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81.
During the past two decades, the drive to rein in rising health care costs has shifted some of the power in health care policy making from professional groups, government agencies, and not-for-profit health care organizations to large for-profit corporations (1-4). This has been a world-wide phenomenon, as the provision and financing of health care services is shifted from governments to private health care organizations (5,6). In the United States, the shift in power is manifested in profound ways. Market competition and bottom-line economics have permeated the health care system, creating powerful new incentives for mergers, other corporate restructuring, and the shift to for-profit status by formerly not-for-profit insurance companies and providers. Private sector health care is now increasingly influenced by for-profit organizations (3). Moreover, the health insurance industry has been transformed as traditional indemnity insurance is replaced by versions of managed care. The role of government, or the public sector, in setting parameters for health care financing and standards for the delivery of health care services is increasingly outpaced in cost cutting by organizations that directly face the bottom line. In addition, private foundations, many of which are under the auspices of managed care organizations, now fund a large proportion of health care research and demonstration projects, a task once largely within the realm of the government. Through education and experience, nurses have developed political sophistication and understanding of policy making in the public sector (7). The challenge now is to educate nurses to adapt their political and policy strategies to the new health care milieu. This challenge is particularly crucial for advanced practice nurses, who must survive in a managed care environment.  相似文献   
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We studied the effects of recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSFrh) on the internal pH of granulocytes using the fluorescent probe BCECF. GM-CSFrh did not directly alter the resting pH of granulocytes isolated from the peripheral blood; however, when the cells were preincubated for 90 minutes with the growth factor and then activated with the chemotactic peptide N-formyl met leu phe (fMLP), they exhibited both an acceleration in the initial rate of acidification and a marked delay in realkalinization. The kinetic changes both in initial acidification and in subsequent realkalinization induced by GM-CSFrh priming were not prevented by protein synthesis inhibitors and were observed in granulocytes harvested from patients with both sex-linked and autosomal recessive chronic granulomatous disease (CGD). By directly quantitating H+ ion secretion, by monitoring the effects of sodium repletion on intracellular pH, and through use of the sodium channel inhibitors amiloride and dimethyl amiloride and the Na+/K+-ATPase inhibitor ouabain, we showed that the altered kinetics of intracellular acidification and alkalinization following fMLP stimulation of GM-CSFrh- primed granulocytes could not be accounted for by changes in transmembrane proton exportation regulated by the Na+/H+ antiport channel. Although the initial acidification following fMLP was abrogated by 2-deoxy-D-glucose in both GM-CSFrh-pretreated and GM-CSFrh- untreated granulocytes, retardation of the subsequent phase of alkalinization was observed in GM-CSFrh-primed cells even after inhibition of both glycolytic and mitochondrial metabolism. Our data indicate that the increased cytosolic acidification following fMLP stimulation in granulocytes "primed" with GM-CSFrh does not result from disordered proton excretion but instead from increased release of intracellular free acid which is only partially coupled to glucose catabolism or to the generation of superoxide anion (O2-).  相似文献   
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Twenty patients with poor prognosis B-cell chronic lymphocytic leukemia (B-CLL) underwent uniform high-dose chemoradiotherapy followed by rescue with multiple monoclonal antibody-purged autologous bone marrow (BM) (12 patients) or T-cell-depleted allogeneic BM from HLA-identical siblings (8 patients) in a pilot study to assess the feasibility of BM transplantation (BMT) in this disease. All had poor prognosis disease by either staging, BM pattern, tumor doubling time criteria, or cytogenetics. All patients achieved remission criteria (defined as < or = 2 adenopathy, absence of splenomegaly, < or = 20% of the intertrabecular space involved on BM biopsy) before BMT. Despite the use of fludarabine, a median of three treatment regimens were required to achieve BMT eligibility. After BMT, all patients achieved complete hematologic engraftment. Toxicities were not significantly different between autologous versus allogeneic BMT. Two toxic deaths were observed. Of 19 evaluable patients, 17 clinical complete clinical remissions (89%) were observed, with 2 patients (1 allogeneic and 1 autologous) exhibiting persistent BM disease. Complete clinical remissions were documented at the phenotypic and molecular level for the majority of patients in whom dual fluorescence for CD5 and CD20 (15 of 15; 100%) and Ig gene rearrangements (11 of 14; 79%) were performed. Although long-term follow-up is needed to assess any potential impact on the disease-free and overall survival of these patients, this study shows the feasibility of using high-dose chemoradiotherapy and BMT in patients with poor prognosis B-CLL.  相似文献   
84.
