Quantifying the Coordinated Effects of Partial Horizontal Acquisitions

The growth of private-equity investment strategies in which rms often hold partial ownership interests in competing rms has led competition agencies to take an increased interest in as- sessing the competitive e¤ects of partial horizontal acquisitions. We propose a methodology to evaluate the coordinated e¤ects of such acquisitions on di¤erentiated products industries. The acquisitions may be direct and indirect, and may or not correspond to control. The method- ology, that nests full mergers, evaluates the impact on the range of discount factors for which coordination can be sustained. We provide an empirical application to several acquisitions in the wet shaving industry.info:eu-repo/semantics/publishedVersio

Overlapping ownership, endogenous quality, and welfare

This paper investigates how overlapping ownership affects quality levels, consumer surplus, firms' profits and welfare when the industry is a vertically differentiated duopoly and quality choice is endogenous. This issue is particularly relevant since recent empirical evidence suggests that overlapping ownership constitutes an important feature of a multitude of vertically differentiated industries. We show that overlapping ownership while detrimental for welfare, may increase or decrease the quality gap, consumer surplus and firms' profits. In particular, when the overlapping ownership structure is such that the high quality firm places a positive weight on the low quality firm's profits, the incentives of the high quality firm to compete aggressively reduce. This may increase the equilibrium quality of the low quality firm, which in turn may lead to higher consumer surplus, despite higher prices.info:eu-repo/semantics/publishedVersio

Modelling the objective function of managers in the presence of overlapping shareholding

The objective function of managers in the presence of overlapping shareholding may differ from the traditional own-firm profit maximization, as they may internalize the externalities their strategies impose on other firms. The dominant formulation of the objective function in such cases has, however, been critiqued for yielding counter-intuitive profit weights when the ownership of non-overlapping shareholders is highly dispersed. In this paper, we examine this issue. First, we make use of a probabilistic voting model (in which shareholders vote to elect the manager) to microfound an alternative formulation of the objective function of managers, which solves the above-mentioned criticism. Second, we apply the two formulations to the set of S&P 500 firms. We show that ownership dispersion of non-overlapping shareholders is, in fact, a relevant empirical issue, which may induce an over-quantification of the profit weights computed from the dominant formulation, particularly under a proportional control assumption.info:eu-repo/semantics/publishedVersio

Modeling horizontal shareholding with ownership dispersion

The dominantformulationformodelingtheobjectivefunctionofmanagersofcompeting rms withhorizontalshareholdinghasbeencritiquedforproducingtheresultthat,ifnon-horizontal shareholdersarehighlydispersed,managerswouldmimictheinterestsofhorizontalsharehold- ers eveniftheyownashareofthe rmthatdoesnotinducefullcontrol.Weshowthatthis issuecanbeavoided(whilemaintainingtheremainingfeaturesofthedominantapproach) withanalternativeformulationthatisderivedfromaprobabilisticvotingmodelthatassumes shareholderswithhigher nancialstakeswilltakegreaterinterestinthemanagerialactions, whichyieldstheresultthatmanagersmaximizeacontrol-weightedsumoftheshareholders relativereturns.info:eu-repo/semantics/publishedVersio

Hemodynamic, respiratory conditions and their safety when performing exercises in an intensive care unit

