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Background: Congestion predicts a poor prognosis, but its assessment is challenging in clinical practice and requires a multiparametric approach. We investigated if the coronary sinus (CS) diameter can predict mortality in a human model of rapid fluid unloading. Methods: We measured by echocardiography the CS, and the inferior vena cava (IVC) for comparison, in 60 patients with end-stage chronic kidney disease (ESKD) immediately before and after hemodialysis (HD; age 76 [57–81] years, 40% female, left ventricular ejection fraction 57 [53–56]%). Patients were prospectively followed up for all-cause mortality. Results: HD-induced decongestion decreased the maximum diameters of both CS and IVC (p ≤ 0.001 for all). The maximum diameter of the CS (CSmax) was as accurate as the IVC maximum diameter and collapsibility for the identification of congestion, defined as pre-hemodialysis status (AUROC CSmax = 0.902 vs IVC = 0.895, p = n.s.). A CSmax diameter after hemodialysis > 9 mm predicted all-cause mortality at 12 months (Log-rank Chi square = 11.49, p

Objectives: We aimed to evaluate the pCR rate in patients receiving NAC for the treatment of breast cancer (BC) in a multicenter cohort in Brazil. Additionally, we aimed to use RWD to assess the impact of pCR on OS and DFS. Methods: This was a retrospective, multicenter cohort study that included female patients over 18 years of age who were diagnosed with nonmetastatic breast cancer and received NAC. OS and DFS at five years were estimated by the Kaplan‒Meier method. Additionally, we conducted a multivariate analysis to identify factors that were significantly associated with pCR and OS. Results: From 2011 to 2020, 1891 patients were included in the study, and 421 (22,3%) achieved pCR (ypT0 ypN0). Considering the presence of residual DCIS, pCR was achieved in 467 patients (23,5%). The pCR rate varied between the subtypes: HER-2+ (p = 0,016) and clinical stage IIIA and IIIB (p

Introducción: durante la transición de la vía enteral a la vía oral, es frecuente la presencia de una inadecuación al requerimiento calórico en los pacientes críticos posextubación, lo que conlleva un elevado riesgo de malnutrición. Objetivos: determinar la adecuación al requerimiento calórico en pacientes críticos en la unidad de cuidados intensivos (UCI) que se encuentran en transición alimentaria hacia la vía oral y determinar el motivo de finalización de la nutrición enteral. Métodos: se implementó un estudio de tipo cohorte prospectiva; se calculó la media del porcentaje de adecuación al requerimiento calórico mediante un registro visual previo y posterior a la ingesta diaria, y mediante el control diario del volumen infundido para la vía enteral, y se determinó la frecuencia del motivo de finalización de la nutrición enteral según el registro de la historia clínica. Resultados: la muestra inicial quedó conformada por 28 pacientes mayores de 18 años posextubación en transición a la vía oral. Los pacientes se evaluaron los días 1, 3, 5, 7 y al alta. La media del porcentaje de adecuación calórica al alta fue de 59 % y 48,5 % para la vía oral y la nutrición enteral, respectivamente. El principal motivo de finalización del soporte nutricional fue por indicación médica. Conclusiones: a medida que transcurren los días de internación, los pacientes posextubación aumentan la adecuación del requerimiento calórico, pero de forma lenta, con tendencia a ser desprovistos de la nutrición enteral de manera precoz por indicación médica.

Introdução/Objetivo: O diagnóstico precoce da infecção pelo HIV deve ser uma das prioridades para o controle da aids. Houve um grande avanço no tratamento, diagnóstico e prevenção, mas ainda há diversas barreiras para enfretamento e controle do HIV. Os hospitais ainda recebem pacientes com doença avançada, apesar de todos os esforços para o diagnóstico oportuno. O estudo visou identificar os fatores associados ao diagnóstico tardio e monitorar clinicamente pacientes recém diagnosticados com HIV/aids. Método: Estudo longitudinal retrospectivo, baseado em dados secundários de uma unidade especializada, em um hospital terciário no interior paulista. A coleta de dados incluiu dados sociodemográficos, comportamentais, clínicos e laboratoriais de pacientes recém diagnosticados com HIV, coletados do prontuário eletrônico que chegaram para primeiro atendimento hospitalar entre 2015-2019. A análise dos dados utilizou os softwares estatísticos SPSS e abordou estatística descritiva e inferencial: teste do Qui-Quadrado, Exato de Fisher, T pareado, regressão logística multivariada e multinominal, com significância estatística de 5% (α ≤ 0,05). O estudo foi apreciado pelo CEP sob n° do parecer 4.143.945. Resultados: 314 pessoas foram recém diagnosticadas com HIV/aids. 70,3% (208) tiveram diagnóstico tardio e 57,1% (169) muito tardio. Houve associação do diagnóstico muito tardio com as variáveis sexo e escolaridade e com: origem, entrada, ocorrência de doenças oportunistas, uso de TARV e óbito, essas com diagnóstico tardio e muito tardio, respectivamente. O seguimento clínico do dia zero e doze meses após apresentou melhora na contagem de CD4, carga viral e indivíduos indetectáveis. A regressão multinominal mostrou uma chance de ocorrência de óbito - 6,17 vezes maior em 2017 quanto em 2015 e chance de ocorrência de perda de seguimento 4,31 vezes maior no mesmo período. A modalidade de entrada pelo primeiro atendimento teve uma chance menor de ocorrência de óbito do que os pacientes originários de enfermaria (87,73%). Conclusão: Este estudo evidenciou alta prevalência de diagnóstico tardio e muito tardio em pacientes recém diagnosticados para o HIV, na maioria homens, que se apresentavam com doenças oportunistas, necessitando de internação hospitalar, com grande risco de evoluir para óbito. Recomenda-se novas medidas e campanhas protetoras na redução de casos de apresentação tardia, ampliação da testagem e ações para efetivação da política nacional de saúde do homem.

