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Background and purpose Some studies have shown that air pollution, often assessed by thin particulate matter with diameter below 2.5 µg/m3 (PM2.5), may contribute to severe COVID‐19 courses, as well as play a role in the onset and evolution of multiple sclerosis (MS). However, the impact of air pollution on COVID‐19 has never been explored specifically amongst patients with MS (PwMS). This retrospective observational study aims to explore associations between PM2.5 and COVID‐19 severity amongst PwMS. Methods Data were retrieved from an Italian web‐based platform (MuSC‐19) which includes PwMS with COVID‐19. PM2.5 2016–2018 average concentrations were provided by the Copernicus Atmospheric Monitoring Service. Italian patients inserted in the platform from 15 January 2020 to 9 April 2021 with a COVID‐19 positive test were included. Ordered logistic regression models were used to study associations between PM2.5 and COVID‐19 severity. Results In all, 1087 patients, of whom 13% required hospitalization and 2% were admitted to an intensive care unit or died, were included. Based on the multivariate analysis, higher concentrations of PM2.5 increased the risk of worse COVID‐19 course (odds ratio 1.90; p = 0.009). Conclusions Even if several other factors explain the unfavourable course of COVID‐19 in PwMS, the role of air pollutants must be considered and further investigated., Air pollution, often assessed by particulate matter with diameter below 2.5 µg/m3, may contribute to severe COVID‐19 courses. 1087 patients were included, of whom 13% required hospitalization and 2% were admitted to an intensive care unit or died. Even if several other factors explain the unfavourable course of COVID‐19 in patients with multiple sclerosis, the role of air pollutants must be considered and further investigated.

Bartolina Xixa desarma el relato de una argentinidad blanca, heteronormada y homogénea, a través de su arte transformista. Al bailar una vidala usando como escenario un basural a cielo abierto, cuestiona la cultura afectiva del folklore y presenta una estructura de sentimientos elaborada sobre la experiencia de la exclusión permanente. Bartolina lleva a la coreografía el movimiento que la desplaza entre diferentes identificaciones: se muestra como “vestida”, indígena, de género fluido, fronteriza y precaria. La vidala titulada “Ramita seca”, mediante la fusión de sonoridades provenientes de la vidala y el rap, ofrece formas de retención que permiten elaborar una narración colectiva del dolor incorporando lo abyecto, lo excluido y lo antagónico a la narrativa del folklore. “Ramita seca” interpretada por Bartolina, propone la emergencia de un folklore de resistencia que habilita otros repertorios sociales y estilos emocionales bajo los cuales devenir sujeto.

The organic development of European Criminal Law and the entry into force of the Treaty of Lisbon have opened the path towards the creation of the first investigative and prosecutorial authority with supranational characteristics, which was realised albeit with limited participation from the Member States of the European Union. However, due to the lack of unanimity, the idea to create unified authority from Eurojust foreseen by the Treaty on the Functioning of the European Union has fallen. Since the European Public Prosecutor’s Office (‘EPPO’) is dependent on the national authorities and on the already existing European jurisdictional bodies, it was necessary to create an efficient cooperation framework in order to fruit their decade-long know-how and to secure the effective transfer of information. In this paper, I analyse the cooperation framework of the EPPO with EU justice institutions, such as Eurojust, Olaf, and Europol, through its historical development and its jurisdictional limitations.

Background and purpose: Clinical outcomes of multiple sclerosis (MS) patients affected by coronavirus disease 2019 (COVID-19) have been thoroughly investigated, but a further analysis on main signs and symptoms and their risk factors still needs attention. The objective of this study was to group together and describe based on similarity the most common signs and symptoms of COVID-19 in MS patients and identify all factors associated with their manifestation. Method: Logistic and linear regression models were run to recognize factors associated with each pooled group of symptoms and their total number. Results: From March 2020 to November 2021, data were collected from 1354 MS patients with confirmed infection of COVID-19. Ageusia and anosmia was less frequent in older people (odds ratio [OR] 0.98; p=0.005) and more in smoker patients (OR 1.39; p=0.049). Smoke was also associated with an incremental number of symptoms (OR 1.24; p=0.031), substance abuse (drugs or alcohol), conjunctivitis and rash (OR 5.20; p=0.042) and the presence of at least one comorbidity with shortness of breath, tachycardia or chest pain (OR 1.24; p=0.008). Some disease-modifying therapies were associated with greater frequencies of certain COVID-19 symptoms (association between anti-CD20 therapies and increment in the number of concomitant symptoms: OR 1.29; p=0.05). Differences in frequencies between the three waves were found for flu-like symptoms (G1, p=0.024), joint or muscle pain (G2, p=0.013) and ageusia and anosmia (G5, p < 0.001). All cases should be referred to variants up to Delta. Conclusion: Several factors along with the choice of specific therapeutic approaches might have a different impact on the occurrence of some COVID-19 symptoms.

Silva invasion pattern can help predict lymph node metastasis risk in endocervical adenocarcinoma. We analysed Silva pattern of invasion and lymphovascular invasion to determine associations with clinical outcomes in stage IA and IB1 endocervical adenocarcinomas. International Federation of Gynecology and Obstetrics (FIGO; 2019 classification) stage IA-IB1 endocervical adenocarcinomas from 15 international institutions were examined for Silva pattern, presence of lymphovascular invasion, and other prognostic parameters. Lymph node metastasis status, local/distant recurrences, and survival data were compared using appropriate statistical tests. Of 399 tumours, 152 (38.1%) were stage IA [IA1, 77 (19.3%); IA2, 75 (18.8%)] and 247 (61.9%) were stage IB1. On multivariate analysis, lymphovascular invasion (p=0.008) and Silva pattern (p0.001) were significant factors when comparing stage IA versus IB1 endocervical adenocarcinomas. Overall survival was significantly associated with lymph node metastasis (p=0.028); recurrence-free survival was significantly associated with lymphovascular invasion (p=0.002) and stage (1B1 versus 1A) (p=0.002). Five and 10 year overall survival and recurrence-free survival rates were similar among Silva pattern A cases and Silva pattern B cases without lymphovascular invasion (p=0.165 and p=0.171, respectively). Silva pattern and lymphovascular invasion are important prognostic factors in stage IA1-IB1 endocervical adenocarcinomas and can supplement 2019 International Federation of Gynecology and Obstetrics staging. Our binary Silva classification system groups patients into low risk (patterns A and B without lymphovascular invasion) and high risk (pattern B with lymphovascular invasion and pattern C) categories.

