Tectono-stratigraphic evolution and crustal architecture of the Orphan Basin during North Atlantic rifting

The Orphan Basin is located in the deep offshore of the Newfoundland margin, and it is bounded by the continental shelf to the west, the Grand Banks to the south, and the continental blocks of Orphan Knoll and Flemish Cap to the east. The Orphan Basin formed in Mesozoic time during the opening of the North Atlantic Ocean between eastern Canada and western Iberia–Europe. This work, based on well data and regional seismic reflection profiles across the basin, indicates that the continental crust was affected by several extensional episodes between the Jurassic and the Early Cretaceous, separated by events of uplift and erosion. The preserved tectono-stratigraphic sequences in the basin reveal that deformation initiated in the eastern part of the Orphan Basin in the Jurassic and spread towards the west in the Early Cretaceous, resulting in numerous rift structures filled with a Jurassic–Lower Cretaceous syn-rift succession and overlain by thick Upper Cretaceous to Cenozoic post-rift sediments. The seismic data show an extremely thinned crust (4–16 km thick) underneath the eastern and western parts of the Orphan Basin, forming two sub-basins separated by a wide structural high with a relatively thick crust (17 km thick). Quantifying the crustal architecture in the basin highlights the large discrepancy between brittle extension localized in the upper crust and the overall crustal thinning. This suggests that continental deformation in the Orphan Basin involved, in addition to the documented Jurassic and Early Cretaceous rifting, an earlier brittle rift phase which is unidentifiable in seismic data and a depth-dependent thinning of the crust driven by localized lower crust ductile flow

Targeting Bone Alleviates Osteoarthritis in Osteopenic Mice and Modulates Cartilage Catabolism

Subchondral bone modifications occur early in the development of osteoarthritis (OA). The level of bone resorption might impact cartilage remodeling. We therefore assessed the in vivo and in vitro effects of targeting bone resorption in OA and cartilage metabolism.OA was induced by meniscectomy (MNX) in ovariectomized osteopenic mice (OP) treated with estradiol (E2), pamidronate (PAM), or phosphate buffered saline (PBS) for 6 weeks. We assessed the subchondral bone and cartilage structure and the expression of cartilage matrix proteases. To assess the involvement of bone soluble factors in cartilage metabolism, supernatant of human bone explants pre-treated with E2 or PAM were transferred to cartilage explants to assess proteoglycan release and aggrecan cleavage. OPG/RANKL mRNA expression was assessed in bone explants by real-time quantitative PCR. The role of osteoprotegerin (OPG) in the bone-cartilage crosstalk was tested using an OPG neutralizing antibody.Bone mineral density of OP mice and osteoclast number were restored by E2 and PAM (p<0.05). In OP mice, E2 and PAM decreased ADAMTS-4 and -5 expression, while only PAM markedly reduced OA compared to PBS (2.0±0.63 vs 5.2±0.95; p<0.05). OPG/RANKL mRNA was increased in human bone explants treated with both drugs (2.2-3.7-fold). Moreover, supernatants from bone explants cultured with E2 or PAM reduced aggrecan cleavage and cartilage proteoglycan release (73±8.0% and 80±22% of control, respectively, p<0.05). This effect was reversed with osteoprotegerin blockade.The inhibition of bone resorption by pamidronate in osteopenic mice alleviates the histological OA score with a reduction in the expression of aggrecanases. Bone soluble factors, such as osteoprotegerin, impact the cartilage response to catabolic factors. This study further highlights the importance of subchondral bone in the regulation of joint cartilage damage in OA

Cardiac resynchronization therapy guided by cardiovascular magnetic resonance

Cardiac resynchronization therapy (CRT) is an established treatment for patients with symptomatic heart failure, severely impaired left ventricular (LV) systolic dysfunction and a wide (> 120 ms) complex. As with any other treatment, the response to CRT is variable. The degree of pre-implant mechanical dyssynchrony, scar burden and scar localization to the vicinity of the LV pacing stimulus are known to influence response and outcome. In addition to its recognized role in the assessment of LV structure and function as well as myocardial scar, cardiovascular magnetic resonance (CMR) can be used to quantify global and regional LV dyssynchrony. This review focuses on the role of CMR in the assessment of patients undergoing CRT, with emphasis on risk stratification and LV lead deployment

Reduced costs with bisoprolol treatment for heart failure - An economic analysis of the second Cardiac Insufficiency Bisoprolol Study (CIBIS-II)

Background Beta-blockers, used as an adjunctive to diuretics, digoxin and angiotensin converting enzyme inhibitors, improve survival in chronic heart failure. We report a prospectively planned economic analysis of the cost of adjunctive beta-blocker therapy in the second Cardiac Insufficiency BIsoprolol Study (CIBIS II). Methods Resource utilization data (drug therapy, number of hospital admissions, length of hospital stay, ward type) were collected prospectively in all patients in CIBIS . These data were used to determine the additional direct costs incurred, and savings made, with bisoprolol therapy. As well as the cost of the drug, additional costs related to bisoprolol therapy were added to cover the supervision of treatment initiation and titration (four outpatient clinic/office visits). Per them (hospital bed day) costings were carried out for France, Germany and the U.K. Diagnosis related group costings were performed for France and the U.K. Our analyses took the perspective of a third party payer in France and Germany and the National Health Service in the U.K. Results Overall, fewer patients were hospitalized in the bisoprolol group, there were fewer hospital admissions perpatient hospitalized, fewer hospital admissions overall, fewer days spent in hospital and fewer days spent in the most expensive type of ward. As a consequence the cost of care in the bisoprolol group was 5-10% less in all three countries, in the per them analysis, even taking into account the cost of bisoprolol and the extra initiation/up-titration visits. The cost per patient treated in the placebo and bisoprolol groups was FF35 009 vs FF31 762 in France, DM11 563 vs DM10 784 in Germany and pound 4987 vs pound 4722 in the U.K. The diagnosis related group analysis gave similar results. Interpretation Not only did bisoprolol increase survival and reduce hospital admissions in CIBIS II, it also cut the cost of care in so doing. This `win-win' situation of positive health benefits associated with cost savings is Favourable from the point of view of both the patient and health care systems. These findings add further support for the use of beta-blockers in chronic heart failure