Cash budget versus financial budget : advantages and disadvantages : a case study

O objetivo desta tese foi o de apresentar um orçamento alternativo ao orçamento de tesouraria. Esse projeto é interessante porque permite consolidar o conhecimento sobre orçamentos e colocar o que foi aprendido em prática. Esta tese também pretende mostrar com dois exemplos de orçamento diferentes como estes podem ser aplicados numa empresa específica. O método de pesquisa escolhido foi o estudo de caso, porque pretende-se explicar com este trabalho, quais são as vantagens e desvantagens verificadas com o orçamento financeiro e com o orçamento de tesouraria. Algumas das vantagens verificadas com o orçamento de tesouraria são as informações detalhadas que contém; o foco no curto prazo e a descrição de e para onde vai o fluxo monetário. Por outro lado, temos o orçamento financeiro. Ele tem algumas vantagens em comum com o orçamento de tesouraria - o foco de curto prazo. Ele permite-nos estimar se a empresa vai ter lucro ou prejuízo no final do mês ou do ano em análise. O orçamento financeiro foi criado com as informações da empresa. Ambos os tipos de orçamento tem informações importantes e diferentes que se complementam. Os meus resultados foram obtidos numa empresa específica, mas que podem ser aplicáveis a outras empresas.The purpose of this thesis is to present an alternative budget to the cash budget. This project is interesting because it allows me to consolidate my knowledge about budget and put what I have been learning into practise. This thesis also pretends to show two budget examples and how they could be applied in a specific company. The research method chosen was a case study because this work pretends to explain what are the advantages and disadvantages verified with the financial budget and with the cash budget. Some of the advantages verified with the cash budget are the detailed information because it contains short-term focus, and more information about how the cash flows. On the other hand, we have the financial budget. It has some advantages in common with the cash budget – short-term focus. It provides an expectation if the company is going to have profit/loss in the end of the month or year in analysis. The financial budget was created with the company information. Both types of budget have important and different information and they complement each other. My results were obtained related to a specific company but these results could be applicable to other companies

Estudo do efeito anti-angiogénico de novos alvos terapêuticos no tratamento do carcinoma mamário

Dissertação para obtenção do Grau de Mestre em Genética Molecular e BiomedicinaO ligando Delta-like 4 (Dll4), através da via de sinalização Notch, é um potente regulador da angiogénese, sendo expresso na componente arterial do sistema vascular. Nos adultos, a sua expressão encontra-se aumentada numa grande variedade de condições patológicas. Neste trabalho avaliou-se o desenvolvimento tumoral em ratinhos com perda parcial de função de Dll4 (Dll4+/-). A mutação Dll4+/- conduz a um aumento da densidade vascular, mas devido à fraca maturação dos vasos neoformados estes não são totalmente funcionais, têm fraca perfusão e elevada extravasação. A área primordial onde a terapia anti-Dll4 se revela promissora é na oncologia. Neste trabalho efectuaram-se ensaios com perda parcial de função de Dll4 e com proteína solúvel EphB4 usando como modelo ratinhos transgénicos que desenvolvem tumores mamários autonomamente e metástases pulmonares, por sobreexpressão transgénica do gene neu (erbB2/her2) sob o controlo do promotor do Mouse Mammary Tumor Virus (MMTV) – ratinhos MMTV-NeuNDL2-5. Os resultados indicaram que tanto a perda parcial de Dll4 como o bloqueio da via EfrinaB2/EphB4 conduzem a uma redução significativa do desenvolvimento tumoral e da metastização pulmonar, tendo o efeito mais pronunciado sido obtido mediante a administração da proteína solúvel EphB4

Combination of Dll4/Notch and Ephrin-B2/EphB4 targeted therapy is highly effective in disrupting tumor angiogenesis

<p>Abstract</p> <p>Background</p> <p>Dll4/Notch and Ephrin-B2/EphB4 pathways play critical roles in tumor vessel development and maturation. This study evaluates the efficacy of the inhibition of both signaling pathways, alone and in combination, in reducing the growth of an autochthonous mouse tumor and assesses potential adverse effects.</p> <p>Methods</p> <p>We used the transgenic RIP1-Tag2 tumor model to study the effects of 1) inhibition of Dll4/Notch by either <it>Dll4 </it>allelic deletion or use of a soluble extracellular Dll4 (sDll4), 2) inhibition of Ephrin-B2/EphB4 signaling by a soluble extracellular EphB4 fused to albumin (sEphB4-Alb), and 3) inhibition of both pathways by sEphB4-Alb combined with either <it>Dll4 </it>allelic deletion or sDll4. To investigate adverse effects, we used inducible endothelial-specific <it>Dll4 </it>knock-out mice, treated with sEphB4-Alb, and carried out histopathological analysis.</p> <p>Results</p> <p><it>Dll4 </it>allele deletion or soluble Dll4 treatment resulted in increased tumor vessel density, reduced mural cell recruitment and vessel perfusion which resulted in reduced tumor size. The soluble EphB4 instead reduced vessel density and vessel perfusion, leading to reduction of tumor size. Greater efficacy was observed when sEphB4-Alb was combined with either <it>Dll4 </it>allele deletion or sDll4 in regards to tumor size, vessel perfusion and mural cell recruitment. Induced endothelial specific <it>Dll4 </it>loss-of-function caused hepatic vascular alterations, which were prevented by concomitant sEphB4-Alb treatment.</p> <p>Conclusion</p> <p>Combination targeting of Dll4/Notch and Ephrin-B2/EphB4 has potential for clinical investigation, providing cumulative efficacy and increased safety over Dll4/Notch inhibition alone.</p

