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Executive compensation tied to ESG performance: international evidence
Get PDFUsing a wide sample of international publicly traded firms, this paper studies the rapidly increasing practice of incorporating Environmental, Social, and Governance (ESG) metrics in executive compensation contracts. Our evidence suggests that this compensation practice varies at the country, industry, and firm levels in ways that are consistent with efficient incentive contracting. We also observe that reliance on ESG metrics in executive compensation arrangements is associated with engagement, voting, and trading by institutional investors, which suggests that firms could be adopting this practice to align their management's objectives with the preferences of certain shareholder groups. Finally, we find that the adoption of ESG Pay is accompanied by improvements in key ESG outcomes, but not by improvements in financial performance
American Catholics and Religious Intolerance in Franco’s Spain
No full textRoman Catholics in Francoist Spain and in the United States share a
common faith, but the history of Catholicism in these two countries
followed very different paths. Before key transformations that the Second
Vatican Council ushered in, Catholic attitudes towards religious freedom
in these two countries were sharply divergent. Each nation’s political
system, with its own historical circumstances, was also very different. The
United States, for its part, was a democracy in which religious freedom had
become a substantial part of its own political tradition. Francisco Franco’s
Spain was instead a military dictatorship that some critics mocked as a
“National-Catholic” state, if not a “clerical-fascist” regime, as the famous
American anti-Catholic author Paul Blanshard once put it. As a result,
Catholics in Spain and the United States approached the matter of religious
freedom, as well as the closely related issue of the separation between
church and state, very differently. However, Vatican II crucial changes
radically transformed Spanish Catholics’ attitudes, which eventually
resembled American ones
Functional engagement of the PD-1/PD-L1 complex but not PD-l1 expression is highly predictive of patient response to immunotherapy in non-small-cell lung cancer
No full textPURPOSEIn many cancers, the expression of immunomodulatory ligands leads to immunoevasion, as exemplified by the interaction of PD-L1 with PD-1 on tumor-infiltrating lymphocytes. Profound advances in cancer treatments have come with the advent of immunotherapies directed at blocking these immuno-suppressive ligand-receptor interactions. However, although there has been success in the use of these immune checkpoint interventions, correct patient stratification for these therapies has been challenging.MATERIALS AND METHODSTo address this issue of patient stratification, we have quantified the intercellular PD-1/PD-L1 interaction in formalin-fixed paraffin-embedded tumor samples from patients with non-small cell lung carcinoma, using a high-throughput automated quantitative imaging platform (quantitative functional proteomics [QF-Pro]).RESULTSThe multisite blinded analysis across a cohort of 188 immune checkpoint inhibitor-treated patients demonstrated the intra- and intertumoral heterogeneity of PD-1/PD-L1 immune checkpoint engagement and notably showed no correlation between the extent of PD-1/PD-L1 interaction and PD-L1 expression. Importantly, PD-L1 expression scores used clinically to stratify patients correlated poorly with overall survival; by contrast, patients showing a high PD-1/PD-L1 interaction had significantly better responses to anti-PD-1/PD-L1 treatments, as evidenced by increased overall survival. This relationship was particularly strong in the setting of first-line treatments.CONCLUSIONThe functional readout of PD-1/PD-L1 interaction as a predictive biomarker for the stratification of patients with non-small-cell lung carcinoma, combined with PD-L1 expression, should significantly improve the response rates to immunotherapy. This would both capture patients excluded from checkpoint immunotherapy (high PD-1/PD-L1 interaction but low PD-L1 expression, 24% of patients) and additionally avoid treating patients who despite their high PD-L1 expression do not respond and suffer from side effects
Identification and experimental validation of druggable epigenetic targets in hepatoblastoma
No full textBackground & Aims: Hepatoblastoma (HB) is the most frequent childhood liver cancer. Patients with aggressive tumors have
limited therapeutic options; therefore, a better understanding of HB pathogenesis is needed to improve treatment. HBs have a
very low mutational burden; however, epigenetic alterations are increasingly recognized. We aimed to identify epigenetic regulators consistently dysregulated in HB and to evaluate the therapeutic efficacy of their targeting in clinically relevant models.
Methods: We performed a comprehensive transcriptomic analysis of 180 epigenetic genes. Data from fetal, pediatric, adult,
peritumoral (n = 72) and tumoral (n = 91) tissues were integrated. Selected epigenetic drugs were tested in HB cells. The most
relevant epigenetic target identified was validated in primary HB cells, HB organoids, a patient-derived xenograft model, and a
genetic mouse model. Transcriptomic, proteomic and metabolomic mechanistic analyses were performed.
