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Harold Merle,1 Laurence Béral,2 Maxime Rocher,3 Mitta Pierre,1 Albert Jean-Charles,1 Odile Béra,4 Laurie-Anne Rosamont,4 Pierre-Yves Robert,3 Agnes Lézin4 1Department of Ophthalmology, University Hospital of Martinique, Fort de France, French West Indies, France; 2Department of Ophthalmology, University Hospital of Guadeloupe, Pointe à Pitre, French West Indies, France; 3Department of Ophthalmology, University Hospital of Limoges, France; 4Department of Genetics, University Hospital of Martinique, Fort de France, French West Indies, FranceCorrespondence: Harold Merle, Department of Ophthalmology, University Hospital of Martinique, Hôpital Pierre Zobda Quitman, BP 632, Martinique, Fort de France, 97261 Cedex, French West Indies, France, Tel +596 596 552 251, Fax +596 596 758 447, Email harold.merle@chu-martinique.frPurpose: To evaluate how the HLA genotype is associated to the polypoidal choroidal vasculopathy (PCV) in a population of patients of Afro-Caribbean descent.Methods: Forty-seven patients were diagnosed with PCV. The number of control patients was 457. All affected patients and control patients were of Afro-Caribbean descent and natives to Martinique. HLA typing was based on blood sample, using the polymerase chain reaction technique. Comparison of HLA alleles between the 2 groups was done using chi-2 test, odds ratio (OR) and confidence interval using Woolf’s method. The Bonferroni correction was considered significant when p-value ≤ 0.05. Alleles frequency was analyzed for DRB1 and DQB1 locus.Results: HLA-DRB1&ast;13 allele was significantly associated to PCV (OR = 2.02, CI = [1.3; 3.13], p = 0.003). In group DRB1, the Bonferroni correction significance threshold was < 0.004. HLA-DQB1&ast;04 allele was significantly associated to PCV (OR = 3.5, CI = [1.48; 8.3], p = 0.006). In group DQB1, the Bonferroni correction significance threshold was < 0.006.Conclusion: Two HLA alleles are positively associated to PCV. The possible association between PCV and certain alleles suggest HLA implication in PCV pathogeny, most likely by modeling the immune system response.Keywords: polypoidal choroidal vasculopathy, major histocompatibility complex, human leucocyte antigen, genetic predisposition

