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El síndrome de desmielinización osmótica incluye a la mielinólisis pontina y extrapontina, siendo la primera su forma de presentación clásica. Usualmente relacionado a correcciones rápidas de hiponatremia (sodio sérico menor de 135mEq/L), ha sido descrito en múltiples condiciones que pueden alterar la osmolaridad plasmática. La sintomatología es muy variada e incluye tetraparesia espástica, parálisis pseudobulbar, coma, convulsiones o el característico síndrome “locked in”, además de trastornos del comportamiento como falta de control en los impulsos, agresividad, síndromes depresivos, catatonia, mutismo y labilidad emocional. Años atrás fue una entidad de muy difícil diagnóstico, pero con la introducción de la resonancia magnética muchos casos oligosintomáticos o asintomáticos se han podido detectar, aunque no existe tratamiento conocido, puede ocurrir la recuperación espontánea.

Population-based cancer registries (PBCRs) are advanced public health systems providing ongoing surveillance through systematic collection, analysis, interpretation, and dissemination of high-quality data on cancer incident cases registered in a defined population residing in a specific geographical area (1, 2). Basically, PBCRs are well equipped for strengthening cancer surveillance, playing a strategic role in making geographic and temporal variation comparisons to highlight cancer epidemics, while assessing the effectiveness of preventive interventions and oncological care (3). Furthermore, many PBCRs provide cancer risk communication to local communities and authorities by using valuable tools to spread epidemiological data on cancer in intelligible ways to better address preventive intervention and changes in lifestyles (4). To these ends, PBCRs link records and merge data from different administrative, demographic and health sources, following international standards, recommendations, and guidelines (5– 7). Standards in cancer surveillance have been defined in Europe and several cancer research domains are continuously alimented by the cancer registries networks in support of public health and clinical research, with specific regard to aetiologic research, mass screening evaluation, quality of care, translational prognostics, and survivorship (3). More recently, progress has been documented regarding the PBCRs’ capability to estimate the effectiveness of immunisation programmes against vaccine preventable viral infections associated to cancer as well as of cancer screening programmes to decrease late-stage incidence and mortality (8–10). Much more fruits can be harvested from “RegisTrees” having strong roots (11), including the ones allowing the deterministic linkage between cancer registries and clinical registries to generate real-world evidence on treatments, particularly on elderly patients as well, a target population that is usually not included in clinical trials (12, 13). However, the latest revision of the European Union (EU) data protection framework and of the General Data Protection Regulation (GDPR), while suggesting a harmonization of health registries requirements for confidentiality and individual consent to data processing, made it raise concerns from researchers and epidemiologists experiencing some excessive restrictions that may hamper data linkages between cancer registries and other sources (14–16). As documented by a survey on how GDPR could have impacted the running of the daily activities of the cancer registries in different EU countries, conducted in 2018 by the European network of cancer registries (ENCR), some critical points related to the implementation and interpretation of the GDPR emerged from PBCRs (17, 18). Of interest, in 2017 the European Commission adopted a strategy to implement an interoperability framework, in order to improve “the ability of organizations to interact towards mutually beneficial goals, involving the sharing of information and knowledge by means of the exchange of data between the respective ICT systems” (19). As the digital interoperability was conceived to maximize the use of huge amounts of data, by contrast an unnecessarily strict interpretation of EU data protection regulation may lead to missed data linkages in cancer registration and other epidemiological activities (20). Therefore, the nature and the use of data from cancer registries in public health and research purposes, and their potentialities in the age of health digital interoperability, are herein discussed (16).

The SARS-CoV-2 Omicron variant emerged in South Africa in November 2021, and has later been identified worldwide, raising serious concerns. A real-time RT-PCR assay was designed for the rapid screening of the Omicron variant, targeting characteristic mutations of the spike gene. The assay was used to test 737 sewage samples collected throughout Italy (19/21 Regions) between 11 November and 25 December 2021, with the aim of assessing the spread of the Omicron variant in the country. Positive samples were also tested with a real-time RT-PCR developed by the European Commission, Joint Research Centre (JRC), and through nested RT-PCR followed by Sanger sequencing. Overall, 115 samples tested positive for Omicron SARS-CoV-2 variant. The first occurrence was detected on 7 December, in Veneto, North Italy. Later on, the variant spread extremely fast in three weeks, with prevalence of positive wastewater samples rising from 1.0% (1/104 samples) in the week 5-11 December, to 17.5% (25/143 samples) in the week 12-18, to 65.9% (89/135 samples) in the week 19-25, in line with the increase in cases of infection with the Omicron variant observed during December in Italy. Similarly, the number of Regions/Autonomous Provinces in which the variant was detected increased from one in the first week, to 11 in the second, and to 17 in the last one. The presence of the Omicron variant was confirmed by the JRC real-time RT-PCR in 79.1% (91/115) of the positive samples, and by Sanger sequencing in 66% (64/97) of PCR amplicons. In conclusion, we designed an RT-qPCR assay capable to detect the Omicron variant, which can be successfully used for the purpose of wastewater-based epidemiology. We also described the history of the introduction and diffusion of the Omicron variant in the Italian population and territory, confirming the effectiveness of sewage monitoring as a powerful surveillance tool.

Background: Evidence about late effects in adolescent and young adult (AYA) cancer survivors is scarce. This study assessed the risk of subsequent malignant neoplasms (SMNs) to identify the most common SMNs to be considered in follow-up care. Methods: Population-based cancer registries retrospectively identified first primary tumors (between 1976 and 2013) and SMNs in AYAs (15-39years old at their cancer diagnosis). AYA cancer survivors were those alive at least 5years after their first cancer diagnosis. The excess risk of SMNs was measured as standardized incidence ratios (SIRs) and absolute excess risk together with the cumulative incidence of SMNs. Results: The cohort included 67,692 AYA cancer survivors. The excess risk of developing any SMN (SIR, 1.6; 95% confidence interval, 1.5-1.7) was 60%. The excess risk of SMNs was significantly high for survivors of lymphomas; cancers of the breast, thyroid, female genital tract, digestive organs, gonads, and urinary tract; and melanomas. The cumulative incidence of all SMNs in AYA cancer survivors within 25years of their first cancer diagnosis was approximately 10%. Subsequent tumors contributing to approximately 60% of all SMNs were breast cancer, colorectal cancer, corpus uteri cancer, and ovarian cancer in females and colorectal cancer, bladder cancer, prostate cancer, lung cancer, and lymphomas in males. Conclusions: These results highlight the need to personalize follow-up strategies for AYA cancer survivors.

This study adds insight regarding the occurrence and spread of SARS-CoV-2 Variants of Concern (VOCs) and Var-iants of Interest (VOIs) in Italy in October and November 2022, by testing urban wastewater collected through-out the country. A total of 332 wastewater samples were collected from 20 Italian Regions/Autonomous Provinces (APs) within the framework of national SARS-CoV-2 environmental surveillance. Of these, 164 were collected in the first week of October and 168 in the first week of November. A similar to 1600 bp fragment of the spike protein was sequenced by Sanger (for individual samples) and long-read nanopore sequencing (for pooled Region/AP samples).In October, mutations characteristic of Omicron BA.4/BA.5 were detected in the vast majority (91 %) of the samples amplified by Sanger sequencing. A fraction of these sequences (9 %) also displayed the R346T mutation. Despite the low prevalence documented in clinical cases at the time of sampling, amino acid substitutions characteristic of sublineages BQ.1 or BQ.1.1 were detected in 5 % of sequenced samples from four Regions/APs. A significantly higher variability of sequences and variants was documented in November 2022, when the rate of se-quences harbouring mutations of lineages BQ.1 and BQ1.1 increased to 43 %, and the number of Regions/APs positive for the new Omicron subvariant more than tripled (n = 13) compared to October. Moreover, an increase in the number of sequences with the mutation package BA.4/BA.5 + R346T (18 %), as well as the detection of variants never observed before in wastewater in Italy, such as BA.2.75 and XBB.1 (the latter in a Region where no clinical cases asso-ciated with this variant had ever been documented) was recorded.The results suggest that, as predicted by the ECDC, BQ.1/BQ.1.1 is rapidly becoming dominant in late 2022. Environ-mental surveillance proves to be a powerful tool for tracking the spread of SARS-CoV-2 variants/subvariants in the population.

