Letters from Adam Mather to his brother Robert Mather between London and Van Diemen's Land

Two letters, the first from Adam Mather in London to his brother Robert Mather in 1823 before the Mathers sailed to Van Diemen's Land and the second from Adam Mather and his sister Mary Mather in London to Robert in Van Diemen's Land

Cardiovascular consequences of metabolic syndrome

The metabolic syndrome (MetS) is defined as the concurrence of obesity-associated cardiovascular risk factors including abdominal obesity, impaired glucose tolerance, hypertriglyceridemia, decreased HDL cholesterol, and/or hypertension. Earlier conceptualizations of the MetS focused on insulin resistance as a core feature, and it is clearly coincident with the above list of features. Each component of the MetS is an independent risk factor for cardiovascular disease and the combination of these risk factors elevates rates and severity of cardiovascular disease, related to a spectrum of cardiovascular conditions including microvascular dysfunction, coronary atherosclerosis and calcification, cardiac dysfunction, myocardial infarction, and heart failure. While advances in understanding the etiology and consequences of this complex disorder have been made, the underlying pathophysiological mechanisms remain incompletely understood, and it is unclear how these concurrent risk factors conspire to produce the variety of obesity-associated adverse cardiovascular diseases. In this review, we highlight current knowledge regarding the pathophysiological consequences of obesity and the MetS on cardiovascular function and disease, including considerations of potential physiological and molecular mechanisms that may contribute to these adverse outcomes

Combination GLP-1 and Insulin Treatment Fails to Alter Myocardial Fuel Selection Versus Insulin Alone in Type 2 Diabetes

Context Glucagon-like peptide-1 (GLP-1) and the clinically available GLP-1 agonists have been shown to exert effects on the heart. It is unclear whether these effects occur at clinically used doses in vivo in humans, possibly contributing to CVD risk reduction. Objective To determine whether liraglutide at clinical dosing augments myocardial glucose uptake alone or in combination with insulin compared to insulin alone in metformin-treated Type 2 diabetes mellitus. Design Comparison of myocardial fuel utilization after 3 months of treatment with insulin detemir, liraglutide, or combination detemir+liraglutide. Setting Academic hospital Participants Type 2 diabetes treated with metformin plus oral agents or basal insulin. Interventions Insulin detemir, liraglutide, or combination added to background metformin Main Outcome Measures Myocardial blood flow, fuel selection and rates of fuel utilization evaluated using positron emission tomography, powered to demonstrate large effects. Results We observed greater myocardial blood flow in the insulin-treated groups (median[25th, 75th percentile]: detemir 0.64[0.50, 0.69], liraglutide 0.52[0.46, 0.58] and detemir+liraglutide 0.75[0.55, 0.77] mL/g/min, p=0.035 comparing 3 groups and p=0.01 comparing detemir groups to liraglutide alone). There were no evident differences between groups in myocardial glucose uptake (detemir 0.040[0.013, 0.049], liraglutide 0.055[0.019, 0.105], detemir+liraglutide 0.037[0.009, 0.046] µmol/g/min, p=0.68 comparing 3 groups). Similarly there were no treatment group differences in measures of myocardial fatty acid uptake or handling, and no differences in total oxidation rate. Conclusions These observations argue against large effects of GLP-1 agonists on myocardial fuel metabolism as mediators of beneficial treatment effects on myocardial function and ischemia protection

Multi-Scale CNT-Based Reinforcing Polymer Matrix Composites for Lightweight Structures

