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991.
Black carbon (BC) aerosol plays an important role in the Earth’s climate system because it absorbs solar radiation and therefore potentially warms the climate; however, BC can also act as a seed for cloud particles, which may offset much of its warming potential. If BC acts as an ice nucleating particle (INP), BC could affect the lifetime, albedo, and radiative properties of clouds containing both supercooled liquid water droplets and ice particles (mixed-phase clouds). Over 40% of global BC emissions are from biomass burning; however, the ability of biomass burning BC to act as an INP in mixed-phase cloud conditions is almost entirely unconstrained. To provide these observational constraints, we measured the contribution of BC to INP concentrations ([INP]) in real-world prescribed burns and wildfires. We found that BC contributes, at most, 10% to [INP] during these burns. From this, we developed a parameterization for biomass burning BC and combined it with a BC parameterization previously used for fossil fuel emissions. Applying these parameterizations to global model output, we find that the contribution of BC to potential [INP] relevant to mixed-phase clouds is ∼5% on a global average.

Black carbon (BC) is the primary light-absorbing aerosol in the atmosphere. Its short lifetime (days to weeks) relative to CO2 and methane makes it an intriguing target for near-term climate mitigation (1). Errors associated with BC climate forcing, however, obfuscate its efficacy as a climate mitigator. The largest contributions to BC’s forcing uncertainties are often attributed to its effects on clouds, in particular mixed-phase clouds [i.e., clouds containing supercooled cloud droplets and ice particles, (2)]. Efforts to reduce these uncertainties are hindered by the complexity of aerosol–cloud interactions (3). Particularly vexing is quantifying the abundance and identity of ice nucleating particles (INPs). INPs provide the only pathway for primary ice formation in mixed-phase clouds; however, they are rare [e.g., 1 in 106 particles are INPs at −20 °C (4)]. Despite their rarity, INPs influence mixed-phase cloud ice concentrations and precipitation and therefore alter cloud albedo and lifetime (5). Furthermore, the INP properties of aerosols, such as BC, will affect their own lifetime, vertical structure, and transport to climate-sensitive regions such as the Arctic (6). Despite its importance to the Earth’s climate and near-term climate mitigation strategies, the INP efficiency of BC relevant to mixed-phase clouds remains almost entirely unconstrained from direct observations, encumbering attempts to estimate BC’s impact on mixed-phase clouds in modeling studies (7).BC’s efficacy as an immersion-freezing INP (henceforth, INP will refer only to freezing by particles encapsulated within supercooled cloud droplets, termed immersion freezing and pertinent to mixed-phase cloud conditions) has been studied in the laboratory for decades, with starkly conflicting results. Early laboratory studies showed that acetylene and kerosene flame-generated soot can nucleate ice below −20 °C. (8, 9); after normalizing for surface area, these studies indicated that BC may be more ice active than the well-known INP mineral dust (10). Results from later laboratory studies were contradictory, suggesting that BC was not active as an INP above instrument limits of detection. These included soot aerosols from miniCAST soot generators, graphite spark generator soot, hydrocarbon flame-generated soot, and fullerene soot, as well as various lamp blacks and carbon blacks (1115).Unfortunately, field study measurements of the contribution of BC to INP concentrations ([INP]) have also been inconclusive. For example, in-cloud measurements from the high-altitude observatory at Jungfraujoch, Switzerland saw that BC is enriched in ice-particle residuals and therefore may efficiently nucleate ice (16); later measurements at the same site, however, saw that BC is depleted in the ice phase, which suggests that BC does not play a significant role in mixed-phase cloud ice nucleation (17, 18).These contradictions in laboratory and field studies suggest that fuel type and combustion conditions determine the ice nucleation properties of BC. Such conditions prescribe BC’s physical and morphological properties as well as its coemitted and coagulated species. Major BC fuel types include fossil fuels and flammable biomass, and major combustion sources include diesel exhaust, residential fuel burning, prescribed burns, and wildfires (2). BC particles from fossil fuel combustion and anthropogenic pollution are not significant