BackgroundFor adults aged 76–85, guidelines recommend individualizing decision-making about whether to continue colorectal cancer (CRC) testing. These conversations can be challenging as they need to consider a patient’s CRC risk, life expectancy, and preferences.ObjectiveTo promote shared decision-making (SDM) for CRC testing decisions for older adults.DesignTwo-arm, multi-site cluster randomized trial, assigning physicians to Intervention and Comparator arms. Patients were surveyed shortly after the visit to assess outcomes. Analyses were intention-to-treat.Participants and SettingPrimary care physicians affiliated with 5 academic and community hospital networks and their patients aged 76–85 who were due for CRC testing and had a visit during the study period.InterventionsIntervention arm physicians completed a 2-h online course in SDM communication skills and received an electronic reminder of patients eligible for CRC testing shortly before the visit. Comparator arm received reminders only.Main MeasuresThe primary outcome was patient-reported SDM Process score (range 0–4 with higher scores indicating more SDM); secondary outcomes included patient-reported discussion of CRC screening, knowledge, intention, and satisfaction with the visit.Key ResultsSixty-seven physicians (Intervention n=34 and Comparator n=33) enrolled. Patient participants (n=466) were on average 79 years old, 50% with excellent or very good self-rated overall health, and 66% had one or more prior colonoscopies. Patients in the Intervention arm had higher SDM Process scores (adjusted mean difference 0.36 (95%CI (0.08, 0.64), p=0.01) than in the Comparator arm. More patients in the Intervention arm reported discussing CRC screening during the visit (72% vs. 60%, p=0.03) and had higher intention to follow through with their preferred approach (58.0% vs. 47.1, p=0.03). Knowledge scores and visit satisfaction did not differ significantly between arms.ConclusionPhysician training plus reminders were effective in increasing SDM and frequency of CRC testing discussions in an age group where SDM is essential.Trial RegistrationThe trial is registered on clinicaltrials.gov (NCT03959696).Supplementary InformationThe online version contains supplementary material available at 10.1007/s11606-022-07738-4.KEY WORDS: shared decision-making, colorectal cancer screening, patient preferences/patient engagement, online training  相似文献   
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Constraining the climate crisis requires urgent action to reduce anthropogenic emissions while simultaneously removing carbon dioxide from the atmosphere. Improved information about the maximum magnitude and spatial distribution of opportunities for additional land-based removals of CO2 is needed to guide on-the-ground decision-making about where to implement climate change mitigation strategies. Here, we present a globally consistent spatial dataset (approximately 500-m resolution) of current, potential, and unrealized potential carbon storage in woody plant biomass and soil organic matter. We also provide a framework for prioritizing actions related to the restoration, management, and maintenance of woody carbon stocks and associated soils. By comparing current to potential carbon storage, while excluding areas critical to food production and human habitation, we find 287 petagrams (PgC) of unrealized potential storage opportunity, of which 78% (224 PgC) is in biomass and 22% (63 PgC) is in soil. Improved management of existing forests may offer nearly three-fourths (206 PgC) of the total unrealized potential, with the majority (71%) concentrated in tropical ecosystems. However, climate change is a source of considerable uncertainty. While additional research is needed to understand the impact of natural disturbances and biophysical feedbacks, we project that the potential for additional carbon storage in woody biomass will increase (+17%) by 2050 despite projected decreases (−12%) in the tropics. Our results establish an absolute reference point and conceptual framework for national and jurisdictional prioritization of locations and actions to increase land-based carbon storage.

