Increased Expression of Tissue Factor and Receptor for Advanced Glycation End Products in Peripheral Blood Mononuclear Cells of Patients With Type 2 Diabetes Mellitus with Vascular Complications

The aim of the study was to determine the correlation between the expression of tissue factor (TF) and the receptor for advanced glycation end products (RAGEs) and vascular complications in patients with longstanding uncontrolled type 2 diabetes (T2D). TF and RAGE mRNAs as well as TF antigen and activity were investigated in 21 T2D patients with and without vascular complications. mRNA expression was assessed by reverse transcriptase–polymerase chain reaction (RT-PCR) in nonstimulated and advanced glycation end product (AGE) albumin–stimulated peripheral blood mononuclear cells (PBMCs). TF antigen expression was determined by enzyme-linked immunosorbent assay (ELISA) and TF activity by a modified prothrombin time assay. Basal RAGE mRNA expression was 0.2 ± 0.06 in patients with complications and 0.05 ± 0.06 patients without complications (P = .004). Stimulation did not cause any further increase in either group. TF mRNA was 0.58 ± 0.29 in patients with complications and 0.21 ± 0.18 in patients without complications (P = .003). Stimulation resulted in a nonsignificant increase in both groups. Basal TF activity (U/106 PBMCs) was 18.4 ± 13.2 in patients with complications and 6.96 ± 5.2 in patients without complications (P = .003). It increased 3-fold in both groups after stimulation (P = .001). TF antigen (pg/106 PBMCs) was 33.7 ± 28.6 in patients with complications, 10.4 ± 7.8 in patients without complications (P = .02). Stimulation tripled TF antigen in both groups of patients (P = .001). The RAGE/TF axis is up-regulated inT2Dpatients with vascular complications as compared to patients without complications. This suggests a role for this axis in the pathogenesis of vascular complications in T2D

Evidence for subaerial development of the Caribbean oceanic plateau in the Late Cretaceous and palaeo-environmental implications

The formation of oceanic plateaus in the Pacific in the Mesozoic has been proposed to create major environmental impacts, including global anoxic events OAE-1 in the Aptian (ca. 120 Ma) and OAE-2 in the Cenomanian–Turonian (ca. 90 Ma). However, our understanding of the formation of these large volcanic systems and their environmental effects are strongly limited by difficulties in accessing them and characterising their volcanic evolution. In particular, it remains significant to determine whether Pacific oceanic plateaus experience a phase of subaerial volcanic activity as this has critical implications in terms of their environmental impacts. Herein we provide the first unequivocal evidence for an emergent volcanic phase of the Caribbean oceanic plateau in the Late Cretaceous. This subaerial phase is evidenced by accreted oceanic sequences in Colombia that include fallout tuffs with accretionary lapilli and lahar deposits. This facies assemblage, recognised for the first time in an oceanic plateau, reflects phreatomagmatic eruptions coeval with subaerial erosion on an oceanic island. This result, combined with previous evidence of subaerial development of the Ontong Java Plateau and Shatsky Rise, suggests that syn-volcanic emergence of oceanic plateaus was common in the Pacific during the Mesozoic. Although temporal and spatial scales of these emergences remain poorly constrained it confirms that emergence of the Caribbean plateau in the Late Cretaceous (ca. 90 Ma) could have actively contributed to atmospheric changes and the establishment of OAE-2. Significantly, emergence of the Caribbean plateau occurred synchronously to the beginning of its tectonic displacement between the Americas. We propose that this unusual volcanic and tectonic evolution led to drastic reduction of the flow of Pacific oxygenated bottom waters into the early Atlantic basin, leading to a series of regional anoxic events previously documented between the Coniacian and Santonian (OAE-3, ca. 89 to 84 Ma). In addition, emergence of the Caribbean Plateau in the early inter-American seaway could have facilitated migration of terrestrial organisms between the Americas in the Late Cretaceous. The formation of the Caribbean plateau had therefore a large range of possible environmental effects, from atmospheric to palaeo-oceanographic and biotic impacts

Domestic thermal upgrades, community action and energy saving: a three-year experimental study of prosperous households

A three-year field experiment was conducted with 185 prosperous households to assess whether behavioural interventions by a community environmental group during and after thermal upgrades (cavity wall and/or loft insulation) can achieve reductions in households’ energy use, including reductions in direct and indirect rebound. The engineering interventions on the thermal efficiency of dwellings appear effective in reducing energy use in both treatment and control groups: a direct rebound effect is estimated to be at most 40 per cent from the engineering interventions. However, across a range of measures of energy use, we observe no significant effect of the community behavioural intervention across the total lifetime of the project. Qualitative data collected on similar community groups suggests substantial constraints on their capacity to realise reductions in energy use amongst households

Integrated care at home reduces unnecessary hospitalizations of community-dwelling frail older adults: a prospective controlled trial.