This paper proposes to use a type of machine learning network called artificial neural networks to design a circularity accounting network. The network is composed of human and non-human actors and accounts for the impact of products’ CO2 emissions and sequestration along global supply chains. The network serves to connect people and other actors that share a CO2 indicator and allows users to visualize the level of (un-) circularity of different products through specific diagrams calculated by a CO2 estimator drawing on insights from actor-network theory. Unlike most previous circular economy accounting studies that develop some type of framework or indicator that represent measurements at micro, meso or macro levels, the circularity accounting network is not confined to a particular level of analysis but is designed to build relationships between multiple users at different levels (e.g., government, corporate or consumer actors). The paper presents the conceptual design and a preliminary test of the network using real data, helping to advance the underexplored potential of artificial intelligence in the field of circular economy accounting. The main contribution of this network is that data provided by the indicator: (i) is derived from the network itself learning from open sources, the network (ii) is not static but keeps flowing as new relationships are built within the network, moving toward self-regulating, (iii) contemplates both emissions and sequestrations along supply chains.

ObjectiveTo examine whether sustained minimal manifestation status (MMS) with complete withdrawal of prednisone is better achieved in thymectomized patients with myasthenia gravis (MG).MethodsThis study is a post hoc analysis of data from a randomized trial of thymectomy in MG (Thymectomy Trial in Non-Thymomatous Myasthenia Gravis Patients Receiving Prednisone Therapy [MGTX]). MGTX was a multicenter, randomized, rater-blinded 3-year trial that was followed by a voluntary 2-year extension for patients with acetylcholine receptor (AChR) antibody-positive MG without thymoma. Patients were randomized 1:1 to thymectomy plus prednisone vs prednisone alone. Participants were age 18-65 years at enrollment with disease duration less than 5 years. All patients received oral prednisone titrated up to 100 mg on alternate days until they achieved MMS, which prompted a standardized prednisone taper as long as MMS was maintained. The achievement rate of sustained MMS (no symptoms of MG for 6 months) with complete withdrawal of prednisone was compared between the thymectomy plus prednisone and prednisone alone groups.ResultsPatients with MG in the thymectomy plus prednisone group achieved sustained MMS with complete withdrawal of prednisone more frequently (64% vs 38%) and quickly compared to the prednisone alone group (median time 30 months vs no median time achieved, p < 0.001) over the 5-year study period. Prednisone-associated adverse symptoms were more frequent in the prednisone alone group and distress level increased with higher doses of prednisone.ConclusionsThymectomy benefits patients with MG by increasing the likelihood of achieving sustained MMS with complete withdrawal of prednisone.Clinicaltrialsgov identifierNCT00294658.Classification of evidenceThis study provides Class II evidence that for patients with generalized MG with AChR antibody, those receiving thymectomy plus prednisone are more likely to attain sustained MMS and complete prednisone withdrawal than those on prednisone alone.

Background: Nonagenarians and centenarians (NCs) are an extremely fragile population, particularly in regard to their physical and cognitive function. The aim of this study was to define the neurocognitive profiles among 29 NCs and their 49 younger cohabitants aged 50-75 years from The Cilento Initiative on Aging Outcomes (CIAO) Pilot study in the South of Italy that had provided initial hypotheses regarding positive psychological traits related to exceptional longevity. Methods: During the home visits, lifestyle information with specific questionnaires, functional autonomy and the neuropsychological Mini Mental Scale Examination (MMSE), and the Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog) scale were obtained by qualified study personnel. The total blood oxidative capacity was also determined by testing the reactive derivative of oxygen metabolites (d-ROM) and by the Biological Antioxidant Potential (BAP). In all individuals, the APOE genotype determination was also performed. Results: All the subjects in both groups showed high adherence to the Mediterranean Diet. None of the NCs had severe cognitive impairment, and a very low incidence of dementia was found. The data obtained on the Activities ed Instrumental Activities of Daily Living (ADL-IADL) scale showed that the majority of NCs (16/29) were autonomous in daily life activities. The comparative assessment of NCs and cohabitants showed no significant differences in the laboratory assessment of oxidative stress and APOE genotype. Conclusion: In the Cilento Region of Southern Italy, NCs seemed to have good cognitive status when compared to younger cohabitants aging 50-65 years without significant differences in oxidative stress markers or APOE genotype. These results might be related to optimal adherence to the Mediterranean diet, although other lifestyle factors and positive personality traits may also contribute to their healthy aging. Further studies on a larger population should be performed to confirm the results of this pilot study.