Introduction: The prolonged stay in the Intensive Care Unit (ICU) compromises the functionality and quality of life of patients. Physical exercise can contribute to improving functional status and accelerating return to activities. Objective: to assess the safety of patient mobilization in the ICU, describing the hemodynamic and respiratoryconditions and the occurrence of adverse effects. Methods: This is an uncontrolled, “before and after” study, carried out with 42 patients hospitalized in the ICU, submitted to mobilization through passive kinesiotherapy, active kinesiotherapy, seating and walking. In addition to epidemiological and clinical data, the adverse effects of mobilization were evaluated. Hemodynamic and respiratory variables were measured at the bedside, at three times: before, during and immediately after mobilization. Results: Elderly patients (65.8±13.7 years), predominantly women (59.5%), with a clinical admission diagnosis (64.3%) were studied. Patients on mechanical ventilation predominantly performed passive kinesiotherapy (57.1%) and those on spontaneous ventilation predominantly performed seating (28.6%) and walking (28.6%). Among the adverse effects, there was an unsatisfactory ventilatory muscle pattern (7.1%), peripheral oxygen saturation less than 90% (4.8%), and changes in blood pressure (7.1%). There was no record of changes in heart rate, accidental extubation or loss of venous access during mobilizations, as well as changes in hemodynamic, respiratory and oxygenation behavior before, during and after mobilization were not observed. Conclusion: physical exercises proved to be safe, viable in any clinical environment, respecting safety limits, and may bring potential benefits to patients admitted to the ICU.Introdução: A permanência prolongada na Unidade de Terapia Intensiva (UTI) compromete a funcionalidade e a qualidade de vida dos pacientes. Programas de exercícios podem contribuir na melhora do status funcional e aceleração do retorno às atividades. Objetivo: avaliar a segurança de exercícios em pacientes na UTI, descrevendo as condições hemodinâmicas e respiratórias e a ocorrência de efeitos adversos. Métodos: trata-se de um estudo não controlado, do tipo “antes e depois”, realizado com 42 pacientes internados em UTI, submetidos à mobilização através de cinesioterapia passiva, cinesioterapia ativa, sedestração e deambulação. Além dos dados epidemiológicos e clínicos, foram avaliados os efeitos adversos da mobilização. As variáveis hemodinâmicas e respiratórias foram mensuradas à beira do leito, em três momentos: antes, durante e imediatamente após a mobilização. Resultados: Foram estudados pacientes idosos (65,8±13,7 anos), predominantemente mulheres (59,5%), com diagnóstico admissional de natureza clínica (64,3%). Os pacientes em ventilação mecânica realizaram predominantemente cinesioterapia passiva (57,1%) e aqueles em ventilação espontânea realizaram predominantemente sedestração (28,6%) e deambulação (28,6%). Dentre os efeitos adversos, observou-se padrão muscular ventilatório insatisfatório (7,1%), saturação periférica de oxigênio inferior a 90% (4,8%), alteração da pressão arterial (7,1%). Não houve registro de alteração da frequência cardíaca, extubação acidental ou perda de acesso venoso durante as mobilizações, assim como não foram observadas alterações no comportamento hemodinâmico, respiratório e da oxigenação antes, durante e após a mobilização. Conclusão: exercícios físicos demonstraram-se seguros, viáveis em qualquer âmbito clínico, respeitando-se os limites de segurança, podendo trazer benefícios potenciais para pacientes internados em UTI

Condições hemodinâmicas, respiratórias e sua segurança na realização de exercícios em unidade de terapia intensiva

Introdução: A permanência prolongada na Unidade de Terapia Intensiva (UTI) compromete a funcionalidade e a qualidade de vida dos pacientes. Programas de exercícios podem contribuir na melhora do status funcional e aceleração do retorno às atividades. Objetivo: avaliar a segurança de exercícios em pacientes na UTI, descrevendo as condições hemodinâmicas e respiratórias e a ocorrência de efeitos adversos. Métodos: trata-se de um estudo não controlado, do tipo “antes e depois”, realizado com 42 pacientes internados em UTI, submetidos à mobilização através de cinesioterapia passiva, cinesioterapia ativa, sedestração e deambulação. Além dos dados epidemiológicos e clínicos, foram avaliados os efeitos adversos da mobilização. As variáveis hemodinâmicas e respiratórias foram mensuradas à beira do leito, em três momentos: antes, durante e imediatamente após a mobilização. Resultados: Foram estudados pacientes idosos (65,8±13,7 anos), predominantemente mulheres (59,5%), com diagnóstico admissional de natureza clínica (64,3%). Os pacientes em ventilação mecânica realizaram predominantemente cinesioterapia passiva (57,1%) e aqueles em ventilação espontânea realizaram predominantemente sedestração (28,6%) e deambulação (28,6%). Dentre os efeitos adversos, observou-se padrão muscular ventilatório insatisfatório (7,1%), saturação periférica de oxigênio inferior a 90% (4,8%), alteração da pressão arterial (7,1%). Não houve registro de alteração da frequência cardíaca, extubação acidental ou perda de acesso venoso durante as mobilizações, assim como não foram observadas alterações no comportamento hemodinâmico, respiratório e da oxigenação antes, durante e após a mobilização. Conclusão: exercícios físicos demonstraram-se seguros, viáveis em qualquer âmbito clínico, respeitando-se os limites de segurança, podendo trazer benefícios potenciais para pacientes internados em UTI