Objectives We aimed to assess the performance of radiomics and machine learning (ML) for classification of non-cystic benign and malignant breast lesions on ultrasound images, compare ML’s accuracy with that of a breast radiologist, and verify if the radiologist’s performance is improved by using ML. Methods Our retrospective study included patients from two institutions. A total of 135 lesions from Institution 1 were used to train and test the ML model with cross-validation. Radiomic features were extracted from manually annotated images and underwent a multistep feature selection process. Not reproducible, low variance, and highly intercorrelated features were removed from the dataset. Then, 66 lesions from Institution 2 were used as an external test set for ML and to assess the performance of a radiologist without and with the aid of ML, using McNemar’s test. Results After feature selection, 10 of the 520 features extracted were employed to train a random forest algorithm. Its accuracy in the training set was 82% (standard deviation, SD, ± 6%), with an AUC of 0.90 (SD ± 0.06), while the performance on the test set was 82% (95% confidence intervals (CI) = 70–90%) with an AUC of 0.82 (95% CI = 0.70–0.93). It resulted in being significantly better than the baseline reference (p = 0.0098), but not different from the radiologist (79.4%, p = 0.815). The radiologist’s performance improved when using ML (80.2%), but not significantly (p = 0.508). Conclusions A radiomic analysis combined with ML showed promising results to differentiate benign from malignant breast lesions on ultrasound images. Key Points • Machine learning showed good accuracy in discriminating benign from malignant breast lesions • The machine learning classifier’s performance was comparable to that of a breast radiologist • The radiologist’s accuracy improved with machine learning, but not significantly

Research has identified a wide range of psychosocial factors associated to choosing to engage in ongoing cancer screenings. Nevertheless, a systematic review of the theoretical frameworks and constructs underpinning studies on breast, cervical, and colorectal cancer screening participation has yet to be conducted. As part of the action-research project “Miriade,” the present study aims to identifying the main theoretical frameworks and constructs adopted in the literature over the past five years to explain cancer screening participation. According to the PRISMA guidelines, a search of the MEDLINE/PubMed and PsycINFO databases was made. Empirical studies conducted from 2017 to 2021 were included. The following keywords were used: breast OR cervical OR colorectal screening AND adhesion OR participation OR engagement AND theoretical framework OR conceptual framework OR theory. Overall, 24 articles met the inclusion criteria. Each theoretical framework highlighted clinical and psychosocial constructs of cancer screening participation, focusing on the individuals (psycho-emotional functioning and skills plan) and/or the health services perspectives. Findings from the present study acknowledge the plurality of the theoretical frameworks and constructs adopted to predict or promote breast, cervical, and colorectal cancer screening adhesion and the need for new research efforts to improve the effectiveness of cancer screening promotion interventions.

Objective: The present study aims at systematically reviewing research conducted on factors promoting breast, cervical and colorectal cancer screenings participation. Methods: A literature search in MEDLINE/PubMed and PsycInfo from January 2017 to October 2021 was performed. Data extraction, researchers' full agreement and the inclusion criteria produced 102 eligible studies. Data were narratively synthesized and critically interpreted. Results: Multiple factors favoring or hindering breast, cervical and colorectal cancer screenings were identified and summarized as factors operating at the individual level (background information, individual characteristics, emotions related to screening procedure and to cancer, knowledge and awareness), at the relational level (relationships with healthcare staff, significant others, community members), and at the healthcare system level (systems barriers/policy, lack of staff). A critical appraisal of studies revealed a fragmentation in the literature, with a compartmentalization of studies by type of cancer screening, country and specific populations of destination. Conclusions: Overall findings indicated that greater integration of research results obtained independently for each cancer diagnosis and within the different countries/populations could foster a more comprehensive understanding of factors potentially enhancing the participation in breast, cervical and colorectal cancer screenings worldwide. This review, which is grounded in the current context of globalization and superdiversification in population, can help to enhance a better integration between research and practices, by supporting the development of more effective and inclusive evidence-based interventions and health-promotion campaigns worldwide. Research and practical implications are highlighted and discussed.

Foodborne infections cause illness and death every year worldwide. The aim of this study was to describe trends in 2013–2019 in the occurrence of human cases of salmonellosis, campylobacteriosis, listeriosis, and hepatitis A in the Campania region. Human case data were provided by the National Surveillance System of disease and were grouped by year, province, age group, and sex. Moreover, the number of people hospitalized was recorded. In the Campania region, the total number of confirmed human cases for the diseases investigated was 1924, with Hepatitis A and the Salmonellosis as the first most reported (1009 and 825 cases, respectively). The incidence rates of gastroenteritis under study were lower than those in Italy and European Union in the same period, with the exception of Hepatitis A whose incidence was higher than that recorded in Italy. Data on hospitalizations pointed out the onset of severe forms of infection also for listeriosis and campylobacteriosis, whose incidence was very low (27 and 63 cases, respectively). Unfortunately, no information on the foods implicated is available. Although probably underestimated, gastroenteritis due to foodborne agents still represents a burden in Campania, and continuous monitoring and implementation of the currently available regional surveillance system is required.

Background Walking or cycling regularly instead of using motorised vehicles returns benefits not only to our health but also to the environment: in Europe, during 2020 a spotlight has also been put on the importance of accessibility to zero-emission transport, for promoting an inclusive framework that involves everyone. Policies in favour of a diffused active mobility in the general population encourage also to take steps effectively in order to achieve the longer-term goal of a European continent that is carbon-neutral. Methods In the Italian Behavioural Risk Factor Surveillance System PASSI, active mobility identifies both adults (aged 18-69) who cycle or walk to go to work or to school or for their usual commuting and those who, thanks to this habit, reach out recommended levels of physical activity to gain health benefits. Basing on their own active mobility levels, people are classified in: physically active (they reach out at least 150 minutes per week by walking or cycling for usual commuting, in bouts of at least 10 minutes); partially active (they use bicycle and/or walk usually, but not till 150 minutes weekly); non-active (they do not practise any active mobility or they do for little time duration). Results PASSI data 2016-2019 show that 44% among adults residing in Italy has practised active mobility by cycling (11%) and/or walking (41%) for usual commuting. They do in average for 4-5 days per week: people who cycle and those who walk sum up an average of, respectively, 144 and 181 minutes weekly. In the North, active mobility is experienced more than in the other parts of the Country. Active mobility definitively contributes to reach out recommended levels of physical activity that ensure health benefits and, in Italy, 21% of the resident adult population results to be physically active just thanks to this healthy lifestyle. Conclusions Walking or cycling for urban commuting, at least for 150 minutes per week in bouts of 10 minutes each, can help to meet the recommendations for physical activity by the WHO, without counting movement in spare time or at work.