Jose Guell,1 Anders Behndig,2 Uwe Pleyer,3 Stéphane Jaulerry,4 Pascal Rozot,5 Pierre-Jean Pisella,6 Pierre-Yves Robert,7 Ines Lanzl,8 Sayeh Pourjavan,9 Carlos Aguiar,10 Joaquin Fernandez,11 Gunther Grabner,12 Rita Mencucci,13 Frédéric Chiambaretta,14 Marc Labetoulle15 On behalf of the Intracameral Mydrane (ICMA) and Ethics Group 1Cornea and Refractive Surgery Unit, Instituto de Microcirugía Ocular, Barcelona, Spain; 2Department of Clinical Science/Ophthalmology, Umeå University Hospital, Umeå, Sweden; 3Universitäts-Augenklinik, Charité Campus Virchow-Klinik, Berlin, Germany; 4Centre Hospitalier de Bigorre, Tarbes, France; 5Clinique Monticelli, Marseille, France; 6Hôpital Bretonneau, CHRU de Tours, Tours, France; 7Hôpital Dupuytren, CHU de Limoges, Limoges, France; 8Chiemsee Augen Tagesklinik, Prien, Germany; 9Cliniques Universitaires Saint-Luc, Bruxelles, Belgium; 10Hospital de Santo Antonio, Porto, Portugal; 11Hospital Torrecárdenas, Almeria, Spain; 12Universitätsklinik Für Augenheilkunde Und Optometrie, Der Paracelsus, Austria; 13AOU Careggi, Clinica Oculistica, Università Degli Studi di Firenze, Firenze, Italy; 14Hôpital Gabriel Montpied, CHU de Clermont-Ferrand, Clermont-Ferrand, France; 15Hôpital Bicêtre, Université Paris Sud, Paris, France Objective: The objective of this study was to compare systemic exposure to tropicamide/phenylephrine following intracameral or topical administration before cataract surgery. Patients and methods: Mydriatics exposure was calculated in patients randomized to intracameral fixed combination of mydriatics and anesthetic ([ICMA]: tropicamide 0.02%, phenylephrine 0.31%, and lidocaine 1%, N=271) or mydriatic eye drops ([EDs]: tropicamide 0.5% and phenylephrine 10%, N=283). Additional doses were permitted if required. Mydriatic plasma levels were determined by mass spectrometric HPLC in 15 patients per group before and after administration.Results: Most ICMA patients (73.6%) received a single dose (200 µL) representing an exposure to tropicamide of 0.04 mg and phenylephrine of 0.62 mg. None of these patients received additional mydriatics. In the control group (three administrations), the exposure was 0.45 (11.3-fold higher than ICMA) and 10.2 (16.5-fold higher) mg. When additional ED was used in this group (9.2% of patients), it was 37.5-fold higher for tropicamide (10 drops, 1.5 mg) and 54.8-fold higher for phenylephrine (10 drops, 34 mg) than the recommended ICMA dose. Tropicamide plasma levels were not detectable at any time point in ICMA patients while it was detectable in all ED patients at 12 and 30 minutes. Phenylephrine was detectable in 14.3% of ICMA patients compared to all ED patients at least at one time point. More ED patients experienced a meaningful increase in blood pressure and/or heart rate (11.2% vs 6.0% of ICMA patients; P=0.03).Conclusion: Systemic exposure to tropicamide/phenylephrine was lower and cardiovascular (CV) effects were less frequent with ICMA. This could be of particular significance in patients at CV risk. Keywords: cataract surgery, intracameral mydriasis, topical mydriasis, systemic influence, cardiovascular safety

Myxomatosis in Europe is the result of the release of a South America strain of myxoma virus in 1952. Several attenuated strains with origins in South America or California have since been used as vaccines in the rabbit industry. We sequenced the genome of the SG33 myxoma virus vaccine strain and compared it with those of other myxoma virus strains. We show that SG33 genome carries a large deletion in its right end. Furthermore, our data strongly suggest that the virus isolate from which SG33 is derived results from an in vivo recombination between a wild-type South America (Lausanne) strain and a California MSD-derived strain. These findings raise questions about the use of insufficiently attenuated virus in vaccination.

The advent of advanced coatings has transformed material functionalities, extending their roles from basic coverage and visual appeal to include unique properties such as self-healing, superior hydrophobicity, and antimicrobial action. However, the traditional dependency on petrochemical-derived materials for these coatings raises environmental concerns. This study proposes the use of renewable and alternative materials for coating development. We present the use of bioengineered spider silk-inspired protein (SSIP), produced through recombinant technology, as a viable, eco-friendly alternative due to their ease of processing under ambient pressure and the utilization of water as a solvent, alongside their exceptional physicochemical properties. Our research investigates the effects of different thermal treatments and protein concentrations on the mechanical strength and surface water repellency of coatings on silica bases. Our findings reveal a direct correlation between the temperature of heat treatment and the enhancements in surface hydrophobicity and mechanical strength, where elevated temperatures facilitate increased resistance to water and improved mechanical integrity. Consequently, we advocate SSIPs present a promising, sustainable choice for advanced coatings, providing a pathway to fine-tune coating recipes for better mechanical and hydrophobic properties with a reduced ecological footprint, finding potential uses in various fields such as electronics.