Purpose This paper aims to investigate the application of the Italian Banking Association (ABI) industry-specific reporting standard in microfinance institutions by determining whether or not a banking sector reporting standard can enhance non-financial reporting (NFR) quality and volume to meet stakeholders’ information needs in the specific setting investigated. Design/methodology/approach This paper develops an analysis of available ABI documents from 2006 to 2013 to conduct a content analysis of the quality and volume of the NFR of 98 Italian cooperative banks (CBs) during the 2008–2009 ABI implementation year. These data are analysed using two regression models to investigate the quality and volume of NFR disclosures. Findings The findings suggest that for CBs in the Italian banking sector, the information provided in the non-financial reports in adherence to the ABI sector reporting standard is relevant in terms of both volume and quality. However, when investigating specific categories of disclosure such as the community, the relevance of the ABI reporting standard is fairly low. The authors question the “one-size-fits-all” approach favouring a more sector-tailored approach to ensure that the NFR covers key sectoral concerns. Practical implications The high heterogeneity in the sector could negatively affect the capability of sector-specific standards to truly foster reliable, complete and extensive NFR. Therefore, NFR standard-setters, such as the International Sustainability Standards Board, should consider these heterogeneities. Social implications Reporting standardisation should be multi-voiced and include different – even contrasting – perspectives to promote expert and non-expert engagements. Originality/value This paper focuses on hybrid organisations and shows how the theoretical approach of dialogic accountability can improve the quality of sector-specific reporting standards.

Purpose This paper discusses the evolution of sustainability reporting and the role of the Global Reporting Initiative (GRI) in relation to the social and environmental accounting (SEA) literature calling for a revolution in the standardization of sustainability reporting and the inherent complexities. This paper focuses on the future role of GRI in light of the changes resulting from harmonization supported by the International Sustainability Standards Board and the European Financial Reporting Advisory Group’s draft European Sustainability Reporting Directive. Design/methodology/approach Building on Bourdieu (1983, 1992) and SEA studies, the authors adopt a critical and qualitative approach to theorize power dynamics in the sustainability reporting field. After identifying the main issues arising from the complexity of the sustainability reporting standards and practices according to SEA scholars, the authors connect them with Bourdieu’s (1992, 1983) field theory to discuss the future role of GRI. Findings The findings suggest two distinct but intertwined roles that GRI could play in the future, namely, power related and theoretical/technical, aimed at engendering revolutionary rather than evolutionary changes in sustainability reporting. Practical implications This study offers practical implications for GRI to strengthen its future role in sustainability reporting standardization. Social implications The limited time available to mitigate the disastrous consequences of non-sustainable business on society and the environment calls for urgently addressing the complexities of sustainability accounting to foster a positive impact on society and the environment. Originality/value The authors’ reflections reclaim the SEA literature as central to identifying sustainability complexity and Bourdieu’s (1983, 1992) notions of power as key to understanding the role of GRI in the sustainability field. Furthermore, this paper emphasizes the intersection of different critical concepts, including power, complexity, value, capital and materiality.

A MATLAB toolbox, also compatible with GNU Octave, was developed in order to allow a user not necessarily expert in programming to calculate the strain rate field of an area by means of a procedure with a high level of automation starting from coordinate time series. The results can be used to investigate the crustal tectonic deformations of the studied area. These steps are implemented:time series download from a data repository, e.g. the Nevada Geodetic Laboratory (NGL), or another similar database (the download function can be easily edited to allow the use of input time series having different format); calculation of the station velocities by means of the Maximum Likelihood Estimation (MLE) method, including modeling of offsets, outliers, noise and periodic components. The MLE modeling is carried out by using the external package Hector (Bos et al., 2013. J. Geod., 87, 351-360), automatically called by means of a specifically developed MATLAB function; estimation of Common Mode Error and, if necessary, its removal from time series of some stations and recalculation of the corresponding velocities. calculation of the strain rate field on a regular grid with the modified least squares method, in which a scale factor can be introduced to define the locality of the deformation analysis. Besides the strain rate field, the toolbox provides the corresponding uncertainty estimation and geometric evaluation of the significance of the results; visualization of the results for their interpretation for scientific purposes, including the map of principal strain and the contour plots of change in area (or dilatation), engineering shear normalized to the change in area, second invariant of the strain, prevailing eigenvalue, corresponding uncertainties and geometric significance. The toolbox, which is available free of charge to any interested user, is characterized by considerable flexibility, and can be easily adapted to different data sources.The toolbox was recently used in order to refine the rates of active crustal deformation in the upper plate of subduction zones in the specific case of the E-dipping West Crati fault (Calabria) and to evaluate the convergence rate in the Main Thrust Fault (also called Sicilian Basal Thrust) north to Hyblean Plateau (South-Eastern Sicily).

This is a multicenter cohort study including consecutive, hospitalized patients ≥18 years, with moderate to severe COVID-19, carried out to evaluate the relationship between the timing of convalescent plasma administration and 28-day mortality. Data were prospectively collected between May 14, 2020 and October 31, 2020. Patients were grouped according to the timing of administration of convalescent plasma as 7 days. The main outcome variable was 28-day mortality. Independent predictors of mortality were identified by logistic regression. Of 4719 patients receiving convalescent plasma, 3036 (64.3%) were in the general ward, 1171 (24.8%) in the intensive care unit (ICU), and 512 (10.8%) in the ICU on mechanical ventilation. Convalescent plasma was administered to 3113 (66%) patients within the first 3 days of hospital admission, to 1380 (29.2%) between 3 and 7 days, and to 226 after 7 days; 28-day mortality was, respectively, 18.1%, 30.4% and 38.9% (p

This article describes the trajectories of collaboration experienced by three individuals in three different roles (informant, research assistant, and supervisor) in two research projects about English as a foreign language reading in a higher education context in Argentina. Data come from reflection logs and retrospective narratives written by them from 2009 to 2016 which were analyzed using content analysis, focusing on a continuum of collaboration. The article aligns with the critique of the discourse of “newer researcher” as a linear developmental trajectory as it illustrates the participants’ fluid, critical, complex, and personally relevant pathways. Placed within the debate regarding the affordances, complexities and challenges of the measured university, this research contributes perspectives from a peripheral setting generally underrepresented in the literature.

Long-term predictions of reservoir sedimentation require an objective consideration of the preceding catchment processes. In this study, we apply a complex modeling chain to predict sedimentation processes in the Banja reservoir (Albania). The modeling chain consists of the water balance model WaSiM, the soil erosion and sediment transport model combination RUSLE-SEDD, and the 3d hydro-morphodynamic reservoir model SSIIM2 to accurately represent all relevant physical processes. Furthermore, an ensemble of climate models is used to analyze future scenarios. Although the capabilities of each model enable us to obtain satisfying results, the propagation of uncertainties in the modeling chain cannot be neglected. Hence, approximate model parameter uncertainties are quantified with the First-Order Second-Moment (FOSM) method. Another source of uncertainty for long-term predictions is the spread of climate projections. Thus, we compared both sources of uncertainties and found that the uncertainties generated by climate projections are 408% (for runoff), 539% (for sediment yield), and 272% (for bed elevation in the reservoir) larger than the model parameter uncertainties. We conclude that (i) FOSM is a suitable method for quantifying approximate parameter uncertainties in a complex modeling chain, (ii) the model parameter uncertainties are smaller than the spread of climate projections, and (iii) these uncertainties are of the same order of magnitude as the change signal for the investigated low-emission scenario. Thus, the proposed method might support modelers to communicate different sources of uncertainty in complex modeling chains, including climate impact models.