BackgroundThere is currently no undisputed, validated, clinically meaningful measure for deficits in the broad spectrum of PSP phenotypes.ObjectiveTo develop a scale to monitor clinical deficits in patients with PSP across its broad phenotypes.MethodsThe Progressive Supranuclear Palsy Clinical Deficits Scale was conceptualized to cover seven clinical domains (Akinesia-rigidity, Bradyphrenia, Communication, Dysphagia, Eye movements, Finger dexterity, and Gait & balance), each scored from 0 to 3 (no, mild, moderate, or severe deficits). User guidelines were developed to standardize its application. Progressive Supranuclear Palsy Clinical Deficits Scale scores were collected in patients fulfilling the MDS-PSP diagnostic criteria in two independent, multicenter, observational studies, both cross-sectionally (exploratory DescribePSP cohort; confirmatory ProPSP cohort) and longitudinally (12-months' follow-up, both cohorts).ResultsCognitive pretesting demonstrated easy scale utility. In total, 164 patients were scored (70.4 ± 7.6 years; 62% males, 35% variant phenotypes). Mean Progressive Supranuclear Palsy Clinical Deficits Scale completion time was 4 minutes. The Progressive Supranuclear Palsy Clinical Deficits Scale total score correlated with existing scales (e.g., Progressive Supranuclear Palsy Rating Scale: R = 0.88; P

BackgroundThe Cilento region of southern Italy has a high prevalence of nonagenarians and centenarians. Few studies of the oldest old have included echocardiographic and/or electrocardiographic data, in a home-based setting.ObjectivesThe objective of this pilot study was to delineate the key lifestyle, medical, echocardiographic, and electrocardiographic features of a sample of nonagenarians and centenarians and their younger cohabitants from Cilento, via a comprehensive, home-based cardiovascular assessment. The ultimate aim is to identify the cardiovascular profile and lifestyle factors associated with longevity.MethodsTwenty-six nonagenarians and centenarians (mean age 94 ± 3 years) and 48 younger cohabitants aged 50-75 years (mean 62 ± 5) underwent a comprehensive cardiovascular evaluation in their homes.ResultsIn contrast to their younger cohabitants, nonagenarians and centenarians did not smoke, had lower fasting glucose levels, and lower LDL cholesterol despite being half as likely to be taking statins, and showing similar adherence to a Mediterranean diet. Over half of nonagenarians and centenarians (15/26) remained autonomous with their activities of daily living. Prevalence of self-reported coronary artery disease and stroke among nonagenarians and centenarians was low (11.5%), though a significant number had atrial fibrillation (31%) or congestive heart failure (27%). Although 62% of nonagenarians and centenarians had at least moderate valvular disease on echocardiography, less than 25% of those affected reported dyspnea.ConclusionNonagenarians and centenarians in the Cilento region had a healthy metabolic profile and a low prevalence of clinical cardiovascular disease. Even among nonagenarians and centenarians with structural heart abnormalities, report of symptoms is low. Larger studies in the Cilento population may help elucidate the mechanisms underlying cardiovascular health in the oldest old.

As part of the State Targeted Response to the opioid epidemic, California has adopted the Hub and Spoke model to expand access to medications for opioid use disorder, particularly buprenorphine, throughout the state. By aligning opioid treatment programs as hubs with primary care, office-based practitioners, and other health care settings as spokes, a broader treatment model can reach more people with opioid use disorder, improve access to medications for opioid use disorders, and decrease overdose deaths. Expanding access requires expanding knowledge and intensive implementation support of new practices. This paper describes the rationale, specific activities and anticipated impact of the implementation plan in California's Hub and Spoke system. Training and technical assistance are designed to: increase the number and capacity of waivered prescribers; enhance skills of prescribers and multidisciplinary teams; and create systems change. Activities include buprenorphine waiver trainings and provider support, a practice facilitator program, Project ECHO sessions, webinars, clinical skills trainings, and regional learning collaboratives. This overview highlights the steps California is taking to build treatment capacity to address the opioid epidemic.

Introduction: In this retrospective case-series study we discuss the clinical and radiographic outcomes obtained following the “tibia-first concept” in the treatment of distal tibia fractures, both in patients with fibular comminution and in cases with a simple fibula fracture. Materials and methods: We analysed a consecutive series of 64 patients who presented at our emergency department with a distal articular tibial and fibular fracture from January 2015 to September 2020. A total of 22 patients met the inclusion and exclusion criteria and were included in the study. Clinical and radiographic examination were performed at each follow-up. To quantify pain and functional disability, the Foot and Ankle Outcome Score (FAOS) and the American Orthopaedic Foot and Ankle Society’s ankle- hindfoot scale (AOFAS) were applied. Results: The overall mean age was 52.8 years, and the mean follow-up was 13.18 months. Multiple scales data from the FAOS were as follows: pain score 80.70; symptoms score 81.69; activities of daily living score 87.22; quality of life 76.05. The mean AOFAS ankle-hindfoot score was 74.36. Conclusions: Even though the principles of Rüedi and Allgöwer are still valid, in specific circumstances, the tibia- first concept could be considered as a valid option for the treatment of these demanding fractures. If a good reduction is obtained intra-operatively by ligamentotaxis, we recommend fixing the tibia first, avoiding surgical stress on tissues derived from a previous fibular fixation.