Abstract Aim The aim of this study was to analyse the outcomes of patients with large B‐cell lymphoma (LBCL) treated with chimeric antigen receptor T‐cell therapy (CAR‐Tx), with a focus on outcomes after CAR T‐cell failure, and to define the risk factors for rapid progression and further treatment. Methods We analysed 107 patients with LBCL from the Czech Republic and Slovakia who were treated in ≥3rd‐line with tisagenlecleucel or axicabtagene ciloleucel between 2019 and 2022. Results The overall response rate (ORR) was 60%, with a 50% complete response (CR) rate. The median progression‐free survival (PFS) and overall survival (OS) were 4.3 and 26.4 months, respectively. Sixty‐three patients (59%) were refractory or relapsed after CAR‐Tx. Of these patients, 39 received radiotherapy or systemic therapy, with an ORR of 22% (CR 8%). The median follow‐up of surviving patients in whom treatment failed was 10.6 months. Several factors predicting further treatment administration and outcomes were present even before CAR‐Tx. Risk factors for not receiving further therapy after CAR‐Tx failure were high lactate dehydrogenase (LDH) levels before apheresis, extranodal involvement (EN), high ferritin levels before lymphodepletion (LD) and ECOG PS >1 at R/P. The median OS‐2 (from R/P after CAR‐Tx) was 6.7 months (6‐month 57.9%) for treated patients and 0.4 months (6‐month 4.2%) for untreated patients (p limit of the normal range (LNR) before LD, albumin < LNR and ECOG PS > 1 at R/P. All these factors, together with LDH > LNR before LD and EN involvement at R/P, predicted OS‐2 for treated patients. Conclusion Our findings allow better stratification of CAR‐Tx candidates and stress the need for a proactive approach (earlier restaging, intervention after partial remission achievement).

The French territorial system is marked by a historical very large communal dispersion. Strangely the French State, although considered very strong, has never managed to impose the merger of these municipalities, as was the case in most other European countries. This resistance of local elected representatives, often also national parliamentarians, then led the central government to use another strategy: their grouping in public institutions of intermunicipal cooperation (EPCI). The creation of the Metropolis of Lyon is, therefore, very original. Created by the law of 27th January, 2014, it is the only “metropolis” with the status of territorial collectivity and merges on its territory the Rhône department and the former “urban community” of Lyon. This metropolis is thus unique in France, and the authors will tend to verify whether it could serve as a model to follow by other metropolises, considering the case of the first institutionalised metropolis in Poland, namely the GZM Metropolis, which is struggling with structural problems. The GZM Metropolis was established in 2017 by the Polish Parliament’s law and provided with a specific governance regime comparable to the “manager and council model” and decision-making based on a double majority of the municipalities and population. After the first five years of functioning, the leaders of this first Polish metropolis seem to be ready to adjust their metropolitan institutions, understanding its limits and searching for inspiration at the international level.

The article’s starting point is the assumption that, because of their socio-cultural and economic diversity, density, and complexity of interaction systems, metropolises provide a sufficient basis for creating innovation – including social innovation emerging from residents’ grassroots activities. Such perspective emphasises the importance of the creative potential of residents, as materialised in emerging innovation places and collectives operating and dispersed throughout the city. Assuming such a perspective made it possible to build an original model for this study of an innovation place that combines the features of classical and dynamic theories of place. In the empirical portion of the article, the data obtained during the study of ten selected innovation places located in three European metropolises are analysed. The study used qualitative methodology: in-depth interviews and observations. The study’s main objective was to assess the utility of the model of the innovation place as a tool for identifying and analysing metropolitan social innovation. This objective has been achieved, and the data obtained showed that, by using the model with characteristics typical of an innovation place, it is possible to effectively analyse the process of creating social innovation, indicate its determinants, and reveal differences in the innovation places under study.