Among moral philosophers in the analytic tradition it has become customary to draw a distinction between thin and thick terms (or concepts). Paradigmatic instances of the former are words like ‘good,’ ‘bad,’ ‘right,’ ‘ought,’ ‘permissible,’ while the latter are exemplified by terms such as ‘cruel,’ ‘courageous,’ ‘kind,’ ‘treacherous,’ ‘generous’ or ‘dishonorable’. During the 1950s some philosophers variously influenced by Wittgenstein started to draw attention to the latter with the intuition that there was something special about them that was important to take into account for a fully satisfying explanation of moral language and thought. In the last decade or so there has been a lively, technically sophisticated debate about thick terms, centered on the question of whether they are separable into a nonevaluative and a thinly evaluative component or not. In my dissertation I argue that both sides of the current debate are governed by an assumption I call representationalism and define as the idea that i) the aim of moral language use is to “get it right” about a moral situation and that ii) a philosophical theory can help justify use of that language by laying out its correctness-conditions. I suggest that representationalism distorts the ways in which we actually use thick terms and is an unreliable account of their meaning. I hence develop an “ordinary language philosophy” conception of thick terms according to which use of thick terms is to be understood as the making of a moral move in a context of utterance rather than a mere attempt to get it right about what is morally the case. On this conception one can argue that there are things we do morally with thick terms which we cannot do otherwise, thereby showing why they are morally important.

Additional file 2: Table S1. Diagnostic and therapeutic (ICD-9-CM and ATC) codes used in the current study for drawing records and fields from Healthcare Utilization databases. Lombardy, Italy, 2020–2021. Table S2. Use of specific healthcare services during the 6 months after the matching date (follow-up period), during the corresponding 6 months of the prior year (baseline period) and during the 6 months preceding the matching date (wash-out period) among subjects who did not use Dupilumab and were 1:1 matched to those who used it.

A fundamental issue in biology is the nature of evolutionary transitions from unicellular to multicellular organisms. Volvocine algae are models for this transition, as they span from the unicellular biflagellate Chlamydomonas to multicellular species of Volvox with up to 50,000 Chlamydomonas-like cells on the surface of a spherical extracellular matrix. The mechanism of phototaxis in these species is of particular interest since they lack a nervous system and intercellular connections; steering is a consequence of the response of individual cells to light. Studies of Volvox and Gonium, a 16-cell organism with a plate-like structure, have shown that the flagellar response to changing illumination of the cellular photosensor is adaptive, with a recovery time tuned to the rotation period of the colony around its primary axis. Here, combining high-resolution studies of the flagellar photoresponse of micropipette-held Chlamydomonas with 3D tracking of freely swimming cells, we show that such tuning also underlies its phototaxis. A mathematical model is developed based on the rotations around an axis perpendicular to the flagellar beat plane that occur through the adaptive response to oscillating light levels as the organism spins. Exploiting a separation of timescales between the flagellar photoresponse and phototurning, we develop an equation of motion that accurately describes the observed photoalignment. In showing that the adaptive timescales in Volvocine algae are tuned to the organisms' rotational periods across three orders of magnitude in cell number, our results suggest a unified picture of phototaxis in green algae in which the asymmetry in torques that produce phototurns arise from the individual flagella of Chlamydomonas, the flagellated edges of Gonium, and the flagellated hemispheres of Volvox.

Background & Aims: Inhalation of welding fume may cause pulmonary disease known as welder's lung. At our centre we came across a number of welders with systemic iron overload and prolonged occupational history and we aimed at characterizing this novel clinical form of iron overload. Methods: After exclusion of other known causes of iron overload, 20 welders were fully evaluated for working history, hepatic, metabolic and iron status. MRI iron assessment was performed in 19 patients and liver biopsy in 12. We included 40 HFE-HH patients and 24 healthy controls for comparison. Results: 75% of patients showed lung HRCT alterations; 90% had s-FERR > 1000 ng/mL and 60% had TSAT > 45%. Liver iron overload was mild in 8 and moderate-severe in 12. The median iron removed was 7.8 g. Welders showed significantly lower TSAT and higher SIS and SIS/TIS ratio than HFE-HH patients. Serum hepcidin was significantly higher in welders than in HFE-HH patients and healthy controls. At liver biopsy, 50% showed liver fibrosis that was mild in four, and moderate-severe in two. Liver staging correlated with liver iron overload. Conclusions: Welders with prolonged fume exposure can develop severe liver iron overload. The mechanism of liver iron accumulation is quite different to that of HFE-HH suggesting that reticuloendothelial cells may be the initial site of deposition. We recommend routine measurement of serum iron indices in welders to provide adequate diagnosis and therapy, and the inclusion of prolonged welding fume exposure in the list of acquired causes of hyperferritinemia and iron overload.

Background Sarcopenia gained importance in the evaluation of patients with chronic respiratory diseases, including idiopathic pulmonary fibrosis (IPF), since it may impact negatively on clinical outcomes. Aim Aim of this study is to evaluate the prevalence and factors associated with sarcopenia, defined according to the European Working Group on Sarcopenia in Older People 2 (EWGSOP2) 2019 definition, and to evaluate the prevalence of the single criteria that define the EWGSOP2 definition (muscle strength, muscle quantity and physical performance), in a cohort of consecutive patients with IPF prospectively followed up in 9 hospitals in Northern Italy between December 2018 and May 2021. Methods Enrolled patients underwent an extensive pulmonary and nutritional assessment, including bioelectrical impedance analysis, dynamometry and 4-m gait speed test, both at IPF diagnosis and at 6-month follow-up. Results Out of the 83 patients (81% males, mean age 72.5 years) with IPF at disease diagnosis enrolled in the study, 19 (22.9%) showed sarcopenia, including 2 (2.4%) with severe sarcopenia, 5 (6.0%) with confirmed sarcopenia and 12 (14.5%) with probable sarcopenia. Sarcopenia was associated with a significantly higher severity of the disease and sedentary lifestyle, while no differences were observed in regards to body mass index, history of weight loss and comorbidities between patients with and without sarcopenia. Out of the 64 patients without sarcopenia at baseline, 16 cases showed alteration of muscle quantity and/or physical performance. In the 51 patients with complete data at 6-month follow-up, there were no cases of severe sarcopenia, 1 case (2.0%) showed confirmed sarcopenia, while the prevalence of probable sarcopenia was 19.6% (10 cases). No differences in regards to antifibrotic treatment received and onset of gastrointestinal side effects were observed between patients with and without sarcopenia at follow-up. Conclusions The prevalence of sarcopenia in patients with IPF both at diagnosis and at 6-month follow-up was low but not negligible and was associated with higher severity of the disease and sedentary lifestyle. In IPF patients, a comprehensive diagnostic work-up including all the criteria defining the EWGSOP2 definition might be more useful than a series testing for prompt recognition of nutritional and physical performance abnormalities.