Abstract The Laser Interferometer Space Antenna (LISA) will be a transformative experiment for gravitational wave astronomy, and, as such, it will offer unique opportunities to address many key astrophysical questions in a completely novel way. The synergy with ground-based and space-born instruments in the electromagnetic domain, by enabling multi-messenger observations, will add further to the discovery potential of LISA. The next decade is crucial to prepare the astrophysical community for LISA’s first observations. This review outlines the extensive landscape of astrophysical theory, numerical simulations, and astronomical observations that are instrumental for modeling and interpreting the upcoming LISA datastream. To this aim, the current knowledge in three main source classes for LISA is reviewed; ultra-compact stellar-mass binaries, massive black hole binaries, and extreme or interme-diate mass ratio inspirals. The relevant astrophysical processes and the established modeling techniques are summarized. Likewise, open issues and gaps in our understanding of these sources are highlighted, along with an indication of how LISA could help making progress in the different areas. New research avenues that LISA itself, or its joint exploitation with upcoming studies in the electromagnetic domain, will enable, are also illustrated. Improvements in modeling and analysis approaches, such as the combination of numerical simulations and modern data science techniques, are discussed. This review is intended to be a starting point for using LISA as a new discovery tool for understanding our Universe.

Thyroid hormones have an important role in fostering tumour progression, however their upstream regulators are less clear. Here, the authors identify the thyroid hormone activating enzyme type 2 deiodinase as a p53 target gene and demonstrate its contribution to tumour progression in p53 mutant squamous cell carcinoma.

Claudia Carmassi,1 Virginia Pedrinelli,1,2 Corinna Antonini,1 Valerio Dell’Oste,1,2 Davide Gravina,1 Benedetta Nardi,1 Carlo Antonio Bertelloni,1 Gabriele Massimetti,1 Joaquín Nieto-Munuera,3 Liliana Dell’Osso1 1Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy; 2Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Siena, Italy; 3Department of Psychiatry and Social Psychology, University of Murcia, Murcia, SpainCorrespondence: Virginia Pedrinelli, Department of Clinical and Experimental Medicine, University of Pisa, Via Roma 67, Pisa, 56100, Italy, Tel +39 050 2219760, Fax +39 050 2219787, Email virginiapedrinelli@gmail.comBackground: The present study aimed at reporting about the validity and reliability of the Spanish version of the Trauma and Loss Spectrum-Self Report (TALS-SR), an instrument based on a multidimensional approach to Post-Traumatic Stress Disorder (PTSD) and Prolonged Grief Disorder (PGD), including a range of threatening or traumatic experiences and significant losses, besides the spectrum of peri-traumatic stress reactions and post-traumatic stress symptoms that may occur.Methods: A sample of 87 Health Care Workers (HCWs) employed in the COVID-19 Emergency Department at the Virgen de la Arrixaca and Reina Sofia Hospitals (Murcia, Spain) during the pandemic, was consecutively recruited and fulfilled the TALS-SR. Assessments also included the Impact of Event Scale-Revised (IES-R), to examine post-traumatic stress symptoms and probable PTSD. Nineteen HCWs fulfilled the TALS-SR again after three weeks from baseline for test–retest reliability.Results: This study provides evidence of good internal consistency and test–retest reliability of the Spanish version of the TALS-SR. Strong support for the internal validity structure was obtained, with positive and significant correlations between the five symptomatologic domains and the symptomatologic total score. Significant and good correlations between the TALS-SR symptomatologic domains and the IES-R total and single domains’ scores were found. The Questionnaire also demonstrated to discriminate between subjects with and without PTSD, with subjects with PTSD showing significantly higher mean scores in each domain of the TALS-SR.Conclusion: This study validates the Spanish version of TALS-SR, providing a useful instrument for a spectrum approach to PTSD and confirms the potential utility of this psychometric tool in both clinical practice and research settings.Keywords: mental health, stress disorders, traumatic, PTSD, psychological distress, health personnel, psychological tests

Abstract According to holography, entanglement is the building block of spacetime; therefore, drastic changes of entanglement will lead to interesting transitions in the dual spacetime. In this paper, we study the effect of projective measurements on the Sachdev-Ye-Kitaev (SYK) model’s thermofield double state, dual to an eternal black hole in Jackiw-Teitelboim (JT) gravity. We calculate the (Renyi-2) mutual information between the two copies of the SYK model upon projective measurement of a subset of fermions in one copy. We propose a dual JT gravity model that can account for the change of entanglement due to measurement, and observe an entanglement wedge phase transition in the von Neumann entropy. The entanglement wedge for the unmeasured side changes from the region outside the horizon to include the entire time reversal invariant slice of the two-sided geometry as the number of measured Majorana fermions increases. Therefore, after the transition, the bulk information stored in the measured subsystem is not entirely lost upon projection in one copy of the SYK model, but rather teleported to the other copy. We further propose a decoding protocol to elucidate the teleportation interpretation, and connect our analysis to the physics of traversable wormholes.

