13,000,000 responses. Daily anosmia reports during peak engagement with the app on September 16, 2020, were spatially correlated with the peak in daily COVID-19–related hospitalizations in November 2020 (Spearman rank correlation coefficient [ρ]=0.77; P

BackgroundIn the French Territories in the Americas (FTA), the risk of birth defects possibly associated with Zika virus (ZIKV) infection was 7.0% (95%CI: 5.0 to 9.5) among foetuses/infants of 546 women with symptomatic RT-PCR confirmed ZIKV infection during pregnancy. Many of these defects were isolated measurement-based microcephaly (i.e. without any detected brain or clinical abnormalities) or mild neurological conditions. We wanted to estimate the proportion of such minor findings among live births of women who were pregnant in the same region during the outbreak period but who were not infected with ZIKV.MethodsIn Guadeloupe, pregnant women were recruited at the time of delivery and tested for ZIKV infection. The outcomes of live born infants of ZIKV non-infected women were compared to those of ZIKV-exposed live born infants in Guadeloupe, extracted from the FTA prospective cohort.ResultsOf 490 live born infants without exposure to ZIKV, 42 infants (8.6%, 95%CI: 6.2-11.4) had mild abnormalities that have been described as 'potentially linked to ZIKV infection'; all but one of these was isolated measurement-based microcephaly. Among the 241 live born infants with ZIKV exposure, the proportion of such abnormalities, using the same definition, was similar (6.6%, 95%CI: 3.8-10.6).ConclusionsIsolated anthropometric abnormalities and mild neurological conditions were as prevalent among infants with and without in-utero ZIKV exposure. If such abnormalities had not been considered as 'potentially linked to ZIKV' in the original prospective cohort in Guadeloupe, the overall estimate of the risk of birth defects considered due to the virus would have been significantly lower, at approximately 1.6% (95% CI: 0.4-4.1).Trial registrationClinicalTrials.gov (NCT02916732).

BackgroundHospitals are suspected of playing a key role in HCV epidemic dynamics in Egypt. This work aimed at assessing HCV prevalence and associated risk factors in patients and health-care workers (HCWs) of Ain Shams University (ASU) hospitals in Cairo.MethodsWe included 500 patients admitted to the internal medicine or surgery hospital from February to July, 2017, as well as 50 HCWs working in these same hospitals. Participants were screened for anti-HCV antibodies and HCV RNA. A questionnaire was administered to collect data on demographic characteristics and medical/surgical history. For HCWs, questions on occupational exposures and infection control practices were also included.ResultsThe overall prevalence of anti-HCV antibodies was 19.80% (95% CI: 16.54-23.52) among participating patients, and 8.00% (95% CI: 0.48-15.52) among participating HCWs. In HCWs, the only risk factors significantly associated with anti-HCV antibodies were age and profession, with higher prevalence in older HCWs and those working as cleaners or porters. In patients, in a multivariate logistic regression, age over 50 (aOR: 3.4 [1.9-5.8]), living outside Cairo (aOR: 2.1 [1.2-3.4]), admission for liver or gastro-intestinal complaints (aOR: 4.2 [1.8-9.9]), and history of receiving parenteral anti-schistosomiasis treatment (aOR: 2.7 [1.2-5.9]) were found associated with anti-HCV antibodies.ConclusionsWhile HCV prevalence among patients has decreased since the last survey performed within ASU hospitals in 2008, it is still significantly higher than in the general population. These results may help better control further HCV spread within healthcare settings in Egypt by identifying at-risk patient profiles upon admission.

Tunnelling under the York University Schulich Building was one of the milestones of the Toronto-York Spadina Subway Extension Project. The challenge was to bore the tunnel under a flagship building only one diameter below the foundation without a compensation grouting process. Intensive finite element structural and geotechnical analyses of the building and the tunnel were performed, together with monitoring field measurements. The results showed that compensation, included in the initial design, was not necessary to ensure the building's structural integrity. The tunnel monitoring during crossing confirmed the results of the performed analyses. The paper highlights the difficulty of deciding whether a compensation grouting is necessary or not when tunnelling under buildings and explains the procedure that was followed in this particular case.Key words: tunnels, monitoring, buildings, settlements.Le creusement d'un tunnel sous l'edifice Schulich de l'Universite York etait un des jalons du projet de prolongement de la ligne de metro de Toronto-York Spadina. Le defi etait de forer le tunnel sous un immeuble de prestige seulement un diametre au-dessous de la fondation sans une compensation par injection de coulis. D'intensifs calculs des structures et d'analyses geotechniques par elements finis de l'edifice et du tunnel ont ete effectues, ainsi que des mesures sur le terrain pour faire un suivi. Les resultats ont montre que la compensation, faisant partie de la conception initiale, n'etait pas necessaire pour assurer l'integrite structurale de l'edifice. La surveillance du tunnel pendant le croisement a confirme les resultats des analyses effectuees. Cette etude met en evidence la difficulte de prendre une decision a savoir si la compensation par injection de coulis est necessaire ou non dans le cas de creusement de tunnel sous des edifices et explique la procedure qui a ete suivie dans ce cas particulier. [Traduit par la Redaction]Mots-cles: tunnels, surveillance, edifices, tassements., 1. IntroductionTunnelling under existing structures is a challenge that engineers often face in urban underground projects. Therefore, great efforts were devoted in the past to predict the impact of tunnelling [...]