Predictive and therapeutic implications of a novel PLCγ1/SHP2-driven mechanism of cetuximab resistance in metastatic colorectal cancer

© 2022 The Authors; Published by the American Association for Cancer Research. This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 International (CC BY-NC-ND)Purpose: Cetuximab is an EGFR-targeted therapy approved for the treatment of RAS wild-type (WT) metastatic colorectal cancer (mCRC). However, about 60% of these patients show innate resistance to cetuximab. To increase cetuximab efficacy, it is crucial to successfully identify responder patients, as well as to develop new therapeutic approaches to overcome cetuximab resistance. Experimental design: We evaluated the value of EGFR effector phospholipase C gamma 1 (PLCγ1) in predicting cetuximab responses, by analyzing progression-free survival (PFS) of a multicentric retrospective cohort of 94 treated patients with mCRC (log-rank test and Cox regression model). Furthermore, we used in vitro and zebrafish xenotransplant models to identify and target the mechanism behind PLCγ1-mediated resistance to cetuximab. Results: In this study, levels of PLCγ1 were found increased in RAS WT tumors and were able to predict cetuximab responses in clinical samples and in vitro and in vivo models. Mechanistically, PLCγ1 expression was found to bypass cetuximab-dependent EGFR inhibition by activating ERK and AKT pathways. This novel resistance mechanism involves a noncatalytic role of PLCγ1 SH2 tandem domains in the propagation of downstream signaling via SH2-containing protein tyrosine phosphatase 2 (SHP2). Accordingly, SHP2 inhibition sensitizes PLCγ1-resistant cells to cetuximab. Conclusions: Our discoveries reveal the potential of PLCγ1 as a predictive biomarker for cetuximab responses and suggest an alternative therapeutic approach to circumvent PLCγ1-mediated resistance to cetuximab in patients with RAS WT mCRC. In this way, this work contributes to the development of novel strategies in the medical management and treatment of patients with mCRC.M. Martins' research was supported by Liga Portuguesa Contra o Cancro (LPCC): Terry Fox Fundation; Investigador FCT- Fundação para a Ciência e Technologia (IF/00409/2014) and IMM Bridge grant; RC-D research was supported by Fundação para a Ciência e Technologia (SFRH/BD/139138/2018). A. Fernandes was supported by LPCC-IMM BIOBANK; R. Fior was supported by Champalimaud Foundation and L. Costa was supported by Merck Serono.info:eu-repo/semantics/publishedVersio

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear un derstanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5–7 vast areas of the tropics remain understudied.8–11 In the American tropics, Amazonia stands out as the world’s most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepre sented in biodiversity databases.13–15 To worsen this situation, human-induced modifications16,17 may elim inate pieces of the Amazon’s biodiversity puzzle before we can use them to understand how ecological com munities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple or ganism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region’s vulnerability to environmental change. 15%–18% of the most ne glected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lostinfo:eu-repo/semantics/publishedVersio

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear understanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5,6,7 vast areas of the tropics remain understudied.8,9,10,11 In the American tropics, Amazonia stands out as the world's most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepresented in biodiversity databases.13,14,15 To worsen this situation, human-induced modifications16,17 may eliminate pieces of the Amazon's biodiversity puzzle before we can use them to understand how ecological communities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple organism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region's vulnerability to environmental change. 15%–18% of the most neglected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lost