Tisagenlecleucel (tisa-cel) is a CD19-specific CAR-T cell product approved for the treatment of relapsed/refractory (r/r) DLBCL or B-ALL. We have followed a group of patients diagnosed with childhood B-ALL (n = 5), adult B-ALL (n = 2), and DLBCL (n = 25) who were treated with tisa-cel under non-clinical trial conditions. The goal was to determine how the intensive pretreatment of patients affects the produced CAR-T cells, their in vivo expansion, and the outcome of the therapy. Multiparametric flow cytometry was used to analyze the material used for manufacturing CAR-T cells (apheresis), the CAR-T cell product itself, and blood samples obtained at three timepoints after administration. We present the analysis of memory phenotype of CD4/CD8 CAR-T lymphocytes (CD45RA, CD62L, CD27, CD28) and the expression of inhibitory receptors (PD-1, TIGIT). In addition, we show its relation to the patients’ clinical characteristics, such as tumor burden and sensitivity to prior therapies. Patients who responded to therapy had a higher percentage of CD8+CD45RA+CD27+ T cells in the apheresis, although not in the produced CAR-Ts. Patients with primary refractory aggressive B-cell lymphomas had the poorest outcomes which was characterized by undetectable CAR-T cell expansion in vivo. No clear correlation of the outcome with the immunophenotypes of CAR-Ts was observed. Our results suggest that an important parameter predicting therapy efficacy is CAR-Ts’ level of expansion in vivo but not the immunophenotype. After CAR-T cells’ administration, measurements at several timepoints accurately detect their proliferation intensity in vivo. The outcome of CAR-T cell therapy largely depends on biological characteristics of the tumors rather than on the immunophenotype of produced CAR-Ts.

Postindustrial agglomerations struggling with image deficits and environmental problems are looking for new development paths to take. One of these paths can bring about the development of business tourism, including the industry of the organisation of meetings and events. The unique and attractive character of the place can favour taking such a direction. The business tourism sector can therefore become an instrument contributing to the sustainable metropolisation of the city by building up its position in the global network of flows. The development of the meetings and events sector allows, therefore, for a change of image, for a re-evaluation of endogenous resources, including those relating to the industrial past, and for tapping into the unlimited resources of the global network. Increased attention in this network may lead to an influx of more events, and of investors as well. Replacing heavy industry with an enlarged service sector and modern industry based on flexible and innovative small and medium-sized enterprises fosters sustainable development. The meetings and events industry can become a tool for sustainable development and the promotion of its ideas, related to the UN Sustainable Development Goals (SDGs). The trajectory outlined above seems very promising. However, to some extent, it is just a hypothesis. The author undertakes to test it on the example of Katowice, a former industrial city which has decided to follow the route outlined above to become a city that hosts many events, including the COP24 summit in 2018. In the article, the author presents empirical research studies whose authors tried to determine whether the path the city has chosen has a real impact on its image and development. The author also deals with the question of the sustainability of such a development path and the conditions for its self-support in the context of the COVID-19 pandemic crisis.

Objective This study examined bereavement‐related risk markers (number of deaths, cause of death, and relationship to deceased) of mental and behavioral health problems (suicidal thoughts or behaviors, self‐injury, depression, posttraumatic stress, and substance use) in a national sample of clinic‐referred bereaved adolescents. Method Participants included 1281 bereaved youth aged 12–21 years (M=15, SD=1.8; 62.1% female), from the National Child Traumatic Stress Network Core Data Set. Results Generalized linear mixed‐effects regression models controlling for demographics and other traumas revealed that youth bereaved by multiple deaths had higher posttraumatic stress scores than youth bereaved by a single death (Estimated difference ±SE=3.36 ± 1.11, p=0.003). Youth bereaved by suicide were more likely to report experiencing suicidal thoughts or behaviors (AOR=1.68, p=0.049) and alcohol use (AOR=2.33, p