HIK1083 and trefoil factor 2 (TFF2) are known to be expressed in gastric-type carcinoma (GAS), but they do not reliably mark all GASs, and focal expression can be missed in biopsy specimens. We aimed to investigate whether claudin-18 and alpha-methylacyl-CoA racemase (AMACR) could be surrogate markers to separate GAS from other types of endocervical adenocarcinoma (ECA) and to compare their usefulness with that of HIK1083 and TFF2. Claudin-18 and AMACR immunohistochemistry was performed, and the results were compared with that of TFF2 and HIK1083, using whole sections of 75 ECAs (22 GASs and 53 non-GASs) and 179 ECAs with tissue microarrays (TMAs). TMAs were built to simulate the assessment of immunohistochemical stains in small biopsies. Any membranous (claudin-18) or cytoplasmic/membranous (AMACR, TFF2, HIK1083) staining of5% of tumor cells was considered positive. Of 75 ECAs with whole sections, claudin-18 was significantly more frequently expressed in GASs (21/22) compared with non-GASs (8/53) (P0.01). In ECAs with TMAs, claudin-18 expression was significantly frequent in GASs (15/23, 65.2%) than in non-GASs (3/152, 2.0%; all usual-type) (P0.01). All claudin-18-positive GASs showed intense staining except 1 case. Claudin-18 shared the same degree of sensitivity and specificity with HIK1083 and TFF2. Three clear cell carcinomas were positive for claudin-18, but none showed intense staining. AMACR was expressed in a subset of ECAs and showed no impact in distinguishing between GAS and other ECAs. Our results suggest that claudin-18 is a promising surrogate marker to separate GAS from other types of ECA, including clear cell carcinoma.

Background: Growing evidence from clinical trials and epidemiological studies suggests that statins can have clinically significant antidepressant effects, potentially related to anti-inflammatory action on several neurobiological structures. However, the underlying neuropsychological mechanisms of these effects remain unexplored. Aims: In this experimental medicine trial, we investigated the 7-day effects of the lipophilic statin, atorvastatin on a battery of neuropsychological tests and inflammation in healthy volunteers. Methods: Fifty healthy volunteers were randomised to either 7 days of atorvastatin 20 mg or placebo in a double-blind design. Participants were assessed with psychological questionnaires and a battery of well-validated behavioural tasks assessing emotional processing, which is sensitive to putative antidepressant effects, reward learning and verbal memory, as well as the inflammatory marker, C-reactive protein. Results: Compared to placebo, 7-day atorvastatin increased the recognition ( p = 0.006), discriminability ( p = 0.03) and misclassifications ( p = 0.04) of fearful facial expression, independently from subjective states of mood and anxiety, and C-reactive protein levels. Otherwise, atorvastatin did not significantly affect any other psychological and behavioural measure, nor peripheral C-reactive protein. Conclusions: Our results reveal for the first time the early influence of atorvastatin on emotional cognition by increasing the processing of anxiety-related stimuli (i.e. increased recognition, discriminability and misclassifications of fearful facial expression) in healthy volunteers, in the absence of more general effects on negative affective bias. Further studies exploring the effects of statins in depressed patients, especially with raised inflammatory markers, may clarify this finding and inform future clinical trials.

PURPOSE: The 2018 International Federation of Gynecology and Obstetrics (FIGO) update on cervical cancer staging eliminated horizontal tumor extent (HZTE) as a staging parameter in stage IA (microscopic) disease. We aimed to determine whether HZTE correlates with outcomes in early stage ECAs and FIGO should reinstate HZTE as a staging parameter in futures updates. METHODS: We retrospectively analyzed 416 FIGO 2009 stage I ECAs from 17 institutions and re-assigned stage using FIGO 2018. Correlation between HZTE, overall (OS) and recurrence free survival (RFS) was performed using univariable and multivariable analyses. RESULTS: Re-staging 416 cases resulted in 126 (30.3%) IA and 290 (69.7%) IB cases; 85 (67.5%) IA tumors had HZTE ≤7mm, while 41 (32.5%) were >7mm; 32 (11%) IB tumors had HZTE ≤7mm, while 258 (89%) were >7mm (p=0.0001). Four (3.2%) IA (1 IA1, 3 IA2) patients developed recurrence (3 ≤7mm, 1 >7mm) compared to 41 (14.1%) IB patients (p=0.002). Fourteen IB and no IA patients died of disease (8 IB1, 1 ≤7mm). Cox univariate analysis demonstrated that only RFS is significantly influenced by HZTE (p=0.01), while OS and RFS were not influenced by HZTE on multivariate analysis. CONCLUSION: HZTE has limited prognostic value in early stage ECAs and is only associated with RFS on univariate but not multivariate analysis. HZTE does not improve prognostication of patients with stage I ECAs as per 2018 FIGO staging. Consequently, the rationale to remove this variable from FIGO staging is justified for ECAs.

1998. július 17-e a nemzetközi igazszolgáltatási struktúra egyik legfontosabb mérföldköve: ezen a napon született meg a Római Statútum (a továbbiakban: Statútum), amelyet a kodifikálásban résztvevő 148 államból 120 támogatott. A Statútum 86. cikke expressis verbis rögzíti, hogy „a Részes Államok [ … kötelesek] teljes mértékben együttműködni a Bírósággal a Bíróság joghatóságába tartozó bűntettek miatti nyomozás és büntetőeljárás során.” Mint minden nemzetközi szerződés, úgy a Statútum esetében is érvényesül a pacta sunt servanda elve, amelyről explicit formában a szerződések jogáról szóló 1969. évi Bécsi Egyezmény (a továbbiakban: Bécsi Egyezmény) 26. cikke rendelkezik, rögzítve, hogy „minden hatályos szerződés kötelezi a részes feleket [amelyet] jóhiszeműen kell végrehajtaniuk.” Ahogy arra az Állandó Nemzetközi Bíróság is rávilágított, egy érvényes és hatályos nemzetközi kötelezettség esetében az érintett állam köteles megtenni minden olyan belső jogi intézkedést, amely annak végrehajtásához szükséges. Miért is fontos mindez? Magyarország ugyan ratifikálta a Statútumot, azonban azt a mai napi napig nem hirdette ki, amely azért tekinthető jelentős mulasztásnak, mert ha a Bíróság együttműködésre hívná fel hazánkat – például egy elfogatási parancs kibocsátása útján – és azt a belső jogi mulasztásunk miatt nem tudnánk teljesíteni, úgy a 86. cikkben rögzített együttműködési kötelezettség megsértése megalapozhatja Magyarország nemzetközi jogi felelősségét. Jelen írás keretében annak a kérdésnek a megválaszolását kísérlem meg, hogy vajon milyen okok vezethettek idáig, és milyen megoldási lehetőségek állnak rendelkezésre.

