Fiduciary Duties of Corporate Directors in Uncertain Times

Directors addressing new political uncertainties, a host of heightened challenges and asserted “best practices” from many sources may understandably ask whether their fiduciary duties have changed as well. This paper synthesizes the latest decisions of the Delaware courts on the standards of conduct for directors and the standards by which their conduct is reviewed. While directors should expect uncertainty to be a fact of corporate life for the foreseeable future, this paper emphasizes that neither the fiduciary duties of directors nor the protections afforded them have changed. Disinterested and independent directors acting in good faith continue to have broad protections under the business judgment rule. The legal framework thus enables and, indeed, encourages directors to act proactively and make hard choices when they need to do so. In an accompanying article, former Delaware Chief Justice E. Norman Veasey and Ira M. Millstein elaborate upon how directors, under existing law, are both empowered and have the freedom to make decisions they deem in the best interests of the corporation. The article urges directors, in reliance on this framework, to have the courage to work towards securing the long-term future of their corporations

Occult Pneumothoraces in Children With Blunt Torso Trauma

Objectives Plain chest x‐ray (CXR) is often the initial screening test to identify pneumothoraces in trauma patients. Computed tomography (CT) scans can identify pneumothoraces not seen on CXR (“occult pneumothoraces”), but the clinical importance of these radiographically occult pneumothoraces in children is not well understood. The objectives of this study were to determine the proportion of occult pneumothoraces in injured children and the rate of treatment with tube thoracostomy among these children. Methods This was a planned substudy from a large prospective multicenter observational cohort study of children younger than 18 years old evaluated in emergency departments (EDs) in the Pediatric Emergency Care Applied Research Network (PECARN) for blunt torso trauma from May 2007 to January 2010. Children with CXRs as part of their trauma evaluations were included for analysis. The faculty radiologist interpretations of the CXRs and any subsequent imaging studies, including CT scans, were reviewed for the absence or presence of pneumothoraces. An “occult pneumothorax” was defined as a pneumothorax that was not identified on CXR, but was subsequently demonstrated on cervical, chest, or abdominal CT scan. Rates of pneumothoraces and placement of tube thoracostomies and rate differences with 95% confidence intervals (CIs) were calculated. Results Of 12,044 enrolled in the parent study, 8,020 (67%) children (median age = 11.3 years, interquartile range [IQR] = 5.3 to 15.2 years) underwent CXRs in the ED, and these children make up the study population. Among these children, 4,276 had abdominal CT scans performed within 24 hours. A total of 372 of 8,020 children (4.6%; 95% CI = 4.2% to 5.1%) had pneumothoraces identified by CXR and/or CT. The CXRs visualized pneumothoraces in 148 patients (1.8%; 95% CI = 1.6% to 2.2%), including one false‐positive pneumothorax, which was identified on CXR, but was not demonstrated on CT. Occult pneumothoraces were present in 224 of 372 (60.2%; 95% CI = 55.0% to 65.2%) children with pneumothoraces. Tube thoracostomies were performed in 85 of 148 (57.4%; 95% CI = 49.0% to 65.5%) children with pneumothoraces