Progression of Lung Disease in Preschool Patients with Cystic Fibrosis

RATIONALE: Implementation of intervention strategies to prevent lung damage in early cystic fibrosis (CF) requires objective outcome measures that capture and track lung disease. OBJECTIVES: To define the utility of the Lung Clearance Index (LCI), measured by multiple breath washout, as a means to track disease progression in preschool children with CF. METHODS: Children with CF between the ages of 2.5 and 6 years with a confirmed diagnosis of CF and age-matched healthy control subjects were enrolled at three North American CF centers. Multiple breath washout tests were performed at baseline, 1, 3, 6, and 12 months to mimic time points chosen in clinical care and interventional trials; spirometry was also conducted. A generalized linear mixed-effects model was used to distinguish LCI changes associated with normal growth and development (i.e., healthy children) from the progression of CF lung disease. MEASUREMENTS AND MAIN RESULTS: Data were collected on 156 participants with 800 LCI measurements. Although both LCI and spirometry discriminated health from disease, only the LCI identified significant deterioration of lung function in CF over time. The LCI worsened during cough episodes and pulmonary exacerbations, whereas similar symptoms in healthy children were not associated with increased LCI values. CONCLUSIONS: LCI is a useful marker to track early disease progression and may serve as a tool to guide therapies in young patients with CF

A Systematic Approach to Multiple Breath Nitrogen Washout Test Quality

Background: Accurate estimates of multiple breath washout (MBW) outcomes require correct operation of the device, appropriate distraction of the subject to ensure they breathe in a manner representative of their relaxed tidal breathing pattern, and appropriate interpretation of the acquired data. Based on available recommendations for an acceptable MBW test, we aimed to develop a protocol to systematically evaluate MBW measurements based on these criteria. Methods: 50MBWtest occasions were systematically reviewed for technical elements and whether the breathing pattern was representative of relaxed tidal breathing by an experienced MBW operator. The impact of qualitative and quantitative criteria on inter-observer agreement was assessed across eight MBW operators (n = 20 test occasions, compared using a Kappa statistic). Results: Using qualitative criteria, 46/168 trials were rejected: 16.6%were technically unacceptable and 10.7% were excluded due to inappropriate breathing pattern. Reviewer agreement was good using qualitative criteria and further improved with quantitative criteria from (κ = 0.53– 0.83%) to (κ 0.73–0.97%), but at the cost of exclusion of further test occasions in this retrospective data analysis. Conclusions: The application of the systematic review improved inter-observer agreement but did not affect reported MBW outcomes

Infected pancreatic necrosis: outcomes and clinical predictors of mortality. A post hoc analysis of the MANCTRA-1 international study

: The identification of high-risk patients in the early stages of infected pancreatic necrosis (IPN) is critical, because it could help the clinicians to adopt more effective management strategies. We conducted a post hoc analysis of the MANCTRA-1 international study to assess the association between clinical risk factors and mortality among adult patients with IPN. Univariable and multivariable logistic regression models were used to identify prognostic factors of mortality. We identified 247 consecutive patients with IPN hospitalised between January 2019 and December 2020. History of uncontrolled arterial hypertension (p = 0.032; 95% CI 1.135-15.882; aOR 4.245), qSOFA (p = 0.005; 95% CI 1.359-5.879; aOR 2.828), renal failure (p = 0.022; 95% CI 1.138-5.442; aOR 2.489), and haemodynamic failure (p = 0.018; 95% CI 1.184-5.978; aOR 2.661), were identified as independent predictors of mortality in IPN patients. Cholangitis (p = 0.003; 95% CI 1.598-9.930; aOR 3.983), abdominal compartment syndrome (p = 0.032; 95% CI 1.090-6.967; aOR 2.735), and gastrointestinal/intra-abdominal bleeding (p = 0.009; 95% CI 1.286-5.712; aOR 2.710) were independently associated with the risk of mortality. Upfront open surgical necrosectomy was strongly associated with the risk of mortality (p < 0.001; 95% CI 1.912-7.442; aOR 3.772), whereas endoscopic drainage of pancreatic necrosis (p = 0.018; 95% CI 0.138-0.834; aOR 0.339) and enteral nutrition (p = 0.003; 95% CI 0.143-0.716; aOR 0.320) were found as protective factors. Organ failure, acute cholangitis, and upfront open surgical necrosectomy were the most significant predictors of mortality. Our study confirmed that, even in a subgroup of particularly ill patients such as those with IPN, upfront open surgery should be avoided as much as possible. Study protocol registered in ClinicalTrials.Gov (I.D. Number NCT04747990)

Ahora / Ara

La cinquena edició del microrelatari per l’eradicació de la violència contra les dones de l’Institut Universitari d’Estudis Feministes i de Gènere «Purificación Escribano» de la Universitat Jaume I vol ser una declaració d’esperança. Aquest és el moment en el qual les dones (i els homes) hem de fer un pas endavant i eliminar la violència sistèmica contra les dones. Ara és el moment de denunciar el masclisme i els micromasclismes començant a construir una societat més igualitària. Cadascun dels relats del llibre és una denúncia i una declaració que ens encamina cap a un món millor