BACKGROUND Leukaemias comprise a heterogenous group of haematological malignancies. In CONCORD-3, we analysed data for children (aged 0-14 years) and adults (aged 15-99 years) diagnosed with a haematological malignancy during 2000-14 in 61 countries. Here, we aimed to examine worldwide trends in survival from leukaemia, by age and morphology, in young patients (aged 0-24 years). METHODS We analysed data from 258 population-based cancer registries in 61 countries participating in CONCORD-3 that submitted data on patients diagnosed with leukaemia. We grouped patients by age as children (0-14 years), adolescents (15-19 years), and young adults (20-24 years). We categorised leukaemia subtypes according to the International Classification of Childhood Cancer (ICCC-3), updated with International Classification of Diseases for Oncology, third edition (ICD-O-3) codes. We estimated 5-year net survival by age and morphology, with 95% CIs, using the non-parametric Pohar-Perme estimator. To control for background mortality, we used life tables by country or region, single year of age, single calendar year and sex, and, where possible, by race or ethnicity. All-age survival estimates were standardised to the marginal distribution of young people with leukaemia included in the analysis. FINDINGS 164 563 young people were included in this analysis: 121 328 (73·7%) children, 22 963 (14·0%) adolescents, and 20 272 (12·3%) young adults. In 2010-14, the most common subtypes were lymphoid leukaemia (28 205 [68·2%] patients) and acute myeloid leukaemia (7863 [19·0%] patients). Age-standardised 5-year net survival in children, adolescents, and young adults for all leukaemias combined during 2010-14 varied widely, ranging from 46% in Mexico to more than 85% in Canada, Cyprus, Belgium, Denmark, Finland, and Australia. Individuals with lymphoid leukaemia had better age-standardised survival (from 43% in Ecuador to ≥80% in parts of Europe, North America, Oceania, and Asia) than those with acute myeloid leukaemia (from 32% in Peru to ≥70% in most high-income countries in Europe, North America, and Oceania). Throughout 2000-14, survival from all leukaemias combined remained consistently higher for children than adolescents and young adults, and minimal improvement was seen for adolescents and young adults in most countries. INTERPRETATION This study offers the first worldwide picture of population-based survival from leukaemia in children, adolescents, and young adults. Adolescents and young adults diagnosed with leukaemia continue to have lower survival than children. Trends in survival from leukaemia for adolescents and young adults are important indicators of the quality of cancer management in this age group. FUNDING Children with Cancer UK, the Institut National du Cancer, La Ligue Contre le Cancer, Centers for Disease Control and Prevention, Swiss Re, Swiss Cancer Research foundation, Swiss Cancer League, Rossy Family Foundation, US National Cancer Institute, and the American Cancer Society.

El elemento clave de la competitividad organizacional es la innovación y las pymes no escapan de ello, en este sentido, el presente trabajo trata de responder, cuáles son las principales actividades de innovación y los obstáculos a esas actividades que más inciden en las empresas industriales uruguayas, y si la cooperación con otras empresas e instituciones y la participación en redes son importantes a la hora de superar dichos obstáculos. Se utilizaron microdatos de la encuesta que realiza la Agencia Nacional de Investigación e Innovación de Uruguay (ANII), que posibilitó elaborar una serie de descriptores estadísticos relacionados con las variables definidas en el estudio. La investigación pone de manifiesto que la principal actividad de innovación que realizan, tanto las pymes como las grandes empresas, es la adquisición de bienes de capital, junto con la I+D interna. Se verifica que los obstáculos más importantes para desarrollar actividades de innovación son aspectos relacionados a temas micro y meso-económicos. Se encuentra una mayor presencia relativa de grandes empresas en los acuerdos de cooperación para compra y desarrollo conjunto de tecnología y se detecta una reducida participación de empresas pymes en acuerdos o redes vinculadas a conocimientos científicos y tecnológicos, lo que indicaría que los mismos no necesariamente contribuyen a levantar algunos de los obstáculos para realizar actividades de innovación.

In the context of sepsis, we tested the relationship between echocardiographic findings and Troponin, and their impact on prognosis. In this prospective study, we enrolled 325 septic patients (41% with shock), not mechanically ventilated, between October, 2012 and June, 2019 among those admitted to our High-Dependency Unit. By echocardiography within 24 h from the admission, sepsis-induced myocardial dysfunction (SIMD) was defined as left ventricular (LV) systolic dysfunction (speckle-tracking-based global longitudinal peak systolic strain, GLS, - 14%) and/or right ventricular (RV) systolic dysfunction (Tricuspid Annular Plane Systolic Excursion, TAPSE 16 mm). Troponin I levels were measured upon admission (T0) and after 24 h (T1); it was considered normal if 0.1 ng/mL. Mortality was assessed at day-7 and day-28 end-points. One-hundred and forty-two patients had normal Troponin level at T0 and T1 (G1), 69 had abnormal levels at T0 or T1 (G2) and 114 showed abnormal Troponin levels at both T0 and T1 (G3). Compared to G1, patients in G3 had worse LV and RV systolic function (GLS - 11.6 ± 3.4% vs - 14.0 ± 3.5%, p 0.001; TAPSE 18 ± 0.5 vs 19 ± 0.5 mm, p = 0.047) and greater day-28 (34% vs 20%, p = 0.015) mortality. In a Cox survival analysis including age, Troponin and SOFA score, mortality was predicted by the presence of SIMD (RR 3.24, 95% CI 1.72-6.11, p 0.001) with no contribution of abnormal Troponin level. While abnormal Troponin levels were associated with SIMD diagnosed by echocardiography, only the presence of SIMD predicted the short- and medium-term mortality rate, without an independent contribution of increased Troponin levels.

SARS-CoV-2 infection after vaccination can occur because COVID-19 vaccines do not offer 100% protection. The study aim was to assess duration of vaccination coverage, disease symptoms and type of hospitalization among non-vaccinated and vaccinated subjects to evaluate the vaccination trend over time. A retrospective cohort study was carried out among people testing COVID-19 positive in Campania Region using information from the Health Information System of Campania Region (Sinfonia). Vaccination status was assessed considering: no vaccination, partial vaccination and effective vaccination. Univariate and multivariate logistic regression models were constructed to evaluate the association between ICU admissions caused by COVID-19 and gender, age groups and vaccine type. Vaccine coverage duration trends were investigated using segmented linear regression and breakpoint estimations. Vaccination coverage was assessed by analyzing COVID-19 positive subjects in the 9 months after an effective dose vaccination. A significant risk of hospitalization in the ICU was caused by vaccination status: subjects non-vaccinated (OR: 7.14) and partially vaccinated (OR: 3.68) were 3 and 7 times more at risk of hospitalization, respectively, than subjects effectively vaccinated. Regarding subjects with an effective vaccination, the vaccine’s ability to protect against infection in the months following vaccination decreased. The risk of contracting COVID-19 after vaccination was higher 5 months (β = 1441, p < 0.001) and 7 months (β = 3110, p < 0.001) after administration of an effective dose. COVID-19 vaccines were demonstrated to protect from symptomatic infection by significantly reducing hospitalization risk, and their full protection against SARS-CoV-2 was demonstrated to decrease after 5 months regardless of age, gender or vaccine type.