BackgroundWe developed a self-triage web application for COVID-19 symptoms, which was launched in France in March 2020, when French health authorities recommended all patients with suspected COVID-19 call an emergency phone number. ObjectiveOur objective was to determine if a self-triage tool could reduce the burden on emergency call centers and help predict increasing burden on hospitals. MethodsUsers were asked questions about their underlying conditions, sociodemographic status, postal code, and main COVID-19 symptoms. Participants were advised to call an emergency call center if they reported dyspnea or complete loss of appetite for over 24 hours. Data on COVID-19–related calls were collected from 6 emergency call centers and data on COVID-19 hospitalizations were collected from Santé Publique France and the French Ministry of Health. We examined the change in the number of emergency calls before and after the launch of the web application. ResultsFrom March 17 to April 2, 2020, 735,419 questionnaires were registered in the study area. Of these, 121,370 (16.5%) led to a recommendation to call an emergency center. The peak number of overall questionnaires and of questionnaires leading to a recommendation to call an emergency center were observed on March 22, 2020. In the 17 days preceding the launch of the web application, emergency call centers in the study area registered 66,925 COVID-19–related calls and local hospitals admitted 639 patients for COVID-19; the ratio of emergency calls to hospitalizations for COVID-19 was 104.7 to 1. In the 17 days following the launch of the web application, there were 82,347 emergency calls and 6009 new hospitalizations for COVID-19, a ratio of 13.7 calls to 1 hospitalization (chi-square test: P

Yersinia pestis, the bacterial causative agent of plague, remains an important threat to human health. Plague is a rodent-borne disease that has historically shown an outstanding ability to colonize and persist across different species, habitats, and environments while provoking sporadic cases, outbreaks, and deadly global epidemics among humans. Between September and November 2017, an outbreak of urban pneumonic plague was declared in Madagascar, which refocused the attention of the scientific community on this ancient human scourge. Given recent trends and plague's resilience to control in the wild, its high fatality rate in humans without early treatment, and its capacity to disrupt social and healthcare systems, human plague should be considered as a neglected threat. A workshop was held in Paris in July 2018 to review current knowledge about plague and to identify the scientific research priorities to eradicate plague as a human threat. It was concluded that an urgent commitment is needed to develop and fund a strong research agenda aiming to fill the current knowledge gaps structured around 4 main axes: (i) an improved understanding of the ecological interactions among the reservoir, vector, pathogen, and environment; (ii) human and societal responses; (iii) improved diagnostic tools and case management; and (iv) vaccine development. These axes should be cross-cutting, translational, and focused on delivering context-specific strategies. Results of this research should feed a global control and prevention strategy within a "One Health" approach.

BackgroundWe developed a self-assessment and participatory surveillance web application for coronavirus disease (COVID-19), which was launched in France in March 2020. ObjectiveOur objective was to determine if self-reported symptoms could help monitor the dynamics of the COVID-19 outbreak in France. MethodsUsers were asked questions about underlying conditions, sociodemographic status, zip code, and COVID-19 symptoms. Depending on the symptoms reported and the presence of coexisting disorders, users were told to either stay at home, contact a general practitioner (GP), or call an emergency phone number. Data regarding COVID-19–related hospitalizations were retrieved from the Ministry of Health. ResultsAs of March 29, 2020, the application was opened 4,126,789 times; 3,799,535 electronic questionnaires were filled out; and 2,477,174 users had at least one symptom. In total, 34.8% (n=1,322,361) reported no symptoms. The remaining users were directed to self-monitoring (n=858,878, 22.6%), GP visit or teleconsultation (n=1,033,922, 27.2%), or an emergency phone call (n=584,374, 15.4%). Emergency warning signs were reported by 39.1% of participants with anosmia, a loss of the sense of smell (n=127,586) versus 22.7% of participants without anosmia (n=1,597,289). Anosmia and fever and/or cough were correlated with hospitalizations for COVID-19 (Spearman correlation coefficients=0.87 and 0.82, respectively; P

