Προοπτική, πολυκεντρική μελέτη καταγραφής επίπτωσης συστηματικών μυκητιάσεων σε νοσηλευόμενους ενήλικους ασθενείς με αιματολογικές κακοήθειες και/ή μεταμόσχευση μυελού των οστών: το φορτίο σιδήρου ως παράγων κινδύνου

Οι διηθητικές μυκητιακές λοιμώξεις αποτελούν κύρια αιτία θνητότητας και θνησιμότητας για τους ασθενείς με αιματολογικές κακοήθειες. Ο σίδηρος διαδραματίζει σημαντικό ρόλο στην παθογένεση των λοιμώξεων, συμπεριλαμβανομένων και των διηθητικών μυκητιάσεων. Έρευνες έχουν δείξει ότι η υπερφόρτωση του οργανισμού με σίδηρο είναι πιθανό να αποτελεί έναν ακόμη παράγοντα κινδύνου για την ανάπτυξη διηθητικών μυκητιακών λοιμώξεων. Διεξήγαμε μια προοπτική, πολυκεντρική μελέτη σε ασθενείς με νεοδιάγνωση οξείας μυελογενούς λευχαιμίας ή μυελοδυσπλαστικού συνδρόμου σε εκτροπή, για να αποσαφηνίσουμε εάν η αυξημένη συγκέντρωση σιδήρου στις αποθήκες σιδήρου του μυελού των οστών και τα αυξημένα επίπεδα σιδήρου ορού και φερριτίνης είναι ανεξάρτητοι παράγοντες κινδύνου για την ανάπτυξη διηθητικών μυκητιακών λοιμώξεων. Συνολικά, 98 ασθενείς καταγράφηκαν (76 με οξεία μυελογενή λευχαιμία) και παρακολουθήθηκαν για ένα έτος μετά τη διάγνωσή τους. 22 ασθενείς διεγνώσθησαν με διηθητική μυκητίαση κατά το διάστημα παρακολούθησης (διηθητική ασπεργίλλωση n=16, καντινταιμία n=5, μουκορμύκωση n=1). Αυξημένος σίδηρο στις αποθήκες σιδήρου του μυελού των οστών εντοπίστηκε σε 39 ασθενείς (31/76 ασθενείς χωρίς διηθητική μυκητίαση και 7/22 ασθενείς με διηθητική μυκητίαση). Η μονοπαραγοντική ανάλυση έδειξε ότι μόνο η διάγνωση της οξείας μυελογενούς λευχαιμίας αυτή καθ’ αυτή αποτελεί ανεξάρτητο παράγοντα για την ανάπτυξη διηθητικής μυκητιακής λοίμωξης [OR (95% CI) 7.40 (1.05 – 325.42)]. Στη μονοπαραγοντική και στην πολυπαραγοντική ανάλυση, το αυξημένο BMIS score (≥3) στη διάγνωση δε φάνηκε να αποτελεί ανεξάρτητο παράγοντα κινδύνου. Ομοίως, ο σίδηρος και η φερριτίνη ορού δε διέφεραν στις δύο ομάδες που είχαν παρόμοια δημογραφικά χαρακτηριστικά. Στην κοορτή μας που αποτελείται από Έλληνες ασθενείς με πρωτοδιάγνωση οξείας μυελογενούς λευχαιμίας ή μυελοδυσπλαστικό σύνδρομο σε εκτροπή, οι δείκτες υπερφόρτωσης του οργανισμού με σίδηρο δεν αποτελούν ανεξάρτητο παράγοντα κινδύνου για διηθητικές μυκητιάσεις.Iron plays an important role in the pathogenesis of infections, including invasive fungal infections (IFIs). Studies suggested that iron overload might represent an additional risk factor for IFIs among patients with hematological malignancies. We conducted a prospective, multi-center study amongst adult patients with newly diagnosed acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) in transformation, to determine whether baseline iron overload as measured using the bone marrow iron stores (BMIS) score is an independent risk factor for the development of IFIs. We also measured baseline serum iron and ferritin levels. A total of 98 patients were enrolled (76 with AML) and were followed for 12 months. Twenty-two patients developed IFI during the follow up period (invasive aspergillosis n=16, candidemia n=5, mucormycosis n=1). A baseline BMIS score ≥3, indicating iron overload was relatively common (38/98 patients, 38%) and its frequency was comparable between patients with no IFIs (31/76, 40.7%) and in those with IFIs (8/22, 36.4%). Univariate analysis showed that only the presence of AML was associated with increased risk for IFIs [OR (95% CI) 7.40 (1.05 – 325.42)]. Both univariate and multivariate analyses showed that an increased BMIS score (≥3) at baseline was not an independent risk factor for IFIs. Similarly, there was no difference in serum iron and ferritin between the two groups that had similar demographic characteristics. Indices of iron overload were not independent risk factors for IFIs in our cohort of Greek patients with newly diagnosed AML/MDS in transformation

Γεωπολιτική ανάλυση της διαστημικής πολιτικής της Τουρκίας με χρήση της Συστημικής Γεωπολιτικής Ανάλυσης

