Human liver sinusoidal endothelial cells support the development of functional human pluripotent stem cell-derived Kupffer cells.

In mice, the first liver-resident macrophages, known as Kupffer cells (KCs), are thought to derive from yolk sac (YS) hematopoietic progenitors that are specified prior to the emergence of the hematopoietic stem cell (HSC). To investigate human KC development, we recapitulated YS-like hematopoiesis from human pluripotent stem cells (hPSCs) and transplanted derivative macrophage progenitors into NSG mice previously humanized with hPSC-liver sinusoidal endothelial cells (LSECs). We demonstrate that hPSC-LSECs facilitate stable hPSC-YS-macrophage engraftment for at least 7 weeks.

Primitive macrophages induce sarcomeric maturation and functional enhancement of developing human cardiac microtissues via efferocytic pathways.

Yolk sac macrophages are the first to seed the developing heart, however we have no understanding of their roles in human heart development and function due to a lack of accessible tissue. Here, we bridge this gap by differentiating human embryonic stem cells (hESCs) into primitive LYVE1 macrophages (hESC-macrophages) that stably engraft within contractile cardiac microtissues composed of hESC-cardiomyocytes and fibroblasts. Engraftment induces a human fetal cardiac macrophage gene program enriched in efferocytic pathways.

Primitive macrophages enable long-term vascularization of human heart-on-a-chip platforms.

The intricate anatomical structure and high cellular density of the myocardium complicate the bioengineering of perfusable vascular networks within cardiac tissues. In vivo neonatal studies highlight the key role of resident cardiac macrophages in post-injury regeneration and angiogenesis. Here, we integrate human pluripotent stem-cell-derived primitive yolk-sac-like macrophages within vascularized heart-on-chip platforms.

Seismic reflection images of a near-axis melt sill within the lower crust at the Juan de Fuca ridge.

The oceanic crust extends over two-thirds of the Earth's solid surface, and is generated along mid-ocean ridges from melts derived from the upwelling mantle. The upper and middle crust are constructed by dyking and sea-floor eruptions originating from magma accumulated in mid-crustal lenses at the spreading axis, but the style of accretion of the lower oceanic crust is actively debated. Models based on geological and petrological data from ophiolites propose that the lower oceanic crust is accreted from melt sills intruded at multiple levels between the Moho transition zone (MTZ) and the mid-crustal lens, consistent with geophysical studies that suggest the presence of melt within the lower crust.

Seismic reflection images of the Moho underlying melt sills at the East Pacific Rise.

The determination of melt distribution in the crust and the nature of the crust-mantle boundary (the 'Moho') is fundamental to the understanding of crustal accretion processes at oceanic spreading centres. Upper-crustal magma chambers have been imaged beneath fast- and intermediate-spreading centres but it has been difficult to image structures beneath these magma sills. Using three-dimensional seismic reflection images, here we report the presence of Moho reflections beneath a crustal magma chamber at the 9 degrees 03' N overlapping spreading centre, East Pacific Rise.

Frozen magma lenses below the oceanic crust.

The Earth's oceanic crust crystallizes from magmatic systems generated at mid-ocean ridges. Whereas a single magma body residing within the mid-crust is thought to be responsible for the generation of the upper oceanic crust, it remains unclear if the lower crust is formed from the same magma body, or if it mainly crystallizes from magma lenses located at the base of the crust. Thermal modelling, tomography, compliance and wide-angle seismic studies, supported by geological evidence, suggest the presence of gabbroic-melt accumulations within the Moho transition zone in the vicinity of fast- to intermediate-spreading centres.

Need for coronary artery bypass grafting in Newfoundland and Labrador: the impact of increased demand.

Background: In the past decade, growth of coronary revascularization in Canada has been substantial. It was hypothesized that as coronary angiography (CA) rates increased, referral for necessary coronary artery bypass grafting (CABG) would also increase, and include patients with multivessel disease and class I to III angina who required elective surgery. Furthermore, it was proposed that the number of CABG surgeries needed would increase at a similar rate to that of CA.