T-cell malignancies can be divided into precursor (T-acute lymphoblastic leukemia/lymphoblastic lymphoma, T-ALL/LBL) and mature T-cell neoplasms, which are comprised of 28 different entities. Most of these malignancies are aggressive with rather poor prognosis. Prognosis of relapsed/refractory (R/R) disease is especially dismal, with an expected survival only several months after progression. Targeted therapies, such as antiCD30 immunotoxin brentuximab vedotin, antiCD38 antibody daratumumab, and anti-CCR4 antibody mogamulizumab are effective only in subsets of patients with T-cell neoplasms. T-cells equipped with chimeric antigen receptor (CAR-Ts) are routinely used for treatment of R/R B-cell malignancies, however, there are specific obstacles for their use in T-cell leukemias and lymphomas which are fratricide killing, risk of transfection of malignant cells, and T-cell aplasia. The solution for these problems relies on target antigen selection, CRISPR/Cas9 or TALEN gene editing, posttranslational regulation of CAR-T surface antigen expression, and safety switches. Structural chromosomal changes and global changes in gene expression were observed with gene-edited products. We identified 49 studies of CAR-based therapies registered on www.clinicaltrials.gov. Most of them target CD30 or CD7 antigen. Results are available only for a minority of these studies. In general, clinical responses are above 50% but reported follow-up is very short. Specific toxicities of CAR-based therapies, namely cytokine release syndrome (CRS), seem to be connected with the antigen of interest and source of cells for manufacturing. CRS is more frequent in antiCD7 CAR-T cells than in antiCD30 cells, but it is mild in most patients. More severe CRS was observed after gene-edited allogeneic CAR-T cells. Immune effector cell associated neurotoxicity (ICANS) was mild and infrequent. Graft-versus-host disease (GvHD) after allogeneic CAR-T cells from previous hematopoietic stem cell donor was also observed. Most frequent toxicities, similarly to antiCD19 CAR-T cells, are cytopenias. CAR-based cellular therapy seems feasible and effective for T-cell malignancies, however, the optimal design of CAR-based products is still unknown and long-term follow-up is needed for evaluation of their true potential.

IntroductionWe analyzed the incidence, risk factors of central nervous system (CNS) relapse, and outcome of CNS involvement in patients with peripheral T-cell lymphomas (PTCL) from the Czech Lymphoma Study Group Registry NiHiL (Clinical Trial gov. NCT03199066).Materials and MethodsOut of 1,040 patients with PTCL, we identified 29 patients (2.79%) with CNS involvement: 2 patients with primary CNS T cell lymphoma, 11 patients with CNS and systemic disease at diagnosis, and 16 patients (1.54%) at CNS relapse. The most common histology with CNS disease was PTCL, not otherwise specified. Progression-free survival (PFS) was defined as the time interval from diagnosis to progression or death. PFS-2 was defined as the interval from the date of a new relapse until the next relapse.ResultsPatients with testicular involvement received intrathecal prophylaxis with methotrexate. High-dose methotrexate-based treatment was administered in 44.8% of patients with CNS disease. Median follow-up was 71.3 months. The difference between the median PFS of 1,027 patients without initial CNS disease (32.6 months) and 11 patients with initial CNS and systemic disease (4.8 months) was significant (p = 0.04). The difference between the median PFS2 in CNS relapses (10.1 months) and 493 relapses outside of CNS (9.1 months) was not significant (p = 0.6). Risk factors for CNS relapses included the following: involvement of more than one extranodal site (p = 0.008), soft tissue involvement (p = 0.003), testicular involvement (p = 0.046), and the presence of B symptoms (p = 0.035). The difference between the median OS of 1,027 patients without initial CNS disease (46.0 months) and 11 patients with initial CNS and systemic disease (18.2 months) was significant (p = 0.02). The median OS2 in CNS relapses was 11.8 months and that in relapses outside of CNS was 21.3 months. CNS involvement was not associated with a significantly worse OS compared to relapsed/refractory patients without CNS involvement (p = 0.1).ConclusionsThe incidence of CNS disease at the time of diagnosis and at relapse in PTCL is low and usually associated with other systemic involvement. The prognosis of PTCL with initial CNS involvement is significantly worse when compared to patients without CNS disease at diagnosis. The outcome of CNS relapse is comparable with relapsed PTCL outside of CNS. The optimal treatment is not defined yet.

