Ramgopal Venkataraman

Perinatal chronic hypoxia induces cortical inflammation, hypomyelination, and peripheral myelin-specific T cell autoreactivity

pCH is an important risk factor for brain injury and long‐term morbidity in children, occurring during the developmental stages of neurogenesis, neuronal migration, and myelination. We show that a rodent model of pCH results in an early decrease in mature myelin. Although pCH does increase progenitor oligodendrocytes in the developing brain, BrdU labeling revealed a loss in dividing progenitor oligodendrocytes, indicating a defect in mature cell replacement and myelinogenesis. Mice continued to exhibited hypomyelination, concomitant with long‐term impairment of motor function, weeks after cessation of pCH. The implication of a novel neuroimmunologic interplay, pCH also induced a significant egress of infiltrating CD4 T cells into the developing brain. This pCH‐mediated neuroinflammation included oligodendrocyte‐directed autoimmunity, with an increase in peripheral myelin‐specific CD4 T cells. Thus, both the loss of available, mature, myelin‐producing glial cells and an active increase in autoreactive, myelin‐specific CD4 T cell infiltration into pCH brains may contribute to early pCH‐induced hypomyelination in the developing CNS. The elucidation of potential mechanisms of hypoxia‐driven autoimmunity will expand our understanding of the neuroimmune axis during perinatal CNS disease states that may contribute to long‐term functional disability.

Leaders and Followers Among Security Analysts: Analysis of Impact and Accuracy

We examine how analysts whose forecasts lag those of timely analysts aid the price discovery process. We classify analysts as lead and follower analysts for a given firm based on the relative timeliness of their earnings forecasts over a two-year period. We find that news in forecasts of lead analysts has a higher price impact relative to that of follower analysts and this difference in impact cannot be explained by analyst reputation or experience. The price impact of follower analysts’ forecasts is significant, although it dissipates as follower analysts become less timely. Moreover, we find that the forecast issued by even the least timely analyst conveys incremental information to the market. The significant market impact of follower analysts arises mostly due to the private information conveyed by their forecast and partly because their forecasts incorporate public information including their predecessor’s forecast. While in general the price impact of the forecast component that mimics prior information is consistent with the post-revision drift documented by prior studies, we find that this impact is significant only when the follower analyst’s forecast confirms the information conveyed by the predecessor analyst. We also find that follower analysts issue more accurate forecasts than lead analysts who appear to trade off accuracy for timeliness. Overall, we conclude that the complementary roles of timely and late forecasters combine the merits of timely and accurate information and facilitate price discovery.

An International Survey on Ventilator Practices Among Extracorporeal Membrane Oxygenation Centers.

Although the optimal ventilation strategy is unknown for patients placed on extracorporeal support, there are increasing reports of extubation being used. Our objective was to describe the change in ventilation strategies and use of tracheostomy and bronchoscopy practices among extracorporeal membrane oxygenation (ECMO) centers across the world. A descriptive, cross-sectional 22 item survey of neonatal, pediatric, and adult ECMO centers was used to evaluate ventilator strategies, extubation, bronchoscopy, and tracheostomy practices. Extubation practices are increasing among all types of ECMO centers, representing 27% of all patients in pediatric centers, 41% of all patients in mixed centers, and 52% of all patients in adult centers. The most common mode of ventilation during ECMO is pressure control. There is a trend toward increased use of bilevel ventilation particularly for lung recruitment. Additionally, there is a trend toward increase in performance of bronchoscopy (pediatrics: 69%, mixed centers: 81%, adults: 76%) and tracheostomy. Among the centers performing tracheostomies, 45% reported the percutaneous method (pediatric: 31%, mixed: 46%, adult: 57%), 19% reported the open method (pediatric: 9%, mixed: 27%, adult: 24%), and 10% reported using both types of tracheostomies (pediatric: 2%, mixed: 8%, adult: 16%). Our study shows that ECMO centers are extubating their patients, performing tracheostomies and bronchoscopies on their patients more than in the previous years. There remains significant variation in ECMO ventilator strategies and management internationally. Future studies are needed to correlate these changes in practices to outcome benefits.