Abstract Neurological manifestations are common in COVID-19, the disease caused by SARS-CoV-2. Despite reports of SARS-CoV-2 detection in the brain and cerebrospinal fluid of COVID-19 patients, it is still unclear whether the virus can infect the central nervous system, and which neuropathological alterations can be ascribed to viral tropism, rather than immune-mediated mechanisms. Here, we assess neuropathological alterations in 24 COVID-19 patients and 18 matched controls who died due to pneumonia/respiratory failure. Aside from a wide spectrum of neuropathological alterations, SARS-CoV-2-immunoreactive neurons were detected in the dorsal medulla and in the substantia nigra of five COVID-19 subjects. Viral RNA was also detected by real-time RT-PCR. Quantification of reactive microglia revealed an anatomically segregated pattern of inflammation within affected brainstem regions, and was higher when compared to controls. While the results of this study support the neuroinvasive potential of SARS-CoV-2 and characterize the role of brainstem inflammation in COVID-19, its potential implications for neurodegeneration, especially in Parkinson’s disease, require further investigations.

Abstract Background The initial policy response to the COVID-19 pandemic has differed widely across countries. Such variability in government interventions has made it difficult for policymakers and health research systems to compare what has happened and the effectiveness of interventions across nations. Timely information and analysis are crucial to addressing the lag between the pandemic and government responses to implement targeted interventions to alleviate the impact of the pandemic. Methods To examine the effect government interventions and technological responses have on epidemiological and economic outcomes, this policy paper proposes a conceptual framework that provides a qualitative taxonomy of government policy directives implemented in the immediate aftermath of a pandemic announcement and before vaccines are implementable. This framework assigns a gradient indicating the intensity and extent of the policy measures and applies the gradient to four countries that share similar institutional features but different COVID-19 experiences: Italy, New Zealand, the United Kingdom and the United States of America. Results Using the categorisation framework allows qualitative information to be presented, and more specifically the gradient can show the dynamic impact of policy interventions on specific outcomes. We have observed that the policy categorisation described here can be used by decision-makers to examine the impacts of major viral outbreaks such as SARS-CoV-2 on health and economic outcomes over time. The framework allows for a visualisation of the frequency and comparison of dominant policies and provides a conceptual tool to assess how dominant interventions (and innovations) affect different sets of health and non-health related outcomes during the response phase to the pandemic. Conclusions Policymakers and health researchers should converge toward an optimal set of policy interventions to minimize the costs of the pandemic (i.e., health and economic), and facilitate coordination across governance levels before effective vaccines are produced. The proposed framework provides a useful tool to direct health research system resources and build a policy benchmark for future viral outbreaks where vaccines are not readily available.

In 2020, the emergency due to the COVID-19 pandemic brought a drastic and sudden change in teaching practices, from the physical space of the classrooms to the virtual space of an e-environment. In this paper, through a qualitative analysis of 44 collected essays composed by Italian mathematics teachers from primary school to undergraduate level during the spring of 2020, we investigate how the Italian teachers perceived the changes due to the unexpected transition from a face-to-face setting to distance education. The analysis is carried out through a double theoretical lens, one concerning the whole didactic system where the knowledge at stake is mathematics and the other regarding affective aspects. The integration of the two theoretical perspectives allows us to identify key elements and their relations in the teachers' narratives and to analyze how teachers have experienced and perceived the dramatic, drastic, and sudden change. The analysis shows the process going from the disruption of the educational setting to the teachers' discovery of key aspects of the didactic system including the teacher's roles, a reflection on mathematics and its teaching, and the attempt to reconstruct the didactic system in a new way.

Designing sustainable and, at the same moment, resilient buildings is a necessity to reach the UN Sustainable Development Goals by 2030. However, these two building design approaches - sustainability and resilience - are usually treated separately. Typically, resilience-improving strategies are placed only after a disruptive event and not at the design stage. It is clear that there is a substantial intersection between sustainability and resilience and this manuscript aims to determine more precisely the commonalities and contradictions seen in building design sustainable and resilient approaches as crucial elements for improving their cooperation in buildings. To accomplish this, the authors qualitatively analysed two case studies - respectively claiming to be sustainable and resilient - to understand if a sustainable building can also be considered resilient and vice versa. This paper is addressed to the private and public sectors that have a decisive role in building design and are determined to take tangible steps to influence decision-making and resilience-based solutions already at the design phase. In conclusion, once the commonalities of resilience and sustainability are highlighted, a building designed as sustainable or resilient will be in line with both long-term perspectives.

Housing is the main environmental impact generator (62 %) of the whole building sector, but it also has the greatest reduction potential. Enhancing its performance is thus crucial to sustainable development. Social Housing (SH) represents a critical asset within the residential segment, due to the recurrent investment shortage and several environmental, social, and economic related implications. In Italy, SH is held by around one hundred public agencies facing endemic resource constraints for both maintenance and retrofitting, which are limited further by a diffused lack of information regarding the conditions and features of the buildings they manage. In cooperation with an Italian SH agency (ACER Bologna), we developed a speedy tool to compare the technical and economic effects of different refurbishment scenarios on a case-by-case basis. This is not a tool to manage retrofitting works, as the many already available, but a means to help large housing managers overcome the intention-action gap that limit their capacity to properly prioritize interventions based on reliable information. The research focuses on the validation of the fast procedure for estimating the baseline energy scenario, arguing that the relatively small inaccuracies are irrelevant for the scope of the tool and are compensated for by the time saved.

