The Global Dynamics of Inequality (GINI) project: analysing archaeological housing data

The GINI project investigates the dynamics of inequality among populations over the long term by synthesising global archaeological housing data. This project brings archaeologists together from around the world to assess hypotheses concerning the causes and consequences of inequality that are of relevance to contemporary societies globally

Early Treatment with Fumagillin, an Inhibitor of Methionine Aminopeptidase-2, Prevents Pulmonary Hypertension in Monocrotaline-Injured Rats

Pulmonary Hypertension (PH) is a pathophysiologic condition characterized by hypoxemia and right ventricular strain. Proliferation of fibroblasts, smooth muscle cells, and endothelial cells is central to the pathology of PH in animal models and in humans. Methionine aminopeptidase-2 (MetAP2) regulates proliferation in a variety of cell types including endothelial cells, smooth muscle cells, and fibroblasts. MetAP2 is inhibited irreversibly by the angiogenesis inhibitor fumagillin. We have previously found that inhibition of MetAP2 with fumagillin in bleomycin-injured mice decreased pulmonary fibrosis by selectively decreasing the proliferation of lung myofibroblasts. In this study, we investigated the role of fumagillin as a potential therapy in experimental PH. In vivo, treatment of rats with fumagillin early after monocrotaline injury prevented PH and right ventricular remodeling by decreasing the thickness of the medial layer of the pulmonary arteries. Treatment with fumagillin beginning two weeks after monocrotaline injury did not prevent PH but was associated with decreased right ventricular mass and decreased cardiomyocyte hypertrophy, suggesting a direct effect of fumagillin on right ventricular remodeling. Incubation of rat pulmonary artery smooth muscle cells (RPASMC) with fumagillin and MetAP2-targeting siRNA inhibited proliferation of RPASMC in vitro. Platelet-derived growth factor, a growth factor that is important in the pathogenesis of PH and stimulates proliferation of fibroblasts and smooth muscle cells, strongly increased expression of MetP2. By immunohistochemistry, we found that MetAP2 was expressed in the lesions of human pulmonary arterial hypertension. We propose that fumagillin may be an effective adjunctive therapy for treating PH in patients

Novel computed tomographic chest metrics to detect pulmonary hypertension

<p>Abstract</p> <p>Background</p> <p>Early diagnosis of pulmonary hypertension (PH) can potentially improve survival and quality of life. Detecting PH using echocardiography is often insensitive in subjects with lung fibrosis or hyperinflation. Right heart catheterization (RHC) for the diagnosis of PH adds risk and expense due to its invasive nature. Pre-defined measurements utilizing computed tomography (CT) of the chest may be an alternative non-invasive method of detecting PH.</p> <p>Methods</p> <p>This study retrospectively reviewed 101 acutely hospitalized inpatients with heterogeneous diagnoses, who consecutively underwent CT chest and RHC during the same admission. Two separate teams, each consisting of a radiologist and pulmonologist, blinded to clinical and RHC data, individually reviewed the chest CT's.</p> <p>Results</p> <p>Multiple regression analyses controlling for age, sex, ascending aortic diameter, body surface area, thoracic diameter and pulmonary wedge pressure showed that a main pulmonary artery (PA) diameter ≥29 mm (odds ratio (OR) = 4.8), right descending PA diameter ≥19 mm (OR = 7.0), true right descending PA diameter ≥ 16 mm (OR = 4.1), true left descending PA diameter ≥ 21 mm (OR = 15.5), right ventricular (RV) free wall ≥ 6 mm (OR = 30.5), RV wall/left ventricular (LV) wall ratio ≥0.32 (OR = 8.8), RV/LV lumen ratio ≥1.28 (OR = 28.8), main PA/ascending aorta ratio ≥0.84 (OR = 6.0) and main PA/descending aorta ratio ≥ 1.29 (OR = 5.7) were significant predictors of PH in this population of hospitalized patients.</p> <p>Conclusion</p> <p>This combination of easily measured CT-based metrics may, upon confirmatory studies, aid in the non-invasive detection of PH and hence in the determination of RHC candidacy in acutely hospitalized patients.</p

In Heart Failure Patients with Left Bundle Branch Block Single Lead MultiSpot Left Ventricular Pacing Does Not Improve Acute Hemodynamic Response To Conventional Biventricular Pacing. A Multicenter Prospective, Interventional, Non-Randomized Study.