Long-term changes in left ventricular hypertrophy after renal transplantation.

Background: Concentric and eccentric left ventricular hypertrophy are common progressive disorders in dialysis patients and are associated with cardiac failure and death. Although partial regression of these abnormalities is known to occur during the first post-transplant year, their long-term evolution is unknown.

Methods: A total of 143 of 433 dialysis patients participating in a long-term prospective cohort study received renal transplants.

Evidence from three-dimensional seismic reflectivity images for enhanced melt supply beneath mid-ocean-ridge discontinuities.

Quantifying the melt distribution and crustal structure across ridge-axis discontinuities is essential for understanding the relationship between magmatic, tectonic and petrologic segmentation of mid-ocean-ridge spreading centres. The geometry and continuity of magma bodies beneath features such as overlapping spreading centres can strongly influence the composition of erupted lavas and may give insight into the underlying pattern of mantle flow. Here we present three-dimensional images of seismic reflectivity beneath a mid-ocean ridge to investigate the nature of melt distribution across a ridge-axis discontinuity.

Comparative hospitalization of hemodialysis and peritoneal dialysis patients in Canada.

Background: Most comparisons of hemodialysis (HD) and peritoneal dialysis (PD) have used mortality as an outcome. Relatively few studies have directly compared the hospitalization rates, an outcome of perhaps equal importance, of patients using these different dialysis modalities.

Methods: Eight hundred twenty-two consecutive patients at 11 Canadian institutions with irreversible renal failure had an extensive assessment of comorbid illness and initial mode of dialysis collected prospectively immediately prior to starting dialysis therapy.

Serial change in echocardiographic parameters and cardiac failure in end-stage renal disease.

Echocardiographic abnormalities are the rule in patients starting dialysis therapy and are associated with the development of cardiac failure and death. It is unknown, however, whether regression of these abnormalities is associated with an improvement in prognosis. As part of a prospective cohort study with mean follow-up of 41 mo, 227 patients had echocardiography at inception and after 1 yr of dialysis therapy.

Comparative mortality of hemodialysis and peritoneal dialysis in Canada.

Background: Comparisons of mortality rates in patients on hemodialysis versus those on peritoneal dialysis have been inconsistent. We hypothesized that comorbidity has an important effect on differential survival in these two groups of patients.

Methods: Eight hundred twenty-two consecutive patients at 11 Canadian institutions with irreversible renal failure had an extensive assessment of comorbid illness collected prospectively, immediately prior to starting dialysis therapy.

Effective management of spinal pain in one hundred seventy-seven patients evaluated for manipulation under anesthesia.

Objective: To demonstrate that manipulation under anesthesia (MUA), a conservative treatment modality, is both safe and efficacious in the treatment of both acute and chronic spinal pain disorders in appropriately selected patients. MUA can be safely used to treat pain arising from the cranial, cervical, thoracic, and lumbar spine, as well as the sacroiliac and pelvic region.

Setting: An ambulatory surgical center.

Long-term evolution of cardiomyopathy in dialysis patients.

Background: Left ventricular enlargement is very common at the inception of dialysis therapy, and highly predictive of future cardiac morbidity and mortality. It is not known whether cardiac size increases further while on dialysis therapy and whether potentially reversible risk factors for later progression can be identified. METHODS; Baseline and yearly echocardiograms were performed in a prospective inception cohort of 433 dialysis patients.

Mode of dialysis therapy and mortality in end-stage renal disease.

Despite considerable differences in technique and blood purification characteristics, hemodialysis and peritoneal dialysis have been thought to have similar patient outcomes. An inception cohort of 433 end-stage renal disease patients was followed prospectively for a mean of 41 mo. The outcomes of hemodialysis (HD) and peritoneal dialysis (PD) patients were compared using intention to treat analysis based on the mode of therapy at 3 mo.

Cardiac disease in diabetic end-stage renal disease.

