Recent laboratory and field studies have indicated that glyoxal is a potentially large contributor to secondary organic aerosol mass. We present in situ glyoxal measurements acquired with a recently ...developed, high sensitivity spectroscopic instrument during the CalNex 2010 field campaign in Pasadena, California. We use three methods to quantify the production and loss of glyoxal in Los Angeles and its contribution to organic aerosol. First, we calculate the difference between steady state sources and sinks of glyoxal at the Pasadena site, assuming that the remainder is available for aerosol uptake. Second, we use the Master Chemical Mechanism to construct a two‐dimensional model for gas‐phase glyoxal chemistry in Los Angeles, assuming that the difference between the modeled and measured glyoxal concentration is available for aerosol uptake. Third, we examine the nighttime loss of glyoxal in the absence of its photochemical sources and sinks. Using these methods we constrain the glyoxal loss to aerosol to be 0–5 × 10−5 s−1 during clear days and (1 ± 0.3) × 10−5 s−1 at night. Between 07:00–15:00 local time, the diurnally averaged secondary organic aerosol mass increases from 3.2 μg m−3 to a maximum of 8.8 μg m−3. The constraints on the glyoxal budget from this analysis indicate that it contributes 0–0.2 μg m−3 or 0–4% of the secondary organic aerosol mass.
Key Points
We used a new field instrument to measure glyoxal in Los Angeles during 2010
We constrain glyoxal contribution to aerosol using three methods
During daytime, glyoxal contributes 0–4% of secondary organic aerosol mass
Flattening filter free (FFF) linear accelerators allow for an increase in instantaneous dose-rate of the x-ray pulses by a factor of 2-6 over the conventional flattened output. As a result, ...radiobiological investigations are being carried out to determine the effect of these higher dose-rates on cell response. The studies reported thus far have presented conflicting results, highlighting the need for further investigation. To determine the radiobiological impact of the increased dose-rates from FFF exposures a Varian Truebeam medical linear accelerator was used to irradiate two human cancer cell lines in vitro, DU-145 prostate and H460 non-small cell lung, with both flattened and FFF 6 MV beams. The fluence profile of the FFF beam was modified using a custom-designed Nylon compensator to produce a similar dose profile to the flattened beam (6X) at the cell surface but at a higher instantaneous dose-rate. For both cell lines there appeared to be no significant change in cell survival. Curve fitting coefficients for DU145 cells irradiated with constant average dose-rates were 6X: α = 0.09 ± 0.03, β = 0.03 ± 0.01 and 6FFF: α = 0.14 ± 0.13, β = 0.03 ± 0.02 with a significance of p = 0.75. For H460 cells irradiated with the same instantaneous dose-rate but different average dose-rate the fit coefficients were 6FFF (low dose-rate): α = 0.21 ± 0.11, 0.07 ± 0.02 and 6FFF (high dose-rate): α = 0.21 ± 0.16, 0.07 ± 0.03, with p = 0.79. The results indicate that collective damage behaviour does not occur at the instantaneous dose-rates investigated here and that the use of either modality should result in the same clinical outcome, however this will require further validation in vivo.
Context: Pasireotide (SOM230) is a novel multireceptor ligand somatostatin analog with affinity for somatostatin receptor subtypes sst1–3 and sst5. Because most GH-secreting pituitary adenomas ...express sst2 and sst5, pasireotide has the potential to be more effective than the sst2-preferential somatostatin analogs octreotide and lanreotide.
Objective: Our objective was to evaluate the efficacy and safety of three different doses of pasireotide in patients with acromegaly.
Design: We conducted a phase II, randomized, multicenter, open-label, three-way, crossover study.
Patients: Sixty patients with acromegaly, defined by a 2-h five-point mean GH level higher than 5 μg/liter, lack of suppression of GH to less than 1 μg/liter after oral glucose tolerance test, and elevated IGF-I for age- and sex-matched controls. Patients could have had previous surgery, radiotherapy, and/or medical therapy or no previous treatment.
Intervention: After treatment with octreotide 100 μg sc three times daily for 28 d, each patient received pasireotide 200, 400, and 600 μg sc twice daily in random order for 28 d.
Main Outcome Measure: A biochemical response was defined as a reduction in GH to no more than 2.5 μg/liter and normalization of IGF-I to age- and sex-matched controls.