Abstract Holography has taught us that spacetime is emergent and its properties depend on the entanglement structure of the dual theory. In this paper, we describe how changes in the entanglement due to a local projective measurement (LPM) on a subregion A of the boundary theory modify the bulk dual spacetime. We find that LPMs destroy portions of the bulk geometry, yielding post-measurement bulk spacetimes dual to the complementary unmeasured region A c that are cut off by end-of-the-world branes. Using a bulk calculation in AdS 3 and tensor network models of holography (in particular, the HaPPY code and random tensor networks), we show that the portions of the bulk geometry that are preserved after the measurement depend on the size of A and the state we project onto. The post-measurement bulk dual to A c includes regions that were originally part of the entanglement wedge of A prior to measurement. This suggests that LPMs performed on a boundary subregion A teleport part of the bulk information originally encoded in A into the complementary region A c . In semiclassical holography an arbitrary amount of bulk information can be teleported in this way, while in tensor network models the teleported information is upper-bounded by the amount of entanglement shared between A and A c due to finite-N effects. When A is the union of two disjoint subregions, the measurement triggers an entangled/disentangled phase transition between the remaining two unmeasured subregions, corresponding to a connected/disconnected phase transition in the bulk description. Our results shed new light on the effects of measurement on the entanglement structure of holographic theories and give insight on how bulk information can be manipulated from the boundary theory. They could also represent a first step towards a holographic description of measurement-induced phase transitions.

Twenty-two pluriparous single-foetus-bearing Angora goats, housed 3 weeks pre-partum in mid-December, and in transition from pregnancy to lactation were used to test the efficacy of post-partum supplementation (Group S: 11 goats) or not (Group C: 11 goats) with 300 g/head/day of whole field bean seeds (WFBS) to a diet based on mixed hay ad libitum and natural pasture. The goats were maintained with the suckling of their kids for 90 days. Significant decreases in liveweight (LW) and body condition score (BCS), were documented post-parturition in both groups and were then maintained throughout. These suggest a mobilisation in body tissue that was not mitigated by WFBS supplementation. However, the faster growth of the suckled kids and greater elongation of mohair fibre recorded (Group S > Group C), suggested improvement in partition towards production indices of lactation and hair fibre deposition, respectively. Greater concentrations of total thyroid hormones, T3 and T4 in supplemented does were recorded. Overall mean (pre-prandial) plasma insulin concentrations, not different between treatments, decreased (p

Osilodrostat is a novel, orally administered cortisol synthesis inhibitor, approved in 2020 by the European Medicines Agency (EMA) for the treatment of Cushing’s syndrome in adults. A significant amount of the studies currently available in the literature focus on treatment in patients with Cushing’s disease. However, data collected from patients treated with osilodrostat in real-life settings still represents a small entity. For this reason, in this article, we will discuss two real-life cases of patients with Cushing’s disease treated with this drug. The first report is about a 35-year-old woman with an adrenocorticotrophic hormone (ACTH)-secreting adenoma. After non-curative trans-nasal-sphenoidal (TNS) surgery, due to a small remnant of the adenoma, medical therapy with osilodrostat achieved fast and effective biochemical and clinical response. During treatment, progressive increase of ACTH levels and an enlargement of the pituitary remnant were documented, with planned radiosurgical treatment. The second case reports a 32-year-old man diagnosed with Cushing’s disease in 2020, who, after surgery refusal, started osilodrostat at progressively up-titrated doses, according to 24 h urinary free cortisol levels, up to 5 mg twice a day. With osilodrostat, the patient reached biochemical and clinical control of disease until TNS surgery in October 2021, with complete remission. The first post-surgical biochemical assessment was equivocal in spite of a transient clinical hypoadrenalism, reverted after 2 months with the restoration of physiological hypothalamic-pituitary-adrenal axis (HPA) function.

Abstract In the present work, we report the obtaining of nanostructured porous Nb2O5 by anodizing process, with Pt, Ta, Cu, or Ti impregnation, and by magnetron sputtering process. The techniques of scanning electron microscopy, X‐ray diffraction, and X‐ray photoelectron spectroscopy were used to evaluate the morphology, and the composition and crystalline structure of nanoporous Nb2O5. The photocatalytic activity was evaluated by electrochemical photocurrent tests under UV light illumination. Nanostructured porous Nb2O5 with Pt, Ta, Cu, and Ti impregnation presented bandgap reduction and 10 times higher photocurrent density in the presence of UV light when compared to the not impregnated nanoporous Nb2O5.

