Aerobic glycolysis as a marker of tumor aggressiveness: Preliminary data in high grade human brain tumors

Objectives. Glucose metabolism outside of oxidative phosphorylation, or aerobic glycolysis (AG), is a hallmark of active cancer cells that is not directly measured with standard 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET). In this study, we characterized tumor regions with elevated AG defined based on PET measurements of glucose and oxygen metabolism. Methods. Fourteen individuals with high-grade brain tumors underwent structural MR scans and PET measurements of cerebral blood flow (CBF), oxygen (CMRO2) and glucose (CMRGlu) metabolism, and AG, using 15O-labeled CO, O2 and H2O, and FDG, and were compared to a normative cohort of 20 age-matched individuals. Results. Elevated AG was observed in most high-grade brain tumors and it was associated with decreased CMRO2 and CBF, but not with significant changes in CMRGlu. Elevated AG was a dramatic and early sign of tumor growth associated with decreased survival. AG changes associated with tumor growth were differentiated from the effects of nonneoplastic processes such as epileptic seizures. Conclusions. Our findings demonstrate that high-grade brain tumors exhibit elevated AG as a marker of tumor growth and aggressiveness. AG may detect areas of active tumor growth that are not evident on conventional FDG PET

State Control and the Effects of Foreign Relations on Bilateral Trade

Do states use trade to reward and punish partners? WTO rules and the pressures of globalization restrict states’ capacity to manipulate trade policies, but we argue that governments can link political goals with economic outcomes using less direct avenues of influence over firm behavior. Where governments intervene in markets, politicization of trade is likely to occur. In this paper, we examine one important form of government control: state ownership of firms. Taking China and India as examples, we use bilateral trade data by firm ownership type, as well as measures of bilateral political relations based on diplomatic events and UN voting to estimate the effect of political relations on import and export flows. Our results support the hypothesis that imports controlled by state-owned enterprises (SOEs) exhibit stronger responsiveness to political relations than imports controlled by private enterprises. A more nuanced picture emerges for exports; while India’s exports through SOEs are more responsive to political tensions than its flows through private entities, the opposite is true for China. This research holds broader implications for how we should think about the relationship between political and economic relations going forward, especially as a number of countries with partially state-controlled economies gain strength in the global economy

Comparison of the Safety and Pharmacokinetics of ST-246® after IV Infusion or Oral Administration in Mice, Rabbits and Monkeys

ST-246® is an antiviral, orally bioavailable small molecule in clinical development for treatment of orthopoxvirus infections. An intravenous (IV) formulation may be required for some hospitalized patients who are unable to take oral medication. An IV formulation has been evaluated in three species previously used in evaluation of both efficacy and toxicology of the oral formulation. plasma concentrations. These effects were eliminated using slower IV infusions. associated toxicity. Shorter infusions at higher doses in NHP resulted in decreased clearance, suggesting saturated distribution or elimination. Elimination half-lives in all species were similar between oral and IV administration. The administration of ST-246 was well tolerated as a slow IV infusion

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Identifying local cognitive representations in the brain across age spans through voxel searchlights and representational similarity analysis

Localizing function in the brain has been an elusive long-term goal in the study of cognition. Prior studies have utilized four reference abilities (RAs) to capture cognition (Salthouse, 2009). Full-brain cortical networks have been tied to these abilities using common multi-voxel patterns across subjects in distinct age groups. Using voxel searchlights the current study explores purely local cortical representations of cognition, less commonly explored. This work analyzes 240 subjects’ responses to cognitive tasks from the four RAs. The current study further employs representational similarity analysis (RSA, Kriegeskorte, Mur, & Bandettini, 2008) to the similarity of brain activities from tasks within the same RA; RSA can capture representational consistencies within each subject even when exact voxel pattern may vary across subjects. We found distinct topographical localizations for each RA that were mostly consistent across age and suggested refinements of broader functional divisions of the brain from prior literature

Identifying local cognitive representations in the brain across age spans through voxel searchlights and representational similarity analysis

Localizing function in the brain has been an elusive long-term goal in the study of cognition. Prior studies have utilized four reference abilities (RAs) to capture cognition (Salthouse, 2009). Full-brain cortical networks have been tied to these abilities using common multi-voxel patterns across subjects in distinct age groups. Using voxel searchlights the current study explores purely local cortical representations of cognition, less commonly explored. This work analyzes 240 subjects’ responses to cognitive tasks from the four RAs. The current study further employs representational similarity analysis (RSA, Kriegeskorte, Mur, & Bandettini, 2008) to the similarity of brain activities from tasks within the same RA; RSA can capture representational consistencies within each subject even when exact voxel pattern may vary across subjects. We found distinct topographical localizations for each RA that were mostly consistent across age and suggested refinements of broader functional divisions of the brain from prior literature

Exploration of complex visual feature spaces for object perception.

<p>The mid- and high-level visual properties supporting object perception in the ventral visual pathway are poorly understood. In the absence of well-specified theory, many groups have adopted a data-driven approach in which they progressively interrogate neural units to establish each unit's selectivity. Such methods are challenging in that they require search through a wide space of feature models and stimuli using a limited number of samples. To more rapidly identify higher-level features underlying human cortical object perception, we implemented a novel functional magnetic resonance imaging method in which visual stimuli are selected in real-time based on BOLD responses to recently shown stimuli. This work was inspired by earlier primate physiology work, in which neural selectivity for mid-level features in IT was characterized using a simple parametric approach (Hung et al., 2012). To extend such work to human neuroimaging, we used natural and synthetic object stimuli embedded in feature spaces constructed on the basis of the complex visual properties of the objects themselves. During fMRI scanning, we employed a real-time search method to control continuous stimulus selection within each image space. This search was designed to maximize neural responses across a pre-determined 1 cm(3) brain region within ventral cortex. To assess the value of this method for understanding object encoding, we examined both the behavior of the method itself and the complex visual properties the method identified as reliably activating selected brain regions. We observed: (1) Regions selective for both holistic and component object features and for a variety of surface properties; (2) Object stimulus pairs near one another in feature space that produce responses at the opposite extremes of the measured activity range. Together, these results suggest that real-time fMRI methods may yield more widely informative measures of selectivity within the broad classes of visual features associated with cortical object representation.</p