Introduction Recent efforts to increase CRT response by multiSPOT pacing (MSP) from multiple bipols on the same left ventricular lead are still inconclusive. Aim The Left Ventricular (LV) MultiSPOTpacing for CRT (iSPOT) study compared the acute hemodynamic response of MSP pacing by using 3 electrodes on a quadripolar lead compared with conventional biventricular pacing (BiV). Methods Patients with left bundle branch block (LBBB) underwent an acute hemodynamic study to determine the %change in LV+dP/dtmax from baseline atrial pacing compared to the following configurations: BiV pacing with the LV lead in a one of lateral veins, while pacing from the distal, mid, or proximal electrode and all 3 electrodes together (i.e. MSP). All measurements were repeated 4 times at 5 different atrioventricular delays. We also measured QRS-width and individual Q-LV durations. Results Protocol was completed in 24 patients, all with LBBB (QRS width 171±20 ms) and 58% ischemic aetiology. The percentage change in LV+dP/dtmax for MSP pacing was 31.0±3.3% (Mean±SE), which was not significantly superior to any BiV pacing configuration: 28.9±3.2% (LV-distal), 28.3±2.7% (LV-mid), and 29.5±3.0% (LV-prox), respectively. Correlation between LV+dP/dtmax and either QRS-width or Q-LV ratio was poor. Conclusions In patients with LBBB MultiSPOT LV pacing demonstrated comparable improvement in contractility to best conventional BiV pacing. Optimization of atrioventricular delay is important for the best performance for both BiV and MultiSPOT pacing configurations. Trial Registration ClinicalTrials.gov NTC0188314

The “Missing” Link Between Acute Hemodynamic Effect and Clinical Response

The hemodynamic, mechanical and electrical effects of cardiac resynchronization therapy (CRT) occur immediate and are lasting as long as CRT is delivered. Therefore, it is reasonable to assume that acute hemodynamic effects should predict long-term outcome. However, in the literature there is more evidence against than in favour of this idea. This raises the question of what factor(s) do relate to the benefit of CRT. There is increasing evidence that dyssynchrony, presumably through the resultant abnormal local mechanical behaviour, induces extensive remodelling, comprising structure, as well as electrophysiological and contractile processes. Resynchronization has been shown to reverse these processes, even in cases of limited hemodynamic improvement. These data may indicate the need for a paradigm shift in order to achieve maximal long-term CRT response

Animal Models of Dyssynchrony

Cardiac resynchronization therapy (CRT) is an important therapy for patients with heart failure and conduction pathology, but the benefits are heterogeneous between patients and approximately a third of patients do not show signs of clinical or echocardiographic response. This calls for a better understanding of the underlying conduction disease and resynchronization. In this review, we discuss to what extent established and novel animal models can help to better understand the pathophysiology of dyssynchrony and the benefits of CRT

British randomised controlled trial of AV and VV optimization ("BRAVO") study:rationale, design, and endpoints

Background Echocardiographic optimization of pacemaker settings is the current standard of care for patients treated with cardiac resynchronization therapy. However, the process requires considerable time of expert staff. The BRAVO study is a non-inferiority trial comparing echocardiographic optimization of atrioventricular (AV) and interventricular (VV) delay with an alternative method using non-invasive blood pressure monitoring that can be automated to consume less staff resources. Methods/Design BRAVO is a multi-centre, randomized, cross-over, non-inferiority trial of 400 patients with a previously implanted cardiac resynchronization device. Patients are randomly allocated to six months in each arm. In the echocardiographic arm, AV delay is optimized using the iterative method and VV delay by maximizing LVOT VTI. In the haemodynamic arm AV and VV delay are optimized using non-invasive blood pressure measured using finger photoplethysmography. At the end of each six month arm, patients undergo the primary outcome measure of objective exercise capacity, quantified as peak oxygen uptake (VO2) on a cardiopulmonary exercise test. Secondary outcome measures are echocardiographic measurement of left ventricular remodelling, quality of life score and N-terminal pro B-type Natriuretic Peptide (NT-pro BNP). The study is scheduled to complete recruitment in December 2013 and to complete follow up in December 2014. Discussion If exercise capacity is non-inferior with haemodynamic optimization compared with echocardiographic optimization, it would be proof of concept that haemodynamic optimization is an acceptable alternative which has the potential to be more easily implemented

Multidisciplinary investigations of the diets of two post-medieval populations from London using stable isotopes and microdebris analysis

This paper presents the first multi-tissue study of diet in post-medieval London using both the stable light isotope analysis of carbon and nitrogen and analysis of microdebris in dental calculus. Dietary intake was explored over short and long timescales. Bulk bone collagen was analysed from humans from the Queen’s Chapel of the Savoy (QCS) (n = 66) and the St Barnabas/St Mary Abbots (SB) (n = 25). Incremental dentine analysis was performed on the second molar of individual QCS1123 to explore childhood dietary intake. Bulk hair samples (n = 4) were sampled from adults from QCS, and dental calculus was analysed from four other individuals using microscopy. In addition, bone collagen from a total of 46 animals from QCS (n = 11) and the additional site of Prescot Street (n = 35) was analysed, providing the first animal dietary baseline for post-medieval London. Overall, isotopic results suggest a largely C3-based terrestrial diet for both populations, with the exception of QCS1123 who exhibited values consistent with the consumption of C4 food sources throughout childhood and adulthood. The differences exhibited in δ15Ncoll across both populations likely reflect variations in diet due to social class and occupation, with individuals from SB likely representing wealthier individuals consuming larger quantities of animal and marine fish protein. Microdebris analysis results were limited but indicate the consumption of domestic cereals. This paper demonstrates the utility of a multidisciplinary approach to investigate diet across long and short timescales to further our understanding of variations in social status and mobility