Abstract COVID-19 is the global pandemic that affected our population in the past 2 years. Considerable research has been done to better understand the pathophysiology of this disease and to identify new therapeutic targets, especially for severe cases. Galectin-3 (Gal-3) is a receptor present at the surface of different cell types, namely epithelial and inflammatory cells, which has been described as a severity marker in COVID-19. The activation of Gal-3 through its binding protein (Gal-3BP) is directly linked to the production of pro-inflammatory cytokines that contribute for the cytokine storm (CS) observed in severe COVID-19 patients. Here, we show that D2, a recombinant fragment of the lectin-binding region of Gal-3BP was able to stimulate the expression of IL-6 in colon and lung epithelial cell lines in β-galactoside dependent manner. We further show that D2-induced IL-6 augmentation was reduced by the anti-Gal-3BP monoclonal antibody 1959. Our data confirm and extend prior findings of Gal-3BP mediated IL-6 induction, enlightening the potential of its antibody-mediated s blockage for the prevention and treatment of CS and severe disease in COVID-19 patients.

Abstract Storage of digital data is becoming challenging for humanity due to the relatively short life-span of storage devices. Furthermore, the exponential increase in the generation of digital data is creating the need for constantly constructing new resources to handle the storage of this data volume. Recent studies suggest the use of the DNA molecule as a promising novel candidate which can hold 500 Gbyte/mm $$^3$$ 3 (1000 times more than HDD drives). Any digital information can be synthesized into DNA in vitro and stored in special tiny storage capsules that can promise reliability for hundreds of years. The stored DNA sequence can be retrieved whenever needed using special machines that are called sequencers. This whole process is very challenging, as the process of DNA synthesis is expensive in terms of money and sequencing is prone to errors. However, studies have shown that when respecting several rules in the encoding, the probability of sequencing error is reduced. Consequently, the encoding of digital information is not trivial, and the input data need to be efficiently compressed before encoding so that the high synthesis cost is reduced. In this paper, we present a survey on the storage of digital data in synthetic DNA, explaining the problem which is tackled by this novel field of study, present the main processes included in the storage workflow as well as the history of different studies and the most well-known algorithms that have been proposed in the bibliography on DNA data storage.

Les matériaux hétérogènes sont utilisés dans l’industrie notamment pour alléger les structures ou renforcer certaines propriétés mécaniques ou chimiques propres à chacun des matériaux combinés tout en visant l’optimisation des cycles de production. Ils peuvent être déclinés sous la forme d’assemblages collés ou soudés ou sous forme de composites. Ils répondent à des enjeux de plus en plus élevés dans des secteurs exigeants comme l’aérospatial, la défense, les transports ou l’énergie. En raison de la complexité de leurs procédés de fabrication et d’un retour d’expérience limité sur ces matériaux en exploitation, ces derniers nécessitent des moyens de contrôle avancés permettant de détecter leurs défauts internes ou d’évaluer les propriétés internes qui pourraient notamment affecter leurs performances que ce soit au stade de la production ou en cours d’exploitation. Les matériaux assemblés peuvent être affectés par différents types de défaut, cohésif ou adhésif, tels que des porosités dans la colle, des défauts de polymérisation, des mauvaises transformations de la matière chauffée ou encore des décollements. Pour les matériaux composites, dans le cadre de leur production, il s’agit notamment de défauts d’imprégnation, de défauts d’alignement ou d’orientation des fibres alors qu’en cours d’exploitation, plutôt de délaminations ou de perte d’épaisseur. De ce fait, la possibilité d’apporter des garanties supplémentaires sur les performances de ces matériaux en s’appuyant sur un contrôle de leur volume intérieur, suscite un intérêt grandissant pour les techniques de contrôle non destructif et rapide pour qualifier 100% des produits en production et de suivre le vieillissement de ces matériaux en exploitation. Dans ce cadre, la technologie d’imagerie THz, méthode de contrôle non destructif rapide, sans contact et portative, est une solution prometteuse. Basée sur de nouvelles ondes électromagnétiques, appelées THz, elle associe une capacité de pénétration importante dans la plupart des matériaux diélectriques (i.e. non conducteurs), comme les polymères, élastomères et céramiques, avec une forte sensibilité de détection des hétérogénéités de la matière et de leur anisotropie en proposant une capacité de résolution d’imagerie compatible avec la taille des défauts courants recherchés par le monde industriel. Une technique d’imagerie THz innovante en mode réflexion ou transmission permet notamment de réaliser des cartographies 2D de leurs hétérogénéités en temps réel, compatible avec du contrôle à haute cadence sur ligne de production ou pour des pièces de grandes dimensions. Lors de cette communication, TERAKALIS, société spécialisée dans la fabrication d’équipements THz, présentera le domaine des ondes THz, les principales techniques de mesure, un état de la maturité des systèmes THz actuels avec leurs niveaux de performance et limites pour le contrôle de la qualité des assemblages collés ou soudés et aussi des matériaux composites. Elle s’appuiera sur des cas applicatifs automatisés en guise d’illustration dans le cadre de production ou d’exploitation.

