The Global Stratotype Section and Point (GSSP) for the base of the Lutetian Stage at the Gorrondatxe section, Spain

The GSSP for the base of the Lutetian Stage (early/ middle Eocene boundary) is defined at 167.85 metres in the Gorrondatxe sea-cliff section (NW of Bilbao city, Basque Country, northern Spain; 43º22'46.47" N, 3º 00' 51.61" W). This dark marly level coincides with the lowest occurrence of the calcareous nannofossil Blackites inflatus (CP12a/b boundary), is in the middle of polarity Chron C21r, and has been interpreted as the maximumflooding surface of a depositional sequence that may be global in extent. The GSSP age is approximately 800 kyr (39 precession cycles) younger than the beginning of polarity Chron C21r, or ~47.8 Ma in the GTS04 time scale. The proposal was approved by the International Subcommission on Paleogene Stratigraphy in February 2010, approved by the International Commission of Stratigraphy in January 2011, and ratified by the International Union of Geological Sciences in April 2011.Published86-1082.2. Laboratorio di paleomagnetismoJCR Journalrestricte

Cystatin A, a Potential Common Link for Mutant Myocilin Causative Glaucoma

Myocilin (MYOC) is a 504 aa secreted glycoprotein induced by stress factors in the trabecular meshwork tissue of the eye, where it was discovered. Mutations in MYOC are linked to glaucoma. The glaucoma phenotype of each of the different MYOC mutation varies, but all of them cause elevated intraocular pressure (IOP). In cells, forty percent of wild-type MYOC is cleaved by calpain II, a cysteine protease. This proteolytic process is inhibited by MYOC mutants. In this study, we investigated the molecular mechanisms by which MYOC mutants cause glaucoma. We constructed adenoviral vectors with variants Q368X, R342K, D380N, K423E, and overexpressed them in human trabecular meshwork cells. We analyzed expression profiles with Affymetrix U133Plus2 GeneChips using wild-type and null viruses as controls. Analysis of trabecular meshwork relevant mechanisms showed that the unfolded protein response (UPR) was the most affected. Search for individual candidate genes revealed that genes that have been historically connected to trabecular meshwork physiology and pathology were altered by the MYOC mutants. Some of those had known MYOC associations (MMP1, PDIA4, CALR, SFPR1) while others did not (EDN1, MGP, IGF1, TAC1). Some, were top-changed in only one mutant (LOXL1, CYP1B1, FBN1), others followed a mutant group pattern. Some of the genes were new (RAB39B, STC1, CXCL12, CSTA). In particular, one selected gene, the cysteine protease inhibitor cystatin A (CSTA), was commonly induced by all mutants and not by the wild-type. Subsequent functional analysis of the selected gene showed that CSTA was able to reduce wild-type MYOC cleavage in primary trabecular meshwork cells while an inactive mutated CSTA was not. These findings provide a new molecular understanding of the mechanisms of MYOC-causative glaucoma and reveal CSTA, a serum biomarker for cancer, as a potential biomarker and drug for the treatment of MYOC-induced glaucoma

Regional development gaps in Argentina: A multidimensional approach to identify the location of policy priorities

Spatial inequalities within Latin American countries have historically attracted the interest ofacademics, policy-makers, and international agencies. This article aims to provide amultidimensional diagnosis of provincial development gaps in Argentina, in order to identifythe location of policy priorities. Therefore, we built a large database, which covers sevendevelopment dimensions, and applied multivariate analysis techniques to overcome someanalytical limitations of previous studies. Results show the stability of provincial developmentgaps between 2003 and 2013 and some heterogeneity within geographic regions. Instead,cluster analysis offers a better classification of Argentine provinces according to theirdevelopment gaps, which can help the government to prioritize the places wheredevelopment policies are strategic.Fil: Niembro, Andrés Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte; Argentina. Universidad Nacional de Río Negro; ArgentinaFil: Sarmiento, Jesica Isabel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte; Argentina. Universidad Nacional de Río Negro; Argentin

Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine

[This corrects the article DOI: 10.1186/s13054-016-1208-6.]

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

Background Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide.Methods A multimethods analysis was performed as part of the GlobalSurg 3 study-a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital.Findings Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3.85 [95% CI 2.58-5.75]; p<0.0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63.0% vs 82.7%; OR 0.35 [0.23-0.53]; p<0.0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer.Interpretation Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised

The Global Stratotype Section and Point (GSSP) for the base of the Lutetian Stage at the Gorrondatxe section, Spain

The GSSP for the base of the Lutetian Stage (early/ middle Eocene boundary) is defined at 167.85 metres in the Gorrondatxe sea-cliff section (NW of Bilbao city, Basque Country, northern Spain; 43º22'46.47" N, 3º 00' 51.61" W). This dark marly level coincides with the lowest occurrence of the calcareous nannofossil Blackites inflatus (CP12a/b boundary), is in the middle of polarity Chron C21r, and has been interpreted as the maximumflooding surface of a depositional sequence that may be global in extent. The GSSP age is approximately 800 kyr (39 precession cycles) younger than the beginning of polarity Chron C21r, or ~47.8 Ma in the GTS04 time scale. The proposal was approved by the International Subcommission on Paleogene Stratigraphy in February 2010, approved by the International Commission of Stratigraphy in January 2011, and ratified by the International Union of Geological Sciences in April 2011