Antitrust Energy

Marking the centennial anniversary of Standard Oil Co. v. United States, we argue that much of the critique of antitrust enforcement and the skepticism about its social significance suffer from “Nirvana fallacy” — comparing existing and feasible policies to ideal normative policies, and concluding that the existing and feasible ones are inherently inefficient because of their imperfections. Antitrust law and policy have always been and will always be imperfect. However, they are alive and kicking. The antitrust discipline is vibrant, evolving, and global. This essay introduces a number of important innovations in scholarship related to Standard Oil and its modern applications and identifies shifts in antitrust that will keep the field energized for some time to come

Antitrust Energy

Marking the centennial anniversary of Standard Oil Co. v. United States, we argue that much of the critique of antitrust enforcement and the skepticism about its social significance suffer from “Nirvana fallacy” — comparing existing and feasible policies to ideal normative policies, and concluding that the existing and feasible ones are inherently inefficient because of their imperfections. Antitrust law and policy have always been and will always be imperfect. However, they are alive and kicking. The antitrust discipline is vibrant, evolving, and global. This essay introduces a number of important innovations in scholarship related to Standard Oil and its modern applications and identifies shifts in antitrust that will keep the field energized for some time to come

The Impact of a 22-Month Multistep Implementation Program on Speaking-Up Behavior in an Academic Anesthesia Department.

BACKGROUND Speaking-up is a method of assertive communication that increases patient safety but often encounters barriers. Numerous studies describe programs introducing speaking-up with varying success; the common denominator seems to be the need for a multimodal and sustained approach to achieve the required change in behavior and culture for safer health care. METHODS Before implementing a 22-month multistep program for establishing and strengthening speaking-up at our institution, we assessed perceived safety culture using the "Safety Attitudes Questionnaire." After program completion, participants completed parts of the same Safety Attitudes Questionnaire relevant to speaking-up, and preresult and postresult were compared. In addition, levels of speaking-up and assertive communication were compared with a Swiss benchmark using results from the "Speaking-up About Patient Safety Questionnaire." RESULTS Safety Attitudes Questionnaire scores were significantly higher after program completion in 2 of 3 answered questions (median [first quartile, third quartile), 5.0 [4.0, 5.0] versus 4.0 [4.0, 5.0], P = 0.0002, and 5.0 [4.0, 5.0] versus 4.0 [4.0, 4.0] P = 0.002; n = 34). Our composite score on the Speaking-up About Patient Safety Questionnaire was significantly higher (mean ± SD, 5.9 ± 0.7 versus 5.2 ± 1.0;P < 0.001) than the benchmark (n = 65). CONCLUSIONS A long-term multimodal program for speaking-up was successfully implemented. Attitude and climate toward safety generally improved, and postprogram perceived levels of assertive communication and speaking-up were higher than the benchmark. These results support current opinion that multimodal programs and continued effort are required, but that speaking-up can indeed be strengthened

Intraoperative pain during caesarean delivery: Incidence, risk factors and physician perception

Background: Intraoperative pain is a possible complication of neuraxial anaesthesia for caesarean delivery. There is little information available about its incidence, risk factors and physician perception. Methods: Parturients undergoing spinal anaesthesia for elective caesarean delivery were enrolled. Before surgery, parturients were asked about preoperative anxiety on a verbal numerical scale (VNS), anticipated analgesic requirement, postoperative pain levels, Spielberger STATE-TRAIT inventory index, Pain Catastrophizing Scale. After surgery, parturients were asked to answer questions (intraoperative VNS pain). The anaesthesiologist and obstetrician were asked to fill out a questionnaire asking about perceived intraoperative pain. Influence of preoperative anxiety on intraoperative pain (yes/no) was assessed using logistic regression. Mc Fadden's R2 was calculated. The agreement in physician perception of intraoperative pain with reported pain by the parturient was examined by calculating Cohen's kappa and 95% Confidence Intervals (CI). Results: We included 193 parturients in our analysis. Incidence of intraoperative pain was 11.9%. Median intraoperative VNS pain of parturients with pain was 4.0 (1st quartile 4.0; 3rd quartile 9.0). Preoperative anxiety was not a good predictor of intraoperative pain (p-value of β-coefficient = 0.43, Mc Fadden's R2 = 0.01). Including further preoperative variables did not result in a good prediction model. Cohen's kappa between reported pain by parturient and by the obstetrician was 0.21 (95% CI: 0.01, 0.41) and by the anaesthesiologist was 0.3 (95% CI: 0.12, 0.48). Conclusions: We found a substantial incidence (11.9%) of intraoperative pain during caesarean delivery. Preoperative anxiety did not predict intraoperative pain. Physicians did not accurately identify parturients' intraoperative pain. Significance: Intraoperative pain occurred in 11.9% and severe intraoperative pain occurred in 1.11% of parturients undergoing elective caesarean delivery under spinal anaesthesia. We did not find any preoperative variables that could reliably predict intraoperative pain. Obstetricians and anaesthesiologists underestimated the incidence of intraoperative pain in our cohort and thus, more attention must be put to parturients' pain

Desmoplastic small round cell tumor:from state of the art to future clinical prospects

