Busulfan, a bifunctional alkylating agent, is a mainstay of myeloablative preparative regimens be... more Busulfan, a bifunctional alkylating agent, is a mainstay of myeloablative preparative regimens before hematopoietic stem cell transplantation. The apparent oral clearance of busulfan expressed relative to body surface area is 2-3-fold higher in children 1-4 years old than it is in adults. The first step in busulfan elimination is the formation of a tetrahydrothiophenium ion (THT+) in a glutathione S-transferase-catalyzed reaction. We present computer simulations that demonstrate that the ratio of the AUC of THT+ to that of busulfan over 6 h [(AUC(THT+)/AUC(BU))(0-->6)] is highly correlated (r2 = 0.805) with the determinants of THT+ formation and is virtually independent of the determinants of its elimination (r2 = 0.0201). We compared (AUC(THT+)/AUC(BU))(0-->6) determined in 14 children (0.5-4 years) to that of 11 adults (12-54 years) and found a 1.5-fold elevation in the area ratio (P = 0.0098) and a similarly significant increase in busulfan apparent oral clearance expressed relative to body surface area (P = 0.042). The only common explanation for the elevated busulfan apparent oral clearance and (AUC(THT+)/AUC(BU))(0-->6) is an enhanced ability of children to metabolize busulfan through glutathione conjugation.
The apparent oral clearance (CL/F, mL/min) of busulfan was measured in 279 adolescent and adult p... more The apparent oral clearance (CL/F, mL/min) of busulfan was measured in 279 adolescent and adult patients. Significant (P< .05) determinants of CL/F by linear regression were: actual body weight (BW; r2 = 0.300), body surface area (BSA; r2 = 0.277), adjusted ideal body weight (AIBW; r2 = 0.265), and ideal body weight (IBW; r2= 0.173); whereas body mass index (BMI), height, age, gender, and disease were less important predictors. CL/F (mL/min) for normal weight patients (BMI, 18 to 27 kg/m2) was 16.2% lower (P< .001) than for obese patients (BMI, 27 to 35 kg/m2). Thus, expressing CL/F relative to BW did not eliminate statistically significant differences between normal and obese patients. However, busulfan CL/F expressed relative to BSA (110 ± 24 v 110 ± 24 mL/min/m2, P = 1.0) or AIBW (3.04 ± 0.65 v 3.19 ± 0.67 mL/min/kg, P = .597) were similar in normal and obese patients. Non-Hodgkin’s lymphoma patients (n = 10) had approximately 32% lower mean busulfan CL/F expressed relative...
The AMC's citizen scientist monitoring program, Mountain Watch, engages hikers in observatio... more The AMC's citizen scientist monitoring program, Mountain Watch, engages hikers in observational monitoring while recreating in the northern Appalachian Mountains. The program uses two monitoring activities:1) tracking the phenology of 11 mountain flowers species, and 2) the visitors real world perception of on-mountain visibility and its `quality' with proximate monitored air quality parameters. The Mountain Watch program objectives are a) to engage and educate the public through hands-on monitoring, b) to motivate the participant to take further action towards environmental stewardship, and c) to provide supplemental data to AMC's ongoing science-based research to further our understanding of the impact of human activity on mountain ecosystems. The Mountain Watch plant monitoring includes recording the time and location of alpine and forest plants flowering and other phenological phases using AMC field guides and datasheets. In the White Mountains of New Hampshire concurrent meteorological data, including soil temperature, is paired with the phenology observations as part of AMC's research to develop spatial and temporal phenology models with air and soil temperature for northeastern mountains. Mountain Watch's visibility monitoring program has hikers record visual range and rate the view at select vistas in comparison to a clear day view photo guide when visiting AMC's backcountry huts. The results are compared to proximate air quality measurements, which assists in determining how White Mountain National Forest air quality related values and natural resources management objectives are being met. Since 2006 the Mountain Watch program has received over 3,500 citizen datasheets for plant reproductive phenology and visibility monitoring. We estimate that we have reached more than 15,000 hikers through our facility based education programming focused on air quality and phenology and field monitoring hikes. While we consider this good success in engaging hikers to date, the ratio of resource expenditures in recruiting volunteers and QA/QCing their data for actual research application has been high. Mountain Watch staff are now refining the program to achieve education and research goals a manner that is sustainable into the future with limited fiscal and staff resources. The quality of our citizen phenology observations, in comparison to staff monitoring, has lead to refinements including directing general audience hikers to well-defined trailside observation stations, growing our more skilled amateur botanist volunteer base, and use of remote cameras for quality controls and better temporal coverage. Visibility monitoring at four mountain vistas has recently been analyzed in the context of policy applications. Refinements will be presented that will further inform natural resource management of air quality in relation to Clean Air Act Air Quality Related Values and a potential visibility focused particulate matter secondary National Ambient Air Quality Standard. Overall lessons learned, regarding audience considerations, resource needs, and long-term sustainability, from our 5-year field based geoscience programs will be discussed.