Abstract Twenty percent of patients with high‐tumor‐burden (HTB) follicular lymphoma (FL) develop progression/relapse of disease (POD) within 24 months of frontline immunochemotherapy. Unfortunately, about 50% of these patients die within 5 years since POD event. Rituximab maintenance was proven to reduce relapse rate in responding FL, but its role on preventing POD was not defined. We analyzed 1360 HTB‐FL patients from the Czech Lymphoma Study Group registry treated with frontline rituximab‐containing regimen. Of those, 950 cases received rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R‐CHOP) and achieved complete or partial remission: 712 patients received rituximab maintenance (MAINT) and 238 were a historical observational cohort (OBS). We have proposed a modified POD24 (mPOD24) endpoint for the chemosensitive patients calculated from the end‐of‐induction (EOI). Survival rates since EOI were as follows: 5‐year overall survival (OS) 86.2% versus 94.5% in the OBS and MAINT groups, respectively (P

Autor podejmuje kwestię reorganizacji terytorialnej obszarów metropolitalnych w warunkach kanadyjskiego federalizmu na przykładzie Toronto i Montrealu. Wyniki badań autora wskazują, że realizowane strategie adaptacyjne państw zmierzające do upodmiotowienia metropolii są uzależnione m.in. od generalnej autonomii samorządu terytorialnego w danym systemie politycznym. Funkcjonowanie silnego samorządu terytorialnego może sprzyjać tworzeniu jednostek współpracy międzygminnej przy zachowaniu szczebla lokalnego. Reorganizacja terytorialna obszarów miejskich w państwach o niskim poziomie samodzielności samorządu lokalnego może natomiast spowodować likwidację dotychczasowych jednostek samorządowych przez łączenie ich w nowe samorządy o szerszym, „metropolitalnym” zasięgu terytorialnym (amalgamation). Kanada jest w tym kontekście bardzo ciekawym obiektem badań. Z uwagi na jej ewolucyjny federalizm, ograniczoną samodzielność szczebla lokalnego, w tym miast, oraz krzyżowanie się tradycji europejskich i amerykańskich można tam odnaleźć niemal wszystkie wspomniane wyżej wymiary reform i strategie adaptacyjne. Rozwijana w przypadku Toronto i Montrealu zaawansowana współpraca międzygminna sięgająca połowy XX w. została poddana rewizji przez fuzję współpracujących gmin w nowe, poszerzone terytorialnie metropolie Toronto w 1998 r. i Montrealu w 2002 r., co w obu wypadkach spotkało się z silnym sprzeciwem części mieszkańców i wywołało destabilizację współpracy w obszarze metropolitalnym. Trudne doświadczenia związane z procesem fuzji jednostek samorządowych spowodowały i w Toronto, i w Montrealu rezygnację z dalszych reform strukturalno-terytorialnych na rzecz reform funkcjonalnych, przybierających postać umów na linii prowincja – metropolie, mających na celu poszerzenie autonomii finansowej i kompetencyjnej tych ostatnich. Opisywane trudności w poszukiwaniu właściwego reżimu metropolitalnego i optymalnego ulokowania metropolii w strukturze systemu politycznego i terytorialnego państwa w przypadku analizowanych miast kanadyjskich idą w parze z osiąganymi przez nie pozytywnymi efektami gospodarczymi oraz wysoką jakością życia.