Complete blood count parameters as biomarkers of retinopathy of prematurity: a Portuguese multicenter study

© The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.Purpose: To evaluate complete blood count (CBC) parameters in the first week of life as predictive biomarkers for the development of retinopathy of prematurity (ROP). Methods: Multicenter, prospective, observational study of a cohort of preterm infants born with gestational age (GA) < 32 weeks or birth weight < 1500 g in eight Portuguese neonatal intensive care units. All demographic, clinical, and laboratory data from the first week of life were collected. Univariate logistic regression was used to assess risk factors for ROP and then multivariate regression was performed. Results: A total of 455 infants were included in the study. The median GA was 29.6 weeks, and the median birth weight was 1295 g. One hundred and seventy-two infants (37.8%) developed ROP. Median values of erythrocytes (p < 0.001), hemoglobin (p < 0.001), hematocrit (p < 0.001), mean corpuscular hemoglobin concentration (p < 0.001), lymphocytes (p = 0.035), and platelets (p = 0.003) of the group of infants diagnosed with ROP any stage were lower than those without ROP. Mean corpuscular volume (MCV) (p = 0.044), red blood cell distribution width (RDW) (p < 0.001), erythroblasts (p < 0.001), neutrophils (p = 0.030), neutrophils-lymphocytes ratio (p = 0.028), and basophils (p = 0.003) were higher in the ROP group. Higher values of MCV, erythroblasts, and basophils remained significantly associated with ROP after multivariate regression. Conclusion: In our cohort, the increase in erythroblasts, MCV, and basophils in the first week of life was significantly and independently associated with the development of ROP. These CBC parameters may be early predictive biomarkers for ROP.Open access funding provided by FCT|FCCN (b-on). This work was supported by the Laboratório de Genética and the Instituto de Saúde Ambiental (ISAMB) of the Faculdade de Medicina of Universidade de Lisboa and the Instituto de Investigação Científica Bento da Rocha Cabral. The writing of the manuscript was also supported by funds from Fundação para a Ciência e a Tecnologia to ISAMB (ref. UIDB/04295/2020 and UIDP/04295/2020). This work was also part of a doctoral project funding by the company CUF with a PhD grant in Medicine awarded in 2021 and by the Portuguese Society of Ophthalmology with a PhD grant awarded in 2019.info:eu-repo/semantics/publishedVersio

Low-Dosage Inhibition of DII4 Signaling Promotes Wound Healing by Inducing Functional Neo-Angiogenesis

Recent findings regarding Dll4 function in physiological and pathological conditions indicate that this Notch ligand may constitute an important therapeutic target. Dll4 appears to be a major anti-angiogenic agent, occupying a central role in various angiogenic pathways. The first trials of anti-Dll4 therapy in mice demonstrated a paradoxical effect, as it reduced tumor perfusion and growth despite leading to an increase in vascular density. This is seen as the result of insufficient maturation of the newly formed vasculature causing a circulatory defect and increased tumor hypoxia. As Dll4 function is known to be closely dependent on expression levels, we envisioned that the therapeutic anti-Dll4 dosage could be modulated to result in the increase of adequately functional blood vessels. This would be useful in conditions where vascular function is a limiting factor for recovery, like wound healing and tissue hypoxia, especially in diabetic patients. Our experimental results in mice confirmed this possibility, revealing that low dosage inhibition of Dll4/Notch signaling causes improved vascular function and accelerated wound healing

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P &lt; 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Low-dosage sDll4-Fc does not affect perfusion levels and leads to only a small increase in extravasation while higher dosages cause decreased perfusion and highly increased extravasation.

<p>A) Representative anti-PECAM and anti-Lectin immunofluorescence images of neo-vasculature in granulation tissue of wounds treated with 0,05 mg/kg or 2,5 mg/kg compared with control mice injected with PBS, in day 6. B) The percentage of lectin-perfused blood vessels is similar between PBS- and 0,05 mg/kg sDll4-Fc injected mice but since vascular density is increased in the latter this result represents an effective increase in vascular function in the wound basin. Vascular perfusion is highly decreased in wounds of mice injected with 2,5 mg/kg sDll4-Fc. C) Representative anti-PECAM and Evans Blue immunofluorescence images of neo-vasculature in granulation tissue of wounds treated with 0,05 mg/kg or 2,5 mg/kg compared with control mice injected with PBS, in day 6. Vascular extravasation is highly increased in wounds of mice injected with 2,5 mg/kg sDll4-Fc but displays only a small increase in the case of 0,05 mg/kg sDll4-Fc injected mice. * In graphics represents p<0,05.</p