Murray et al "Influence of partial harvesting on stream temperatures, chemistry, and turbidi... more Murray et al "Influence of partial harvesting on stream temperatures, chemistry, and turbidity in forests on the Western Olympic Peninsula, Washington." Northwest Science. 2000; 74(2): 151-164
We measured ecosystem respiration (ER: or CO[sub 2] flux), methane (CH[sub 4]) fluxes and net eco... more We measured ecosystem respiration (ER: or CO[sub 2] flux), methane (CH[sub 4]) fluxes and net ecosystem production (NEP) near Toolik Lake, Alaska to compare effects of temperature, moisture and nutrients on tundra C balances. We measured fluxes using closed chambers in control, warmed and fertilized plots in wet, moist and dry tundra. ER rankings of tundra types differed between years. In 1992 ER was [approximately]70 g C m[sup [minus]2]y[sup [minus]1] in wet and moist tundra and was 50% lower in dry tundra. In 1993 ER was >150 g C m[sup [minus]2]y[sup [minus]1] in moist tundra and [approximately]55 g C m[sup [minus]2]y[sup [minus]1] in wet and dry tundra. CH[sub 4] emissions ranged from 3.5 to 7 g C m[sup [minus]2]y[sup [minus]1] in wet and from 0.6 to 2.8 g C m[sup [minus]2]y[sup [minus]1] in moist tundra. Dry tundra consumed about 0.1 g CH[sub 4]-C m[sup [minus]2]y[sup [minus]1]. In wet tundra ER increased slightly with warming but dramatically with fertilization. Wet tundra NEP increased with fertilization but not with warming. CH[sub 4] emissions from wet tundra increased with warming but decreased with fertilization. Warming and fertilization increased ER but neither treatment affected NEP in moist tundra. CH[sub 4] emissions from moist tundra responded similarly but less dramatically to treatments than did wet tundra CH[sub 4] fluxes. Warming did not affect ER or NEP in dry tundra, fertilization increased both process. Consumption of CH[sub 4] in dry tundra increased with warming but decreased with fertilization.
We examined the importance of temperature (7°C or 15°C) and soil moisture regime (saturated or fi... more We examined the importance of temperature (7°C or 15°C) and soil moisture regime (saturated or field capacity) on the carbon (C) balance of arctic tussock tundra microcosms (intact blocks of soil and vegetation) in growth chambers over an 81-day simulated growing season. We measured gaseous CO2 exchanges, methane (CH4) emissions, and dissolved C losses on intact blocks of tussock (Eriophorum
Discrimination of the type of air mass along mountain slopes can be a challenge and is not common... more Discrimination of the type of air mass along mountain slopes can be a challenge and is not commonly performed, but is critical for identifying factors responsible for influencing montane weather, climate, and air quality. A field campaign to measure air mass type and transitions on the summit of Mount Washington, New Hampshire, USA was performed on 19 August 2016. Meteorological observations were taken at the summit and at several sites along the east and west slopes. Ozone concentrations were measured at the summit and on the valley floor. Additionally, water vapor stable isotopes were measured from a truck that drove up and down the Mount Washington Auto Road concurrent with radiosonde launches that profiled the free atmosphere. This multivariate perspective revealed thermal, moisture, and air mass height differences among the free atmosphere, leeward, and windward mountain slopes. Both thermally and mechanically forced upslope flows helped shape these differences by altering the ...
Overstory litterfall rates and nutrient returns were determined in an old-growth temperate rainfo... more Overstory litterfall rates and nutrient returns were determined in an old-growth temperate rainforest watershed in the Hoh River valley, Olympic National Park, Washington. Litter was sorted into green needles, senescent needles, fine wood, reproductive, and miscellaneous litter (mostly arboreal lichens and mosses). Understory and coarse woody debris inputs were not determined. Total annual overstory litterfall averaged 3594 kg·ha1 and varied among the six plant communities in the watershed. There was a trend for litterfall to be higher in the upper watershed; elevations ranged from 180 to 850 m. Needles provided the greatest amount of litterfall (60%) with woody litter and other material averaging 18 and 22%, respectively. Highest senescent needle litterfall occurred from July to October, but highest woody litterfall was from January to April. Green needles provided only 3% of annual needle litterfall. Green and senescent needle litterfall were related to western hemlock (Tsuga heterophylla (Raf.) Sarg.) basal area, suggesting that this shade-tolerant species was the greatest contributor to needle litterfall. The following quantities (kg·ha1) of nutrients were returned to the forest floor annually: Ca, 26.8; N, 24.6; K, 4.0; Mg, 3.0; P, 2.9; Mn, 1.7; and Na, 1.2.