Impairment of cerebral autoregulation in pediatric extracorporeal membrane oxygenation associated with neuroimaging abnormalities

Abstract. Extracorporeal membrane oxygenation (ECMO) is a life-supporting therapy for critically ill patients with severe respiratory and/or cardiovascular failure. Cerebrovascular impairment can result in hemorrhagic and ischemic complications commonly seen in the patients supported on ECMO. We investigated the degree of cerebral autoregulation impairment during ECMO as well as whether it is predictive of neuroimaging abnormalities. Spontaneous fluctuations of mean arterial pressure (MAP) and cerebral tissue oxygen saturation (SctO2) were continuously measured during the ECMO run. The dynamic relationship between the MAP and SctO2 fluctuations was assessed based on wavelet transform coherence (WTC). Neuroimaging was conducted during and/or after ECMO as standard of care, and the abnormalities were evaluated based on a scoring system that had been previously validated among ECMO patients. Of the 25 patients, 8 (32%) had normal neuroimaging, 7 (28%) had mild to moderate neuroimaging abnormalities, and the other 10 (40%) had severe neuroimaging abnormalities. The degrees of cerebral autoregulation impairment quantified based on WTC showed significant correlations with the neuroimaging scores (R=0.66; p<0.0001). Evidence that cerebral autoregulation impairment during ECMO was related to the patients’ neurological outcomes was provided.

High Hemoglobin Is an Independent Risk Factor for the Development of Hemolysis During Pediatric Extracorporeal Life Support

Objective: To evaluate risk factors for hemolysis in pediatric extracorporeal life support. Design: Retrospective, single-center study. Setting: Pediatric intensive care unit. Patients: Two hundred thirty-six children who received extracorporeal membrane oxygenation. Interventions: None. Measurements and Main Results: Risk factors for hemolysis were retrospectively analyzed from a single center in a total of 236 neonatal and pediatric patients who received extracorporeal membrane oxygenation support (ECMO). There was no difference in the incidence of hemolysis between centrifugal (127 patients) and roller head (109 patients) pump type or between venoarterial and venovenous ECMO. High hemoglobin (Hb) was found to be an independent risk factor for hemolysis in both pump types. The Hb level >12 g/dL was significant in the roller group and the Hb level >13 g/dL was significant in the centrifugal group for the development of hemolysis for the cumulative ECMO run. The presence of high Hb levels on any given day increased the risk of hemolysis for that day of the ECMO run regardless of ECMO pump type. Higher revolutions per minute (RPMs) and higher inlet pressures on any given day increased the risk for the development of hemolysis in the centrifugal pump. Lower inlet venous pressures and RPMs were not associated with hemolysis in the roller group. Conclusions: An Hb level greater than 13 g/dL was associated with an increased risk of hemolysis, and a high Hb on a given day was associated with a significantly higher risk of hemolysis on the same day. Higher RPMs and lower inlet venous pressures were associated with an increased risk of hemolysis in the centrifugal pump only.

Discussion of dividend increases and future earnings

Ali and Urcan (this issue) examine the relation between dividend increases and unexpected changes in future earnings to test the signaling theory of dividends. Prior research has generally found weak and conflicting results. The primary contribution of this paper is that they recognize the interaction between the signaling theory of dividend and the catering theory proposed by Baker and Wurgler (2004). The catering theory posits that investors have a time-varying preference for dividends and that managers cater to this preference by paying dividends when preference for dividends is high. This makes it difficult to demonstrate empirical support for the dividend signaling theory because managers could be increasing dividends either to signal future changes in value or to cater to investors’ preferences or both. Therefore, in this paper, the authors examine the relationship between future earnings changes and dividends by studying this relationship separately in periods when investors exhibit a high preference for dividends as opposed to those periods when they exhibit a low preference for dividends. The authors closely follow existing research in designing their tests. They document a positive relationship between dividend increases and future changes in earnings only for periods when the dividend premium is low and attribute this to the signaling theory of dividends. They replicate the results of the most closely related papers (Nissim and Ziv 2001 and Grullon et al. 2005) and demonstrate that their results are due to controlling for the time-varying dividend preference and not an artifact of their sample or earnings expectations model. The authors have been very careful in staying very close to the literature they build on in terms of sample selection as well as empirical models, so that they can interpret their results similarly. My discussion, however, is broader in scope and raises issues with this literature in general that I believe are important in drawing significant conclusions from this line of research. Broadly speaking, I focus on issues related to choice of dividends as the signaling mechanism, the timing of the signal, and the implications of these for the tests of these signaling models.