sources of INPs. For example, studies on diesel exhaust have shown that less than 1 in 109 BC particles are ice nucleation active at −30 °C (19). Furthermore, ambient [INP] in Beijing, China were relatively constant over several weeks despite BC concentrations varying by a factor of 30 and reaching values as high as 17.26 μgm3 (20).Elevated [INP] have been observed in biomass-burning smoke during laboratory and field studies (2123); however, it is unclear from these studies if the INPs are actually BC. Some studies have shown that BC may be the dominant INP type in select biomass burning conditions. For example, soot particles were found to contribute up to 64% of the INPs in prescribed burns within a predominantly wiregrass understory (24). Furthermore, BC contributed up to 70% to [INP] in controlled laboratory burns of grasses (25). As biomass burning represents 40% of global BC emissions (2), BC from biomass burning could be a significant source of INP globally. In both of these studies, however, the overall ice-active fractions may be too low to influence [INP], even on the regional level (21). Thus, it remains unclear whether BC contributes to [INP] outside of thick plumes and on a global scale (26).Regional- and global-scale estimates of BC [INP] rely on models that can implement theory-based or empirical ice nucleation parameterizations. Using parameterizations based on BC INP activity from the acetylene and kerosene-burner soot studies, models have found that BC contributes 50% to [INP] in springtime low-level Arctic mixed-phase clouds (27), and 23 to 61% to global [INP] depending on dust loadings (28). Taking into account the aforementioned negative results, these modeling studies highlight that BC’s contribution to [INP] is poorly constrained and is estimated to vary from no contribution to being the most abundant INP globally.To assess the role of BC from biomass burning as an INP, we determined the contribution of refractory BC (rBC)-containing particles to [INP] from field measurements of both prescribed burns and wildfires using the single-particle soot photometer coupled to a continuous-flow diffusion chamber (SP2-CFDC) (29, 30). The SP2-CFDC selectively removes rBC from an aerosol stream and quantifies that effect on [INP]. From these burns, we found that rBC-containing particles contributed 10% to [INP]. From these results, we developed a surface-area normalized parameterization for BC INPs from biomass burning. The parameterization aligns well with other surface-area normalized parameterizations derived from laboratory proxies of BC and diesel exhaust BC (15, 19, 31). These parameterizations are over four orders of magnitude lower than the parameterization derived from acetylene and kerosene-burner soot studies and used in the aforementioned modeling studies. Assuming the INP characteristics of BC from the burns in this study can be extended to different biomass-burning fuel types and combustion conditions, this study strongly suggests that BC is not an efficient INP. Under this assumption, we assessed the global importance of BC as an INP by applying our parameterization to simulated biomass-burning aerosol from a global chemical transport model. A similar parameterization for diesel exhaust (19) was applied to simulated fossil fuel BC. From these treatments, we estimate that BC’s contribution to simulated, potential [INP] is only 5% on a global average.  相似文献   
992.
We studied single molecular interactions between surface-attached rat CD2, a T-lymphocyte adhesion receptor, and CD48, a CD2 ligand found on antigen-presenting cells. Spherical particles were coated with decreasing densities of CD48–CD4 chimeric molecules then driven along CD2-derivatized glass surfaces under a low hydrodynamic shear rate. Particles exhibited multiple arrests of varying duration. By analyzing the dependence of arrest frequency and duration on the surface density of CD48 sites, it was concluded that (i) arrests were generated by single molecular bonds and (ii) the initial bond dissociation rate was about 7.8 s−1. The force exerted on bonds was increased from about 11 to 22 pN; the detachment rate exhibited a twofold increase. These results agree with and extend studies on the CD2–CD48 interaction by surface plasmon resonance technology, which yielded an affinity constant of ≈104 M−1 and a dissociation rate of ≥6 s−1. It is concluded that the flow chamber technology can be an useful complement to atomic force microscopy for studying interactions between isolated biomolecules, with a resolution of about 20 ms and sensitivity of a few piconewtons. Further, this technology might be extended to actual cells.  相似文献   
993.