on CXR and in 35 of 224 (15.6%; 95% CI = 11.1% to 21.1%) children with occult pneumothoraces (rate difference = –41.8%; 95% CI = –50.8 to –32.3%). Conclusions In pediatric patients with blunt torso trauma, pneumothoraces are uncommon, and most are not identified on the ED CXR. Nearly half of pneumothoraces, and most occult pneumothoraces, are managed without tube thoracostomy. Observation, including in children requiring endotracheal intubation, should be strongly considered during the initial management of children with occult pneumothoraces. Resumen Objetivos La radiografía de tórax simple (RXT) es a menudo la prueba de despistaje inicial para identificar los neumotórax en los pacientes con traumatismo. La tomografía computarizada (TC) puede identificar neumotórax no vistos en la RXT (“neumotórax ocultos”), aunque la importancia clínica de estos neumotórax radiográficamente ocultos en los niños no está muy estudiada. Los objetivos de este estudio fueron determinar la proporción de neumotórax ocultos en los niños accidentados y el porcentaje de tratamiento con tubo de toracostomía en estos niños. Metodología Subestudio diseñado a partir de un gran estudio observacional de cohorte prospectivo multicéntrico de niños menores de 18 años atendidos en los servicios de urgencias (SU) de la Pediatric Emergency Care Applied Research Network (PECARN) que habían sido evaluados por traumatismo torácico cerrado de mayo de 2007 a enero de 2010. Se incluyeron en el análisis los niños en los que la RXT fue parte de la evaluación inicial del traumatismo. Las interpretaciones del radiólogo de las RXT y de cualquier estudio de imagen posterior, incluyendo a TC, se revisaron para la ausencia o presencia de neumotórax. Se definió “neumotórax oculto” como un neumotórax que no fue identificado en la RXT pero que fue posteriormente visualizado en la TC abdominal, torócica o cervical. Se calcularon los porcentajes de neumotórax e inserción de tubo de toracostomía y las diferencias de sus porcentajes con los intervalos de confianza (IC) al 95%. Resultados De los 12.044 incluidos en el estudio principal, se llevo a cabo una RXT en el SU en 8.020 (67%) niños (mediana de edad 11,3 años, rango intercuartílico 5,3 a 15,2), que constituyeron la población de estudio. De estos niños, 4.276 tuvieron una TC realizada en las primeras 24 horas. En 372 de los 8.020 niños (4,6%; IC 95% = 4,2% a 5,1%) se identificó un neumotórax en la RXT y/o la TC. La RXT mostró neumotórax en 148 pacientes (1,8%; IC 95% = 1,6% a 2,2%), incluyendo un falso positivo de neumotórax, que fue identificado en la RXT pero que no fue demostrado en la TC. Los neumotórax ocultos estuvieron presentes en 224 de los 372 niños con neumotórax (60,2%; IC 95% = 55,0% a 65,2%). Se insertaron tubos de toracostomía en 85 de los 148 niños con neumotórax en la RXT (57,4%; IC 95% = 49,0% a 65,5%), y en 35 de los 224 niños con neumotórax oculto (15,6%; IC 95% = 11,1% a 21,1%; diferencia de porcentajes ‐41,8%; IC 95% = ‐50,8 a ‐32,3%). Conclusiones En los pacientes pediátricos con traumatismo torácico cerrado, los neumotórax son poco frecuentes, y la mayoría no son identificados en la RXT en el SU. Casi la mitad de los neumotórax, y la mayoría de los neumotórax ocultos son manejados sin tubo de toracostomía. La observación, incluyendo en los niños que requieren intubación endotraqueal, debería ser especialmente considerada durante el manejo inicial de los niños con neumotórax ocultos.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106913/1/acem12344.pd