Emissions of carbon to the atmosphere must remain below ∼250 petagrams (PgC) (918 PgCO2) from 2021 onward to achieve the Paris Agreement’s goal of limiting global temperature rise to well below 2 °C (13). At present rates, that amount of carbon will be emitted by 2045. It follows that even necessary and drastic cuts in emissions (i.e., a rapid transition from fossil fuels to renewable energy sources) must be accompanied by carbon dioxide removal (CDR) or negative emissions strategies (4). Promising options for large-scale CDR include improved land stewardship (5), commonly referred to as natural climate solutions (NCS) (68). In particular, increasing carbon storage in woody biomass (e.g., forest ecosystems) is widely recognized as having high climate mitigation potential while also affording an array of environmental and socio-economic cobenefits (69). While a growing body of research has estimated the near-term potential for land-based climate mitigation (6, 8, 10), these studies emphasize the climate benefit over short, 10- to 30-y planning horizons. They do not include estimates of the upper limit for additional land-based carbon storage or its spatial distribution. This information is essential for landscape-level planning and targeted implementation of NCS, given that the potential for additional carbon storage is necessarily defined by both the rate at which carbon can be sequestered and the magnitude of the available reservoir. Therefore, we provide 500-m-resolution global maps to quantify the maximum potential for additional carbon storage in ecosystems dominated by woody vegetation (i.e., trees and shrubs), under baseline (1960 to 1990) and future (representative concentration pathway scenario 8.5 [RCP8.5]) climate conditions. This information can be used to help direct NCS toward areas with the greatest maximum opportunity, inform when NCS will saturate, and identify the types of NCS actions that are best suited to a given location.One approach to estimating maximum additional carbon storage—or the difference between current and potential carbon, which we term “unrealized potential” carbon—is a bookkeeping approach that tracks carbon fluxes through time. Under this approach, net land-based emissions since 1850 are estimated to have been 108 to 188 PgC, including both biomass (above and below ground) and soil organic matter (1317). Estimates that account for preindustrial (i.e., pre-1850) land use are more varied and increase post-1850 estimates by as much as 325 to 357 PgC (18) or as little as 48 to 153 PgC (1113, 15). This high uncertainty limits the practical utility of this approach.Other investigators have sought instead to quantify unrealized potential by comparing estimates of current and potential land carbon storage. Sanderman et al. (6), considering only soil organic carbon (SOC), estimated net losses in the upper 2 m of soil from agricultural land use to be 116 PgC since 10,000 BC. Erb et al. (19), focusing on changes in vegetation biomass, found losses in carbon due to human land use to be significantly larger (447 PgC) than the studies cited above that consider only the postindustrial period, but generally consistent with some of those that account for preindustrial human disturbance (18). Bastin et al. (20), in a study focused on the restoration of global tree cover, identified an additional reservoir of 206 PgC when considering all carbon pools (aboveground and belowground biomass, soil, litter, and dead wood) after excluding cropland and urban areas.However, all of these global analyses fall short in delivering the robust spatially explicit information needed for targeted planning and implementation of landscape-level NCS. While the global dataset produced by Bastin et al. (20) has a reasonably high spatial resolution (30 arc seconds; approximately 900 m) and considers all land carbon pools, the product is limited to the storage potential afforded by the expansion of tree cover. Moreover, the result is subject to the uncertainty inherent in indirect estimates of carbon stock from area-based metrics of tree/forest cover (21). In comparison, the data product created by Erb et al. (19), which is based on several disparate yet direct estimates of terrestrial carbon storage, is limited by its treatment of only the biomass carbon pool and coarse spatial resolution (5 arc min; approximately 9.3 km). The authors themselves remark that “the uncertainty range could be narrowed if a single robust, validated method would be applied continuously in the stocktaking efforts” (19).Here, we apply a consistent suite of methods