Introduction: Desmoplastic small round cell tumor (DSRCT) is an extremely rare and highly aggressive soft tissue sarcoma, presenting mainly in male adolescents and young adults with multiple nodules disseminated within the abdominopelvic cavity. Despite a multimodal approach including aggressive cytoreductive surgery, intensive multi-agent chemotherapy, and postoperative whole abdominopelvic radiotherapy, the prognosis for DSRCT remains dismal. Median progression-free survival ranges between 4 and 21 months, and overall survival between 17 and 60 months, with the 5-year overall survival rate in the range of 10–20%. Area covered: This review discusses the treatment strategies used for DSRCT over the years, the state of the art of current treatments, and future clinical prospects. Expert opinion: The unsatisfactory outcomes for patients with DSRCT warrant investigations into innovative treatment combinations. An international multidisciplinary and multi-stakeholder collaboration, involving both pediatric and adult sarcoma communities, is needed to propel preclinical model generation and drug development, and innovative clinical trial designs to enable the timely testing of treatments involving novel agents guided by biology to boost the chances of survival for patients with this devastating disease.</p

A Critical Role for Syk Protein Tyrosine Kinase in Fc Receptor-Mediated Antigen Presentation and Induction of Dendritic Cell Maturation

AbstractDendritic cells (DCs) are the only APCs capable of initiating adaptive immune responses. The initiation of immune responses requires that DCs 1) internalize and present Ags; and 2) undergo a differentiation process, called "maturation", which transforms DCs into efficient APCs. DC maturation may be initiated by the engagement of different surface receptors, including certain cytokine receptors (such as TNFR), Toll-like receptors, CD40, and FcRs. The early activation events that link receptor engagement and DC maturation are not well characterized. We found that FcR engagement by immune complexes induced the phosphorylation of Syk, a protein tyrosine kinase acting immediately downstream of FcRs. Syk was dispensable for DC differentiation in vitro and in vivo, but was strictly required for immune complexes internalization and subsequent Ag presentation to T lymphocytes. Importantly, Syk was also required for the induction of DC maturation and IL-12 production after FcR engagement, but not after engagement of other surface receptors, such as TNFR or Toll-like receptors. Therefore, protein tyrosine phosphorylation by Syk represents a novel pathway for the induction of DC maturation

Treatment at Relapse for Synovial Sarcoma of Children, Adolescents and Young Adults:From the State of Art to Future Clinical Perspectives

While the overall prognosis is generally quite satisfactory in children, adolescents and young adults with localised synovial sarcoma at first diagnosis, the outcome remains poor for patients after relapse. Conversely to the front-line standardised treatment options, patients with relapse generally have an individualised approach and to date, there is still a lack of consensus regarding standard treatment approaches. Studies on relapsed synovial sarcoma were able to identify some prognostic variables that influence post-relapse survival, in order to plan risk-adapted salvage protocols. Treatment proposals must consider previous first-line treatments, potential toxicities, and the possibility of achieving an adequate local treatment by new surgery and/or re-irradiation. Effective second-line drug therapies are urgently needed. Notably, experimental treatments such as adoptive engineered TCR-T cell immunotherapy seem promising in adults and are currently under validation also in paediatric patients.</p

Age-related biological differences in children's and adolescents' very rare tumors

Very rare tumors (VRTs) in pediatric age represent many different diseases. They present an annual incidence < 2/1000,000 and correspond to about 11% of all cancers in patients aged 0–14 years. They can be roughly divided into two groups: one including tumors that are also rare in adults, and the other group includes adult-type tumors rarely encountered in children and adolescents. Although there is an obvious gap in knowledge regarding oncogenesis in pediatric cancers, there is some evidence of the involvement of various signalling pathways in the development of tumors in children and adolescents and sometimes in young adults. In addition, despite the rarity of these neoplasms, several attempts have been made to disclose the underlying mechanisms. More effort and resources have urgently to be devoted to deepening current knowledge and integrating new findings into the therapeutic approach, which nowadays relies on the treatment modalities used in adult oncology. The aim of this paper is to provide a review of the main solid VRTs occurring in both the pediatric and the adult age groups, highlighting the variability between groups in their biological and clinical course

Indeterminate Pulmonary Nodules at Diagnosis in Rhabdomyosarcoma: Are They Clinically Significant? A Report From the European Paediatric Soft Tissue Sarcoma Study Group

PURPOSE: To evaluate the clinical significance of indeterminate pulmonary nodules at diagnosis (defined as ≤ 4 pulmonary nodules < 5 mm or 1 nodule measuring ≥ 5 and < 10 mm) in patients with pediatric rhabdomyosarcoma (RMS). PATIENTS AND METHODS: We selected patients with supposed nonmetastatic RMS treated in large pediatric oncology centers in the United Kingdom, France, Italy, and the Netherlands, who were enrolled in the European Soft Tissue Sarcoma Study Group (E pSSG) RMS 2005 study. Patients included in the current study received a diagnosis between September 2005 and December 2013, and had chest computed tomography scans available for review that were done at time of diagnosis. Local radiologists were asked to review the chest computed tomography scans for the presence of pulmonary nodules and to record their findings on a standardized case report form. In the E pSSG RMS 2005 Study, patients with indeterminate pulmonary nodules were treated identically to patients without pulmonary nodules, enabling us to compare event-free survival and overall survival between groups by log-rank test. RESULTS: In total, 316 patients were included; 67 patients (21.2%) had indeterminate pulmonary nodules on imaging and 249 patients (78.8%) had no pulmonary nodules evident at diagnosis. Median follow-up for survivors (n = 258) was 75.1 months; respective 5-year event-free survival and overall survival rates (95% CI) were 77.0% (64.8% to 85.5%) and 82.0% (69.7% to 89.6%) for patients with indeterminate nodules and 73.2% (67.1% to 78.3%) and 80.8% (75.1% to 85.3%) for patients without nodules at diagnosis ( P = .68 and .76, respectively). CONCLUSION: Our study demonstrated that indeterminate pulmonary nodules at diagnosis do not affect outcome in patients with otherwise localized RMS. There is no need to biopsy or upstage patients with RMS who have indeterminate pulmonary nodules at diagnosis