Abstract The oxidative d-xylose pathway, i.e. Dahms pathway, can be utilised to produce from cheap biomass raw material useful chemical intermediates. In vitro metabolic pathways offer a fast way to study the rate-limiting steps and find the most suitable enzymes for each reaction. We have constructed here in vitro multi-enzyme cascades leading from d-xylose or d-xylonolactone to ethylene glycol, glycolic acid and lactic acid, and use simple spectrophotometric assays for the read-out of the efficiency of these pathways. Based on our earlier results, we focussed particularly on the less studied xylonolactone ring opening (hydrolysis) reaction. The bacterial Caulobacter crescentus lactonase (Cc XylC), was shown to be a metal-dependent enzyme clearly improving the formation of d-xylonic acid at pH range from 6 to 8. The following dehydration reaction by the ILVD/EDD family d-xylonate dehydratase is a rate-limiting step in the pathway, and an effort was made to screen for novel enolase family d-xylonate dehydratases, however, no suitable replacing enzymes were found for this reaction. Concerning the oxidation of glycolaldehyde to glycolic acid, several enzyme candidates were also tested. Both Escherichia coli aldehyde dehydrogenase (Ec AldA) and Azospirillum brasilense α-ketoglutarate semialdehyde dehydrogenase (Ab AraE) proved to be suitable enzymes for this reaction.

In vitro and in vivo analyses are closely connected, and the reciprocal relationship between the two comprises a key assumption with concern to the conducting of meaningful research. The primary purpose of in vitro analysis is to provide a solid background for in vivo and clinical study purposes. The fields of cell therapy, tissue engineering, and regenerative medicine depend upon the high quality and appropriate degree of the expansion of mesenchymal stromal cells (MSCs) under low-risk and well-defined conditions. Hence, it is necessary to determine suitable alternatives to fetal bovine serum (FBS—the laboratory gold standard) that comply with all the relevant clinical requirements and that provide the appropriate quantity of high-quality cells while preserving the required properties. Human serum (autologous and allogeneic) and blood platelet lysates and releasates are currently considered to offer promising and relatively well-accessible MSC cultivation alternatives. Our study compared the effect of heat-inactivated FBS on MSC metabolism as compared to its native form (both are used as the standard in laboratory practice) and to potential alternatives with concern to clinical application—human serum (allogeneic and autologous) or platelet releasate (PR-SRGF). The influence of the origin of the serum (fetal versus adult) was also determined. The results revealed the key impact of the heat inactivation of FBS on MSCs and the effectiveness of human sera and platelet releasates with respect to MSC behaviour (metabolic activity, proliferation, morphology, and cytokine production).

Background. The clinical impact of the distressed communities index (DCI), a composite measure of economic well-being based on the U.S. zip code, is becoming increasingly recognized. Ranging from 0 (prosperous) to 100 (distressed), DCI’s association with cardiovascular outcomes remains unknown. We aimed to study the association of the DCI with presentation and outcomes in adults with severe symptomatic aortic stenosis (AS) undergoing transcatheter aortic valve intervention (TAVR) in an affluent county in New York. Methods. The study population included 286 patients with severe symptomatic AS or degeneration of a bioprosthetic valve who underwent TAVR with a newer generation transcatheter heart valve (THV) from December 2015 to June 2018 at an academic tertiary medical center. DCI for each patient was derived from their primary residence zip code. Patients were classified into DCI deciles and then categorized into 4 groups. The primary and secondary outcomes of interest were 30-day, 1-year, and 3-year mortality, respectively. Results. Among 286 patients studied, 26%, 28%, 28%, and 18% were categorized into DCI groups 1–4, respectively (DCI 30: n = 52). Patients in group 4 were younger with worse kidney function compared to patients in groups 1 and 2. They also had smaller aortic annuli and were more likely to receive a smaller THV. No significant difference in hospital length of stay or distribution of in-hospital, 30-day, 1-year, and 3-year mortality was demonstrated. Conclusions. While the DCI was associated with differences in the clinical and anatomic profile, it was not associated with differences in clinical outcomes in this prospective observational study of adults undergoing TAVR suggesting that access to care is the likely discriminator.

