Reply to Bone mineral density in young adult survivors of acute lymphoblastic leukemia

No abstract.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/64309/1/24456_ftp.pd

Waist circumference percentile thresholds for identifying adolescents with insulin resistance in clinical practice

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72493/1/j.1399-5448.2008.00474.x.pd

Association of Pediatric Heart Transplant Coronary Vasculopathy with Abnormal Hemodynamic Measures

Objective.  Transplant coronary artery disease (TCAD) is the limiting factor to long‐term cardiac allograft survival; however, presymptomatic diagnosis remains challenging. To that concern, we evaluated the association of abnormal catheter‐derived filling pressures with TCAD in pediatric heart transplant (HTx) recipients.Design, Patients, Outcome Measures.  Data from 52 presymptomatic pediatric HTx patients were analyzed. Catheter‐derived right ventricular end‐diastolic pressure (RVEDP) and pulmonary capillary wedge pressure (PCWP) were recorded. Biopsies were collected to verify the absence of rejection.Results.  TCAD was diagnosed an average of 8.3 years post‐HTx in 20 (38%) patients, six of whom died and four of whom underwent retransplantation. Catheter‐derived pressure measurements showed that RVEDP was elevated in TCAD compared with non‐TCAD patients (9.5 ± 6.0 vs. 5.4 ± 4.7; P= .005), as was the PCWP (12.9 ± 5.7 vs. 9.1 ± 5.7; P= .012). Results from logistic regression analysis showed RVEDP > 10 mm Hg or PCWP > 12 mm Hg was associated with TCAD (OR = 5.2; P= .010).Conclusions.  In this series, elevated ventricular filling pressures measured during routine surveillance catheterizations were associated with angiographic TCAD. Recognizing the association between elevated RVEDP/PCWP and TCAD may prompt earlier diagnosis and treatment of this potentially lethal process.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/111940/1/j.1747-0803.2010.00470.x.pd

Impact of Vitamin C on Endothelial Function and Exercise Capacity in Patients with a Fontan Circulation

Objective.  To evaluate the impact of antioxidant therapy on functional health status in Fontan‐palliated patients. Design.  Prospective, randomized, double‐blind, placebo‐controlled trial. Patients.  Fifty‐three generally asymptomatic Fontan patients. Interventions.  Patients were randomized to receive either high‐dose ascorbic acid (vitamin C) or placebo for 4 weeks. Outcome Measures.  Peripheral vascular function, as measured with endothelium‐dependent digital pulse amplitude testing (EndoPAT), and exercise capacity were assessed before and after study drug treatment. Primary outcome measures included the EndoPAT index and peripheral arterial tonometry (PAT) ratio, both validated markers of vascular function. Secondary outcome measures included peak oxygen consumption and work. Results.  Twenty‐three vitamin C‐ and 21 placebo‐assigned subjects completed the protocol (83%). Median age and time from Fontan completion were 15 (interquartile range [IQR] 11.7–18.2) and 11.9 years (IQR 9.0–15.7), respectively. Right ventricular morphology was dominant in 30 (57%). Outcome measures were similar between groups at baseline. Among all subjects, vitamin C therapy was not associated with a statistical improvement in either primary or secondary outcome measures. In subjects with abnormal vascular function at baseline, compared with placebo, vitamin C therapy more frequently resulted in normalization of the EndoPAT index (45% vs. 17%) and PAT ratio (38% vs. 13%). Conclusions.  Short‐term therapy with vitamin C does not alter endothelial function or exercise capacity in an asymptomatic Fontan population overall. Vitamin C may provide benefit to a subset of Fontan patients with abnormal vascular function.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/92126/1/j.1747-0803.2011.00605.x.pd

An analysis of the carbon balance of the Arctic Basin from 1997 to 2006

Author Posting. © The Authors, 2010. This is the author's version of the work. It is posted here by permission of John Wiley & Sons for personal use, not for redistribution. The definitive version was published in Tellus B 62 (2010): 455-474, doi:10.1111/j.1600-0889.2010.00497.x.This study used several model-based tools to analyze the dynamics of the Arctic Basin between 1997 and 2006 as a linked system of land-ocean-atmosphere C exchange. The analysis estimates that terrestrial areas of the Arctic Basin lost 62.9 Tg C yr-1 and that the Arctic Ocean gained 94.1 Tg C yr-1. Arctic lands and oceans were a net CO2 sink of 108.9 Tg C yr-1, which is within the range of uncertainty in estimates from atmospheric inversions. Although both lands and oceans of the Arctic were estimated to be CO2 sinks, the land sink diminished in strength because of increased fire disturbance compared to previous decades, while the ocean sink increased in strength because of increased biological pump activity associated with reduced sea ice cover. Terrestrial areas of the Arctic were a net source of 41.5 Tg CH4 yr-1 that increased by 0.6 Tg CH4 yr-1 during the decade of analysis, a magnitude that is comparable with an atmospheric inversion of CH4. Because the radiative forcing of the estimated CH4 emissions is much greater than the CO2 sink, the analysis suggests that the Arctic Basin is a substantial net source of green house gas forcing to the climate system.This study was supported, in part, by the NSF Arctic System Science Program as part of the Arctic Carbon Cycle Synthesis Project (ARC-0531047, 0531082, 0531119, and 0554811)

Incidence and survival of childhood bone cancer in northern England and the West Midlands, 1981–2002