Computed Tomography With Intravenous Contrast Alone: The Role of Intra‐abdominal Fat on the Ability to Visualize the Normal Appendix in Children

Background Computed tomography ( CT ) with enteric contrast is frequently used to evaluate children with suspected appendicitis. The use of CT with intravenous ( IV ) contrast alone ( CT IV ) may be sufficient, however, particularly in patients with adequate intra‐abdominal fat ( IAF ). Objectives The authors aimed 1) to determine the ability of radiologists to visualize the normal (nondiseased) appendix with CT IV in children and to assess whether IAF adequacy affects this ability and 2) to assess the association between IAF adequacy and patient characteristics. Methods This was a retrospective 16‐center study using a preexisting database of abdominal CT scans. Children 3 to 18 years who had CT IV scan and measured weights and for whom appendectomy history was known from medical record review were included. The sample was chosen based on age to yield a sample with and without adequate IAF . Radiologists at each center reread their site's CT IV scans to assess appendix visualization and IAF adequacy. IAF was categorized as “adequate” if there was any amount of fat completely surrounding the cecum and “inadequate” if otherwise. Results A total of 280 patients were included, with mean age of 10.6 years (range = 3.1 to 17.9 years). All 280 had no history of prior appendectomy; therefore, each patient had a presumed normal appendix. A total of 102 patients (36.4%) had adequate IAF . The proportion of normal appendices visualized with CT IV was 72.9% (95% confidence interval [ CI ] = 67.2% to 78.0%); the proportions were 89% (95% CI  = 81.5% to 94.5%) and 63% (95% CI  = 56.0% to 70.6%) in those with and without adequate IAF (95% CI for difference of proportions = 16% to 36%). Greater weight and older age were strongly associated with IAF adequacy (p < 0.001), with weight appearing to be a stronger predictor, particularly in females. Although statistically associated, there was noted overlap in the weights and ages of those with and without adequate IAF . Conclusions Protocols using CT with IV contrast alone to visualize the appendix can reasonably include weight, age, or both as considerations for determining when this approach is appropriate. However, although IAF will more frequently be adequate in older, heavier patients, highly accurate prediction of IAF adequacy appears challenging solely based on age and weight. Resumen Tomografía Computarizada Únicamente con Contraste Intravenoso: El Papel de la Grasa Intrabadominal en la Capacidad para Visualizar el Apéndice Normal en los Niños Introduction La tomografía computarizada ( TC ) con contraste entérico es usada frecuentemente para evaluar a los niños con sospecha de apendicitis. El uso de la TC únicamente con contraste intravenoso ( TC IV ) puede ser suficiente, especialmente en pacientes con adecuada grasa intrabdominal ( GIA ). Objetivos 1) Determinar la capacidad de los radiólogos para visualizar el apéndice normal (sin enfermedad) con TC IV en niños, y valorar si la cantidad de GIA afecta a esta capacidad; y 2) valorar la asociación entre la idoneidad de la GIA y las características del paciente. Metodología Estudio retrospectivo de 16 hospitales que utilizó una base de datos prexistente de TC abdominales. Se incluyó a los niños entre 3 y 18 años que tenían una TC IV , una medida del peso e historia de apendectomía conocida por la revisión de la historia clínica. La muestra se eligió en base a la edad con el fin de conseguir una muestra con y sin GIA adecuada. Los radiólogos de cada centro releyeron las TC IV de sus centros para valorar la visualización del apéndice y la adecuación de la GIA . La GIA se clasificó como “adecuada” si había cualquier cantidad de grasa completamente alrededor del ciego e “inadecuada” si era de otra manera. Resultados Se incluyeron 280 pacientes, con una media de edad de 10,6 años (rango 3,1 a 17,9 años). Ninguno tenía historia previa de apendectomía; por lo tanto todos los pacientes tuvieron un apéndice presumiblemente normal. Ciento dos pacientes (36,4%) tuvieron GIA adecuada. El porcentaje de apéndices normales visualizados con TC IV fue de 72,9% ( IC 95% = 67,2% a 78,0%); la proporción fue 89% ( IC 95% = 81,5% a 94,5%), y 63% ( IC 95% = 56,0% a 70,6%) en aquéllos con y sin GIA adecuada ( IC 95% para la diferencia de proporciones = 16% a 36%). El mayor peso y la mayor edad se asociaron fuertemente con la adecuación de la GIA (p < 0,001), y el peso resultó ser el mayor factor predictivo, especialmente en mujeres. Aunque se asoció estadísticamente, se vio un solapamiento en los pesos y edades de aquéllos con y sin GIA adecuada. Conclusiones Los protocolos que usan la TC IV para visualizar el apéndice pueden razonablemente incluir el peso, la edad, o ambas como consideraciones para determinar cuándo esta aproximación es apropiada. Sin embargo, aunque la cantidad de GIA será frecuentemente más apropiada en los pacientes más mayores y de mayor peso, la predicción certera de adecuación de GIA es altamente desafiante si se basa sólo en la edad y el peso.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/99695/1/acem12185.pd

Interaction with receptor for activated C-kinase 1 (RACK1) sensitizes the phosphodiesterase PDE4D5 towards hydrolysis of cAMP and activation by protein kinase C

We have previously identified the PKC (protein kinase C)-anchoring protein RACK1 (receptor for activated C-kinase 1), as a specific binding partner for the cAMP-specific phosphodiesterase PDE4D5, suggesting a potential site for cross-talk between the PKC and cAMP signalling pathways. In the present study we found that elevation of intracellular cAMP, with the β2-adrenoceptor agonist isoproterenol (isoprenaline), led to activation of PDE4 enzymes in the particulate and soluble fractions of HEK (human embryonic kidney)-293 cells. In contrast activation of PDE4D5, with isoproterenol and the PKC activator PMA, was restricted to the particulate fraction, where it interacts with RACK1; however, RACK1 is dispensable for anchoring PDE4D5 to the particulate fraction. Kinetic studies demonstrated that RACK1 alters the conformation of particulate-associated PDE4D5 so that it more readily interacts with its substrate cAMP and with rolipram, a PDE4 inhibitor that specifically targets the active site of the enzyme. Interaction with RACK1 was also essential for PKC-dependent and ERK (extracellular-signal-regulated kinase)-independent phosphorylation (on Ser126), and activation of PDE4D5 in response to PMA and isoproterenol, both of which trigger the recruitment of PKCα to RACK1. Together these results reveal novel signalling cross-talk, whereby RACK1 mediates PKC-dependent activation of PDE4D5 in the particulate fraction of HEK-293 cells in response to elevations in intracellular cAMP