In the present study, our aim was to evaluate the clinical and microbiological characteristics of a cohort of patients with bloodstream infections (BSI) due to Carbapenem-Resistant Enterobacteriaceae (CRE) and investigate the independent predictors of mortality.All episodes of carbapenem-resistantDuring the study period, a total of 154 consecutive non-repeated CRE BSI, all due to CRKp, were reported. The most frequently identified genes were KPC in 108 cases (70.1%), followed by metallo-betalactamases (MBL) (16.2%), and OXA-48 (2.6%); in 17 isolates (11%) no carbapenemase was detected. The overall mortality at 90 days was 41.9%. Using a log-rank test, patients without risk factors for CRE infections showed a significantly lower cumulative mortality (The study reported a non-negligible prevalence of MBL-producing organisms among CRKp isolated from blood cultures in our region. This data highlights the importance of molecular characterization of all clinical isolates of carbapenem-resistant organisms.

ObjectiveThe impact of a screening programme on colorectal cancer (CRC) incidence in its target population depends on several variables, including coverage with invitations, participation rate, positivity rate of the screening test, compliance with an invitation to second-level assessment and endoscopists’ sensitivity. We propose a synthetic indicator that may account for all the variables influencing the potential impact of a screening programme on CRC incidence.DesignWe defined the ‘rate of advanced adenoma on the target population’ (AA-TAP) as the rate of patients who received a diagnosis of advanced adenoma within a screening programme, divided by the programme target population. We computed the AA-TAP for the CRC Italian screening programmes (biennial faecal immunochemical test, target population 50–69 year olds) using the data of the Italian National Survey from 2003 to 2016, overall and by region, and assessed the association between AA-TAP and CRC incidence fitting a linear regression between the trend of regional CRC incidence rates in 50–74 year old subjects and the cumulative AA-TAP.ResultsIn 2016, the AA-TAP at a national level was 105×100 000, whereas significant differences were observed between the northern and central regions (respectively 126 and 149×100 000) and the South and Islands (36×100 000). The cumulative AA-TAP from 2004 to 2012 was significantly correlated with the difference between CRC incidence rates in 2013–2014 and those in 2003–2004 (p=0.009).ConclusionThe AA-TAP summarises into a single indicator the potential impact of a screening programme in reducing CRC incidence rates.

Objective To describe clinical features and disease progression of Selenoprotein N‐related myopathy in a large multicenter cohort of patients. Methods Cross‐sectional multicenter data analysis of 60 patients (53 families) with Selenoprotein N‐related myopathy and single‐center retrospective longitudinal analysis of 25 patients (21 families) over a median period of 5.3 years. Results The majority of patients (46/60, 77%) presented before age 2 years with hypotonia, poor head/neck control, and developmental delay. At last assessment (median age 14 years; range 2.5 to 36 years), 10/60 patients had minimal or no ambulation. Ventilatory support was initiated in 50/60 patients at a mean Forced Vital Capacity (FVC) of 38% and at a median age of 13 years. Forty‐five/60 patients developed scoliosis (at median age 12.1 years) and 18 had scoliosis surgery at a median age of 13.6 years. Five children needed nasogastric feeds and/or gastrostomy. Longitudinal data analysis on 25 patients showed progressive decline of Hammersmith functional motor scores (estimated annual change −0.55 point), time to walk 10 meter, time standing from sitting, and from lying. Sixteen patients had weights

El presente artículo aborda el fenómeno de la “celebrificación” en la construcción de la identidad digital de periodistas televisivos ecuatorianos en las plataformas digitales, en concreto en Instagram. A partir de las principales aportaciones de los celebrity studies y el marketing político se han identificado tres variables que permiten reconocer y entender la celebrificación. Estos rasgos se usan para realizar un análisis de contenidos de las cuentas de seis periodistas durante un período de tres meses en el año 2019. Los resultados muestran las características de los contenidos “celebrificados” como parte de la proyección de la identidad digital de los periodistas analizados y su relación con los paradigmas clásicos del periodismo.

We evaluated whether in sepsis, right ventricular (RV) systolic dysfunction (RVSD) predicts short-term all-cause mortality, independently to left ventricular (LV) global longitudinal peak systolic strain (GLS). This is a prospective observational study. We enrolled 252 septic patients (40% with shock) between October 2012 and July 2018 among those admitted to High-Dependency Unit. By echocardiography within 24 h from the admission (T1), RVSD was defined as Tricuspid Annular Plane Systolic Excursion (TAPSE) 16 mm, while left ventricular systolic dysfunction (LVSD) was defined by bi-dimensional speckle-tracking-based global longitudinal peak systolic strain (GLS) -14%. We assessed all-cause mortality at day-7 and at day-28 from admission. Mortality rate was 14% by day-7 and 26% by day-28 follow-up. RVSD was found in 85 patients (34%), was isolated in 29% (25/85) and coexisted with LVSD in 71% (60/85) patients. LVSD was present in 63% of patients (159/252), and was isolated in 99 patients. Day-7 mortality rate was twofold higher in the presence of RVSD (20% vs 11%), without reaching the statistical significance (p = 0.097). By day-28, mortality rate was as high as 44% with and 23% without RVSD (p = 0.001). In a Cox survival analysis, RVSD predicted higher mortality rate by day-28 follow-up (RR 2.43, 95% CI 1.47-4.00, p = 0.001), independent to shock and in addition to LVSD. In sepsis, RVSD predicted all-cause mortality by day-28 follow-up, independent to LVSD.

Presentado en sesión de 5 de junio de 1963

Smart and sustainable mobility systems are crucial elements for tomorrow’s cities, whose facilities will be increasingly connected automated and environmentally friendly. Therefore, many strategies based on alternatively-powered vehicles, shared transport modes and micro-mobility solutions are being developed. However, the promotion of traditional public transport solutions still remains a key factor. Therefore, increasing their attractiveness, thus positively influencing the modal split, turns out to be an important goal to be achieved. In this context, we proposed a methodology, based on the use of Automatic Vehicle Location (AVL) data, for improving transit service performance. Finally, in order to show the feasibility of the proposed approach, it has been applied to a real bus line operating in the south of Italy.

Background: In the present study, our aim was to evaluate the clinical and microbiological characteristics of a cohort of patients with bloodstream infections (BSI) due to Carbapenem-Resistant Enterobacteriaceae (CRE) and investigate the independent predictors of mortality. Methods: All episodes of carbapenem-resistant E.coli (CREc) or K.pneumoniae (CRKp) BSI that were subject to a mandatory notification from January to December 2020 in all acute care hospitals and long-term care facilities of the Campania region in southern Italy were enrolled. All carbapenem-resistant strains were assessed through molecular tests for the presence of five carbapenemase gene families, i.e., K.pneumoniae Carbapenemase (KPC), oxacillinase-48 (OXA-48), New Delhi Metallo-β-lactamase (NDM), Verona integron encoded metallo-β-lactamase (VIM) and Imipenemase (IMP). Results: During the study period, a total of 154 consecutive non-repeated CRE BSI, all due to CRKp, were reported. The most frequently identified genes were KPC in 108 cases (70.1%), followed by metallo-betalactamases (MBL) (16.2%), and OXA-48 (2.6%); in 17 isolates (11%) no carbapenemase was detected. The overall mortality at 90 days was 41.9%. Using a log-rank test, patients without risk factors for CRE infections showed a significantly lower cumulative mortality (p = 0.001). After multivariate logistic regression analysis, the presence of at least one risk factor was the only predictor of mortality (OR: 1.7, 95% CI 1.2–6.1, p = 0.015). Conclusions. The study reported a non-negligible prevalence of MBL-producing organisms among CRKp isolated from blood cultures in our region. This data highlights the importance of molecular characterization of all clinical isolates of carbapenem-resistant organisms.