to generate spatially explicit global estimates of current (ca. 2016) and climate-constrained potential land carbon storage in aboveground woody biomass (AGB), belowground woody biomass (BGB), and SOC pools at a spatial resolution of approximately 500 m. The difference between current and potential land carbon storage represents the unrealized potential for additional carbon accumulation in global woody biomass and soils. We then disaggregate this global estimate of unrealized potential carbon storage using a conceptual framework we term the NCS opportunity space: seven discrete, internally consistent, and spatially explicit categories of broad NCS action (Fig. 1). Categories are defined quantitatively in terms of woody carbon density, thereby avoiding the uncertainty associated with derivative approximations of potential carbon storage based on forest area or canopy cover. After applying safeguards to lands currently utilized for food production, human habitation (e.g., urban areas), and sensitive biodiversity (nonwoody grasslands), we demonstrate the utility of the opportunity space framework for landscape-level NCS planning by analyzing the global, regional, and national potential for additional land carbon storage attributable to restoration (e.g., reforestation), management (e.g., improved natural forest stewardship), and maintenance (i.e., the sequestration benefit accrued through avoided forest conversion) of woody carbon stocks and associated soils. Finally, we evaluate the uncertainty that climate change poses to the magnitude and spatial distribution of the unrealized potential for additional carbon storage through 2050.Open in a separate windowFig. 1.The NCS opportunity space, consisting of seven categories defined by the ratio of current (x axis) to potential (y axis) carbon storage as well as carbon-based thresholds delineating NCS-relevant systems. Categories include: Restore/High suitability for forestry-based NCS (R/H; red), Maintain and manage/High suitability for forestry-based NCS (MM/H; dark green), Maintain/High suitability for forestry-based NCS (M/H; dark blue), Restore/Low suitability for forestry-based NCS (R/L; orange), Maintain and manage/Low suitability for forestry-based NCS (MM/L; light green), Maintain/Low suitability for forestry-based NCS (M/L; light blue), and Nonwoody (yellow). † denotes associated grassland/savanna biodiversity considerations.  相似文献   
87.
One hundred and seventy three children, including 93 with biliary atresia, received liver grafts at Addenbrooke's Hospital between 1983 and 1993. Of these, only seven developed cyanosis due to intrapulmonary shunting as a complication of their liver disease, and all seven of these had the biliary atresia/polysplenia syndrome. Intrapulmonary shunting was confirmed by a radioisotope scan in four children. Only one child with the syndrome did not have cyanosis when undergoing transplantation. Seven of the eight children are alive 6-54 months after transplantation, with normal pulmonary and hepatic function. Cyanosis recurred in one child who developed chronic rejection with liver failure. In conclusion: (a) there is a strong association between the biliary atresia/polysplenia syndrome and cyanosis due to intrapulmonary shunting; (b) intrapulmonary shunting is fully reversible after successful liver transplantation; and (c) cyanosis, once present, is progressive, and these children should be considered for liver transplantation as soon as it occurs.  相似文献   
88.
The primary aim of electron treatment planning for the post mastectomy chest wall is to encompass the volume between the skin surface and the lung-rib interface while limiting dose to the lung. Electron energies for treatment of the chest wall are chosen based on the thickness of tissue between these two areas. Surgical defects or surface irregularities often result in differing thicknesses of tissue across the treatment volume, and patient-specific compensation is necessary to achieve the desired dose distribution. This is true whether the treatment plan is designed using fixed or rotational electrons to treat the chest wall. These clinical requirements are often met using custom shaped wax of varying thickness which conforms to the chest surface. This paper will discuss the treatment planning process used to design these compensators, creation and use of an exact duplicate of the patient's chest wall to aid in the production of these compensators, the production process itself, and verification of the completed compensator.  相似文献   
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