Characterization of Geographical and Meteorological Parameters

[EN]This chapter is devoted to the introduction of some geographical and meteorological information involved in the numerical modeling of wind fields and solar radiation. First, a brief description of the topographical data given by a Digital Elevation Model and Land Cover databases is provided. In particular, the Information System of Land Cover of Spain (SIOSE) is considered. The study is focused on the roughness length and the displacement height parameters that appear in the logarithmic wind profile, as well as in the albedo related to solar radiation computation. An extended literature review and characterization of both parameters are reported. Next, the concept of atmospheric stability is introduced from the Monin–Obukhov similarity theory to the recent revision of Zilitinkevich of the Neutral and Stable Boundary Layers (SBL). The latter considers the effect of the free-flow static stability and baroclinicity on the turbulent transport of momentum and of the Convective Boundary Layers (CBL), more precisely, the scalars in the boundary layer, as well as the model of turbulent entrainment

Conformational Altered p53 as an Early Marker of Oxidative Stress in Alzheimer's Disease

In order to study oxidative stress in peripheral cells of Alzheimer's disease (AD) patients, immortalized lymphocytes derived from two peculiar cohorts of patients, referring to early onset AD (EOSAD) and subjects harboured AD related mutation (ADmut), were used. Oxidative stress was evaluated measuring i) the typical oxidative markers, such as HNE Michel adducts, 3 Nitro-Tyrosine residues and protein carbonyl on protein extracts, ii) and the antioxidant capacity, following the enzymatic kinetic of superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione reductase (GRD). We found that the signs of oxidative stress, measured as oxidative marker levels, were evident only in ADmut but not in EOSAD patients. However, oxidative imbalance in EOSAD as well as ADmut lymphocytes was underlined by a reduced SOD activity and GRD activity in both pathological groups in comparison with cells derived from healthy subjects. Furthermore, a redox modulated p53 protein was found conformational altered in both EOSAD and ADmut B lymphocytes in comparison with control cells. This conformational altered p53 isoform, named “unfolded p53”, was recognized by the use of two specific conformational anti-p53 antibodies. Immunoprecipitation experiments, performed with the monoclonal antibodies PAb1620 (that recognizes p53wt) and PAb240 (that is direct towards unfolded p53), and followed by the immunoblotting with anti-4-hydroxynonenal (HNE) and anti- 3-nitrotyrosine (3NT) antibodies, showed a preferential increase of nitrated tyrosine residues in unfolded p53 isoform comparing to p53 wt protein, in both ADmut and EOSAD. In addition, a correlation between unfolded p53 and SOD activity was further found. Thus this study suggests that ROS/RNS contributed to change of p53 tertiary structure and that unfolded p53 can be considered as an early marker of oxidative imbalance in these patients

Towards a System Level Understanding of Non-Model Organisms Sampled from the Environment: A Network Biology Approach

The acquisition and analysis of datasets including multi-level omics and physiology from non-model species, sampled from field populations, is a formidable challenge, which so far has prevented the application of systems biology approaches. If successful, these could contribute enormously to improving our understanding of how populations of living organisms adapt to environmental stressors relating to, for example, pollution and climate. Here we describe the first application of a network inference approach integrating transcriptional, metabolic and phenotypic information representative of wild populations of the European flounder fish, sampled at seven estuarine locations in northern Europe with different degrees and profiles of chemical contaminants. We identified network modules, whose activity was predictive of environmental exposure and represented a link between molecular and morphometric indices. These sub-networks represented both known and candidate novel adverse outcome pathways representative of several aspects of human liver pathophysiology such as liver hyperplasia, fibrosis, and hepatocellular carcinoma. At the molecular level these pathways were linked to TNF alpha, TGF beta, PDGF, AGT and VEGF signalling. More generally, this pioneering study has important implications as it can be applied to model molecular mechanisms of compensatory adaptation to a wide range of scenarios in wild populations