Chloride intracellular channel 4 (CLIC4) functions in diverse actin-dependent processes. Upon Rho activation, CLIC4 reversibly translocates from the cytosol to the plasma membrane to regulate cell adhesion and migration. At the plasma membrane, CLIC4 counters the formation of filopodia, which requires actin assembly by the formin mammalian Diaphanous (mDia)2. To this end, mDia2 must be activated through conversion from the closed to the open conformation. Thus, CLIC4 could harness the activation or the open conformation of mDia2 to inhibit filopodium formation. Here, we find that CLIC4 silencing enhances the filopodia induced by two constitutively active mDia2 mutants. Furthermore, we report that CLIC4 binds the actin-regulatory region of mDia2 in vitro. These results suggest that CLIC4 modulates the activity of the open conformation of mDia2, shedding new light into how cells may control filopodia.

Objective The incidence of colorectal cancer (CRC) declines among subjects aged 50 years and above. An opposite trend appears among younger adults. In Europe, data on CRC incidence among younger adults are lacking. We therefore aimed to analyse European trends in CRC incidence and mortality in subjects younger than 50 years. Design Data on age-related CRC incidence and mortality between 1990 and 2016 were retrieved from national and regional cancer registries. Trends were analysed by Joinpoint regression and expressed as annual percent change. Results We retrieved data on 143.7 million people aged 20–49 years from 20 European countries. Of them, 187 918 (0.13%) were diagnosed with CRC. On average, CRC incidence increased with 7.9% per year among subjects aged 20–29 years from 2004 to 2016. The increase in the age group of 30–39 years was 4.9% per year from 2005 to 2016, the increase in the age group of 40–49 years was 1.6% per year from 2004 to 2016. This increase started earliest in subjects aged 20–29 years, and 10–20 years later in those aged 30–39 and 40–49 years. This is consistent with an age-cohort phenomenon. Although in most European countries the CRC incidence had risen, some heterogeneity was found between countries. CRC mortality did not significantly change among the youngest adults, but decreased with 1.1%per year between 1990 and 2016 and 2.4% per year between 1990 and 2009 among those aged 30–39 years and 40–49 years, respectively. Conclusion CRC incidence rises among young adults in Europe. The cause for this trend needs to be elucidated. Clinicians should be aware of this trend. If the trend continues, screening guidelines may need to be reconsidered.

Purpose: Adolescent and young adult (AYA, 15-39 years) cancer survivors (alive at least 5 years after cancer diagnosis) are less studied than younger and older cancer survivors and research on their late effects is limited. To facilitate research on long-term outcomes of AYA cancer survivors, we established, in Italy, a population-based AYA cancer survivors' cohort. This article describes the study design and main characteristics of this cohort. Methods: The cohort derives from population-based cancer registries (CRs). Each CR identified AYA cancer patients retrospectively. Treatment for first primary cancer and all health events from diagnosis to death can be traced through linkage with available health databases, such as hospital discharge records (HDRs), mortality files, and outpatient and pharmaceutical databases. Results: Thirty-four CRs participated to the cohort which overall includes 93,291 AYAs with cancer and 67,692 cancer survivors. First primary cancer distribution in AYA cancer survivors differs by sex and age groups because of the different cancer types diagnosed in AYAs. Almost 78% of AYA cancer survivors have HDRs and 14.8% also pharmaceutical and outpatient databases. Conclusion: This cohort will be used to study, for the first time in Italy, the pattern and excess risk of late effects in AYA cancer survivors. HDRs, outpatient and pharmaceutical databases will be used to define primary treatment to assess its impact on AYA cancer survivors' late effects. This cohort exploiting data sources already available at CRs, minimize the data collection effort and it will contribute to assess the feasibility of using administrative database to study cancer survivors' late effects.

The EMBO Journal highlights the multifaceted aspects of tumour biology in a series of complementary review articles published over the course of 2021. [Image: see text]

Este texto pretende ofrecer una mirada sobre la Danza y su carácter de “pensamiento del cuerpo” a través del estudio de la obra y textos de Isadora Duncan (1877 – 1927), bailarina y coreógrafa estadounidense en su empeño por resucitar la danza e ideales de belleza de la Grecia antigua. La riqueza de las reflexiones de Duncan nos permiten ponerla en diálogo con autores contemporáneos a su época, que trataron la danza y el retorno a los clásicos desde una perspectiva filosófica, como son Nietzsche y Schopenhauer. Así como aquellos artistas en los que causó admiración como Rodin, Clará y Walkowitz.

espanolA traves de sus trabajos, la artista Maria Jose Argenzio transmite sus reflexiones sobre las esferas politica, social y economica en el Ecuador contemporaneo. Sus principales proyectos se han centrado en las tensiones que rodean a la identidad mestiza y a las clases sociales de herencia colonial. La exhibicion Fragil Genealogia explora, justamente, las formas en que nuestras conexiones con el pasado se producen y se mantienen en constante tension. El conjunto de obras se centra en las manifestaciones de blanqueamiento que dan forma a su materialidad y evocan el desgarramiento que provoca esa tradicion. EnglishThrough her works, the artist Maria Jose Argenzio transmits her reflections on the political, social and economic spheres in contemporary Ecuador. His main projects have focused on the tensions that surround the mestizo identity and the social classes of colonial heritage. The exhibition ‘Fragile Genealogy’ explores, precisely, the ways in which our connections with the past are produced and maintained in constant tension. The set of works focuses on the manifestations of bleaching that shape their materiality and evoke the tear that this tradition provokes. portuguesAtraves de suas obras, a artista Maria Jose Argenzio transmite suas reflexoes sobre as esferas politica, social e economica do Equador contemporâneo. Seus principais projetos se concentraram nas tensoes que cercam a identidade mestica e as classes sociais da heranca colonial. A exposicao Fragile Genealogy explora, precisamente, as maneiras pelas quais nossas conexoes com o passado sao produzidas e mantidas em constante tensao. O conjunto de trabalhos enfoca as manifestacoes do branqueamento que moldam sua materialidade e evocam a lagrima que essa tradicao provoca.

On March 11, 2020, Italy imposed a national lockdown to curtail the spread of severe acute respiratory syndrome coronavirus 2. We estimate that, 14 days after lockdown, the net reproduction number had dropped below 1 and remained stable at »0.76 (95% CI 0.67-0.85) in all regions for >3 of the following weeks.

Objective: To evaluate short-term (2003–2014) cancer incidence and mortality trends in Italy. Methods: Italian Cancer Registries data, available in the AIRTUM database, from 17 out of 20 regions were used. The number of incident cases and deaths were estimated for those registries and those years with incomplete information. Age-standardized rates, overall and stratified by geographic area, region, sex, cancer site, and major age group, were computed. Time trends were expressed as annual percent change of rates. Results: In Italy, among males, incidence rates for all cancers showed during 2003–2014, a significant decrease (−0.9%/year), with stronger reductions in the northwest (−1.3%/year) and northeast (−2.0%/year since 2006) than in central (−0.7%/year) and southern (−0.4%/year) areas. Among females, a weak but significant overall reduction was detected (−0.1%/year), with a stronger decrease in the northwest (−0.5%/year). Incidence increased among women in the south (0.3%/year) of Italy. Mortality decreased in both sexes (−1.0%/year among males and −0.5%/year among females), but not in the south, where rates had a stable tendency. Conclusions: Incidence among males decreased, supported by trends for prostate, lung, colorectal, and urinary bladder cancers; among females the. The overall cancer incidence trend was stable, or even decreasing, in the northern and central areas and increasing in the southern areas, due to lung, thyroid, and melanoma rising trends. Study results provided information on the outcomes, in terms of cancer incidence and mortality, of primary and secondary prevention measures employed by regional health systems.

