The passive construction być/zostać + V-n-/-on-/-t- in Polish : an aspectual analysis

The idea that passive sentences are equivalent in meaning to their active counterparts has raised numerous questions among linguists particularly for the last several decades. The main dilemma regarding this relationship concerns the very need for an alternative synonymous construction such as the passive. The focus has mostly been on issues concerning the preference for using passive sentences in certain types of discourse as well as the divergent liking for and frequency of using passive in different languages. However, apart from these concerns, there have gradually appeared questions and doubts related to the very nature and meaning of the passive. Many linguists have argued that the passive and its corresponding active are not synonymous (Ziff 1966: 226) and that “most sentences that are good in the active voice are just grotesque curiosities when put into the passive voice” (Allen 1974: 277). Moreover, some actives and passives do not have counterparts in the other voice (Davison 1981: 440). Not only has the semantic equivalence between passives and actives been questioned but also the syntactic correlation, which led linguists to search for new theories and put forward alternative hypotheses. The following work aims to present one of the alternative approaches towards the passive. It is based on the aspectual analysis of the passive and the method of lexical exceptions advanced and applied to English, German, and Russian in Beedham (2005). In this dissertation the method of lexical exceptions will be implemented in an analysis of the passive in Polish and it will be shown that the voice analysis of the passive in Polish is misguided and an alternative aspectual analysis provides answers and explanations to inconsistencies associated with the generally accepted voice analysis of the Polish passive. The dissertation consists of three main parts, which discuss the theoretical background of the passive in general and in Polish; problems associated with the universal definition of passive and synchronic solutions based on an aspectual analysis; and issues concerning the Polish passive, with a presentation of a new alternative analysis of the być/zostać + V-n-/-on-/-t- construction

Ethanol-Induced Oxidative Stress Modifies Inflammation and Angiogenesis Biomarkers in Retinal Pigment Epithelial Cells (ARPE-19): Role of CYP2E1 and its Inhibition by Antioxidants

The retinal pigment epithelium (RPE) plays a key role in retinal health, being essential for the protection against reactive oxygen species (ROS). Nevertheless, excessive oxidative stress can induce RPE dysfunction, promoting visual loss. Our aim is to clarify the possible implication of CYP2E1 in ethanol (EtOH)-induced oxidative stress in RPE alterations. Despite the increase in the levels of ROS, measured by fluorescence probes, the RPE cells exposed to the lowest EtOH concentrations were able to maintain cell survival, measured by the Cell Proliferation Kit II (XTT). However, EtOH-induced oxidative stress modified inflammation and angiogenesis biomarkers, analyzed by proteome array, ELISA, qPCR and Western blot. The highest EtOH concentration used stimulated a large increase in ROS levels, upregulating the cytochrome P450-2E1 (CYP2E1) and promoting cell death. The use of antioxidants such as N-acetylcysteine (NAC) and diallyl sulfide (DAS), which is also a CYP2E1 inhibitor, reverted cell death and oxidative stress, modulating also the upstream angiogenesis and inflammation regulators. Because oxidative stress plays a central role in most frequent ocular diseases, the results herein support the proposal that CYP2E1 upregulation could aggravate retinal degeneration, especially in those patients with high baseline oxidative stress levels due to their ocular pathology and should be considered as a risk factor.LVG was recipient of a pre-doctoral fellowship (EDUCV-PRE-2015-006). Financial support by grant #94/2016 from the PROMETEO program from the Generalitat Valenciana, Valencia, Spain, to FJR

Phase I, multicenter, open-label study of intravenous VCN-01 oncolytic adenovirus with or without nab-paclitaxel plus gemcitabine in patients with advanced solid tumors