Little is known about the epidemiology of cardiac disease in diabetic end-stage renal disease. We therefore prospectively followed a cohort of 433 patients who survived 6 months after the inception of dialysis therapy for an average of 41 months. Clinical and echocardiographic data were collected yearly.

The impact of anemia on cardiomyopathy, morbidity, and and mortality in end-stage renal disease.

To determine the possible association between anemia and clinical and echocardiographic cardiac disease, a cohort of 432 end-stage renal disease patients (261 on hemodialysis and 171 on peritoneal dialysis) who started dialysis therapy between 1982 and 1991 were followed prospectively for an average of 41 months. Baseline demographic, clinical, and echocardiographic assessments were performed, as well as monthly serial clinical and laboratory tests while the patients were on dialysis therapy. The mean (+/-SD) hemoglobin level during dialysis therapy was 8.

Outcome and risk factors for left ventricular disorders in chronic uraemia.

Background: Left ventricular disease occurs frequently in dialysis patients. It may be manifest as concentric LV hypertrophy, LV dilatation with or without LV hypertrophy, or systolic dysfunction. Little is known concerning the clinical outcome and risk factors for these disorders.

Hypoalbuminemia, cardiac morbidity, and mortality in end-stage renal disease.

A cohort of 432 ESRD (261 hemodialysis and 171 peritoneal dialysis) patients was followed up prospectively for an average of 41 months. Baseline and annual demographic, clinical, and echocardiographic assessments were performed, as well as serial clinical and laboratory tests measured monthly while patients were on dialysis therapy. Among hemodialysis patients, after adjustment was made for age, diabetes, and ischemic heart disease, as well as hemoglobin and blood pressure levels measured serially, a 10-g/L fall in mean serum albumin level was independently associated with the the development of de novo (relative risk [RR], 2.

Outcome and risk factors of ischemic heart disease in chronic uremia.

To determine the prognosis and risk factors for ischemic heart disease in chronic uremia, a cohort of 432 dialysis patients were followed prospectively from start of dialysis therapy until death or renal transplantation. Baseline demographic, clinical and echocardiographic data were obtained. After the initiation of dialysis laboratory data were collected at monthly intervals, and clinical and echocardiographic data at yearly intervals.

Impact of hypertension on cardiomyopathy, morbidity and mortality in end-stage renal disease.

A cohort of 432 ESRD (261 hemodialysis and 171 peritoneal dialysis) patients was followed prospectively for an average of 41 months. Baseline and annual demographic, clinical and echocardiographic assessments were performed, as well as serial clinical and laboratory tests measured monthly while on dialysis therapy. The average mean arterial blood pressure level during dialysis therapy was 101 +/- 11 mm Hg.

Hypocalcemia, morbidity, and mortality in end-stage renal disease.

Background: Hypocalcemia and hyperphosphatemia with secondary hyper-parathyroidism are characteristic of end-stage renal disease (ESRD). Although calcium levels critically affect almost all cellular processes, the impact of chronic hypocalcemia and other abnormalities of calcium-phosphate homeostasis on the prognosis of ESRD patients is unknown.

Methods: An inception cohort of 433 patients starting ESRD therapy was followed prospectively for an average of 41 months.

Impact of renal transplantation on uremic cardiomyopathy.

In chronic uremia, cardiomyopathy manifests itself as systolic dysfunction, concentric left ventricular (LV) hypertrophy, or LV dilatation. To determine the impact of renal transplantation on uremic cardiomyopathy, all dialysis patients participating in a long-term cohort study who received a successful renal transplant were followed with echocardiography. The transplanted group comprised 102 of 433 (24%) endstage renal disease (ESRD) patients.

The prognostic importance of left ventricular geometry in uremic cardiomyopathy.

The objective of this study was to determine the effect of left ventricular (LV) mass, volume, and mass-to-volume ratio on mortality in chronic dialysis patients. The Design was a multicenter, prospective inception cohort study with a median follow-up of 41 months. The Setting was three university-affiliated nephrology units.