O direito no campo de públicas: experiências e desafios de ensino

This article seeks to systematize the learnings of teaching Law and Public Policy (LPP) in different training programs. Adapting these courses to different student profiles requires an understanding of multidisciplinary issues, to deal with the typical difficulties of the legal language and, at the same time, to establish a mutually constructive dialogue with the related areas of the Public Field. This article reports some didactic experiences of LPP, seeking to identify paths for the theoretical and empirical development of the LPP approach. Thereby we want to contribute to the organization of a conceptual and analytical repertoire in LPP, to expand its dissemination both in the legal area and in the interdisciplinary relations with the Public FieldEste artículo busca sistematizar lo aprendido desde el enfoque de Derecho y Políticas Públicas (DPP) en diferentes experiencias docentes, como cursos de pregrado o posgrado, ya sea para estudiantes de Derecho o del llamado 'área pública' (administración pública, análisis de políticas públicas y afines). La adecuación de estos cursos a diferentes perfiles de estudiantes requiere una comprensión de los problemas de la multidisciplinariedad, con el fin de hacer frente a las dificultades propias del lenguaje jurídico al mismo tiempo que se abre a un diálogo mutuamente constructivo con áreas afines en el 'área pública'. Este artículo relata algunas experiencias didácticas de DPP, tratando de identificar en ellas líneas comunes para el desarrollo teórico y empírico del enfoque. Con ello queremos contribuir a la organización de un repertorio conceptual y analítico en DPP, facilitando su difusión tanto en el ámbito jurídico como en las relaciones interdisciplinares con el 'área pública'.Este artigo procura sistematizar o acúmulo da abordagem Direito e Políticas Públicas (DPP) em experiências de ensino diversas, como cursos de graduação ou pós-graduação, oferecidos a estudantes de Direito, do Campo de Públicas e em escolas de Advocacia Pública. A adequação desses cursos aos diferentes perfis de estudantes requer a compreensão dos problemas da multidisciplinaridade, para lidar com o fechamento típico da linguagem jurídica ao mesmo tempo em que essa se abre ao diálogo mutuamente construtivo com as áreas afins do Campo de Públicas. Este artigo relata algumas experiências didáticas de DPP, procurando identificar nelas linhas comuns para o desenvolvimento teórico e empírico da abordagem. Com isso quer-se contribuir para a organização de um repertório conceitual e analítico em DPP, facilitando a sua disseminação tanto na área jurídica como nas relações interdisciplinares com o Campo de Públicas

A family of manganese complexes containing heterocyclic-based ligands with cytotoxic properties

We describe the synthesis of three new manganese (II) complexes containing the bidentate ligands 2-(1-methyl-3-pyrazolyl)pyridine (pypz-Me) and ethyl 2-(3-(pyridine-2-yl)-1H–pyrazol-1-yl)acetate (pypz-CH2COOEt), with formula [MnX2(pypz-Me)2] (X = Cl−1, CF3SO3−2) and [Mn(CF3SO3)2(pypz-CH2COOEt)2] 3. Complexes 1–3 have been characterized through analytical, spectroscopic and electrochemical techniques, as well as by monocrystal X-ray diffraction analysis. The complexes show a six-coordinated Mn(II) ion though different stereoisomers have been isolated for the three compounds. Complexes 1–3, together with the previously described compounds [MnCl2(pypz-H)2] 4, [Mn(CF3SO3)2(pypz-H)2] 5, [Mn(NO3)2(pypz-H)2] 6, [MnCl2(H2O)2(pypz-H)2] 7 (pypz-H = 2-(3-pyrazolyl)pyridine) and ([Mn(CF3SO3)2((−)-L)2] 8, ((−)-L = (−)-pinene[5,6]bipyridine), were tested in vitro for cytotoxic activity against NCI-H460 and OVCAR-8 cancer cell lines. The geometry of a specific compound does not seem to influence its activity in a significant extent. However, among the tested compounds those that display hydrophobic substituents on the pyrazole ring and triflate ions as labile ligands show the best antiproliferative properties. Specifically, compound 8 containing the pinene-bipyridine ligand presents an antiproliferative activity similar to that of cisplatin and higher than that of carboplatin, and displays selectivity for tumour cells. Its antiproliferative effect is due to the generation of ROS species that allow the compound to interact with DNAThis research has been financed by Ministerio de Economia y Competitividad (MINECO) Spain, through projects CTQ2015-66143-P and BIO2013-43517, by Universitat de Girona through projects MPCUdG2016-18 and MPCUdG2016/048 and by DGU, Generalitat de Catalunya through projects SGR2014-70 and SGR2014-14

Inter-Reviewer Agreement after independent review of 20 test-occasions (61 trials).

<p>Quantitative limits were applied after qualitative review, however each of the two quantitative limits (%CV V_T and V_T limits for size) were applied independently.</p

Demographics of cross-sectional study population, with results from each step of the quality control criteria applied.

<p>Demographics of cross-sectional study population, with results from each step of the quality control criteria applied.</p

Summary of technical and qualitative criteria used to evaluate MBW tracings.

<p>Summary of technical and qualitative criteria used to evaluate MBW tracings.</p

Distribution of CV% V_T for acceptable and unacceptable trials.

<p>Distribution of CV% V_T for acceptable and unacceptable trials.</p