In vivo clearance of surfactant lipids during acute pulmonary inflammation.

BACKGROUND: A decrease in pulmonary surfactant has been suggested to contribute to the lung dysfunction associated with pulmonary inflammation. A number of studies have implicated surfactant clearance as a possible mechanism for altered pool sizes. The objective of the current study was to specifically investigate the mechanisms of surfactant clearance in a rodent model of acute pulmonary inflammation. METHODS: Inflammation was induced by intrapulmonary instillation of lipopolysaccharide (LPS: 100 μg/kg). Lipid clearance was assessed at 18 and 72 hours post-LPS instillation by intratracheal administration of radiolabel surfactant-like liposomes 2 hours prior to isolation and analysis of inflammatory cells and type II cells. RESULTS: At both 18 and 72 hours after LPS instillation there was significantly less radioactivity recovered in the lavage fluid compared to respective control groups (p < 0.05). At both time points, the number of cells recovered by lavage and their associated radioactivity was greater compared to control groups (p < 0.01). There was no difference in recovery of radioactivity by isolated type II cells or other cells obtained from enzymatic digestion of lung tissue. CONCLUSION: These results show that increased clearance of surfactant lipids in our model of acute pulmonary inflammation is primarily due to the inflammatory cells recruited to the airspace and not increased uptake by alveolar type II cells

Treatment Patterns and Use of Resources in Patients With Tuberous Sclerosis Complex: Insights From the TOSCA Registry

Tuberous Sclerosis Complex (TSC) is a rare autosomal-dominant disorder caused by mutations in the TSC1 or TSC2 genes. Patients with TSC may suffer from a wide range of clinical manifestations; however, the burden of TSC and its impact on healthcare resources needed for its management remain unknown. Besides, the use of resources might vary across countries depending on the country-specific clinical practice. The aim of this paper is to describe the use of TSC-related resources and treatment patterns within the TOSCA registry. A total of 2,214 patients with TSC from 31 countries were enrolled and had a follow-up of up to 5 years. A search was conducted to identify the variables containing both medical and non-medical resource use information within TOSCA. This search was performed both at the level of the core project as well as at the level of the research projects on epilepsy, subependymal giant cell astrocytoma (SEGA), lymphangioleiomyomatosis (LAM), and renal angiomyolipoma (rAML) taking into account the timepoints of the study, age groups, and countries. Data from the quality of life (QoL) research project were analyzed by type of visit and age at enrollment. Treatments varied greatly depending on the clinical manifestation, timepoint in the study, and age groups. GAB Aergics were the most prescribed drugs for epilepsy, and mTOR inhibitors are dramatically replacing surgery in patients with SEGA, despite current recommendations proposing both treatment options. mTOR inhibitors are also becoming common treatments in rAML and LAM patients. Forty-two out of the 143 patients (29.4%) who participated in the QoL research project reported inpatient stays over the last year. Data from non-medical resource use showed the critical impact of TSC on job status and capacity. Disability allowances were more common in children than adults (51.1% vs 38.2%). Psychological counseling, social services and social worker services were needed by <15% of the patients, regardless of age. The long-term nature, together with the variability in its clinical manifestations, makes TSC a complex and resource-demanding disease. The present study shows a comprehensive picture of the resource use implications of TSC

Newly Diagnosed and Growing Subependymal Giant Cell Astrocytoma in Adults With Tuberous Sclerosis Complex: Results From the International TOSCA Study

The onset and growth of subependymal giant cell astrocytoma (SEGA) in tuberous sclerosis complex (TSC) typically occurs in childhood. There is minimal information on SEGA evolution in adults with TSC. Of 2,211 patients enrolled in TOSCA, 220 of the 803 adults (27.4%) ever had a SEGA. Of 186 patients with SEGA still ongoing in adulthood, 153 (82.3%) remained asymptomatic, and 33 (17.7%) were reported to ever have developed symptoms related to SEGA growth. SEGA growth since the previous scan was reported in 39 of the 186 adults (21%) with ongoing SEGA. All but one patient with growing SEGA had mutations in TSC2. Fourteen adults (2.4%) were newly diagnosed with SEGA during follow-up, and majority had mutations in TSC2. Our findings suggest that surveillance for new or growing SEGA is warranted also in adulthood, particularly in patients with mutations in TSC2

Towards better error statistics for atmospheric inversions of methane surface fluxes

We adapt general statistical methods to estimate the optimal error covariance matrices in a regional inversion system inferring methane surface emissions from atmospheric concentrations. Using a minimal set of physical hypotheses on the patterns of errors, we compute a guess of the error statistics that is optimal in regard to objective statistical criteria for the specific inversion system. With this very general approach applied to a real-data case, we recover sources of errors in the observations and in the prior state of the system that are consistent with expert knowledge while inferred from objective criteria and with affordable computation costs. By not assuming any specific error patterns, our results depict the variability and the inter-dependency of errors induced by complex factors such as the misrepresentation of the observations in the transport model or the inability of the model to reproduce well the situations of steep gradients of concentrations. Situations with probable significant biases (e. g., during the night when vertical mixing is ill-represented by the transport model) can also be diagnosed by our methods in order to point at necessary improvement in a model. By additionally analysing the sensitivity of the inversion to each observation, guidelines to enhance data selection in regional inversions are also proposed. We applied our method to a recent significant accidental methane release from an offshore platform in the North Sea and found methane fluxes of the same magnitude than what was officially declared

Towards better error statistics for atmospheric inversions of methane surface fluxes

International audienc

Geomorphological map of Byers Peninsula, Livingston Island

The bedrock geology of the peninsula is described briefly as Upper Jurassic to Lower Cretaceous marine sedimentary, volcanic and volcaniclastic rocks, intruded by igneous bodies. The geomorphological map includes 63 morphogenetic terms differentiated by eight colours. The humid maritime climate of the area, with snow and ice melting in summer, favours the development of a drainage network. Information about the biological and chemical features of its lakes and streams has also been included