Linearization of Cohomology-free Vector Fields

We study the cohomological equation for a smooth vector field on a compact manifold. We show that if the vector field is cohomology free, then it can be embedded continuously in a linear flow on an Abelian group

Effective SARS-CoV-2 antiviral activity of hyperbranched polylysine nanopolymers

The coronavirus pandemic (COVID-19) had spread rapidly since December 2019, when it was first identified in Wuhan, China. As of April 2021, more than 130 million cases have been confirmed, with more than 3 million deaths, making it one of the deadliest pandemics in history. Different approaches must be put in place to confront a new pandemic: community-based behaviours (i.e., isolation and social distancing), antiviral treatments, and vaccines. Although behaviour-based actions have produced significant benefits and several efficacious vaccines are now available, there is still an urgent need for treatment options. Remdesivir represents the first antiviral drug approved by the Food and Drug Administration for COVID-19 but has several limitations in terms of safety and treatment benefits. There is still a strong request for other effective, safe, and broad-spectrum antiviral systems in light of future emergent coronaviruses. Here, we describe a polymeric nanomaterial derived from l-lysine, with an antiviral activity against SARS-CoV-2 associated with a good safety profile in vitro. Nanoparticles of hyperbranched polylysine, synthesized by l-lysine's thermal polymerization catalyzed by boric acid, effectively inhibit the SARS-CoV-2 replication. The virucidal activity is associated with the charge and dimension of the nanomaterial, favouring the electrostatic interaction with the viral surface being only slightly larger than the virions' dimensions. Low-cost production and easiness of synthesis strongly support the further development of such innovative nanomaterials as a tool for potential treatments of COVID-19 and, in general, as broad-spectrum antivirals. This journal i

Recommendations for core critical care ultrasound competencies as a part of specialist training in multidisciplinary intensive care: a framework proposed by the European Society of Intensive Care Medicine (ESICM)

© 2020 The Author(s). Critical care ultrasound (CCUS) is an essential component of intensive care practice. Although existing international guidelines have focused on training principles and determining competency in CCUS, few countries have managed to operationalize this guidance into an accessible, well-structured programme for clinicians training in multidisciplinary intensive care. We seek to update and reaffirm appropriate CCUS scope so that it may be integrated into the international Competency-based Training in Intensive Care Medicine. The resulting recommendations offer the most contemporary and evolved set of core CCUS competencies for an intensive care clinician yet described. Importantly, we discuss the rationale for inclusion but also exclusion of competencies listed. Background/aim: Critical care ultrasound (CCUS) is an essential component of intensive care practice. The purpose of this consensus document is to determine those CCUS competencies that should be a mandatory part of training in multidisciplinary intensive care. Methods: A three-round Delphi method followed by face-to-face meeting among 32 CCUS experts nominated by the European Society of Intensive Care Medicine. Agreement of at least 90% of experts was needed in order to enlist a competency as mandatory. Results: The final list of competencies includes 15 echocardiographic, 5 thoracic, 4 abdominal, deep vein thrombosis diagnosis and central venous access aid. Conclusion: The resulting recommendations offer the most contemporary and evolved set of core CCUS competencies for an intensive care clinician yet described

Desempenho agronômico de genótipos de girassol em cultivo de safra, no município de Espírito Santo do Pinhal-SP.