Objective: To evaluate the trends of colorectal cancer (CRC) incidence and mortality rates from 2003 to 2014 in Italy by age groups and regions. Methods: We used the data of 48 cancer registries from 17 Italian regions to estimate standardized incidence and mortality rates overall and by sex, age groups (Results: Incidence rates decreased from 104.3 (2003) to 89.9 × 100,000 (2014) in men and from 64.3 to 58.4 × 100,000 in women. Among men, incidence decreased during 2007–2010 (APC −4.0, 95% CI −6.0 to −1.9) and 2010–2014 (APC −0.7, 95% CI −1.4 to 0.0), while in women it linearly decreased during the whole period (APC −1.1, 95% CI −1.4 to −0.8). Mortality rates showed a linear reduction both in men (APC −0.7, 95% CI −1.0 to −0.3) and women (APC −0.9, 95% CI −1.2 to −0.6) and decreased respectively from 41.1 to 39.2 × 100,000 and from 24.6 to 23.1 × 100,000. In the 50- to 69-year-old range (screening target age), incidence showed a prescreening increase, followed by a peak after screening started, and a decline thereafter. Incidence and mortality rates significantly decreased in all areas but in the south and islands, where incidence increased and mortality remained stable. Conclusions: A renewed commitment by all regional health systems to invest in primary (i.e., lifestyle) and secondary (i.e., screening programs) prevention is of utmost importance.

Background PASSI d'Argento (PdA) is an Italian population-based surveillance system, coordinated by the Istituto Superiore di Sanità (ISS) and carried out by the Local Health Units (LHUs). PdA monitors wide-ranged health related-behaviours in the elderly (65+) living in Italy as per the three pillars of the “Active Healthy Ageing” framework: Health, Participation, Security. Methods The PdA sample is randomly selected from the LHU lists, stratified by sex and age. 22,811 records have been collected in 2016-2017 on a representative sample of residents aged over65, not being hospitalised, in long-term care, in a nursing home or prison. Results 3,019 respondents resulted cancer-diagnosed elderly (CDE) reporting cancer diagnosis or confirmation, leukaemia and lymphomas included (annual average prevalence of 12.8%, Confidence Intervals 95%: 12.1-13.4%; one million and 729 thousand people). CDE refer: poorer health conditions (22%) than Chronic Elderly Patients (CEP; 18%) and Healthy Elderly (HE; 5%), sight impairment (12%), hearing loss (15%) and chewing problems (14%). CDE (10%) and CEP (11%) are more prone to fall than HE do (6%). Disability accounts for 21% in CDE and CEP vs. 12% in HE. A multivariate analysis confirms a compromised psychophysical health profile in CDE vs. HE, and vs. CEP. CDE behave still unhealthily, are insufficiently advised by health professionals, do not comply with the seasonal flu vaccination [Health]. CDE face increased risk for isolation or cognitive decline: they experience lower social connectedness (17%) than CEP (20%) and HE (28%) [Participation], and perceive higher neighbourhood insecurity (19%) than how CEP (17%) and HE (13%) do [Security]. Conclusions PdA data on the poor biopsychosocial health profile of CDE highlight to what extent healthy behaviours and prevention can ameliorate their quality of life PdA calls for global action strategies in Italy, which aim at taking complete charge of CDE and also CEP. Key messages In Italy, elderly cancer survivors show poor biopsychosocial health profile and overall quality of life. By modifying behaviours, elderly suffering from any cancer or chronic disease can age healthily.

We evaluated the prevalence and prognostic value of left (LV) and right (RV) ventricular systolic dysfunction in the presence of overt and cryptic shock. In this prospective study, between October 2012 and June 2019, we enrolled 354 patients with sepsis, 41% with shock, among those admitted to the Emergency Department High-Dependency Unit. Patients were grouped based on the presence of shock, or by the presence of lactate levels ≥ (LAC +) or 2 mmol/L (LAC-) evaluated within the first 24 h. By echocardiography performed within 24 h from the admission, LV systolic dysfunction was defined as global longitudinal strain (GLS) -14%; RV systolic dysfunction as Tricuspid Annular Plane Systolic Excursion (TAPSE) 16 mm. All-cause mortality was assessed at day-7 and day-28 follow-up. Mean values of LV GLS (-12.3 ± 3.4 vs -12.9 ± 3.8%) and TAPSE (1.8 ± 0.7 vs 1.8 ± 0.5 cm, all p = NS) were similar in patients with and in those without shock. LV GLS was significantly worse in LAC + than LAC- patients (- 11.2 ± 3.1 vs - 12.9 ± 3.7%, p = 0.001). In patients without shock, as well as in those LAC-, LV dysfunction was associated with increased day-28 mortality rate (78% vs 57% in non-survivors and survivors without shock and 74% vs 53% in non-survivors and survivors LAC-, all p 0.01). LV (RR 2.26, 95% CI 1.37-3.74) and RV systolic dysfunction (RR 1.85, 95% CI 1.22-2.81) were associated with increased 28-day mortality rate in addition and independent to LAC + (RR 1.81, 95% CI 1.15-2.84). In conclusion, LV and RV ventricular dysfunction were independently associated with an increased mortality rate, altogether with the presence of cryptic shock.

During the initial assessment of trauma patients, the severity of injury is very often not immediately recognizable. In trauma centers, a total body CT (TBCT) scan is routinely used to evaluate this kind of patients, even if it is burdened with health risk, economical costs, and logistical difficulties. We investigated the use of a clinical guide to establish a safe alternative to this routine practice. We enrolled retrospectively 438 patients referring to the Emergency Department of Careggi University Hospital in Florence (Italy) over a 1-year period from 2014 to 2015, with the evidence of trauma and high-priority triage codes and then subjected to TBCT. We created a tool called VIBS (“Valutazione Integrata Bed Side”) (from the Italian translation of “Bed Side Integrated Evaluation”) which included all clinical, laboratory, and diagnostic data acquired bedside during the primary survey. Every VIBS profile was dichotomized in negative or positive if there was at least one altered item. We performed an analysis of correlation between VIBS and TBCT to determine sensibility, specificity, positive, and negative predictive value and likelihood ratio of VIBS. Sensibility of VIBS in the prediction of positive CT scan was 100% and specificity was 31.7%. Positive and negative predictive value (95% C.I.) was 44.3 (38.8–49.5) and 100 (94.0–99.9). Positive and negative likelihood ratios were 1.464 and 0. Failure rate resulted in 0% and efficiency was 20.54%. VIBS can safely rule out severe thoracic or abdominal injuries. This approach could limit the use of TBCT in one-fifth of suspected major trauma patients.

Introduction Current lengthening of average life and constant increase of population ageing associated to forces that include rapid unplanned urbanisation and globalisation of unhealthy behaviours have determined the huge relevance of noncommunicable diseases (NCDs). Monitoring key modifiable behavioural risk factors has resulted to be crucial both in spatial terms and as per temporal trends in order to allow comparisons between different geographic areas or levels and over time. Materials and Methods In Italy, PASSI (Progressi delle Aziende Sanitarie per la Salute in Italia) and Passi d’Argento are the ongoing Behavioural Risk Factor Surveillance Systems (BRFSSs), respectively, on adults (people aged 18−69) and elderly (65 and older). Results The two Italian surveillances are information systems providing data not only on the third Sustainable Development Goal (SDG) that explicitly addresses ensuring healthy lives and promoting well-being for all, but on a total of nine health-related SDGs (HRSDGs) and 19 HRSDG targets/indicators. We describe these pairs more in detail specifying where in case of BRFSS core indicators (N = 14 HRSDG targets/indicators) concerning six HRSDGs or, on the other hand, as per BRFSS further in-depth analysis (N = five HRSDG targets/indicators) in regard of four different HRSDGs. About the HRSDG 3, HRSDG target 3.4, HRSDG indicator 3.4.1, from the PASSI and Passi d’Argento data it is possible not only to detect the prevalence of NCDs in adults and elderly living in Italy, but also to evaluate the social determinants of health, such as gender, age group, educational level, economic difficulties, as well as the associations with modifiable lifestyle risk factors. Conclusions The two Italian BRFSSs generate accurate data, which are highly relevant to design, implement, monitor, and evaluate programs and policies at different levels (local, regional, national) for NCD prevention and health promotion. They provide numbers which can also serve as propaedeutic or, in some cases, complementary ground to address a robust measurement of several HRSDG patterns.