There is a paucity of population-based studies examining incidence and survival trends in childhood bone tumours. We used high quality data from four population-based registries in England. Incidence patterns and trends were described using Poisson regression. Survival trends were analysed using Cox regression. There were 374 cases of childhood (ages 0–14 years) bone tumours (206 osteosarcomas, 144 Ewing sarcomas, 16 chondrosarcomas, 8 other bone tumours) registered in the period 1981–2002. Overall incidence (per million person years) rates were 2.63 (95% confidence interval (CI) 2.27–2.99) for osteosarcoma, 1.90 (1.58–2.21) for Ewing sarcoma and 0.21 (0.11–0.31) for chondrosarcoma. Incidence of Ewing sarcoma declined at an average rate of 3.1% (95% CI 0.6–5.6) per annum (P=0.04), which may be due to tumour reclassification, but there was no change in osteosarcoma incidence. Survival showed marked improvement over the 20 years (1981–2000) for Ewing sarcoma (hazard ratio (HR) per annum=0.95 95% CI 0.91–0.99; P=0.02). However, no improvement was seen for osteosarcoma patients (HR per annum=1.02 95% CI 0.98–1.05; P=0.35) over this time period. Reasons for failure to improve survival including potential delays in diagnosis, accrual to trials, adherence to therapy and lack of improvement in treatment strategies all need to be considered

Trends in the sources and sinks of carbon dioxide

Efforts to control climate change require the stabilization of atmospheric CO2 concentrations. This can only be achieved through a drastic reduction of global CO2 emissions. Yet fossil fuel emissions increased by 29% between 2000 and 2008, in conjunction with increased contributions from emerging economies, from the production and international trade of goods and services, and from the use of coal as a fuel source. In contrast, emissions from land-use changes were nearly constant. Between 1959 and 2008, 43% of each year's CO2 emissions remained in the atmosphere on average; the rest was absorbed by carbon sinks on land and in the oceans. In the past 50 years, the fraction of CO2 emissions that remains in the atmosphere each year has likely increased, from about 40% to 45%, and models suggest that this trend was caused by a decrease in the uptake of CO2 by the carbon sinks in response to climate change and variability. Changes in the CO2 sinks are highly uncertain, but they could have a significant influence on future atmospheric CO2 levels. It is therefore crucial to reduce the uncertainties

Molecular Imaging of Pulmonary Tuberculosis in an Ex-Vivo Mouse Model Using Spectral Photon-Counting Computed Tomography and Micro-CT

Assessment of disease burden and drug efficacy is achieved preclinically using high resolution micro computed tomography (CT). However, micro-CT is not applicable to clinical human imaging due to operating at high dose. In addition, the technology differences between micro-CT and standard clinical CT prevent direct translation of preclinical applications. The current proof-of-concept study presents spectral photon-counting CT as a clinically translatable, molecular imaging tool by assessing contrast uptake in an ex-vivo mouse model of pulmonary tuberculosis (TB). Iodine, a common contrast used in clinical CT imaging, was introduced into a murine model of TB. The excised mouse lungs were imaged using a standard micro-CT subsystem (SuperArgus) and the contrast enhanced TB lesions quantified. The same lungs were imaged using a spectral photoncounting CT system (MARS small-bore scanner). Iodine and soft tissues (water and lipid) were materially separated, and iodine uptake quantified. The volume of the TB infection quantified by spectral CT and micro-CT was found to be 2.96 mm(3) and 2.83 mm(3), respectively. This proof-of-concept study showed that spectral photon-counting CT could be used as a predictive preclinical imaging tool for the purpose of facilitating drug discovery and development. Also, as this imaging modality is available for human trials, all applications are translatable to human imaging. In conclusion, spectral photon-counting CT could accelerate a deeper understanding of infectious lung diseases using targeted pharmaceuticals and intrinsic markers, and ultimately improve the efficacy of therapies by measuring drug delivery and response to treatment in animal models and later in humans

Metabolic Syndrome and Cardiovascular Disease after Hematopoietic Cell Transplantation: Screening and Preventive Practice Recommendations from the CIBMTR and EBMT

Metabolic syndrome (MetS) is a constellation of cardiovascular risk factors that increases the risk of cardiovascular disease, diabetes mellitus, and all-cause mortality. Long-term survivors of hematopoietic cell transplantation (HCT) have a substantial risk of developing MetS and cardiovascular disease, with an estimated prevalence of MetS of 31% to 49% among HCT recipients. Although MetS has not yet been proven to impact cardiovascular risk after HCT, an understanding of the incidence and risk factors for MetS in HCT recipients can provide the foundation to evaluate screening guidelines and develop interventions that may mitigate cardiovascular-related mortality. A working group was established through the Center for International Blood and Marrow Transplant Research and the European Group for Blood and Marrow Transplantation with the goal to review literature and recommend practices appropriate to HCT recipients. Here we deliver consensus recommendations to help clinicians provide screening and preventive care for MetS and cardiovascular disease among HCT recipients. All HCT survivors should be advised of the risks of MetS and encouraged to undergo recommended screening based on their predisposition and ongoing risk factors

Optical control of L-Type Ca2+ channels using a diltiazem photoswitch

L-type Ca2+ channels (LTCCs) play a crucial role in excitation-contraction coupling and release of hormones from secretory cells. They are targets of antihypertensive and antiarrhythmic drugs such as diltiazem. Here, we present a photoswitchable diltiazem, FHU-779, which can be used to reversibly block endogenous LTCCs by light. FHU-779 is as potent as diltiazem and can be used to place pancreatic β-cell function and cardiac activity under optical control