Reinforcing critical areas in carbon polymer matrix composites (PMCs), also known as fiber reinforced composites (FRCs), is advantageous for structural durability. Since carbon nanotubes (CNTs) have extremely high tensile strength, they can be used as a functional additive to enhance the mechanical properties of FRCs. However, CNTs are not readily dispersible in the polymer matrix, which leads to lower than theoretically predicted improvement in mechanical, thermal, and electrical properties of CNT composites. The inability to align CNTs in a polymer matrix is also a known issue. The feasibility of incorporating aligned CNTs into an FRC was demonstrated using a novel, yet commercially viable nanofiber approach, termed NRMs (nanofiber-reinforcing mats). The NRM concept of reinforcement allows for a convenient and safe means of incorporating CNTs into FRC structural components specifically where they are needed during the fabrication process. NRMs, fabricated through a novel and scalable process, were incorporated into FRC test panels using layup and vacuum bagging techniques, where alternating layers of the NRM and carbon prepreg were used to form the reinforced FRC structure. Control FRC test panel coupons were also fabricated in the same manner, but comprised of only carbon prepreg. The FRC coupons were machined to size and tested for flexural, tensile, and compression properties. This effort demonstrated that FRC structures can be fabricated using the NRM concept, with an increased average load at break during flexural testing versus that of the control. The NASA applications for the developed technologies are for lightweight structures for in-space and launch vehicles. In addition, the developed technologies would find use in NASA aerospace applications such as rockets, aircraft, aircraft/spacecraft propulsion systems, and supporting facilities. The reinforcing aspect of the technology will allow for more efficient joining of fiber composite parts, thus offering additional weight savings. More robust structures capable of withstanding micrometeoroid and space debris impacts will be possible with the enhanced mechanical properties imparted by the aligned CNTs incorporated into the fiber composite structure, as well as the potential for improved electrical and thermal properties. The materials fabrication approach developed in the present effort is a platform for customer applications where additional reinforcement is required or would be beneficial, especially in FRC structures and component parts. Depending upon the specific customer application, the NRM could be tailored to the specific matrix resin and desired property enhancement

CARDIOVASCULAR AND HEMODYNAMIC EFFECTS OF GLUCAGON-LIKE PEPTIDE-1

Glucagon-like peptide-1 (GLP-1) is an incretin hormone that has been shown to have hemodynamic and cardioprotective capacity in addition to its better characterized glucoregulatory actions. Because of this, emerging research has focused on the ability of GLP-1 based therapies to drive myocardial substrate selection, enhance cardiac performance and regulate heart rate, blood pressure and vascular tone. These studies have produced consistent and reproducible results amongst numerous laboratories. However, there are obvious disparities in findings obtained in small animal models versus those of higher mammals. This species dependent discrepancy calls to question, the translational value of individual findings. Moreover, few studies of GLP-1 mediated cardiovascular action have been performed in the presence of a pre-existing comorbidities (e.g. obesity/diabetes) which limits interpretation of the effectiveness of incretin-based therapies in the setting of disease. This review addresses cardiovascular and hemodynamic potential of GLP-1 based therapies with attention to species specific effects as well as the interaction between therapies and disease

Relationship of dysglycemia to acute myocardial infarct size and cardiovascular outcome as determined by cardiovascular magnetic resonance

<p>Abstract</p> <p>Background</p> <p>Improved outcomes for normoglycemic patients suffering acute myocardial infarction (AMI) over the last decade have not been matched by similar improvements in mortality for diabetic patients despite similar levels of baseline risk and appropriate medical therapy. Two of the major determinants of poor outcome following AMI are infarct size and left ventricular (LV) dysfunction.</p> <p>Methods</p> <p>Ninety-three patients with first AMI were studied. 22 patients had diabetes mellitus (DM) based on prior history or admission blood glucose ≥11.1 mmol/l. 13 patients had dysglycemia (admission blood glucose ≥7.8 mmol/l but <11.1 mmol/l) and 58 patients had normoglycemia (admission blood glucose <7.8 mmol/l). Patients underwent cardiac magnetic resonance (CMR) imaging at index presentation and median follow-up of 11 months. Cine imaging assessed LV function and late gadolinium contrast-enhanced imaging was used to quantify infarct size. Clinical outcome data were collected at 18 months median follow-up.</p> <p>Results</p> <p>Patients with dysglycemia and DM had larger infarct sizes by CMR than normoglycemic patients; at baseline percentage LV scar (mean (SD)) was 23.0% (10.9), 25.6% (12.9) and 15.8% (10.3) respectively (p = 0.001), and at 11 months percentage LV scar was 17.6% (8.9), 19.1% (9.6) and 12.4% (7.8) (p = 0.017). Patients with dysglycemia and DM also had lower event-free survival at 18 months (p = 0.005).</p> <p>Conclusions</p> <p>Patients with dysglycemia or diabetes mellitus sustain larger infarct sizes than normoglycemic patients, as determined by CMR. This may, in part, account for their adverse prognosis following AMI.</p