Busulfan, a bifunctional alkylating agent, is a mainstay of myeloablative preparative regimens be... more Busulfan, a bifunctional alkylating agent, is a mainstay of myeloablative preparative regimens before hematopoietic stem cell transplantation. The apparent oral clearance of busulfan expressed relative to body surface area is 2-3-fold higher in children 1-4 years old than it is in adults. The first step in busulfan elimination is the formation of a tetrahydrothiophenium ion (THT+) in a glutathione S-transferase-catalyzed reaction. We present computer simulations that demonstrate that the ratio of the AUC of THT+ to that of busulfan over 6 h [(AUC(THT+)/AUC(BU))(0-->6)] is highly correlated (r2 = 0.805) with the determinants of THT+ formation and is virtually independent of the determinants of its elimination (r2 = 0.0201). We compared (AUC(THT+)/AUC(BU))(0-->6) determined in 14 children (0.5-4 years) to that of 11 adults (12-54 years) and found a 1.5-fold elevation in the area ratio (P = 0.0098) and a similarly significant increase in busulfan apparent oral clearance expressed relative to body surface area (P = 0.042). The only common explanation for the elevated busulfan apparent oral clearance and (AUC(THT+)/AUC(BU))(0-->6) is an enhanced ability of children to metabolize busulfan through glutathione conjugation.
The apparent oral clearance (CL/F, mL/min) of busulfan was measured in 279 adolescent and adult p... more The apparent oral clearance (CL/F, mL/min) of busulfan was measured in 279 adolescent and adult patients. Significant (P< .05) determinants of CL/F by linear regression were: actual body weight (BW; r2 = 0.300), body surface area (BSA; r2 = 0.277), adjusted ideal body weight (AIBW; r2 = 0.265), and ideal body weight (IBW; r2= 0.173); whereas body mass index (BMI), height, age, gender, and disease were less important predictors. CL/F (mL/min) for normal weight patients (BMI, 18 to 27 kg/m2) was 16.2% lower (P< .001) than for obese patients (BMI, 27 to 35 kg/m2). Thus, expressing CL/F relative to BW did not eliminate statistically significant differences between normal and obese patients. However, busulfan CL/F expressed relative to BSA (110 ± 24 v 110 ± 24 mL/min/m2, P = 1.0) or AIBW (3.04 ± 0.65 v 3.19 ± 0.67 mL/min/kg, P = .597) were similar in normal and obese patients. Non-Hodgkin’s lymphoma patients (n = 10) had approximately 32% lower mean busulfan CL/F expressed relative...
The AMC's citizen scientist monitoring program, Mountain Watch, engages hikers in observatio... more The AMC's citizen scientist monitoring program, Mountain Watch, engages hikers in observational monitoring while recreating in the northern Appalachian Mountains. The program uses two monitoring activities:1) tracking the phenology of 11 mountain flowers species, and 2) the visitors real world perception of on-mountain visibility and its `quality' with proximate monitored air quality parameters. The Mountain Watch program objectives are a) to engage and educate the public through hands-on monitoring, b) to motivate the participant to take further action towards environmental stewardship, and c) to provide supplemental data to AMC's ongoing science-based research to further our understanding of the impact of human activity on mountain ecosystems. The Mountain Watch plant monitoring includes recording the time and location of alpine and forest plants flowering and other phenological phases using AMC field guides and datasheets. In the White Mountains of New Hampshire concurrent meteorological data, including soil temperature, is paired with the phenology observations as part of AMC's research to develop spatial and temporal phenology models with air and soil temperature for northeastern mountains. Mountain Watch's visibility monitoring program has hikers record visual range and rate the view at select vistas in comparison to a clear day view photo guide when visiting AMC's backcountry huts. The results are compared to proximate air quality measurements, which assists in determining how White Mountain National Forest air quality related values and natural resources management objectives are being met. Since 2006 the Mountain Watch program has received over 3,500 citizen datasheets for plant reproductive phenology and visibility monitoring. We estimate that we have reached more than 15,000 hikers through our facility based education programming focused on air quality and phenology and field monitoring hikes. While we consider this good success in engaging hikers to date, the ratio of resource expenditures in recruiting volunteers and QA/QCing their data for actual research application has been high. Mountain Watch staff are now refining the program to achieve education and research goals a manner that is sustainable into the future with limited fiscal and staff resources. The quality of our citizen phenology observations, in comparison to staff monitoring, has lead to refinements including directing general audience hikers to well-defined trailside observation stations, growing our more skilled amateur botanist volunteer base, and use of remote cameras for quality controls and better temporal coverage. Visibility monitoring at four mountain vistas has recently been analyzed in the context of policy applications. Refinements will be presented that will further inform natural resource management of air quality in relation to Clean Air Act Air Quality Related Values and a potential visibility focused particulate matter secondary National Ambient Air Quality Standard. Overall lessons learned, regarding audience considerations, resource needs, and long-term sustainability, from our 5-year field based geoscience programs will be discussed.