Η διαστημική πολιτική αποτελεί στο νέο γεωπολιτικό τοπίο της ταχείας τεχνολογικής εξέλιξης θεμελιώδη παράμετρο γεωπολιτικού ενδιαφέροντος, καθώς σχετίζεται με πολλαπλούς τομείς ενδιαφερόντων των κρατικών και μη κρατικών δρώντων στο διεθνές σύστημα. Η διαστημική πολιτική συναρτάται με την προβολή ισχύος των κρατικών δρώντων στο διεθνές σύστημα και ειδικότερα με επιμέρους παραμέτρους αυτής, όπως τις στρατιωτικές εφαρμογές, την οικονομική διάσταση, την επιστημονική διάσταση και την εικόνα κύρους στο εσωτερικό και εξωτερικό. Ειδικώς η στρατιωτική παράμετρος των εφαρμογών της διαστημικής τεχνολογίας, η οποία συναρτάται με τον Πυλώνα Άμυνα/Ασφάλεια, αποτελεί ζήτημα μεγάλου ενδιαφέροντος για την γεωπολιτική ανάλυση.In the new geopolitical landscape of rapid technological development, space policy is a fundamental parameter of geopolitical interest, as it is related to multiple areas of interest of state and non-state actors in the international system. Space policy is related to the power projection of state actors in the international system and in particular to its individual parameters, such as military applications, the economic dimension, the scientific dimension and the image of prestige at home and abroad

On the separability of the restriction functor

Let G be a group, Λ = L σ∈G Λσ a strongly graded ring by G, H a subgroup of G and ΛH = L σ∈H Λσ. We give a necessary and sufficient condition for the ring Λ/ΛH to be separable, generalizing the corresponding result for the ring extension Λ/Λ1. As a consequence of this result we give a condition for Λ to be a hereditary order in case Λ is a strongly graded by finite group R-order in a separable K-algebra, for R a Dedekind domain with quotient field K

On strongly graded Gorestein orders

Let G be a finite group and let Λ = ⊕g∈GΛg be a strongly G-graded R-algebra, where R is a commutative ring with unity. We prove that if R is a Dedekind domain with quotient field K, Λ is an R-order in a separable K-algebra such that the algebra Λ1 is a Gorenstein R-order, then Λ is also a Gorenstein R-order. Moreover, we prove that the induction functor ind : ModΛH → ModΛ defined in Section 3, for a subgroup H of G, commutes with the standard duality functor

Long‐term validation of virtual sensing of a railway bridge with ballasted superstructure

Railway bridges have a long lifespan, which is challenged by the constant development of vehicles leading to increased loads that they were not originally designed for. To ensure the longest possible use of existing structures, a sensor‐based structural health monitoring system can make a significant contribution. However, due to economic reasons and the inaccessibility of many points of interest, sensors cannot be installed everywhere. Therefore, in most cases, only a few sensors are available at a few points of interest, and methods that aim to reconstruct structural responses at unmeasured points from these measurements are referred to as virtual sensing. In this paper, we have analyzed 19,075 passages recorded on a steel trough bridge with a ballast superstructure and a span of 16.4 m, together with weather data. Our findings show that the influence of train type and speed has a significantly higher impact on the results than environmental factors. The investigation revealed that the model‐based analysis produced similar results to the data‐driven analysis concerning acceleration signals. However, when analyzing strain signals, the two approaches yielded distinctly different results

Impact of primary kidney disease on the effects of empagliflozin in patients with chronic kidney disease: secondary analyses of the EMPA-KIDNEY trial

BACKGROUND: The EMPA-KIDNEY trial showed that empagliflozin reduced the risk of the primary composite outcome of kidney disease progression or cardiovascular death in patients with chronic kidney disease mainly through slowing progression. We aimed to assess how effects of empagliflozin might differ by primary kidney disease across its broad population. METHODS: EMPA-KIDNEY, a randomised, controlled, phase 3 trial, was conducted at 241 centres in eight countries (Canada, China, Germany, Italy, Japan, Malaysia, the UK, and the USA). Patients were eligible if their estimated glomerular filtration rate (eGFR) was 20 to less than 45 mL/min per 1·73 m2, or 45 to less than 90 mL/min per 1·73 m2 with a urinary albumin-to-creatinine ratio (uACR) of 200 mg/g or higher at screening. They were randomly assigned (1:1) to 10 mg oral empagliflozin once daily or matching placebo. Effects on kidney disease progression (defined as a sustained ≥40% eGFR decline from randomisation, end-stage kidney disease, a sustained eGFR below 10 mL/min per 1·73 m2, or death from kidney failure) were assessed using prespecified Cox models, and eGFR slope analyses used shared parameter models. Subgroup comparisons were performed by including relevant interaction terms in models. EMPA-KIDNEY is registered with ClinicalTrials.gov, NCT03594110. FINDINGS: Between May 15, 2019, and April 16, 2021, 6609 participants were randomly assigned and followed up for a median of 2·0 years (IQR 1·5–2·4). Prespecified subgroupings by primary kidney disease included 2057 (31·1%) participants with diabetic kidney disease, 1669 (25·3%) with glomerular disease, 1445 (21·9%) with hypertensive or renovascular disease, and 1438 (21·8%) with other or unknown causes. Kidney disease progression occurred in 384 (11·6%) of 3304 patients in the empagliflozin group and 504 (15·2%) of 3305 patients in the placebo group (hazard ratio 0·71 [95% CI 0·62–0·81]), with no evidence that the relative effect size varied significantly by primary kidney disease (pheterogeneity=0·62). The between-group difference in chronic eGFR slopes (ie, from 2 months to final follow-up) was 1·37 mL/min per 1·73 m2 per year (95% CI 1·16–1·59), representing a 50% (42–58) reduction in the rate of chronic eGFR decline. This relative effect of empagliflozin on chronic eGFR slope was similar in analyses by different primary kidney diseases, including in explorations by type of glomerular disease and diabetes (p values for heterogeneity all >0·1). INTERPRETATION: In a broad range of patients with chronic kidney disease at risk of progression, including a wide range of non-diabetic causes of chronic kidney disease, empagliflozin reduced risk of kidney disease progression. Relative effect sizes were broadly similar irrespective of the cause of primary kidney disease, suggesting that SGLT2 inhibitors should be part of a standard of care to minimise risk of kidney failure in chronic kidney disease. FUNDING: Boehringer Ingelheim, Eli Lilly, and UK Medical Research Council