This research examines the extent to which a Farm-to-Table restaurant prompted social and ecological changes in the food system. Chefs and restaurants are uniquely positioned to both generate consumer interest in certain foods and motivate farmers to grow such products. Despite their central role in Alternative Food Networks (AFNs), the influence of restaurants on farming practices and the re-localization of food sourcing is under-explored. In this research, we used archival document review, interviews, surveys, and social network mapping to understand the mechanisms by which direct market connections between farmers and the Chez Panisse restaurant grew over time and influenced farmers’ growing practices. Founded in Berkeley by Alice Waters in 1971, Chez Panisse is frequently credited with pioneering the Farm-to-Table model and spurring the slow, local, and organic food movements. Our study suggests that Chez Panisse inspired farmers toward more sustainable agriculture practices, but the restaurant was not the only influential actor in the network. We found that local food hub managers and the restaurant’s “foragers” were key intermediaries. Our findings demonstrate that social embeddedness in AFNs is pertinent to fostering sustainable agriculture, the long-term survival of network actors, and network growth. Acronyms: AFN: Alternative Food Network; DTC: Direct-to-consumer; CSA: Community-Supported Agriculture.

Interpersonal interactions rely on various communication channels, both verbal and non-verbal, through which information regarding one’s intentions and emotions are perceived. Here, we investigated the neural correlates underlying the visual processing of hand postures conveying social affordances (i.e., hand-shaking), compared to control stimuli such as hands performing non-social actions (i.e., grasping) or showing no movement at all. Combining univariate and multivariate analysis on electroencephalography (EEG) data, our results indicate that occipito-temporal electrodes show early differential processing of stimuli conveying social information compared to non-social ones. First, the amplitude of the Early Posterior Negativity (EPN, an Event-Related Potential related to the perception of body parts) is modulated differently during the perception of social and non-social content carried by hands. Moreover, our multivariate classification analysis (MultiVariate Pattern Analysis - MVPA) expanded the univariate results by revealing early (

Acinetobacter baumannii is an insidious emerging nosocomial pathogen that has developed resistance to all available antimicrobials, including the last resort antibiotic, colistin. Colistin resistance often occurs due to mutations in the PmrAB two-component regulatory system. To better understand the regulatory mechanisms contributing to colistin resistance, we have biochemically characterized the A. baumannii PmrA response regulator. Initial DNA-binding analysis shows that A. baumannii PmrA bound to the Klebsiella pneumoniae PmrA box motif. This prompted analysis of the putative A. baumannii PmrAB regulon that indicated that the A. baumannii PmrA consensus box is 5′-HTTAAD N5 HTTAAD. Additionally, we provide the first structural information for the A. baumannii PmrA N-terminal domain through X-ray crystallography and we present a full-length model using molecular modelling. From these studies, we were able to infer the effects of two critical PmrA mutations, PmrA::I13M and PmrA::P102R, both of which confer increased colistin resistance. Based on these data, we suggest structural and dynamic reasons for how these mutations can affect PmrA function and hence encourage resistive traits. Understanding these mechanisms will aid in the development of new targeted antimicrobial therapies.

Relato de caso de una paciente con endocarditis de etiología bacteriana por el agente Staphylococcus Aureus en válvula aortica calcificada. Se describe el cuadro clínico de la paciente, los exámenes realizados con los respectivos resultados, métodos terapéuticos y el desfecho del caso. Además, se discuten los hallazgos semiológicos encontrados en el examen físico. Introducción El presente trabajo desarrolla los puntos fundamentales sobre la infección del endocardio producidas por bacterias, enfocando en la amplia agresividad de los Staphylococcus aureus, “La bacteriemia por Staphylococcus aureus meticilina resistente es un problema especialmente importante por la elevada mortalidad que condiciona.” (GUDIOL, F, 2009) Es una enfermedad infecciosa que afecta el endocardio y las válvulas cardíacas (1) capaz de provocar un alto riesgo para la vida, por lo cual el pronóstico depende de muchos factores como la virulencia y el estado del paciente. Las manifestaciones clínicas son la fiebre, el soplo cardíaco que ocurre en 90% de las endocarditis infecciosas izquierdas, astenia, pérdida de peso y alteraciones cutáneos que se describen a continuación (1)(2). La Endocarditis es de difícil diagnóstico, el tratamiento adecuado resulta ser indispensable para prevenir posibles complicaciones. Los Staphylococcus aureus son cocos grampositivos, catalasa-positivos dispuestos en racimos. Los factores de virulencia incluyen componentes estructurales que facilitan la adherencia a los tejidos del hospedador o evitan la fagocitosis, y una variedad de toxinas o de enzimas hidrolíticas. (3) Los factores de riesgo a una infección por Staphylococcus aureus comprenden la presencia de un cuerpo extraño, un procedimiento quirúrgico previo y el empleo de antibióticos que suprimen la flora microbiana normal. (3) Cerca de 90% de los Staphylococcus aureus presentan resistencia a la penicilina G y casi la mitad es resistente a meticilina. (4) Informe de caso Paciente femenina de 32 años acude al consultorio por fiebre de 39º C e inapetencia de tres días de evolución. A la exploración física se encontraba en estado general regular, eupneica, lívida, temperatura de 39º C, Fc 93 Lpm, PA 120/60 mm/Hg. En el examen físico cardiaco la auscultación mostró ritmo cardíaco regular, soplo sistólico 3 + / 6 +(Levine,1933) (5) en el área aórtica, irradiado al borde esternal izquierdo y foco mitral, con soplo diastólico 3 + / 6 + en el área aórtica. En la evaluación de la mucosa oral se constató mal estado de higiene y salud. Presentaba nódulo de Osler (nódulo eritematoso doloroso) en punta de los dedos, lesiones de Janeway (pápulas eritematosas no dolorosas) en planta de las manos y petequias rojo-violáceas en cara y esclera. Paciente reveló antecedentes de fiebre reumática a los 5 años. En el laboratorio: Hemoglobina 10,4g/dl Hematocrito 30,7% Leucocitos 7800 El ecocardiograma mostró válvula aórtica trivalvar calcificada con doble disfunción e imagen a nivel del anillo valvular que se proyectaba hacia el seno coronario con un aspecto rugoso compatible con vegetación crónica. A los 2 días de ingreso se inició tratamiento con penicilina cristalina y gentamicina, hubo una mejoría del estado general, pero con persistencia de la fiebre. Cinco días después se identificó el crecimiento de Staphylococcus aureus en los pares de hemocultivos recogidos. Se cambió el tratamiento a oxacilina + gentamicina (4) con resultado exitoso. Conclusión Según los criterios de Duke (Criterios diagnósticos para la endocarditis infecciosa) (2) la paciente presentaba al inicio: Un criterio mayor, evidencia de afectación endocárdica en ecocardiograma y cuatro criterios menores: fiebre de 39°C, nódulos Osler, lesiones de Janeway y evidencias serológicas de infección, resultante de los hemocultivos. Se inició tratamiento empírico padrón para endocarditis con penicilina cristalina asociada a gentamicina. Tras la información del agente causal anteriormente citado, conocidos por tener cepas resistentes a la meticilina (4), el tratamiento fue modificado para mejor atender la necesidad de la paciente y garantizar la total supresión del microbio con oxacilina asociada a gentamicina que presentan mejor respuesta antimicrobiana específica a este agente. El tratamiento logró buenos resultados devolviendo a la paciente su estado de bienestar físico y el regreso a su vida cotidiana. Es necesario evitar factores de riesgo como mala higiene bucal, monitorear pacientes que tuvieran fiebre reumática y uso adecuado de antibioticoterapia para evitar cepas resistentes.