Results: Altered expression of genes regulating DNA methylation and histone modifications was consistently observed in association with molecular and clinical features of poor prognosis. The histone methyltransferase G9a was markedly upregulated in
tumors with epigenetic and transcriptomic traits of increased malignancy. Pharmacological targeting of G9a significantly inhibited
growth of HB cells, organoids and patient-derived xenografts. Development of HB induced by oncogenic forms of b-catenin and
YAP1 was ablated in mice with hepatocyte-specific deletion of G9a. We observed that HBs undergo significant transcriptional
rewiring in genes involved in amino acid metabolism and ribosomal biogenesis. G9a inhibition counteracted these pro-tumorigenic
adaptations. Mechanistically, G9a targeting potently repressed the expression of c-MYC and ATF4, master regulators of HB
metabolic reprogramming.
Conclusions: HBs display a profound dysregulation of the epigenetic machinery. Pharmacological targeting of key epigenetic
effectors exposes metabolic vulnerabilities that can be leveraged to improve the treatment of these patients
Análisis de costo-efectividad de los cuidados paliativos a pacientes oncológicos de fin de vida
Get PDFEn pacientes con enfermedad terminal, los servicios de cuidados paliativos do-
miciliarios pueden alinear sus preferencias de cuidado en domicilio con resul-
tados sanitarios deseables. El objetivo fue estudiar la costo-efectividad de los
cuidados paliativos domiciliarios en pacientes oncológicos en el último año de
vida en el subsector público de salud de una provincia argentina. Se desarrolló
un modelo de Markov de costo-efectividad desde una perspectiva social y del
financiador de salud, de modo que el mismo pudiera reflejar la realidad de
los cuidados paliativos domiciliarios en el ámbito local, en comparación con
los cuidados habituales. Se calcularon los costos directos para el sistema de
salud, con base en información local, así como también los costos indirectos
de los cuidados informales no remunerados. La provisión de cuidados palia-
tivos incrementó en un 10,32% la probabilidad que los pacientes fallezcan
en el hogar, en relación con los cuidados habituales, con un ahorro anual de
USD 750 y USD 1.012 por paciente desde la perspectiva social y del financia-
dor, respectivamente, en el subsector público de salud de Río Negro. Tanto des-
de la perspectiva social como del financiador, la estrategia de implementación
de un servicio organizado de cuidados tiene una mayor efectividad, medida en
porcentaje de pacientes que fallecen en su domicilio, a un menor costo. El prin-
cipal inductor de costos corresponde, desde la perspectiva social, a los cuidados
informales provistos por las familias, mientras que desde la perspectiva del
financiador corresponde a los salarios del personal de salud.Home palliative care services of terminal patients
may associate home care preferences with desir-
able health outcomes. This study aimed to evalu-
ate the cost-effectiveness of home palliative care of
cancer patients in the last year of life in the pub-
lic health subsector in a province of Argentina. A
cost-effectiveness Markov model was developed
from a social and the health funder’s perspective
in order to reflect the reality of home palliative
care at the local level compared with usual care.
Direct costs to the health system and indirect costs
of unpaid informal care were estimated based on
local information. Palliative care increased the
likelihood of patients dying at home by 10.32%
compared with usual care, with annual savings of
USD 750 and USD 1,012 per patient, respectively,
from both the social and the funder’s perspec-
tive in the public health subsector in Río Negro.
