Cancer diagnosis in Catalonia (Spain) after two years of COVID-19 pandemic: an incomplete recovery

Background: This study aimed to estimate potential undetected cancers over the first 2 years of the COVID-19 pandemic in Catalonia. Methods: Cancer incidence was compared between pre-pandemic (2019) and pandemic (March 2020-January 2022) periods in the Catalan Pathology Registry (CPR) according to sex, age, and tumor site. The correlation between cancer diagnosis and COVID-19 health care workload was also evaluated by means of the Pearson's correlation coefficient (R). The expected incident cancers (E) during the pandemic were estimated by applying 2019 CPR cancer incidence specific rates by sex and 5-year age groups to the 2020 and 2021 Catalan population pyramids. CPR incident cancers were considered observed (O). Standardized incidence ratios (SIR) and 95% confidence intervals (as) were calculated using the 0/E ratio. Results: After two pandemic years, cancer diagnosis decreased by 12% (SIR 0.88, 95% a 0.87-0.89), or similar to 7700 undetected cancers (13 000 with nonmelanoma skin cancer). Without nonmelanoma skin cancer, 72% of the cancer underdiagnosis was generated in 2020. Diagnoses decreased more in men (whole pandemic -14%; 2020 -21%; 2021 8%) than in women (---9%, 19%, 3%, respectively), dropping significantly overall in all pandemic waves but the fifth (first -37%, second -16%, third -8%, fourth -6%, fifth -2%, sixth -6%), and across all adult age groups. In the first wave, CPR cancer diagnosis was inversely correlated with COVID-19 caseload in primary care (R -0.91, 95% CI -0.97 to -0.75) and occupancy in conventional hospital wards (R -0.91, 95% a -0.99 to -0.48) and intensive care (R 0.91, 95% a 95% 0.98 to 0.70). Conclusions: Our study evaluated the overall pandemic impact on cancer diagnosis on a large scale and with minimal selection bias, showing that as of February 2022, cancer detection in Catalonia had not yet recovered to pre-pandemic levels. Pending cancer incidence data from population-based cancer registries, early CPR data could inform the development of Spanish cancer control plans

Kinetics of immune responses elicited after three mRNA COVID-19 vaccine doses in predominantly antibody-deficient individuals

Mass vaccination campaigns reduced COVID-19 incidence and severity. Here, we evaluated the immune responses developed in SARS-CoV-2-uninfected patients with predominantly antibody-deficiencies (PAD) after three mRNA-1273 vaccine doses. PAD patients were classified based on their immunodeficiency: unclassified primary antibody-deficiency (unPAD, n = 9), common variable immunodeficiency (CVID, n = 12), combined immunodeficiency (CID, n = 1), and thymoma with immunodeficiency (TID, n = 1). unPAD patients and healthy controls (HCs, n = 10) developed similar vaccine-induced humoral responses after two doses. However, CVID patients showed reduced binding and neutralizing titers compared to HCs. Of interest, these PAD groups showed lower levels of Spike-specific IFN-γ-producing cells. CVID individuals also presented diminished CD8+T cells. CID and TID patients developed cellular but not humoral responses. Although the third vaccine dose boosted humoral responses in most PAD patients, it had limited effect on expanding cellular immunity. Vaccine-induced immune responses in PAD individuals are heterogeneous, and should be immunomonitored to define a personalized therapeutic strategies.info:eu-repo/semantics/publishedVersio

Continuous-flow in-line solvent-swap crystallization of vitamin D(3)

A continuous tandem in-line evaporation–crystallization is presented. The process includes an in-line solvent-swap step, suitable to be coupled to a capillary based cooler. As a proof of concept, this setup is tested in a direct in-line acetonitrile mediated crystallization of Vitamin D₃. This configuration is suitable to be coupled to a new end-to-end continuous microflow synthesis of Vitamin D₃. By this procedure, vitamin particles can be crystallized in continuous flow and isolated using an in-line continuous filtration step. In one run in just 1 min of cooling time, ∼50% (w/w) crystals of Vitamin D₃ are directly obtained. Furthermore, the polymorphic form as well as crystals shape and size properties are described in this paper.Marc Escribà-Gelonch, Volker Hessel, Manuel C. Maier, Timothy Noël, Maria Fernanda Neira d’Angelo and Heidrun Gruber-Woelfle

Generation and characterization of a defective HIV-1 Virus as an immunogen for a therapeutic vaccine

BACKGROUND: The generation of new immunogens able to elicit strong specific immune responses remains a major challenge in the attempts to obtain a prophylactic or therapeutic vaccine against HIV/AIDS. We designed and constructed a defective recombinant virus based on the HIV-1 genome generating infective but non-replicative virions able to elicit broad and strong cellular immune responses in HIV-1 seropositive individuals. RESULTS: Viral particles were generated through transient transfection in producer cells (293-T) of a full length HIV-1 DNA carrying a deletion of 892 base pairs (bp) in the pol gene encompassing the sequence that codes for the reverse transcriptase (NL4-3/ΔRT clone). The viral particles generated were able to enter target cells, but due to the absence of reverse transcriptase no replication was detected. The immunogenic capacity of these particles was assessed by ELISPOT to determine γ-interferon production in a cohort of 69 chronic asymptomatic HIV-1 seropositive individuals. Surprisingly, defective particles produced from NL4-3/ΔRT triggered stronger cellular responses than wild-type HIV-1 viruses inactivated with Aldrithiol-2 (AT-2) and in a larger proportion of individuals (55% versus 23% seropositive individuals tested). Electron microscopy showed that NL4-3/ΔRT virions display immature morphology. Interestingly, wild-type viruses treated with Amprenavir (APV) to induce defective core maturation also induced stronger responses than the same viral particles generated in the absence of protease inhibitors. CONCLUSIONS: We propose that immature HIV-1 virions generated from NL4-3/ΔRT viral clones may represent new prototypes of immunogens with a safer profile and stronger capacity to induce cellular immune responses than wild-type inactivated viral particles.This study was supported by grants FIS PI050265, FIS PI040503, FIS PI070291, FIS Intrasalud 080752, FIS PS09/01297, FIS PI10/02984, SAF2006-26667-E, FIT 09-010-205-9, FIPSE 36780/08, Fundación Mútua Madrileña, TRA-094, EC10-153, ISCIII-RETIC RD06/0006, HIVACAT–HIV Development Program in Catalonia, FIPSE 36630/07, UE Program Health 2009 CHAARM. Spanish Health Institute Carlos III (ISCIII) and the Health Department of the Catalan Government (Generalitat de Catalunya). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.S

Dealing with Tyranny: International Sanctions and Autocrats’ Duration

This paper enquires into whether economic sanctions are effective in destabilizing authoritarian rulers. We argue that this effect is mediated by the type of authoritarian regime against which sanctions are imposed. Thus, personalist regimes and monarchies, which are more dependent on aid and resource rents to maintain their patronage networks, are more likely to be affected by sanctions. In contrast, single-party and military regimes are able to maintain (and even increase) their tax revenues and to reallocate their expenditures and so increase their levels of cooptation. Data on sanction episodes, authoritarian rulers and regimes covering the period 1946–2000 have allowed us to test our hypotheses. To do so, duration models have been run, and the results confirm that personalist autocrats are more vulnerable to foreign pressure. Concretely, the analysis of the modes of exit reveals that sanctions increase the likelihood of an irregular change of ruler, such as a coup. Sanctions are basically ineffective when targeting single-party or military regimes