Autosomal recessive mutations in the ECEL1 gene have recently been associated with a wide phenotypic spectrum including severe congenital contractural syndromes and distal arthrogryposis type 5D (DA5D). Here, we describe four novel families with ECEL1 gene mutations, reporting 15 years of follow-up for four patients and detailed muscle pathological description for three individuals. In particular, we observed mild myopathic features, prominent core-like areas in one individual, and presence of nCAM positive fibres in three patients from 2 unrelated families suggesting a possible problem with innervation. Our findings expand current knowledge concerning the phenotypic and pathological spectrum associated with ECEL1 gene mutations and may suggest novel insights regarding the underlying pathomechanism of the disease.

Bio-based succinic acid production from lignocellulosic biomass is one of the attractive and prominent alternative technologies to overcome issues associated with the utilization of fossil sources. In this context, it is necessary to find new microorganisms that are able to efficiently ferment this recalcitrant feedstock. The ecological approach developed in this study enabled the isolation of Basfia succiniciproducens BPP7 from a complex rumen ecosystem. This new wild-type strain was able to synthesize up to 6.06 ± 0.05 g/L of succinate (corresponding to 0.84 ± 0.017 g of succinate per gram of consumed glucose + xylose and to 0.14 ± 0.001 g of succinate per gram of glucans + xylans present in the biomass before hydrolysis) from Arundo donax hydrolysate in separate hydrolysis and fermentation (SHF) experiments. Higher titers of succinic acid were obtained through the optimization of growth conditions. The optimal medium composition identified on the smaller scale was then used for 2.5-L batch experiments, which used A. donax hydrolysate and yeast extract as the main C and N sources, respectively. A maximal titer of 9.4 ± 0.4 g/L of succinic acid was obtained after 24 h. The overall results clearly demonstrate the potential of B. succiniciproducens BPP7 for succinate production.

Introduction Peri-implant breast seroma is a late clinical presentation of reconstructive surgery or augmentation mammoplasty with breast implants. Pre-operative cytological evaluation of the peri-implant breast seroma is a common clinical approach, showing mainly an inflammatory reaction or more rarely a breast implant-associated anaplastic large cell lymphoma. Herein, we reported the role of cytology in the evaluation of peri-implant breast seroma and its critical pre-operative implications. Methods Eight cases of peri-implant breast seroma from files at Luigi Vanvitelli University were identified between January and December 2017. In all cases, seroma was aspirated; cytospins were performed and stained by Papanicolaou stain; finally, in all cases, a cell block was obtained for immunocytochemical evaluation and, in one case, for FISH to detect ALK1-gene translocation. Results The median age of patients was 48 years and the mean time between the implant placement and the occurrence of peri-implant breast seroma was 18 months. Microscopic examination showed breast implant-associated anaplastic large cell lymphoma in one case, aspecific inflammatory reaction in six cases and silicon-associated reaction in one case. Conclusions Peri-implant breast seroma may be caused by several pathological conditions with different clinical behaviour. A proper cytological approach to peri-implant breast seroma allows a correct differential diagnosis between inflammatory conditions and breast implant-associated anaplastic large cell lymphoma and an appropriate management of the patient.

Among capsulated bacteria, some produce polysaccharides with unique properties that have been shown to possess relevant industrial applications and commercial value. The capsular polysaccharide (CPS) produced by Escherichia coli K4 is similar to chondroitin sulphate, and recent efforts focused on the development of genetic and fermentation strategies to increase its production titers up to technologically attractive levels. However, the control of the metabolic pathways leading to CPS synthesis together with the effect of varying the concentration of pathway intermediates on CPS final titers, is still quite unexplored, and not fully understood. In the present study four genes involved in the biosynthesis of UDP-sugar CPS precursors, namely kfoA, kfoF, pgm, and galU, were overexpressed in different combinations, and diversely affected the biosynthetic machinery. At the physiological level, results revealed a central role for kfoF, coding for UDP-glucose dehydrogenase, that increased CPS production mostly. In the attempt to unravel the molecular mechanisms regulating CPS biosynthesis, an in depth analysis of the proteome of the recombinant strains overexpressing respectively pgm and galU, and pgm, galU, and kfoF was performed and compared to the wild-type. Although, interestingly, in both strains the impact of the genetic manipulation seemed rather limited at the proteome level, results obtained from the triple mutant indicated a crosstalk between the two pathways leading to UDP-sugar precursors biosynthesis, and also an unexpected link with the purine biosynthetic pathway. Overall our results present new insights into the role of metabolic intermediates for the formation of capsular polysaccharides, utilizing a systematic approach of metabolic engineering, combined with state-of-the-art quantitative proteomic approaches, as well as genetic and physiological information.

Eser, Sultan (Balikesir Author), Background In 2015, the second cycle of the CONCORD programme established global surveillance of cancer survival as a metric of the effectiveness of health systems and to inform global policy on cancer control. CONCORD-3 updates the worldwide surveillance of cancer survival to 2014. Methods CONCORD-3 includes individual records for 37.5 million patients diagnosed with cancer during the 15-year period 2000-14. Data were provided by 322 population-based cancer registries in 71 countries and territories, 47 of which provided data with 100% population coverage. The study includes 18 cancers or groups of cancers: oesophagus, stomach, colon, rectum, liver, pancreas, lung, breast (women), cervix, ovary, prostate, and melanoma of the skin in adults, and brain tumours, leukaemias, and lymphomas in both adults and children. Standardised quality control procedures were applied; errors were rectified by the registry concerned. We estimated 5-year net survival. Estimates were age-standardised with the International Cancer Survival Standard weights.Findings For most cancers, 5-year net survival remains among the highest in the world in the USA and Canada, in Australia and New Zealand, and in Finland, Iceland, Norway, and Sweden. For many cancers, Denmark is closing the survival gap with the other Nordic countries. Survival trends are generally increasing, even for some of the more lethal cancers: in some countries, survival has increased by up to 5% for cancers of the liver, pancreas, and lung. For women diagnosed during 2010-14, 5-year survival for breast cancer is now 89.5% in Australia and 90.2% in the USA, but international differences remain very wide, with levels as low as 66.1% in India. For gastrointestinal cancers, the highest levels of 5-year survival are seen in southeast Asia: in South Korea for cancers of the stomach (68.9%), colon (71.8%), and rectum (71.1%); in Japan for oesophageal cancer (36.0%); and in Taiwan for liver cancer (27.9%). By contrast, in the same world region, survival is generally lower than elsewhere for melanoma of the skin (59.9% in South Korea, 52.1% in Taiwan, and 49.6% in China), and for both lymphoid malignancies (52.5%, 50.5%, and 38.3%) and myeloid malignancies (45.9%, 33.4%, and 24.8%). For children diagnosed during 2010-14, 5-year survival for acute lymphoblastic leukaemia ranged from 49.8% in Ecuador to 95.2% in Finland. 5-year survival from brain tumours in children is higher than for adults but the global range is very wide (from 28.9% in Brazil to nearly 80% in Sweden and Denmark). Interpretation The CONCORD programme enables timely comparisons of the overall effectiveness of health systems in providing care for 18 cancers that collectively represent 75% of all cancers diagnosed worldwide every year. It contributes to the evidence base for global policy on cancer control. Since 2017, the Organisation for Economic Co-operation and Development has used findings from the CONCORD programme as the official benchmark of cancer survival, among their indicators of the quality of health care in 48 countries worldwide. Governments must recognise population-based cancer registries as key policy tools that can be used to evaluate both the impact of cancer prevention strategies and the effectiveness of health systems for all patients diagnosed with cancer., American Cancer Society Centers for Disease Control and Prevention Swiss Re Swiss Cancer Research foundation Swiss Cancer League Institut National du Cancer La Ligue Contre le Cancer Rossy Family Foundation US National Cancer Institute Susan G Komen Foundation