Results: After 4 wk of octreotide, 9% of patients achieved a biochemical response. After 4 wk of pasireotide 200–600 μg sc bid, 19% of patients achieved a biochemical response, which increased to 27% after 3 months of pasireotide; 39% of patients had a more than 20% reduction in pituitary tumor volume. Pasireotide was generally well tolerated.
Conclusions: Pasireotide is a promising treatment for acromegaly. Larger studies of longer duration evaluating the efficacy and safety of pasireotide in patients with acromegaly are ongoing.
Results from this phase II study demonstrate that pasireotide is a promising novel treatment for patients with acromegaly.
Nitrogen oxide (NOx) emissions resulting from fossil fuel combustion lead to unhealthy levels of near‐surface ozone (O3). One of the largest U.S. sources, electric power generation, represented about ...25% of the U.S. anthropogenic NOx emissions in 1999. Here we show that space‐based instruments observed declining regional NOx levels between 1999 and 2005 in response to the recent implementation of pollution controls by utility companies in the eastern U.S. Satellite‐retrieved summertime nitrogen dioxide (NO2) columns and bottom‐up emission estimates show larger decreases in the Ohio River Valley, where power plants dominate NOx emissions, than in the northeast U.S. urban corridor. Model simulations predict lower O3 across much of the eastern U.S. in response to these emission reductions.
Objective The Growth Hormone Research Society (GRS) convened a Workshop in 2017 to evaluate clinical endpoints, surrogate endpoints and biomarkers during GH treatment of children and adults and in ...patients with acromegaly. Participants GRS invited 34 international experts including clinicians, basic scientists, a regulatory scientist and physicians from the pharmaceutical industry. Evidence Current literature was reviewed and expert opinion was utilized to establish the state of the art and identify current gaps and unmet needs. Consensus process Following plenary presentations, breakout groups discussed questions framed by the planning committee. The attendees re-convened after each breakout session to share the group reports. A writing team compiled the breakout session reports into a document that was subsequently discussed and revised by participants. This was edited further and circulated for final review after the meeting. Participants from pharmaceutical companies were not part of the writing process. Conclusions The clinical endpoint in paediatric GH treatment is adult height with height velocity as a surrogate endpoint. Increased life expectancy is the ideal but unfeasible clinical endpoint of GH treatment in adult GH-deficient patients (GHDA) and in patients with acromegaly. The pragmatic clinical endpoints in GHDA include normalization of body composition and quality of life, whereas symptom relief and reversal of comorbidities are used in acromegaly. Serum IGF-I is widely used as a biomarker, even though it correlates weakly with clinical endpoints in GH treatment, whereas in acromegaly, normalization of IGF-I may be related to improvement in mortality. There is an unmet need for novel biomarkers that capture the pleiotropic actions of GH in relation to GH treatment and in patients with acromegaly.
Measurements of aerosol particle size distributions and composition and of trace and reactive gas mixing ratios were made on the NOAA WP‐3D aircraft downwind of mixed urban/industrial sources in the ...northeastern United States (U.S.). These measurements were made in noncloudy air during July and August 2004, under conditions where cloud processing was not likely to play an important role in oxidation chemistry. Under these conditions, particulate sulfate was found to be produced with an exponential time constant of ∼3.5 d from the gas‐phase oxidation of SO2, which was ubiquitous but inhomogeneously distributed in the pollution plumes. When submicron particle mass concentrations exceeded 15 μg m−3, sulfate and associated ammonium dominated the composition; at lower mass concentrations particulate organic matter (OM) dominated. Since most of the urban plumes sampled contained substantial SO2 from nearby industrial sources, the apportionment of aerosol mass between OM and sulfate compounds under noncloudy conditions was governed largely by the differences between the oxidation timescales of SO2 and those of precursor volatile organic compounds (VOCs) relative to their transport time. These differences in oxidation timescales may explain much of the variability in previously published OM/sulfate ratios for this region. These observations indicate that even with higher‐than‐expected secondary OM formation, in the northeastern U.S. the potential inorganic particulate mass from SO2 emissions significantly exceeds the potential secondary OM from anthropogenic VOC emissions.