ObjectivesTo estimate the protection against laboratory-confirmed SARS-CoV-2 infection, hospitalisations, and death after homologous or heterologous third-dose (booster) in individuals with primary vaccination schemes with rAd26-rAd5, ChAdOx1nCoV-19, BBIBP-CorV or heterologous combinations, during the period of Omicron BA.1 predominance.DesignRetrospective, test-negative, case-control study, with matched analysis.SettingProvince of Buenos Aires, Argentina, between 12/1/21-4/1/21.Participants422,144 individuals ≥50 years who had received two or three doses of COVID-19 vaccines and were tested for SARS-CoV-2.Main outcome measures: Odds ratios of confirmed SARS-CoV-2 infection, hospitalisations and death after administering different boosters, compared to a two-dose primary scheme.ResultsOf 221,933(52.5%) individuals with a positive test, 190,884(45.2%) had received a two-dose vaccination scheme and 231,260(54.8%) a three-dose scheme. The matched analysis included 127,014 cases and 180,714 controls.The three-dose scheme reduced infections (OR 0.81[0.80-0.83]) but after 60 days protection dropped (OR 1.04[1.01-1.06]). The booster dose decreased the risk of hospitalisations and deaths after 15-59 days (ORs 0.28[0.25-0.32] and 0.25[0.22-0.28] respectively), which persisted after administration for 75[66-89] days.Administration of a homologous booster after a primary scheme with vectored-vaccines provided low protection against infections (OR 0.94[0.92-0.97] and 1.05[1.01-1.09] before and after 60 days). Protection against hospitalisations and death was significant (OR 0.30[0.26-0.35] and 0.29[0.25-0.33] respectively) but decreased after 60 days (OR 0.59[0.47-0.74] and 0.51[0.41- 0.64] respectively).The inoculation of a heterologous booster after a primary course with ChAdOx1 nCoV-19, rAd26-rAd5, BBIBP-CorV, or heterologous schemes, offered some protection against infection (OR 0.70[0.68-0.71]), which decreased after 60 days (OR 1.01[0.98-1.04]). The protective effect against hospitalisations and deaths (OR 0.26[0.22-0.31] and 0.22[0.18-0.25] respectively) was clear and persisted after 60 days (OR 0.43[0.35-0.53] and 0.33[0.26-0.41]).ConclusionsThis study shows that, during Omicron predominance, heterologous boosters provide an enhanced protection and longer effect duration against COVID-19-related hospitalisations and death in individuals older than 50, compared to homologous boosters.

The water balance in high-alpine glacierized regions is greatly affected by low temperatures and high precipitation. While snow accumulates during winter, maximum runoff driven by snowmelt is observed during spring or summer. Since glaciers act as huge water reservoirs, they might alter the hydrological response of the catchment across time scales, thus affecting the regional water supply or hydropower generation at the regional scale.The Water Flow and Balance Simulation Model (WaSiM) is a deterministic, process-based hydrological model that allows to describe the hydrological response of a catchment including the variability of glacier areas. In this context, an empirical volume-area scaling approach can be internally implemented to describe the glacier’s evolution. Although acceptable estimates can be obtained with this integrated approach, a representation of the explicit ice thickness is still missing. For this reason, a coupling scheme between WaSiM and a more sophisticated glacier model that accounts for glacier geometry including explicit ice dynamics is developed. More specifically, the Open Global Glacier Model (OGGM), which is an open source modelling framework able to simulate almost any glacier in the world, is used.The coupling strategy consists mainly on three steps: i) a static model run of WaSiM (daily resolution) to obtain monthly values of temperature and precipitation that serve as input for the ii) second step, which is running OGGM. Finally, iii) a dynamic model run of WaSiM with the updated output from OGGM (i.e. annual glacier mass-balances) is performed. In this last step, the hydrological response of the catchment can be evaluated (for example, through total runoff). The coupled model is calibrated during the 3rd step, thus only WaSiM parameters are adjusted. In this way, no additional expertise on glacier modelling is required from the user, since OGGM is set up according to its default parameters. Finally, this coupling scheme could serve as a tool to predict the hydrological response of any glacierized catchment under different climate projections in the future.