Drought is the primary cause of agricultural loss globally, and represents a major threat to food security. Currently, plant biotechnology stands as one of the most promising fields when it comes to developing crops that are able to produce high yields in water-limited conditions. From studies of Arabidopsis thaliana whole plants, the main response mechanisms to drought stress have been uncovered, and multiple drought resistance genes have already been engineered into crops. So far, most plants with enhanced drought resistance have displayed reduced crop yield, meaning that there is still a need to search for novel approaches that can uncouple drought resistance from plant growth. Our laboratory has recently shown that the receptors of brassinosteroid (BR) hormones use tissue-specific pathways to mediate different developmental responses during root growth. In Arabidopsis, we found that increasing BR receptors in the vascular plant tissues confers resistance to drought without penalizing growth, opening up an exceptional opportunity to investigate the mechanisms that confer drought resistance with cellular specificity in plants. In this review, we provide an overview of the most promising phenotypical drought traits that could be improved biotechnologically to obtain drought-tolerant cereals. In addition, we discuss how current genome editing technologies could help to identify and manipulate novel genes that might grant resistance to drought stress. In the upcoming years, we expect that sustainable solutions for enhancing crop production in water-limited environments will be identified through joint efforts.

Botryococcus braunii (B. braunii) is a green microalga primarily found in freshwater, reservoirs, and ponds. Photosynthetic pigments from algae have shown many bioactive molecules with therapeutic potential. Herein, we report the purification, characterization, and anticancer properties of photosystem I light-harvesting complex I (PSI-LHCI) from the green microalga B. braunii UTEX2441. The pigment–protein complex was purified by sucrose density gradient and characterized by its distinctive peaks using absorption, low-temperature (77 K) fluorescence, and circular dichroism (CD) spectroscopic analyses. Protein complexes were resolved by blue native-PAGE and two-dimensional SDS-PAGE. Triple-negative breast cancer MDA-MB-231 cells were incubated with PSI-LHCI for all of our experiments. Cell viability was assessed, revealing a significant reduction in a time- and concentration-dependent manner. We confirmed the internalization of PSI-LHCI within the cytoplasm and nucleus after 12 h of incubation. Cell death mechanism by oxidative stress was confirmed by the production of reactive oxygen species (ROS) and specifically superoxide. Furthermore, we monitored autophagic flux, apoptotic and necrotic features after treatment with PSI-LHCI. Treated MDA-MB-231 cells showed positive autophagy signals in the cytoplasm and nucleus, and necrotic morphology by the permeabilization of the cell membrane. Our findings demonstrated for the first time the cytotoxic properties of B. braunii PSI-LHCI by the induction of ROS and autophagy in breast cancer cells.

Abstract Background To assess uncertainty in regulatory decision-making for orphan medicinal products (OMP), a summary of the current basis for approval is required; a systematic grouping of medical conditions may be useful in summarizing information and issuing recommendations for practice. Methods A grouping of medical conditions with similar characteristics regarding the potential applicability of methods and designs was created using a consensus approach. The 125 dossiers for authorised OMP published between 1999 and 2014 on the EMA webpage were grouped accordingly and data was extracted from European Public Assessment Reports (EPARs) to assess the extent and robustness of the pivotal evidence supporting regulatory decisions. Results 88% (110/125) of OMP authorizations were based on clinical trials, with 35% (38/110) including replicated pivotal trials. The mean (SD) number of pivotal trials per indication was 1.4 (0.7), and the EPARs included a median of three additional non-pivotal supportive studies. 10% of OMPs (13/125) were authorised despite only negative pivotal trials. One-third of trials (53/159) did not include a control arm, one-third (50/159) did not use randomisation, half the trials (75/159) were open-label and 75% (119/159) used intermediate or surrogate variables as the main outcome. Chronic progressive conditions led by multiple system/organs, conditions with single acute episodes and progressive conditions led by one organ/system were the groups where the evidence deviated most from conventional standards. Conditions with recurrent acute episodes had the most robust datasets. The overall size of the exposed population at the time of authorisation of OMP − mean(SD) 190.5 (202.5) − was lower than that required for the qualification of clinically-relevant adverse reactions. Conclusions The regulatory evidence supporting OMP authorization showed substantial uncertainties, including weak protection against errors, substantial use of designs unsuited for conclusions on causality, use of intermediate variables, lack of a priorism and insufficient safety data to quantify risks of relevant magnitude. Grouping medical conditions based on clinical features and their methodological requirements may facilitate specific methodological and regulatory recommendations for the study of OMP to strengthen the evidence base.