Metropolises are currently regarded as nodes in a global network of flows, becoming the driving forces for territorial development, characterised by high potential of creativity and the innovations generated as a result. A contemporary challenge is to find adequate concepts for analysing and understanding metropolitan innovativeness. The objective of the article is to provide the necessary features by which a new approach to studying metropolitan inventiveness can be adopted. The formulation of this model was inspired by the independently functioning concepts of metropolisation, innovativeness, and the concepts of place. By considering these three perspectives together and their specific methods of analysis, it is possible to describe and explain the process of generating innovations in contemporary metropolises. This article is divided into three main sections illustrating how the concepts of innovation environments, networks, and districts combined with the dynamic concept of place, all relate to innovation place. The analysis presented serves as the basis for the model of an innovation place, it being essential to future initiatives in this sphere of study. The article concludes with methodological remarks indicating the potential use for “innovation space” model. Santrauka Šiuo metu metropoliai vertinami kaip mazginiai taškai globaliame srautų tinkle, tampantys varomosiomis teritorijų plėtros jėgomis; juos charakterizuoja aukšto kūrybiškumo potencialas ir, kaip to rezultatas, kuriamos inovacijos. Šiuolaikinis iššūkis – rasti adekvačias koncepcijas, tinkamas metropolitenų inovatyvumui analizuoti ir suprasti. Straipsnio tikslas – pateikti būtinų bruožų, kuriais remiantis, galėtų būti pritaikytas naujas požiūris, padedantis tyrinėti metropolitenų inovatyvumą. Šio modelio formavimą inspiravo savarankiškai funkcionuojančios metropolizacijos, inovatyvumo koncepcijos ir vietos koncepcijos. Apžvelgus šias tris perspektyvas kartu ir jų specifinius analizės metodus, atsiranda galimybė apibūdinti ir paaiškinti inovacijų kūrimo procesą šiuolaikiniuose metropoliuose. Šis straipsnis padalytas į tris pagrindines dalis, iliustruojančias, kaip inovacijų aplinkos, tinklų ir rajonų koncepcijos, sujungtos su dinamiška vietos koncepcija, yra susijusios su inovacijų vieta. Pristatoma analizė yra kaip inovacijų vietos modelio pagrindas, ji būtina ateities iniciatyvoms šios srities tyrimų atžvilgiu. Straipsnio pabaigoje pateikiamos metodologinės pastabos, nurodančios inovacijų erdvės modelio taikymo galimybes. Reikšminiai žodžiai: kūrybiškumas, inovacijų vieta, inovacijos, inovatyvi aplinka, metropoliai, vieta.

Po ponad 10 latach dyskusji na temat potrzeby upodmiotowienia obszarów metropolitalnych w Polsce przyjęta została ostatecznie ustawa o związku metropolitalnym w województwie śląskim. Wyznaczenie pułapu demograficznego na poziomie 2 mln mieszkańców potwierdza, że zamierzeniem ustawodawcy było stworzenie pierwszego związku metropolitalnego właśnie w konurbacji górnośląskiej, co podyktowane jest jej unikatową w skali kraju strukturą terytorialną. Powstanie z dniem 1 lipca 2017 r. Górnośląsko-Zagłębiowskiej Metropolii jest zatem wielkim eksperymentem społecznym i znaczącą innowacją w polskim samorządzie terytorialnym. Objęcie zasięgiem związku metropolitalnego 41 gmin górnośląskiego obszaru metropolitalnego było odważnym krokiem i świadczy o wysokim poziomie mobilizacji i determinacji śląskich samorządowców. Specyficzny system decyzyjny oparty na zasadzie podwójnej większości powinien sprzyjać dialogowi dużych i małych gmin związku metropolitalnego. Ogólnie sformułowane w ustawie kompetencje związku dają istotną swobodę jego władzom w wyznaczeniu priorytetowych zadań i projektów. Celem autora artykułu jest analiza architektury instytucjonalnej związku metropolitalnego, będącego połączeniem związku komunalnego i jednostki samorządu terytorialnego, w perspektywie możliwości budowy efektywnego systemu metropolitalnego współrządzenia w górno-śląskim obszarze metropolitalnym.