Resumo: O trabalho teve como objetivo avaliar o desempenho agronômico de genótipos de girassol em cultivo de safra, no município de Espírito Santo do Pinhal-SP, microregião de São João da Boa Vista. Foram testados sete cultivares pré-comerciais de girassol (BRS G34, BRS G35, SYN 3840, SYN 4065, Multissol, V90013 e V90631) e três cultivares comerciais como testemunhas (EMBRAPA 122 (T), HELIO 358 (T), M734(T)) na safra 2012/13; sob delineamento experimental de blocos ao acaso, em quatro repetições. Utilizaram-se parcelas de quatro linhas de 6,00 m, espaçadas 0,75 m entre si e 0,3 m entre plantas, avaliando-se apenas 8,1 m de área útil. As variáveis avaliadas foram: a) altura de plantas (cm); b) início do florescimento (dias); c) estande (número de capítulos m 2); d) diâmetro de capítulo (cm) e e) produtividade (kg ha 2), todas submetidas à análise de variâncias e teste Tukey de comparação de médias. Houve diferenças significativas entre os genótipos para as variáveis: altura de plantas, início do florescimento e produtividade. Os genótipos V90631 e V90013 foram os mais altos de todos estudados. As maiores produtividades foram observadas nos genótipos de ciclo médio (BRSG34, V90013, V90631 e M734). Assim, conclui-se que os genótipos de girassol de ciclo médio apresentam elevado desempenho agronômico durante o período da safra, com produtividades significativamente superiores à média nacional, sendo os mais recomendados para inserção nos sistemas de produção vigentes no município de Espírito Santo do Pinhal-SP. Abstract: The objective of this study was evaluate sunflower genotypes productive performance in Espírito Santo do Pinhal/SP. Therewere tested seven new (BRS G34, BRS G35, SYN 3840, SYN 4065, Multissol, V90013 and V90631) and three commercial (EMBRAPA 122 (T), HELIO 358 (T), M734 (T)) genotypes of sunflower in a randomized block design, with four replications. Each plot consisted of four rows 6.0 m long, spaced from 0.75 m and 0.3 m each plant, which was evaluated just 8,1 m as useful. There was evaluated: a) plant height (cm), b) flowering date (days); c) final plant stand (nº m 2); d) diameter of heads (cm) ; e) production (kg ha ), which was analyzed by variance test and Scott-Knott mean test (P < 0.05). The V90631 and V90013 genotype was the highest than all. Genotypes with medium maturity (BRSG34, V90013, V90631 e M734) were the most productive than early and late maturity genotypes tested. It concludes that sunflower genotypes? with medium maturity have better productive performance than others in the water season and is recommended to be used in Espírito Santo do Pinhal-SP

Selecting b-thalassemia patients for gene therapy: a decision-making algorithm

The Societ\ue0 Italiana Talassemie ed Emoglobinopatie (Italian Society of Thalassemias and Hemoglobinopathies, SITE) has developed this document based on multidisciplinary discussions of a panel of experts to provide guidance on the identification and selection of patients with transfusion-dependent beta-thalassemia (\u3b2-TDT) who could benefit from gene therapy. Currently, allogeneic transplantation of hematopoietic stem cells is the only curative and most widely used therapy treatment for \u3b2-TDT. However, recent trials of gene therapy have reported very promising results in terms of overall survival and thalassemia-free survival and are opening a new landscape of treatment. This algorithm for the selection of patients suitable for gene therapy and the supporting notes were formulated by consensus review after an evaluation of currently available scientific evidence using validated criteria. The evidence was interpreted with caution because clinical trial experience of gene therapy is currently limited, a conventional treatment is available for patients with \u3b2-TDT and the availability of gene therapy will, at least initially, be quite limited. Clinical experience of allogeneic transplantation in \u3b2-TDT, which began in 1981, immediately showed the importance of patient risk stratification in order to achieve the best results (see the Pesaro experience and their classification of patients according to risk). Published data in the literature and the recent analysis of clinical evidence by the European Registry of Hemoglobinopathies of a large number of patients (2011 and 2018 analyses) confirm that young patient age (&lt;14 years) and the availability of a human leukocyte antigen (HLA)-identical family donor are factors that offer the best outcome from allogeneic transplantation. Current knowledge of, and experience with, non-conventional treatments, such as allogeneic transplantation and gene therapy, are discussed in order to identify the best available treatment and indication for these patients according to their characteristics. At this point in time, when we can see the emergence of \u2018the age of gene therapy\u2019, it is essential to establish the optimal patient setting in which gene therapy can be applied, or better, to define the setting that represents the most suitable indication for gene therapy, identify the patients who should have clinical priority for access to the procedure, and set out requirements and recommendations for the identification of qualified treatment centers for gene therapy. When considering changes to the treatment of patients with \u3b2-TDT, including gene therapy, it is essential that a detailed consultation is held with the patient and their caregiver/family to discuss all possible risks and potential benefits from the treatment. Discussion of this aspect of care is outside of the scope of this document but remains an important element of patient care

Dynamic factor model with infinite-dimensional factor space:forecasting

The paper compares the pseudo real-time forecasting performance of three Dynamic Factor Models: (i) The standard principal-component model introduced by Stock and Watson in 2002, (ii) The model based on generalized principal components, introduced by Forni, Hallin, Lippi and Reichlin in 2005, (iii) The model recently proposed by Forni, Hallin, Lippi and Zaffaroni in 2015. We employ a large monthly dataset of macroeconomic and financial time series for the U.S. economy, which includes the Great Moderation, the Great Recession and the subsequent recovery (an update of the so-called Stock and Watson dataset). Using a rolling window for estimation and prediction, we find that (iii) significantly outperforms (i) and (ii) in the Great Moderation period for both Industrial Production and Inflation, that (iii) is also the best method for Inflation over the full sample. However, (iii) is outperformed by (ii) and (i) over the full sample for Industrial Production