OBJECTIVE: To determine patient characteristics associated with patient and proxy perceptions of physicians’ recommendations for life-prolonging care versus comfort care, and with acceptance of such recommendations. DESIGN: Cross-sectional. SETTING: Five teaching hospitals in Denver, Colo. PATIENTS: We studied 239 hospitalized adults believed by physicians to have a high likelihood of dying within 6 months. MEASUREMENTS AND MAIN RESULTS: Interviews with patients or proxies were conducted to determine perceptions of physicians’ recommended goal of care and roles in decision making. RESULTS: Patients’ mean age was 66.6 years; 44% were women. In adjusted analysis, age greater than 70 years and female gender were associated with a higher likelihood of believing that comfort care had been recommended by the physician (odds ratio [OR], 3.70; 95% confidence interval [CI], 1.89 to 7.24; OR, 1.99; 95% CI, 1.04 to 3.84, respectively). Patients and proxies gave substantial decision-making authority to physicians: 29% responded that physicians dominate decision making, 55% that decision making is equally shared by physicians and patients, and only 16% that patients make decisions, Increasing age was associated with an increased likelihood of believing that physicians should dominate decision making (P<.005). CONCLUSIONS: Among patients with advanced illness, perceived comfort care recommendations were related to patient age and gender, raising concern about possible gender and age bias in physicians’ recommendations. Although all patients and proxies gave significant decision-making authority to physicians, older individuals were more likely to give physicians decision-making authority, making them more vulnerable to possible physician bias. Presented at the annual meeting of the American Geriatrics Society, May 19, 1999. Financial support for this work was received from the Hartford/Jahnigen Center of Excellence in Geriatrics at the University of Colorado and the Colorado Collective for Medical Decisions, a nonprofit organization to improve care of the dying in the state of Colorado.  相似文献   
994.
AIMS: Little is known about which patients who have undergone coronary bypass surgery are at risk of future clinical cardiovascular events and may benefit from further medical treatment. We sought to determine if routine non-invasive cardiac investigations performed early after surgery were able to stratify the risk of cardiovascular events in this population. METHODS: Two thousand and sixty-five consecutive patients were enrolled in a prospective multicenter study (PERISCOP). Exercise testing, echocardiography, and 24-h ambulatory ECG monitoring were performed at day 20+/-10 after coronary bypass surgery. Follow-up was performed 1 year after coronary bypass surgery. Causes of all hospitalisation and death occurring within 1 year were documented and classified by an End-point Committee. The principal endpoint was the combination of all-cause deaths and cardiovascular events requiring hospitalisation (myocardial infarction, unstable or severe angina, stroke, congestive heart failure). RESULTS: The 1-year frequency of first events was 155 (8%). In multivariate analysis, exercise duration <420s (RR=1.68; 95% CI: 1.13-2.49), exercise induced ST segment depression >1mm (RR=1.90; 95% CI: 1.18-3.05), and left ventricular (LV) dysfunction (wall motion index <1.15) (RR=1.97; 95% CI: 1.10-3.51) were independent predictors of cardiovascular events and deaths. Ambulatory ECG monitoring had no predictive value. CONCLUSIONS: Exercise testing and echocardiography performed early after coronary bypass surgery are able to identify high-risk patients who may benefit from intensive secondary prevention.  相似文献   
995.
Abstract Vaccination is considered to be one of the most effective tools to decrease morbidity as well as mortality caused by influenza viruses.For the prevention of seasonal influenza, Fluarix and FluLaval™ have been marketed since 1987 and 1992, respectively. Both vaccines have consistently been shown to meet or exceed the regulatory criteria for immunogenicity against the three strains H1N1, H3N2 and B, have a good safety profile, and are recommended for vaccinating children and adults of all ages.For the prevention of pandemic influenza, GlaxoSmithKline (GSK) has obtained licensure of a pre‐pandemic vaccine, Prepandrix . This split‐virus H5N1 adjuvanted with AS03, a proprietary oil‐in‐water emulsion‐based adjuvant system, has demonstrated broad immunity against drifted H5N1 strains and has been shown to be effective in preventing mortality and viral shedding in animal studies.The influenza vaccine portfolio of GSK addresses specific medical needs related to seasonal or pandemic influenza viruses, which remain an important public health threat worldwide.  相似文献   
996.
997.
Early anticancer research involving thalidomide was abandoned in the 1960s as the catastrophe surrounding the drug emerged, but research efforts were picked up in the 1990s when thalidomide's antiangiogenic and anti-tumour necrosis factor properties were explored. More than 50,000 patients with multiple myeloma are estimated to have been treated with thalidomide to date. Research with thalidomide provides clear and convincing evidence that thalidomide monotherapy is efficacious in relapsed and refractory patients with multiple myeloma. Results typically show a consistent 30% (95% confidence interval 27-32%) response rate (partial response + complete response, defined as a reduction of at least 50% in the monoclonal protein). Thalidomide treatment compares favourably with other typical treatments for multiple myeloma. In seven trials that included 332 patients, vincristine, adriamycin and dexamethasone (VAD) had a response rate of 39% (32-45%), while a trial in 193 patients showed a response rate with bortezomib of 27% (21-34%). The use of thalidomide in combination therapy could boost its efficacy further. More studies to look at the toxicity of the drug need to be carried out. Despite thalidomide's dark past, this drug is of major interest and could be brought back to clinical use in a controlled manner.  相似文献   
998.