El cancer de mama en Venezuela representa la primera causa de muerte oncologica en la poblacion femenina. Se han reportado muchos factores de riesgo que favorecen su aparicion; sin embargo, en las ultimas decadas el virus del papiloma humano (VPH) y el virus de Epstein-Barr (VEB) se han asociado como posibles factores de riesgo en el desarrollo de esta malignidad. Objetivo: Detectar la presencia de VPH y VEB en biopsias de cancer de mama, para establecer una posible relacion entre la infeccion por estos agentes virales y el desarrollo de esta patologia. Metodos: Se recolectaron biopsias frescas de pacientes con cancer de mama y de pacientes con patologia benigna de la mama, que asistieron a cirugia en el Hospital Universitario de Caracas. Se realizaron la deteccion y la tipificacion de VPH mediante el estuche comercial INNOLIPA® HPV Genotyping Extra (Innogenetics), y se detecto el genoma del VEB mediante el estuche comercial Epstein-Barr virus BMLF1 (Maxim Biotech, Inc.). Resultados: El 63,6 y el 13,6% de los casos de cancer de mama fueron positivos para ADN de VPH y VEB, respectivamente, mientras que las muestras de patologia benigna presentaron un 4,5% de positividad para cada uno de los virus. El 42,9% de las muestras de cancer de mama presento infeccion mixta con genotipos de alto y bajo riesgo oncogenico de VPH. Conclusion: Podemos sugerir que el VPH y el VEB representan importantes factores de riesgo para el cancer de mama, pero son necesarios estudios que permitan dilucidar mejor el papel de estos virus en el desarrollo de la enfermedad

The present study is based upon previous works on mental imagery and the binocular rivalry protocol. The first aim of this research is to investigate whether the differences between people with typical and atypical mental imagery (aphantasia) can also be found when the reactivation of mental images is involuntary as compared to the classic effects of voluntary mental imagery on perceptual priming. The second aim of this study to adapt and validate this protocol for large-scale studies online - providing an accessible tool for the assessment of visual aphantasia. Note. Pilot experiments will be run before the final study.

Although 2014 World Health Organization criteria require unequivocal glandular and squamous differentiation for a diagnosis of cervical adenosquamous carcinoma, in practice, adenosquamous carcinoma diagnoses are often made in tumors that lack unequivocal squamous and/or glandular differentiation. Considering the ambiguous etiologic, morphological, and clinical features and outcomes associated with adenosquamous carcinomas, we sought to redefine these tumors. We reviewed slides from 59 initially diagnosed adenosquamous carcinomas (including glassy cell carcinoma and related lesions) to confirm an adenosquamous carcinoma diagnosis only in the presence of unequivocal malignant glandular and squamous differentiation. Select cases underwent immunohistochemical profiling as well as human papillomavirus (HPV) testing by in situ hybridization. Of the 59 cases originally classified as adenosquamous carcinomas, 34 retained their adenosquamous carcinoma diagnosis, 9 were reclassified as pure invasive stratified mucin-producing carcinomas, 10 as invasive stratified mucin-producing carcinomas with other components (such as HPV-associated mucinous, usual-type, or adenosquamous carcinomas), and 4 as HPV-associated usual or mucinous adenocarcinomas with benign-appearing squamous metaplasia. Two glassy cell carcinomas were reclassified as poorly differentiated usual-type carcinomas based on morphology and immunophenotype. There were significant immunophenotypic differences between adenosquamous carcinomas and pure invasive stratified mucin-producing carcinomas with regard to HPV (p 0.0001), PAX8 (p = 0.038; more in adenosquamous carcinoma), p40 (p 0.0001; more in adenosquamous carcinoma), p63 (p = 0.0018; more in adenosquamous carcinoma) and MUC6 (p 0.0001; less in adenosquamous carcinoma), HNF-1beta (p = 0.0023), vimentin (p = 0.0003), p53 (p = 0.0004), and CK7 (p = 0.0002) expression. Survival outcomes were similar between all groups. Adenosquamous carcinomas should be diagnosed only in the presence of unequivocal malignant glandular and squamous differentiation. The two putative glassy cell carcinomas studied did not meet our criteria for adenosquamous carcinoma, and categorizing them as such should be reconsidered.

A fundamental issue in biology is the nature of evolutionary transitions from unicellular to multicellular organisms. Volvocine algae are models for this transition, as they span from the unicellular biflagellateChlamydomonasto multicellular species ofVolvoxwith up to 50,000Chlamydomonas-like cells on the surface of a spherical extracellular matrix. The mechanism of phototaxis in these species is of particular interest since they lack a nervous system and intercellular connections; steering is a consequence of the response of individual cells to light. Studies ofVolvoxandGonium, a 16-cell organism with a plate-like structure, have shown that the flagellar response to changing illumination of the cellular photosensor is adaptive, with a recovery time tuned to the rotation period of the colony around its primary axis. Here, combining high-resolution studies of the flagellar photoresponse with 3D tracking of freely-swimming cells, we show that such tuning also underlies phototaxis ofChlamydomonas. A mathematical model is developed based on the rotations around an axis perpendicular to the flagellar beat plane that occur through the adaptive response to oscillating light levels as the organism spins. Exploiting a separation of time scales between the flagellar photoresponse and phototurning, we develop an equation of motion that accurately describes the observed photoalignment. In showing that the adaptive time scale is tuned to the organisms’ rotational period across three orders of magnitude in cell number, our results suggest a unified picture of phototaxis in green algae in which the asymmetry in torques that produce phototurns arise from the individual flagella ofChlamydomonas, the flagellated edges ofGoniumand the flagellated hemispheres ofVolvox.

Background: It is unclear how multiple sclerosis (MS) affects the severity of Covid-19. Methods: Hospitalization, Intensive Care Unit (ICU) admission and death after Covid-19 diagnosis of 1362 MS patients were compared to the age and sex-matched Italian population in a retrospective observational case-cohort study with population-based control. The observed vs the expected events were compared in the whole MS cohort and in different subgroups (higher-risk: EDSS>3 or at least one comorbidity, lower-risk: EDSS

This paper investigates the case of a hybrid organization located in Northern Italy with the aim of providing an understanding of the role of the context, defined in terms of ‘place’ and ‘time’, in shaping organizational changes. A dynamic institutional approach focused on both ‘place’ and ‘time’ as key explanatory factors can provide a valuable framework to understand both the changing institutional demands on the firm and the rationalities behind the changes that occur at organizational, strategic and governance level. Consequently, this paper aims to contribute to the institutional logics literature by describing how these two contextual elements can be used to interpret institutional logic pressures on the organization under investigation as well as govern changes at micro level. The results indicate that the changes were produced by dynamics that are exogenous and endogenous to the organization in the case study and strongly influenced by the context in which it operates. The paper also highlights how changes in terms of service provision, accountability and organizational setting are the results of the ‘place’ and ‘time’ in which these events occur.