Murray et al "Influence of partial harvesting on stream temperatures, chemistry, and turbidi... more Murray et al "Influence of partial harvesting on stream temperatures, chemistry, and turbidity in forests on the Western Olympic Peninsula, Washington." Northwest Science. 2000; 74(2): 151-164
We measured ecosystem respiration (ER: or CO[sub 2] flux), methane (CH[sub 4]) fluxes and net eco... more We measured ecosystem respiration (ER: or CO[sub 2] flux), methane (CH[sub 4]) fluxes and net ecosystem production (NEP) near Toolik Lake, Alaska to compare effects of temperature, moisture and nutrients on tundra C balances. We measured fluxes using closed chambers in control, warmed and fertilized plots in wet, moist and dry tundra. ER rankings of tundra types differed between years. In 1992 ER was [approximately]70 g C m[sup [minus]2]y[sup [minus]1] in wet and moist tundra and was 50% lower in dry tundra. In 1993 ER was >150 g C m[sup [minus]2]y[sup [minus]1] in moist tundra and [approximately]55 g C m[sup [minus]2]y[sup [minus]1] in wet and dry tundra. CH[sub 4] emissions ranged from 3.5 to 7 g C m[sup [minus]2]y[sup [minus]1] in wet and from 0.6 to 2.8 g C m[sup [minus]2]y[sup [minus]1] in moist tundra. Dry tundra consumed about 0.1 g CH[sub 4]-C m[sup [minus]2]y[sup [minus]1]. In wet tundra ER increased slightly with warming but dramatically with fertilization. Wet tundra NEP increased with fertilization but not with warming. CH[sub 4] emissions from wet tundra increased with warming but decreased with fertilization. Warming and fertilization increased ER but neither treatment affected NEP in moist tundra. CH[sub 4] emissions from moist tundra responded similarly but less dramatically to treatments than did wet tundra CH[sub 4] fluxes. Warming did not affect ER or NEP in dry tundra, fertilization increased both process. Consumption of CH[sub 4] in dry tundra increased with warming but decreased with fertilization.
We examined the importance of temperature (7°C or 15°C) and soil moisture regime (saturated or fi... more We examined the importance of temperature (7°C or 15°C) and soil moisture regime (saturated or field capacity) on the carbon (C) balance of arctic tussock tundra microcosms (intact blocks of soil and vegetation) in growth chambers over an 81-day simulated growing season. We measured gaseous CO2 exchanges, methane (CH4) emissions, and dissolved C losses on intact blocks of tussock (Eriophorum
Discrimination of the type of air mass along mountain slopes can be a challenge and is not common... more Discrimination of the type of air mass along mountain slopes can be a challenge and is not commonly performed, but is critical for identifying factors responsible for influencing montane weather, climate, and air quality. A field campaign to measure air mass type and transitions on the summit of Mount Washington, New Hampshire, USA was performed on 19 August 2016. Meteorological observations were taken at the summit and at several sites along the east and west slopes. Ozone concentrations were measured at the summit and on the valley floor. Additionally, water vapor stable isotopes were measured from a truck that drove up and down the Mount Washington Auto Road concurrent with radiosonde launches that profiled the free atmosphere. This multivariate perspective revealed thermal, moisture, and air mass height differences among the free atmosphere, leeward, and windward mountain slopes. Both thermally and mechanically forced upslope flows helped shape these differences by altering the ...
Overstory litterfall rates and nutrient returns were determined in an old-growth temperate rainfo... more Overstory litterfall rates and nutrient returns were determined in an old-growth temperate rainforest watershed in the Hoh River valley, Olympic National Park, Washington. Litter was sorted into green needles, senescent needles, fine wood, reproductive, and miscellaneous litter (mostly arboreal lichens and mosses). Understory and coarse woody debris inputs were not determined. Total annual overstory litterfall averaged 3594 kg·ha1 and varied among the six plant communities in the watershed. There was a trend for litterfall to be higher in the upper watershed; elevations ranged from 180 to 850 m. Needles provided the greatest amount of litterfall (60%) with woody litter and other material averaging 18 and 22%, respectively. Highest senescent needle litterfall occurred from July to October, but highest woody litterfall was from January to April. Green needles provided only 3% of annual needle litterfall. Green and senescent needle litterfall were related to western hemlock (Tsuga heterophylla (Raf.) Sarg.) basal area, suggesting that this shade-tolerant species was the greatest contributor to needle litterfall. The following quantities (kg·ha1) of nutrients were returned to the forest floor annually: Ca, 26.8; N, 24.6; K, 4.0; Mg, 3.0; P, 2.9; Mn, 1.7; and Na, 1.2.
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