Chloride intracellular channel 4 (CLIC4) is a cytosolic protein implicated in diverse actin-based processes, including integrin trafficking, cell adhesion, and tubulogenesis. CLIC4 is rapidly recruited to the plasma membrane by RhoA-activating agonists and then partly colocalizes with 1 integrins. Agonist-induced CLIC4 translocation depends on actin polymerization and requires conserved residues that make up a putative binding groove. However, the mechanism and significance of CLIC4 trafficking have been elusive. Here, we show that RhoA activation by either lysophosphatidic acid (LPA) or epidermal growth factor is necessary and sufficient for CLIC4 translocation to the plasma membrane and involves regulation by the RhoA effector mDia2, a driver of actin polymerization and filopodium formation. We found that CLIC4 binds the G-actin– binding protein profilin-1 via the same residues that are required for CLIC4 trafficking. Consistently, shRNA-induced profilin-1 silencing impaired agonist-induced CLIC4 trafficking and the formation of mDia2-dependent filopodia. Conversely, CLIC4 knockdown increased filopodium formation in an integrin-dependent manner, a phenotype rescued by wild-type CLIC4 but not by the trafficking-incompetent mutant CLIC4(C35A). Furthermore, CLIC4 accelerated LPA-induced filopodium retraction. We conclude that through profilin-1 binding, CLIC4 functions in a RhoA–mDia2–regulated signaling network to integrate cortical actin assembly and membrane protrusion. We propose that agonist-induced CLIC4 translocation provides a feedback mechanism that counteracts formin-driven filopodium formation.

The paradigm of Virtual Power Plants, together with Smart Grids, can unleash the full potential of distributed energy resources, by introducing flexibility to power systems and by managing the increasing uncertainty and unreliability associated to them. The aggregation obtained through a Virtual Power Plant would not only benefit energy producers and users, maximizing their revenues, but it would also reduce the complexity of modern power systems, simplifying the balancing process carried out by Transmission System Operators.

The surveillance system PASSI (Progresses in ASSessing adult population health in Italy) is centrally coordinated by the Istituto Superiore di Sanità (ISS) and carried on by Local Health Units (LHU) from all the 21 Italian Regional Health Authorities since 2008. PASSI monitors the main behavioural health-related risk factors among the adult population in order to better orient and further elaborate interventions for the prevention of major chronic diseases.Basing on outcomes from the first pilot study in 2011, we conducted a second self-audit to investigate and map levels of conformity with recognized implementation standards by the protocol for PASSI local management in the 21 Italian Regional Health Authorities.We designed an online questionnaire supported by an open source application (Google) and sent to the local PASSI coordinators. Data were collected from April to September 2013. 113 out of 148 LHUs from all the 21 Italian Regional Health Authorities participated, with a response rate of 76%.Overall, in the respondent LHUs 1,036 professionals result to differently engage in surveillance activities. Although PASSI is locally-based, where data collection and computerisation are arranged, central support is highly appreciated in terms of quality monitoring, analysis, output processing, professional training, delivery of dissemination material. PASSI data are more used for communication (60%) and planning (80%) than to scientific ends.After a ten-year activity, PASSI as complex public health program requires periodical self-audit rounds in order to assess to what extent relevant performance indicators match the levels indicated in its own operational protocol. The second self-audit showed to be reliable concerning both sustainability and data collection. It then represents an experience that can be renewed and repeated.

In the present work the recently isolated strain Basfia succiniciproducens BPP7 was evaluated for the production of succinic acid up to the pilot fermentation scale in separate hydrolysis and fermentation experiments on Arundo donax, a non-food dedicated energy crop. An average concentration of about 17g/L of succinic acid and a yield on consumed sugars of 0.75mol/mol were obtained demonstrating strain potential for further process improvement. Small scale experiments indicated that the concentration of acetic acid in the medium is crucial to improve productivity; on the other hand, interestingly, short-term (24h) adaptation to higher acetic acid concentrations, and strain recovery, were also observed.

Clathrin lattices at the plasma membrane coat both invaginated and flat regions forming clathrin-coated pits and clathrin plaques, respectively. The function and regulation of clathrin-coated pits in endocytosis are well understood but clathrin plaques remain enigmatic nanodomains. Here we use super-resolution microscopy, molecular genetics and cell biology to show that clathrin plaques contain the machinery for clathrin-mediated endocytosis and cell adhesion, and associate with both clathrin-coated pits and filamentous actin. We also find that actin polymerization promoted by N-WASP through the Arp2/3 complex is crucial for the regulation of plaques but not pits. Clathrin plaques oppose cell migration and undergo actin- and N-WASP-dependent disassembly upon activation of LPA receptor 1, but not EGF receptor. Most importantly, plaque disassembly correlates with the endocytosis of LPA receptor 1 and down-modulation of AKT activity. Thus, clathrin plaques serve as dynamic actin-controlled hubs for clathrin-mediated endocytosis and signalling that exhibit receptor specificity., Clathrin lattices coat flat membrane regions, called plaques, whose regulation and function are poorly understood. Here the authors find that plaques are regulated by actin dynamics and contain both the endocytic and the cell adhesion machineries, and are involved in endocytosis of specific cargos, and cell migration.

Invadosomes are actin-rich membrane protrusions that degrade the extracellular matrix to drive tumor cell invasion. Key players in invadosome formation are c-Src and Rho family GTPases. Invadosomes can reassemble into circular rosette-like superstructures, but the underlying signaling mechanisms remain obscure. Here we show that Src-induced invadosomes in human melanoma cells (A375M and MDA-MB-435) undergo rapid remodeling into dynamic extracellular matrix-degrading rosettes by distinct G protein-coupled receptor agonists, notably lysophosphatidic acid (LPA; acting through the LPA1 receptor) and endothelin. Agonist-induced rosette formation is blocked by pertussis toxin, dependent on PI3K activity and accompanied by localized production of phosphatidylinositol 3,4,5-trisphosphate, whereas MAPK and Ca(2+) signaling are dispensable. Using FRET-based biosensors, we show that LPA and endothelin transiently activate Cdc42 through Gi, concurrent with a biphasic decrease in Rac activity and differential effects on RhoA. Cdc42 activity is essential for rosette formation, whereas G12/13-mediated RhoA-ROCK signaling suppresses the remodeling process. Our results reveal a Gi-mediated Cdc42 signaling axis by which G protein-coupled receptors trigger invadosome remodeling, the degree of which is dictated by the Cdc42-RhoA activity balance.