The collapse of a catenoidal soap film when the rings supporting it are moved beyond a critical separation is a classic problem in interface motion in which there is a balance between surface tension and the inertia of the surrounding air, with film viscosity playing only a minor role. Recently [Goldstein, et al., Phys. Rev. E 104, 035105 (2021)], we introduced a variant of this problem in which the catenoid is bisected by a glass plate located in a plane of symmetry perpendicular to the rings, producing two identical hemicatenoids, each with a surface Plateau border (SPB) on the glass plate. Beyond the critical ring separation, the hemicatenoids collapse in a manner qualitatively similar to the bulk problem, but their motion is governed by the frictional forces arising from viscous dissipation in the SPBs. Here we present numerical studies of a model that includes classical friction laws for SPB motion on wet surfaces and show consistency with our experimental measurements of the temporal evolution of this process. This study can help explain the fragmentation of bubbles inside very confined geometries such as porous materials or microfluidic devices., 9 pages, 9 figures, supplementary videos available at website of REG

In 1990s, the European spiny lobster

ContextThe COVID-19 pandemic caused significant shocks to U.S. food systems at multiple scales. While disturbances to long-distance supply chains received substantial attention in national media, local supply chains experienced mixed impacts. As broad closures of schools, restaurants, and other businesses sourcing from local farmers removed key marketing channels for many direct market farmers, consumer interest in Community Supported Agriculture (CSA), farmers markets, and on-farm and online direct farm sales increased.ObjectiveIn this paper, we examine the resilience and vulnerability of farmers during the March 2020 through December 2020 period of the COVID-19 pandemic. We focus on California farmers and ranchers engaged in direct market sales.MethodsThrough a widely disseminated survey, we collected responses from 364 farmers and used these data to answer the following questions about direct market farmers in California: 1) What were direct market farmers' experiences of the pandemic from March 2020 through December 2020? 2) Which factors (e.g., relationships, institutions, market channels) did farmers report enhanced their resilience during the pandemic? 3) Which individual and operational factors were significantly associated with resilience during the pandemic? And finally, 4) how do the farmer-reported factors compare to the statistically significant factors associated with resilience? We created three dependent variables-ability to respond to the pandemic, concern about pandemic impacts, and change in profitability-to operationalize several aspects of resilience and examine their association with individual and operational characteristics through a series of ordered logistic regression models.Results and conclusionsAcross both the quantitative models and the farmer reported factors, we found that farmers who increased their use of online sales and marketing during the first year of the pandemic, had larger-scale farms, and had more on-farm crop and livestock diversity were more resilient to the shocks of the pandemic. We also found that greater use of non-direct-to-consumer market channels was associated with less resilience. The characteristics of the farming operations played a relatively larger role in predicting resilience compared to the individual characteristics of the farmers surveyed.SignificanceThis study gives a detailed picture of how California direct market farmers fared during the pandemic and the characteristics associated with greater resilience. As short and long-term disruptions become increasingly common in agriculture, policies and programs can leverage support to direct market farmers, particularly direct-to-consumer farmers, as a strategy to strengthen farmer resilience.

Background: Patients with idiopathic pulmonary fibrosis (IPF) treated with PRM-151, a recombinant human pentraxin 2 protein, in a phase 2 double-blind, randomised controlled trial had significantly reduced decline in percentage of predicted forced vital capacity (FVC) and stabilised 6-min walking distance compared with placebo over a 28-week period. Here we report the 76-week results of an open-label extension study. Methods: Patients who completed the 28-week double-blind period of the PRM-151-202 trial were eligible to participate in the open-label extension study. Patients previously enrolled in the PRM-151 group continued this treatment and those previously in the placebo group crossed over to PRM-151. All patients received PRM-151 in 28-week cycles with loading doses of 10 mg/kg by 60 min intravenous infusions on days 1, 3, and 5 in the first week of each cycle followed by one infusion of 10 mg/kg every 4 weeks. The primary objective of the open-label extension study was to assess the long-term safety and tolerability of PRM-151, which were assessed by analysing adverse events (AEs) up to week 76 in all patients who received at least one dose of PRM-151 during the open-label extension study. Exploratory efficacy analyses were done by assessing changes from baseline in percentage of predicted FVC and 6-min walking distance, with descriptive statistics to week 76 and with random-intercept mixed models to week 52. This study is registered with ClinicalTrials.gov, number NCT02550873, and with EudraCT, number 2014-004782-24. Findings: Of 116 patients who completed the double-blind treatment period, 111 entered the open-label extension study (74 from the PRM-151 group and 37 from the placebo group). 84 (76%) of 111 patients received concomitant IPF therapy (pirfenidone n=55 or nintedanib n=29). AEs were consistent with long-term IPF sequelae. 31 (28%) patients had serious AEs. Those occurring in two or more patients were pneumonia (six [5%] of 111), IPF exacerbation (four [4%]), IPF progression (four [4%]), and chest pain (two [2%]). 21 (19%) patients had severe AEs, of which IPF exacerbation and IPF progression each occurred in two (2%) patients. Two (2%) patients experienced life-threatening AEs (one had pneumonia and one had small-cell lung cancer extensive stage). A persistent treatment effect was observed for PRM-151 in patients who continued treatment, with a decline in percentage of predicted FVC of −3·6% per year and in 6-min walking distance of −10·5 m per year at week 52. In patients who started PRM-151 during the open-label extension study, compared with the slopes for placebo, decline reduced for percentage of predicted FVC (from −8·7% per year in weeks 0–28 to −0·9% per year in weeks 28–52, p

The most recent British Thoracic Society/Intensive Care Society (BTS/ICS) guidelines on the use of noninvasive ventilation (NIV) in acute hypercapnic respiratory failure (AHRF) suggest to maximize NIV use in the first 24 hours and to perform a slow tapering. However, a limited number of studies evaluated the phase of NIV weaning. The aim of this study is to describe the NIV weaning protocol used in AHRF due to acute exacerbation of chronic obstructive pulmonary disease (AE-COPD), patients’ characteristics, clinical course, and outcomes in a real-life intermediate respiratory care unit (IRCU) setting. We performed a retrospective study on adult patients hospitalized at the IRCU of San Gerardo Hospital, Monza, Italy, from January 2015 to April 2017 with a diagnosis of AHRF due to COPD exacerbation. The NIV weaning protocol used in our institution consists of the interruption of one of the three daily NIV sessions at the time, starting from the morning session and finishing with the night session. The 51 patients who started weaning were divided into three groups: 20 (39%) patients (median age 80 yrs, 65% males) who completed the protocol and were discharged home without NIV (Completed Group), 20 (39%) did not complete it because they were adapted to domiciliary ventilation (Chronic NIV Group), and 11 (22%) interrupted weaning ex abrupto mainly due to NIV intolerance (Failed Group). Completed Group patients were older, had a higher burden of comorbidities, but a lower severity of COPD compared to Chronic NIV Group. Failed Group patients experienced higher frequency of delirium after NIV discontinuation. None of the patients who completed weaning had AHRF relapse during hospitalization. While other NIV weaning methods have been previously described, our study is the first to describe a protocol that implies the interruption of a ventilation session at the time. The application of a weaning protocol may prevent AHRF relapse in the early stages of NIV interruption and in elderly frail patients.