The COVID emergency has accelerated professional and organizational transformations, prompting a re-signification of activity systems, routines, professional visions, concrete daily operations. An unforeseen scenario emerges, highlighting elements of uncertainty, fatigue, and discomfort, linked, on the one hand, to the challenge raised towards the professional identities of the various players, called to deal with the new organizational constraints, to reposition themselves in changing contexts. On the other hand, the challenge refers to the possibility to achieve a good balance between offering services aimed at the promotion and protection of health and, at the same time, to guarantee working safety and security conditions, in increasingly complex contexts in which tensions and contradictions coexist with reduction of resources and requests for more effective services. At risk is the possibility to cope with increasing situations of social conflicts (i.e. the no vax manifestations) and events such as those related to the aggressiveness of patients, the verbal and often physical aggression against the health professionals, exposed to the temptation to abandon work and devote oneself to something else. Tackling with patients taken in charge by the Services and with characteristics of aggressive behavior, decidedly above the sustainability thresholds (death threats; screams and insults; raids on the service; stalking; shadowing of operators, ... with situations of requesting emergency intervention by the police, which could only be limited to a light intervention in the absence of an explicit complaint against the person), generates understandable fears and dynamics of avoidance/expulsion. These are, more and more (even though not exclusively) at the basis of resignations and retirement from work. This is in evident contrast with the mission of the health service and therefore with the identification of personnel with the aim of taking care of every user with a need. Hence a situation of impasse (disenchantment/impotence/give up/avoidance), having to deal with balancing the threshold of the limit(boundary) and the limit(boundary) of the threshold, defining conditions of survival, of joint elaboration, of collective action agreed. The possibility of conceiving oneself as an emancipatory limit(boundary), avoiding fantasies of ‘expulsive killerage’ and ‘regulatory stiffening’, relies on a collective system alliance, capable of considering both realistic fears with respect to personal safety to be protected, and the elaboration of one's own defensive dynamics in the face of exposure to external aggression. At stake is the lacerating dilemma between the identification with a service that must take charge of the needs (whatever they may be) of a user/patient and, at the same time, with the need to protect one's own and others' (other patients) safety conditions to be able to fulfill the professional task to which one is called.

Coastal hazards represent an existential threat to Italian coastal regions since they host important economic centers related to manufacturing and tourism. Knowledge of potential extreme sea levels (ESL), their component, and their interactions are essential to better evaluate potentially hazardous future extreme events in a changing climate and possible effects on the design of coastal structures. Hence, in this study, we investigate the interaction between tide and surge for extreme conditions of sea level in 9 locations along the Italian coastline facing both the Adriatic and the Tyrrhenian Seas and all in a semi-diurnal tidal regime. First, we introduce a novel dependence metric, i.e., the β factor, in support of the classical Kendall’s τ to preliminary assess the effect of the dependence between tide and surge when conditioned on ESL on the variance of ESL, and then we quantify such effect using a copula-based framework. Here, the surge component is determined via the concept of skew surge, i.e., the difference within a tidal cycle between the maximum observed sea level and the predicted high tide (irrespective of the time of occurrence), to remove any random effect in the interaction due to the timing of the tidal peak. Our results show that ESL components, i.e., tide and skew surge, are negatively dependent, i.e., high/low values of the surge are associated with low/high values of the tide, in all the stations investigated, and that higher values of dependence, measured with Kendall’s τ, can be observed in the Adriatic Sea, around −0.6, while lower values in the Tyrrhenian Sea, around −0.45, with the exception of Palermo. In general, an increase in ESL for higher quantiles is observed when the negative dependence between tide and surge is explicitly modeled. Moreover, our results show that the β factor can help quantify the relative contribution of tide and surge on the variability of ESLs. More specifically, small β refers to cases when tide and surge are similar in their magnitude, e.g., Palermo, while values of β close to 1 refer to the case when one component dominates the other. In the former case, ESLs obtained from a model that does not account for the dependence between tide and surge will result in ESL estimates with larger variability. On the other hand, when one component dominates the other, the variability of ESLs is slightly influenced by the model used for tide and surge, i.e., dependent or independent. We can then conclude that by explicitly modeling the dependence between tide and skew surge we can improve estimates and inference of ESLs.

Resumo Objetivo Construir e validar um e-book sobre risco cardiovascular em pessoas vivendo com o vírus da imunodeficiência humana. Métodos Estudo metodológico fundamentado na teoria da pesquisa avaliativa com análise de resultado. Envolveu a produção tecnológica compreendendo as fases de análise e planejamento, modelagem, implementação e avaliação. Foram discutidos os fatores de risco cardiovascular e as estratégias para reduzi-los. O e-book foi validado por especialistas de todo o país entre outubro de 2017 e agosto de 2018 por meio do Índice de Validade de Conteúdo. Resultados Como o e-book foi escrito para atender as necessidades da população, adotou-se uma linguagem acessível para facilitar a compreensão do conteúdo. Vários aspectos do e-book foram avaliados por especialistas. Em seguida, foram analisadas as críticas e/ou sugestões mais frequentes. Após análise do IVC global, foi encontrada uma taxa de concordância de 80,5%. Todos os itens tiveram índices de concordância satisfatórios, com IVC de 86,6% para impressão geral, 96,8% para objetivo, 92,0% para conteúdo e 90,4% para relevância. Conclusão O e-book foi avaliado em diversos aspectos pelos especialistas, encontrando um índice de concordância global de 80,5%. As sugestões foram acatadas com o objetivo de garantir um material mais completo, coeso, de fácil leitura e atualizado. De acordo com a avaliação dos especialistas, o material se mostrou válido para utilização por pessoas vivendo com HIV, no entendimento de seu risco cardiovascular e conhecimento de hábitos mais saudáveis que ajudem na prevenção de doenças cardiovasculares.