Soil moisture measurements are needed in a large number of applications such as hydro-climate approaches, watershed water balance management and irrigation scheduling. Nowadays, different kinds of methodologies exist for measuring soil moisture. Direct methods based on gravimetric sampling or time domain reflectometry (TDR) techniques measure soil moisture in a small volume of soil at few particular locations. This typically gives a poor description of the spatial distribution of soil moisture in relatively large agriculture fields. Remote sensing of soil moisture provides widespread coverage and can overcome this problem but suffers from other problems stemming from its low spatial resolution. In this context, the DISaggregation based on Physical And Theoretical scale CHange (DISPATCH) algorithm has been proposed in the literature to downscale soil moisture satellite data from 40 to 1 km resolution by combining the low-resolution Soil Moisture Ocean Salinity (SMOS) satellite soil moisture data with the high-resolution Normalized Difference Vegetation Index (NDVI) and land surface temperature (LST) datasets obtained from a Moderate Resolution Imaging Spectroradiometer (MODIS) sensor. In this work, DISPATCH estimations are compared with soil moisture sensors and gravimetric measurements to validate the DISPATCH algorithm in an agricultural field during two different hydrologic scenarios: wet conditions driven by rainfall events and wet conditions driven by local sprinkler irrigation. Results show that the DISPATCH algorithm provides appropriate soil moisture estimates during general rainfall events but not when sprinkler irrigation generates occasional heterogeneity. In order to explain these differences, we have examined the spatial variability scales of NDVI and LST data, which are the input variables involved in the downscaling process. Sample variograms show that the spatial scales associated with the NDVI and LST properties are too large to represent the variations of the average soil moisture at the site, and this could be a reason why the DISPATCH algorithm does not work properly in this field site.

Abstract Background The ASTERIX project developed a number of novel methods suited to study small populations. The objective of this exercise was to evaluate the applicability and added value of novel methods to improve drug development in small populations, using real world drug development programmes as reported in European Public Assessment Reports. Methods The applicability and added value of thirteen novel methods developed within ASTERIX were evaluated using data from 26 European Public Assessment Reports (EPARs) for orphan medicinal products, representative of rare medical conditions as predefined through six clusters. The novel methods included were ‘innovative trial designs’ (six methods), ‘level of evidence’ (one method), ‘study endpoints and statistical analysis’ (four methods), and ‘meta-analysis’ (two methods) and they were selected from the methods developed within ASTERIX based on their novelty; methods that discussed already available and applied strategies were not included for the purpose of this validation exercise. Pre-requisites for application in a study were systematized for each method, and for each main study in the selected EPARs it was assessed if all pre-requisites were met. This direct applicability using the actual study design was firstly assessed. Secondary, applicability and added value were explored allowing changes to study objectives and design, but without deviating from the context of the drug development plan. We evaluated whether differences in applicability and added value could be observed between the six predefined condition clusters. Results and discussion Direct applicability of novel methods appeared to be limited to specific selected cases. The applicability and added value of novel methods increased substantially when changes to the study setting within the context of drug development were allowed. In this setting, novel methods for extrapolation, sample size re-assessment, multi-armed trials, optimal sequential design for small sample sizes, Bayesian sample size re-estimation, dynamic borrowing through power priors and fall-back tests for co-primary endpoints showed most promise - applicable in more than 40% of evaluated EPARs in all clusters. Most of the novel methods were applicable to conditions in the cluster of chronic and progressive conditions, involving multiple systems/organs. Relatively fewer methods were applicable to acute conditions with single episodes. For the chronic clusters, Goal Attainment Scaling was found to be particularly applicable as opposed to other (non-chronic) clusters. Conclusion Novel methods as developed in ASTERIX can improve drug development programs. Achieving optimal added value of these novel methods often requires consideration of the entire drug development program, rather than reconsideration of methods for a specific trial. The novel methods tested were mostly applicable in chronic conditions, and acute conditions with recurrent episodes.

Spiral ganglion neurons (SGNs) of the cochlea receive input from hair cells and project to the auditory brainstem. Here, the authors perform single-cell RNA sequencing to identify four SGN subclasses and characterize their molecular profile, electrophysiological properties and connectivity.