From both the social and financial perspective, the
strategy to implement organized care services was
more effective and lower-cost, measured by the
percentage of patients who died at home. From a
social perspective, the main cost inducer was the
formal care provided by families, but from the
funder’s perspective, it refers to the salaries of the
health team.Os serviços de cuidados paliativos domiciliares de
pacientes terminais podem associar as preferên-
cias de cuidado domiciliar com resultados desejá-
veis de saúde. O objetivo deste texto foi avaliar a
relação custo-efetividade dos cuidados paliativos
domiciliares em pacientes oncológicos no último
ano de vida, no subsetor de saúde pública de uma
província na Argentina. Um modelo Markov de
custo-efetividade foi desenvolvido a partir de uma
perspectiva social e do financiador de saúde para
que pudesse refletir a realidade dos cuidados pa-
liativos domiciliares em âmbito local comparado
aos cuidados habituais. Os custos diretos para o
sistema de saúde e os custos indiretos de cuidados
informais não remunerados foram calculados com
base em informações locais. A prestação de cuida-
dos paliativos aumentou 10,32% a probabilidade
de os doentes morrerem em casa em relação com
os cuidados habituais, com uma economia anual
de USD 750 e USD 1.012 por paciente, respeti-
vamente, na perspectiva social e do financiador,
no subsetor da saúde pública de Rio Negro. Tan-
to do ponto de vista social como no financeiro, a
estratégia de implantação de serviços de cuidados
organizados foi mais eficaz e com menor custo,
medida pelo percentual de pacientes que faleceram
em casa. O principal indutor de custos correspon-
de, do ponto de vista social, aos cuidados infor-
mais prestados pelas famílias, enquanto do ponto
de vista do financiador se refere aos salários da
equipe de saúde
In vivo effectiveness of several antimicrobial locks to eradicate intravascular catheter coagulase-negative staphylococci biofilms
Get PDFTunneled central venous catheter (TCVC) related infection remains a
challenge in the care of hemodialysis patients. We aimed to determine the best antimicrobial lock therapy (ALT) to eradicate coagulase-negative staphylococci (CoNS)
biofilms. We studied the colonization status of the catheter every 30 days by quantitative blood cultures (QBC) drawn through all catheter lumens. Those patients with a
significant culture (i.e.,100 to 1,000 CFU/mL) of a CoNS were classified as patients
with a high risk of developing catheter-related bloodstream infections (CRBSI). They
were assigned to receive daptomycin, vancomycin, teicoplanin lock solution, or the
standard of care (SoC) (i.e., heparin lock). The primary endpoint was to compare
eradication ability (i.e., negative QBC for 30 days after ending ALT) rates between different locks and the SoC. A second objective was to analyze the correlation between
ALT exposure and isolation of CoNS with antimicrobial resistance. Daptomycin lock
was associated with a significant higher eradication success than with the SoC: 85%
versus 30% (relative risk [RR] = 14, 95% confidence interval [CI] = 2.4 – 82.7); followed by teicoplanin locks with a 83.3% success (RR = 11.7; 95% CI = 2 – 70.2). We
observed CoNs isolates with a higher teicoplanin MIC in patients with repeated teicoplanin locks exposure (coefficient = 0.3; 95% CI = 0.11 – 0.47). However, teicoplanin MICs decreased in patients treated with vancomycin locks (coefficient = 20.56;
95% CI = 20.85 – 20.02). Methicillin-resistance decreased with accumulative ALT
(RR = 0.82; 95% CI = 0.69 – 0.98). In this study, daptomycin locks achieve the highest eradication rate of CoNS from hemodialysis catheters in viv
The impact of market-driven revenues on the boundaries of Journalism
No full textDigital innovations have revolutionized the business model of news organizations, which previously relied heavily on advertising. Digital media companies have adopted various revenue streams such as branded or sponsored content, subscriptions or memberships, direct public subsidies or private grants, and electronic commerce to ensure the sustainability of digital outlets. However, these different types of funding have also impacted the boundaries of journalism. A more market-driven approach to news may undermine the crucial social role that journalism plays in modern democracies, as market dynamics may displace journalistic criteria. Additionally, the paywall model, which charges for exclusive and high-quality content, may exacerbate the gap between those who can afford it and the majority who cannot access it
The development and validation of a new simulator for endourology
No full textIntroduction: Simulation in medicine has developed a lot in the last few decades. There is a broad range of simulators available, above all for training in surgical procedures. Endourology can benefit much from simulation because the minimally-invasive procedures of endourology frequently have long learning curves, which can be reduced by training with simulators.
Materials and methods: A low-fidelity simulator was designed for practicing endourology techniques that use cystoscopy. The process of validation involved 5 experts and 19 non-experts. Experts comprised medical professionals working in a department of urology who had performed at least 100 flexible cystoscopy procedures. Non-experts were residents in internal medicine without experience in any type of endoscopy. Information about face and content validity was collected by means of Likert scales from 1 to 5. To evaluate construct validity, we measured the time to complete two tasks, for which the procedure was evaluated by means of the OSATS global evaluation scale.
Results: New simulator was successfully built according to its design. For all evaluated aspects of construct validity, there was a significant difference (p<0.05) between the group of experts and the group of non-experts. Content validity was scored 4.66 (standard deviation ±0.56) by the experts and 4.41 (±0.71) by the non-experts. In the face validity questionnaire, the average score was 4.14 (±0.94), the question receiving the highest score: 4.6 (±0.84) concerned immersion in the procedure.