ObjectivePatients in remission from Cushing's disease (CD) have many clinical features that are difficult to distinguish from those of concomitant GH deficiency (GHD). In this study, we evaluated the ...features of GHD in a large cohort of controlled CD patients, and assessed the effect of GH treatment.Design and methodsData were obtained from KIMS, the Pfizer International Metabolic Database. A retrospective cross-sectional comparison of background characteristics in unmatched cohorts of patients with CD (n=684, 74% women) and nonfunctioning pituitary adenoma (NFPA; n=2990, 39% women) was conducted. In addition, a longitudinal evaluation of 3 years of GH replacement in a subset of patients with controlled CD (n=322) and NFPA (n=748) matched for age and gender was performed.ResultsThe cross-sectional study showed a significant delay in GHD diagnosis in the CD group, who had a higher prevalence of hypertension, fractures, and diabetes mellitus. In the longitudinal, matched study, the CD group had a better metabolic profile but a poorer quality of life (QoL) at baseline, which was assessed with the disease-specific questionnaire QoL-assessment of GHD in adults. After 3 years of GH treatment (mean dose at 3 years 0.39 mg/day in CD and 0.37 mg/day in NFPA), total and low-density lipoprotein cholesterol decreased, while glucose and HbAlc increased. Improvement in QoL was observed, which was greater in the CD group (−6 CD group versus −5 NFPA group, P<0.01).ConclusionIn untreated GHD, co-morbidities, including impairment of QoL, were more prevalent in controlled CD. Overall, both the groups responded similarly to GH replacement, suggesting that patients with GHD due to CD benefit from GH to the same extent as those with GHD due to NFPA.
Daily ozonesondes were launched from 14 North American sites during August 2006, providing the best set of free tropospheric ozone measurements ever gathered across the continent in a single season. ...The data reveal a distinct upper tropospheric ozone maximum above eastern North America and centered over the southeastern USA. Recurring each year, the location and strength of the ozone maximum is influenced by the summertime upper tropospheric anticyclone that traps convectively lofted ozone, ozone precursors and lightning NOx above the southeastern USA. The North American summer monsoon that flows northward along the Rocky Mountains is embedded within the western side of the anticyclone and also marks the westernmost extent of the ozone maximum. Removing the influence from stratospheric intrusions, median ozone mixing ratios (78 ppbv) in the upper troposphere (>6 km) above Alabama, near the center of the anticyclone, were nearly twice the level above the U.S. west coast. Simulations by an atmospheric chemistry general circulation model indicate lightning NOx emissions led to the production of 25–30 ppbv of ozone at 250 hPa above the southern United States during the study period. On the regional scale the ozone enhancement above the southeastern United States produced a positive all‐sky adjusted radiative forcing up to 0.50 W m−2.
The National Food and Nutrient Analysis Program (NFNAP) was implemented in 1997 to update and improve the quality of food composition data maintained by the United States Department of Agriculture ...(USDA). NFNAP was designed to sample and analyze frequently consumed foods in the U.S. food supply using statistically rigorous sampling plans, established sample handling procedures, and qualified analytical laboratories. Methods for careful handling of food samples from acquisition to analysis were developed to ensure the integrity of the samples and subsequent generation of accurate nutrient values. The infrastructure of NFNAP, under which over 1500 foods have been sampled, mandates tested sample handling protocols for a wide variety of foods. The majority of these foods were categorized into several major areas: (1) frozen foods; (2) fresh produce and/or highly perishable foods requiring refrigeration; (3) fast foods and prepared foods; (4) shelf-stable foods; (5) specialized study and non-retail (point of production) foods; and (6) foods from remote areas (e.g. American Indian reservations). This paper describes the sample handling approaches, from the collection and receipt of the food items to the preparation of the analytical samples, with emphasis on the strategies developed for those foods. It provides a foundation for developing sample handling protocols of foods to be analyzed under NFNAP and for other researchers working on similar projects.
...clinicians, coaches, parents, and athletes at all levels of competition are becoming educated about the necessity to treat concussions seriously. ...there is now sufficient literature supporting ...the notion that once you experience a concussion, you are more likely to sustain future concussions 1, 2 ; and a strong likelihood exists that the symptoms following these repeat concussions may be more serious and resolve at a slower rate. 1, 3 Several recent research papers and consensus statements indicate the necessity to use a systematic approach to evaluating the severity and duration of all possible signs and symptoms after a concussion, and to be cautious of not returning players to competition too quickly. 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16 Loss of consciousness and amnesia are two important parameters associated with cerebral concussion, but headaches, dizziness/balance deficits, concentration deficits, and feeling "slowed down" are more common. 1, 2, 6, 9, 14, 17- 20 Extensive research has also been conducted on neuropsychological testing 17, 19- 34 and postural stability testing, 20, 35- 37 both of which are considered to be key markers for tracking recovery after cerebral concussion.
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