SARS-CoV-2 infection in beta thalassemia: Preliminary data from the Italian experience

Patients with pre\u2010existent chronic morbidities are likely to be more severely affected by SARS\u2010Cov2 infection, but no data are available regarding Thalassemic Syndromes (TS). Note, TS and hemoglobin variants represent, according to WHO, one of the most frequent causes of anemia, affecting more than 7% of the world population.1 Thalassemic Syndromes are classified in either transfusion\u2010dependent thalassemia (TDT) or non\u2010transfusion\u2010dependent thalassemia (NTDT). Infectious complications, mainly from bacteria, constitute a common cause of mortality and morbidity in TS. Stress erythropoiesis, iron overload, splenectomy and adrenal insufficiency among others may contribute to increase susceptibility to infection.2 To verify the impact of SARS\u2010CoV\u20102 infection on TS, we set\u2010up a specific survey by electronic Case Report Form (eCRF).3 Inclusion criteria require at least 15\u2009days of follow\u2010up from either the onset of symptoms or SARS\u2010CoV2 positivity. The survey was approved by Ethics Committee and eCRF was shared with the Centers of Italian Hemoglobinopathies Network. The \u201cSociet\ue0 Italiana Talassemie ed Emoglobinopatie\u201d (SITE), has estimated the presence in Italy of approximately 5000 TDT and 1900 NTDT patients.3 As of 10 April 2020, 11 cases of TS and COVID\u201019 have been collected (see supplementary information). All the reported patients are in Northern Italy, where the rate of infection is higher, reflecting the national epidemiology. The mean age is 44\u2009\ub1\u200911\u2009years (range 31\u201061\u2009years) and 55% (6/11) are females. Ten patients are TDT, and one is NTDT. All the patients have thalassemia associated comorbidities, eight are splenectomized, and one patient (#9 in the supplementary table) has pulmonary hypertension treated with sildenafil. The likely source of infection has been detected in 55% (6/11) of cases: two had contacts with COVID\u201019 positive subjects, and four had occupational exposure (three are nurses working in hospital or assisted living facilities). Three patients were asymptomatic. One patient (#3 in supplementary information) was admitted for high fever and bone marrow hypoplasia, lymphopenia, and agranulocytosis (on treatment with deferiprone) and tested positive at the third swab. Six out of 11 were hospitalized, but no one required mechanical ventilation. The patient with more severe symptoms who required more intensive ventilation support with continuous positive airway pressure (CPAP) has a history of diffuse large B\u2010cell lymphoma, treated with chemotherapy in the previous year, currently in complete remission. Of the six people admitted to the hospital, only three received supposedly specific treatment for COVID\u201019: one hydroxychloroquine (HCQ), one HCQ plus ritonavir/darunavir, and one HCQ plus anakinra. Patient #3 did not receive HCQ due to concomitant therapy with amiodarone and an increased risk of life\u2010threatening arrhythmia. The clinical course ranged from 10 to 29\u2009days. Ten patients have clinically recovered and are on a daily remote phone call follow\u2010up. Splenectomy which was present in 8/11 patients did not seem to affect the clinical course. Of note, except for the patient with myelosuppression, no increase in blood requirement was observed. When luspatercept treatment was halted in the NTDT patient, hemoglobin fell from 110 to 82 g/L, a value similar to the pre\u2010luspatercept period. Neither death nor severe SARS or signs of cytokines storm were observed in these 11 subjects, which may be surprising, taking into account the mean age and the presence of severe comorbidities. Our data, although preliminary, do not indicate increased severity of COVID\u201019 in TS. A larger number of cases needs to be collected to define the impact of this new infection and its outcome in these fragile patients

Management of the Sickle Cell Trait: An Opinion by Expert Panel Members.

The number of individuals with the sickle cell trait exceeds 300 million worldwide, making sickle cell disease one of the most common monogenetic diseases globally. Because of the high frequency of sickle cell disease, reproductive counseling is of crucial importance. In addition, unlike other carrier states, Sickle Cell Trait (SCT) seems to be a risk factor for several clinical complications, such as extreme exertional injury, chronic kidney disease, and complications during pregnancy and surgery. This expert panel believes that increasing knowledge about these clinical manifestations and their prevention and management can be a useful tool for all healthcare providers involved in this issue