Background VCN-01 is an oncolytic adenovirus (Ad5 based) designed to replicate in cancer cells with dysfunctional RB1 pathway, express hyaluronidase to enhance virus intratumoral spread and facilitate chemotherapy and immune cells extravasation into the tumor. This phase I clinical trial was aimed to find the maximum tolerated dose/recommended phase II dose (RP2D) and dose-limiting toxicity (DLT) of the intravenous delivery of the replication-competent VCN-01 adenovirus in patients with advanced cancer. Methods Part I: patients with advanced refractory solid tumors received one single dose of VCN-01. Parts II and III: patients with pancreatic adenocarcinoma received VCN-01 (only in cycle 1) and nab-paclitaxel plus gemcitabine (VCN-concurrent on day 1 in Part II, and 7days before chemotherapy in Part III). Patients were required to have anti-Ad5 neutralizing antibody (NAbs) titers lower than 1/350 dilution. Pharmacokinetic and pharmacodynamic analyses were performed. Results 26% of the patients initially screened were excluded based on high NAbs levels. Sixteen and 12 patients were enrolled in Part I and II, respectively: RP2D were 1 x10(13) viral particles (vp)/patient (Part I), and 3.3x10(12) vp/patient (Part II). Fourteen patients were included in Part Ill: there were no DLTs and the RP2D was 1 x10(13) vp/patient. Observed DLTs were grade 4 aspartate aminotransferase increase in one patient (Part I, 1x10(13) vp), grade 4 febrile neutropenia in one patient and grade 5 thrombocytopenia plus enterocolitis in another patient (Part II, 1 x10(13) vp). In patients with pancreatic adenocarcinoma overall response rate were 50% (Part II) and 50% (Part III). VCN-01 viral genomes were detected in tumor tissue in five out of six biopsies (day 8). A second viral plasmatic peak and increased hyaluronidase serum levels suggested replication after intravenous injection in all patients. Increased levels of immune biomarkers (interferon- r,soluble lymphocyte activation ne-3, interleukin (IL)-6, IL-10) were found after VCN-01 administration. Conclusions Treatment with VCN-01 is feasible and has an acceptable safety. Encouraging biological and clinical activity was observed when administered in combination with nab-paditaxel plus gemcitabine to patients with pancreatic adenocarcinoma

Effect of central nervous system (CNS) metastases in a real-world multicenter cohort study of Spanish ALK-positive non-small cell lung cancer (NSCLC) patients (p)

Background: CNS is a common site of metastases in patients with ALK-positive NSCLC. CNS metastases are associated with a number of deleterious effects, such as reduction in quality of life. However, the relationship between brain metastases and prognosis remains unclear. We aimed to evaluate the effect of CNS metastases on overall survival (OS) in a multicenter cohort of Spanish ALK-positive NSCLC patients diagnosed between 2008 and 2017. Methods: We included patients with stage IV at diagnoses, followed up to April 2018; OS (months [m]) was estimated with the Kaplan-Meier method. Survival curves were compared between groups of patients using the log-rank test. Hazard risk (HR) to death was estimated with multivariable Cox model. Results: Out of 163 patients in the cohort, a total of 116 were evaluated, with a median of follow-up of 29.2 m and 59 deaths reported. Characteristics at diagnosis were a median age of 58 years, 50% female, 58.6% never-smokers, 54.3% with comorbidities, PS by ECOG 0-1 93.1%. CNS metastases (median number of lesions 6) were present in 43.1% of patients and 34% of patients with CNS metastases were treated with local therapy (11.8 % local radiotherapy and 76.5% holocraneal radiotherapy). ALK inhibitors as first line and second line treatment were administered to 45.5% and 78.6% of patients, respectively. The median OS was 39 months; OS in patients with CNS metastases at diagnosis was 34.4 m and 39.0 m in those without CNS metastases at diagnosis (p=.9). In patients without CNS metastases at baseline (n=60), 22 developed CNS, with a median OS greater than in those without CNS metastases during follow-up, although the difference is not significant (45.5 m vs 33.3 m; p=.9). There were 81 patients who presented with metastases in more than one organ and 33 patients with metastases in a single organ. The risk of death increased as the number of metastatic organs at diagnoses increased (HR=1.26, p=.0305), with worse OS in those presenting with liver metastases at diagnoses (21.1%, OS: 20 m), compared to those without tumor involvement (OS: 45.4 m; p =.008). Conclusions: OS was similar for ALK-positive NSCLC patients with and without CNS metastases at diagnoses. OS was worse as the number of metastatic organs at diagnosis increased, with liver metastases being associated with the highest risk of mortality

Resumen Ejecutivo del tratamiento antibiótico domiciliario endovenoso: Directrices de la Sociedad Española de Enfermedades Infecciosas y la Sociedad Española de Hospitalización a Domicilio