Effects of empagliflozin on progression of chronic kidney disease: a prespecified secondary analysis from the empa-kidney trial

BACKGROUND: Sodium–glucose co-transporter-2 (SGLT2) inhibitors reduce progression of chronic kidney disease and the risk of cardiovascular morbidity and mortality in a wide range of patients. However, their effects on kidney disease progression in some patients with chronic kidney disease are unclear because few clinical kidney outcomes occurred among such patients in the completed trials. In particular, some guidelines stratify their level of recommendation about who should be treated with SGLT2 inhibitors based on diabetes status and albuminuria. We aimed to assess the effects of empagliflozin on progression of chronic kidney disease both overall and among specific types of participants in the EMPA-KIDNEY trial. METHODS: EMPA-KIDNEY, a randomised, controlled, phase 3 trial, was conducted at 241 centres in eight countries (Canada, China, Germany, Italy, Japan, Malaysia, the UK, and the USA), and included individuals aged 18 years or older with an estimated glomerular filtration rate (eGFR) of 20 to less than 45 mL/min per 1·73 m2, or with an eGFR of 45 to less than 90 mL/min per 1·73 m2 with a urinary albumin-to-creatinine ratio (uACR) of 200 mg/g or higher. We explored the effects of 10 mg oral empagliflozin once daily versus placebo on the annualised rate of change in estimated glomerular filtration rate (eGFR slope), a tertiary outcome. We studied the acute slope (from randomisation to 2 months) and chronic slope (from 2 months onwards) separately, using shared parameter models to estimate the latter. Analyses were done in all randomly assigned participants by intention to treat. EMPA-KIDNEY is registered at ClinicalTrials.gov, NCT03594110. FINDINGS: Between May 15, 2019, and April 16, 2021, 6609 participants were randomly assigned and then followed up for a median of 2·0 years (IQR 1·5–2·4). Prespecified subgroups of eGFR included 2282 (34·5%) participants with an eGFR of less than 30 mL/min per 1·73 m2, 2928 (44·3%) with an eGFR of 30 to less than 45 mL/min per 1·73 m2, and 1399 (21·2%) with an eGFR 45 mL/min per 1·73 m2 or higher. Prespecified subgroups of uACR included 1328 (20·1%) with a uACR of less than 30 mg/g, 1864 (28·2%) with a uACR of 30 to 300 mg/g, and 3417 (51·7%) with a uACR of more than 300 mg/g. Overall, allocation to empagliflozin caused an acute 2·12 mL/min per 1·73 m2 (95% CI 1·83–2·41) reduction in eGFR, equivalent to a 6% (5–6) dip in the first 2 months. After this, it halved the chronic slope from –2·75 to –1·37 mL/min per 1·73 m2 per year (relative difference 50%, 95% CI 42–58). The absolute and relative benefits of empagliflozin on the magnitude of the chronic slope varied significantly depending on diabetes status and baseline levels of eGFR and uACR. In particular, the absolute difference in chronic slopes was lower in patients with lower baseline uACR, but because this group progressed more slowly than those with higher uACR, this translated to a larger relative difference in chronic slopes in this group (86% [36–136] reduction in the chronic slope among those with baseline uACR <30 mg/g compared with a 29% [19–38] reduction for those with baseline uACR ≥2000 mg/g; ptrend<0·0001). INTERPRETATION: Empagliflozin slowed the rate of progression of chronic kidney disease among all types of participant in the EMPA-KIDNEY trial, including those with little albuminuria. Albuminuria alone should not be used to determine whether to treat with an SGLT2 inhibitor. FUNDING: Boehringer Ingelheim and Eli Lilly