OBJECTIVE: To investigate the phenotypic features of infected lymphocytes in patients on prolonged and effective highly active antiretroviral therapy (HAART). DESIGN: We examined highly purified subsets of memory and naive CD4 T lymphocytes for the presence of replication-competent virus. METHODS: In 11 highly selected HAART-treated patients, we isolated highly purified CD45RO CD45RA CD4 T cells using a magnetic bead-based procedure. In some patients, a subsequent cell separation according to CD62L expression was performed. We quantified total viral DNA in freshly isolated T-cell subsets. To verify whether the virus was replication-competent, HIV RNA was measured in supernatants following cell activation. RESULTS: HIV DNA was detectable in the CD45RO and CD45RA CD4 T-cell subsets in 100% and 90% of the patients tested, respectively. In central memory CD45ROCD62L, effector memory CD45RO+CD62L-, truly naive CD45RACD62L, and CD45RA+CD62L- CD4 T cells, HIV DNA was found in 100%, 55%, 88%, and 50% of the patients tested respectively. HIV DNA was significantly higher in the CD45RO fraction than in the CD45RA subset and in the CD45ROCD62L fraction than in the three other CD45RA/ROCD62L+/- subsets. Detectable HIV RNA was found in the culture supernatants of CD45RO and CD45RA CD4 T-cell subsets in 80% and 66% of the patients tested respectively, and in CD45ROCD62L, CD45RO+CD62L-, CD45RACD62L, and CD45RA+CD62L- CD4 T cells in 100%, 100%, 100% and 50% of the patients tested respectively. CONCLUSIONS: In patients on prolonged and effective HAART, the pool of infected CD4 T lymphocytes consists predominantly of memory cells but also contains naive cells.  相似文献   
999.
Little is known about the course of homelessness among youth between the ages of 18 and 25 despite the many characteristics distinguishing them from adolescents and from older street-involved populations. We examined the residential trajectories of homeless young adults in Montréal over a 21-month period and identified determinants of various trajectory profiles. The 365 study participants (79 % men, mean age 21.9 years) were followed for an average of 515 days (range 81–630 days). We assessed housing status with a questionnaire based on the residential follow-back calendar designed by the New Hampshire Dartmouth Research Center. Using latent growth analysis to examine achievement of residential stability over time, we observed three different trajectories: group 1 presented a low probability of housing throughout the entire study period; group 2 showed a high probability of early and stable housing; group 3 displayed a fluctuating pattern. Protective correlates of residential stability included high school education, birth in Canada, and presence of mental health problems. Drug abuse or dependence was associated with a decreased probability of housing.  相似文献   
1000.
Healthy diet, physical activity and appropriate weight gain during pregnancy contribute to healthy birth outcomes. The Institute of Medicine recommends that women receive counseling about diet and exercise during preconception, pregnancy and postpartum periods. We sought to determine how often healthcare providers report counseling women of childbearing age about diet or exercise and if such rates vary by pregnancy, overweight/obesity status or physician specialty. We combined the 2005–2010 National Ambulatory Medical Care Survey and the National Hospital Ambulatory Medical Care Survey to obtain nationally representative estimates of outpatient preventive care visits for women of child-bearing age (15–44 years). Accounting for survey design, we compared proportions of preventive visits that included diet/exercise counseling for pregnant women versus non-pregnant women and performed multivariable logistic regression models to estimate odds ratios. Providers reported counseling pregnant women about diet/exercise during 17.9 % of preventive care visits compared to 22.6 % of visits for non-pregnant women (P < 0.01, adj. OR 0.8, 95 % CI 0.7, 1.0). Overweight/obese pregnant (vs. non-pregnant) women were significantly less likely to receive diet/exercise counseling (adj. OR 0.7, CI 0.5, 0.9) as were women seen by OB/GYNs versus non-OB/GYNs (adj. OR 0.4, CI 0.3, 0.5). Our findings suggest that provider-reported diet/exercise counseling rates during preventive care visits for women of childbearing age vary by overweight/obesity and pregnancy statuses, as well as by provider specialty. Our data suggest that there may be missed opportunities to provide diet/exercise counseling and that increasing rates of counseling could result in improved maternal and infant health outcomes.  相似文献   
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