Conclusion: The simulator presented is valid both for training up new urologists in endourology technique and for experts seeking to perfect their skills.Introducción: La simulación en medicina ha evolucionado sustancialmente en las últimas
décadas. Actualmente hay una gran variedad de simuladores disponibles, especialmente
dise˜nados para la práctica de procedimientos quirúrgicos. Debido a las largas curvas de apren-
dizaje de las técnicas endourológicas mínimamente invasivas, la rama de la endourología se
puede ver muy beneficiada por el uso de estos simuladores.
Materiales y métodos: Se dise˜nó un simulador de baja fidelidad para la práctica de técnicas
endourológicas que utilizan cistoscopia. En el proceso de validación participaron 5 expertos
y 19 no expertos. Los expertos eran profesionales médicos de un Departamento de Urología
con experiencia de al menos 100 procedimientos de cistoscopia flexible. Los no expertos eran
residentes en medicina interna sin experiencia en ningún tipo de técnica endoscópica. Se recogió
información sobre la validez aparente y de contenido mediante escalas de Likert con puntuación
de 1 a 5. Para evaluar la validez de constructo, se midió el tiempo para completar dos tareas,
para lo cual se evaluó el procedimiento mediante la escala de evaluación global OSATS.
Resultados: El nuevo simulador se fabricó satisfactoriamente de acuerdo con su dise˜no. En todos
los aspectos evaluados de la validez de constructo hubo una diferencia significativa (p < 0,05)
entre el grupo de expertos y el de no expertos. La validez de contenido fue puntuada con 4,66
(desviación estándar ±0,56) por los expertos y con 4,41 (±0,71) por los no expertos. En el
cuestionario de validez aparente, la puntuación media fue de 4,14 (±0,94), y la pregunta que
recibió la puntuación más alta 4,6 (±0,84) evaluaba la inmersión en el procedimiento.
Conclusión: El simulador presentado es válido tanto para el entrenamiento de nuevos
endourólogos como para el perfeccionamiento de las técnicas de los médicos expertos
Mechanistic characterization of oscillatory patterns in unperturbed tumor growth dynamics: The interplay between cancer cells and components of tumor microenvironment
No full textMathematical modeling of unperturbed and perturbed tumor growth dynamics (TGD) in preclinical experiments provides an opportunity to establish translational frameworks. The most commonly used unperturbed tumor growth models (i.e. linear, exponential, Gompertz and Simeoni) describe a monotonic increase and although they capture the mean trend of the data reasonably well, systematic model misspecifications can be identified. This represents an opportunity to investigate possible underlying mechanisms controlling tumor growth dynamics through a mathematical framework. The overall goal of this work is to develop a data-driven semi-mechanistic model describing non-monotonic tumor growth in untreated mice. For this purpose, longitudinal tumor volume profiles from different tumor types and cell lines were pooled together and analyzed using the population approach. After characterizing the oscillatory patterns (oscillator half-periods between 8–11 days) and confirming that they were systematically observed across the different preclinical experiments available (p0.05)), allows the evaluation of the different oncologic treatments in a mechanistic way. Drug effects can potentially, be included in relevant processes taking place during tumor growth. In brief, the new model, in addition to describing non-monotonic tumor growth and the interaction between biological factors of the tumor microenvironment, can be used to explore different drug scenarios in monotherapy or combination during preclinical drug development
Creating New Knowledge while Solving a Relevant Practical Problem: Success Factors for an Action Research-Based PhD Thesis in Business and Management
Get PDFThis paper focuses on university–firm relationships in terms of individual interactions between researchers and practitioners. More specifically, we focus on an analysis of the main factors that influence the use of the action research (AR) to achieve a successful doctoral thesis. In order to achieve this, we developed a Delphi study with 15 panelists whose common characteristic is that they defended or supervised an AR-based thesis in the field of business and management. The primary contribution of the research is the development of a reference framework that should be considered in the design of a doctoral thesis for which an AR methodology is put into practice. Four dimensions were defined: profiles of both the PhD candidate and supervisor, PhD program/university, and firm/organization. Three main conclusions were reached. First, it is crucial to have a cooperative “eye-to-eye” relationship between the university and the company. Second, the AR process must respond unequivocally to its own dichotomous nature. Third, there must be a straightforward academic process for the PhD thesis. We believe that this study may impel the development of doctoral theses based on AR as a tool to potentiate collaborative university–firm relationships