Outpatient parenteral antimicrobial therapy (OPAT) programmes make it possible to start or complete intravenous antimicrobial therapy for practically any type of infection at home, provided that patient selection is appropriate for the type of OPAT programme available. Although the clinical management of infections in the home setting is comparable in many respects to that offered in conventional hospitalization (selection of antibiotics, duration of treatment, etc.), there are many aspects that are specific to this care modality. It is essential to be aware of them so that OPAT continues to be as safe and effective as inpatient care. The objective of this clinical guideline is therefore to provide evidence-and expert-based recommendations with a view to standardizing clinical practice in this care modality and contribute to a progressive increase in the number of patients who can be cared for and receive intravenous therapy in their own homes.Los programas de tratamiento antibiótico domiciliario endovenoso (TADE) permiten iniciar o completar el tratamiento antimicrobiano por vía endovenosa de prácticamente cualquier tipo de infección en el domicilio, siempre y cuando se realice una selección del paciente acorde al tipo de programa de TADE que se dispone. Aunque hay aspectos del manejo clínico de las infecciones en el domicilio que son superponibles en la mayoría de los casos a la realizada en la hospitalización convencional (selección de la antibioterapia, duración del tratamiento, etc.), existen numerosos aspectos que son específicos de esta modalidad asistencial. Resulta imprescindible conocerlos para que el TADE siga siendo igual de eficaz y seguro que la hospitalización convencional. El objetivo de esta guía clínica es por tanto proporcionar recomendaciones basadas en la evidencia realizadas por expertos para homogeneizar la práctica clínica de esta modalidad asistencial y contribuir a que se incremente progresivamente el número de pacientes que pueden ser atendidos y recibir tratamiento endovenoso en su propio domicilio

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Penilaian Kinerja Keuangan Koperasi di Kabupaten Pelalawan

This paper describe development and financial performance of cooperative in District Pelalawan among 2007 - 2008. Studies on primary and secondary cooperative in 12 sub-districts. Method in this stady use performance measuring of productivity, efficiency, growth, liquidity, and solvability of cooperative. Productivity of cooperative in Pelalawan was highly but efficiency still low. Profit and income were highly, even liquidity of cooperative very high, and solvability was good

Juxtaposing BTE and ATE – on the role of the European insurance industry in funding civil litigation

One of the ways in which legal services are financed, and indeed shaped, is through private insurance arrangement. Two contrasting types of legal expenses insurance contracts (LEI) seem to dominate in Europe: before the event (BTE) and after the event (ATE) legal expenses insurance. Notwithstanding institutional differences between different legal systems, BTE and ATE insurance arrangements may be instrumental if government policy is geared towards strengthening a market-oriented system of financing access to justice for individuals and business. At the same time, emphasizing the role of a private industry as a keeper of the gates to justice raises issues of accountability and transparency, not readily reconcilable with demands of competition. Moreover, multiple actors (clients, lawyers, courts, insurers) are involved, causing behavioural dynamics which are not easily predicted or influenced. Against this background, this paper looks into BTE and ATE arrangements by analysing the particularities of BTE and ATE arrangements currently available in some European jurisdictions and by painting a picture of their respective markets and legal contexts. This allows for some reflection on the performance of BTE and ATE providers as both financiers and keepers. Two issues emerge from the analysis that are worthy of some further reflection. Firstly, there is the problematic long-term sustainability of some ATE products. Secondly, the challenges faced by policymakers that would like to nudge consumers into voluntarily taking out BTE LEI

Search for stop and higgsino production using diphoton Higgs boson decays

Results are presented of a search for a "natural" supersymmetry scenario with gauge mediated symmetry breaking. It is assumed that only the supersymmetric partners of the top-quark (stop) and the Higgs boson (higgsino) are accessible. Events are examined in which there are two photons forming a Higgs boson candidate, and at least two b-quark jets. In 19.7 inverse femtobarns of proton-proton collision data at sqrt(s) = 8 TeV, recorded in the CMS experiment, no evidence of a signal is found and lower limits at the 95% confidence level are set, excluding the stop mass below 360 to 410 GeV, depending on the higgsino mass