Care of frail and dependent older adults with multiple chronic conditions is a major challenge for health care systems. The study objective was to test the efficacy of providing integrated care at home to reduce unnecessary hospitalizations, emergency room visits, institutionalization, and mortality in community dwelling frail and dependent older adults. A prospective controlled trial was conducted, in real-life clinical practice settings, in a suburban region in Geneva, Switzerland, served by two home visiting nursing service centers. Three hundred and one community-dwelling frail and dependent people over 60 years old were allocated to previously randomized nursing teams into Control (N = 179) and Intervention (N = 122) groups: Controls received usual care by their primary care physician and home visiting nursing services, the Intervention group received an additional home evaluation by a community geriatrics unit with access to a call service and coordinated follow-up. Recruitment began in July 2009, goals were obtained in July 2012, and outcomes assessed until December 2012. Length of follow-up ranged from 5 to 41 months (mean 16.3). Primary outcome measure was the number of hospitalizations. Secondary outcomes were reasons for hospitalizations, the number and reason of emergency room visits, institutionalization, death, and place of death. The number of hospitalizations did not differ between groups however, the intervention led to lower cumulative incidence for the first hospitalization after the first year of follow-up (69.8%, CI 59.9 to 79.6 versus 87 · 6%, CI 78 · 2 to 97 · 0; p = .01). Secondary outcomes showed that the intervention compared to the control group had less frequent unnecessary hospitalizations (4.1% versus 11.7%, p = .03), lower cumulative incidence for the first emergency room visit, 8.3%, CI 2.6 to 13.9 versus 23.2%, CI 13.1 to 33.3; p = .01), and death occurred more frequently at home (44.4 versus 14.7%; p = .04). No significant differences were found for institutionalization and mortality. Integrated care that included a home visiting multidisciplinary geriatric team significantly reduced unnecessary hospitalizations, emergency room visits and allowed more patients to die at home. It is an effective tool to improve coordination and access to care for frail and dependent older adults. Clinical Trials.gov Identifier: NCT02084108 . Retrospectively registered on March 10(th) 2014

Arc-continent collision and orocline formation: Closing of the Central American seaway

Closure of the Central American seaway was a local tectonic event with potentially global biotic and environmental repercussions. We report geochronological (six U/Pb LA-ICP-MS zircon ages) and geochemical (19 XRF and ICP-MS analyses) data from the Isthmus of Panama that allow definition of a distinctive succession of plateau sequences to subduction-related protoarc to arc volcaniclastic rocks intruded by Late Cretaceous to middle Eocene intermediate plutonic rocks (67.6 ± 1.4 Ma to 41.1 ± 0.7 Ma). Paleomagnetic analyses (24 sites, 192 cores) in this same belt reveal large counterclockwise vertical-axis rotations (70.9° ± 6.7°), and moderate clockwise rotations (between 40° ± 4.1° and 56.2° ± 11.1°) on either side of an east-west trending fault at the apex of the Isthmus (Rio Gatun Fault), consistent with Isthmus curvature. An Oligocene-Miocene arc crosscuts the older, deformed and segmented arc sequences, and shows no significant vertical-axis rotation or deformation. There are three main stages of deformation: 1) left-lateral, strike-slip offset of the arc (∼100 km), and counterclockwise vertical-axis rotation of western arc segments between 38 and 28 Ma; 2) clockwise rotation of central arc segments between 28 and 25 Ma; and 3) orocline tightening after 25 Ma. When this reconstruction is placed in a global plate tectonic framework, and published exhumation data is added, the Central American seaway disappears at 15 Ma, suggesting that by the time of northern hemisphere glaciation, deep-water circulation had long been severed in Central America