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Measurement of the likely magnitude of the economic impact of climate change on African agriculture has been a challenge. Using data from a survey of more than 9,000 farmers across 11 African countries, a cross-sectional approach ...
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Measurement of the likely magnitude of the economic impact of climate change on African agriculture has been a challenge. Using data from a survey of more than 9,000 farmers across 11 African countries, a cross-sectional approach estimates how farm net revenues are affected by climate change compared with current mean temperature. Revenues fall with warming for dryland crops (temperature elasticity of -1.9) and livestock (-5.4), whereas revenues rise for irrigated crops (elasticity of 0.5), which arelocated in relatively cool parts of Africa and are buffered by irrigation from the effects of warming. At first, warming has little net aggregate effect as the gains for irrigated crops offset the losses for dryland crops and livestock. Warming, however, will likely reduce dryland farm income immediately. The final effects will also depend on changes in precipitation, because revenues from all farm types increase with precipitation. Because irrigated farms are less sensitive to climate, where water isavailable, irrigation is a practical adaptation to climate change in Africa.
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Multiple delayed rectifier potassium currents, including I(Ks), are responsible for the repolarization and termination of the cardiac action potential, and blockers of these currents may be useful as antiarrhythmic agents. Modific...
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Multiple delayed rectifier potassium currents, including I(Ks), are responsible for the repolarization and termination of the cardiac action potential, and blockers of these currents may be useful as antiarrhythmic agents. Modification of compound 5 produced 19(S) that is the most potent I(Ks) blocker reported to date with >5000-fold selectivity over other cardiac ion channels. Further modification produced 24A with 23% oral bioavailability.
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In the search for a novel water-soluble general anesthetic agent the activity of an alpha-amino acid phenolic ester lead, identified from patent literature, was markedly improved. In addition to improving in vivo activity in mice,...
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In the search for a novel water-soluble general anesthetic agent the activity of an alpha-amino acid phenolic ester lead, identified from patent literature, was markedly improved. In addition to improving in vivo activity in mice, good in vitro activity at GABA(A) receptors was also conferred. Within the series of compounds good enantioselectivity for both in vitro and in vivo activity was found, supporting a protein-mediated mechanism of action for anesthesia involving allosteric modulation of GABA(A) receptors. alpha-Amino acid phenolic ester 19, as the hydrobromide salt Org 25435, was selected for clinical evaluation since it retained the best overall anesthetic profile coupled with improved stability and water solubility. In the clinic it proved to be an effective intravenous anesthetic in man with rapid onset of and recovery from anesthesia at doses of 3 and 4 mg/kg.
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We report the identification and characterization of a novel cytokine-like gene family using structure-based methods to search for novel four-helix-bundle cytokines in genomics databases. There are four genes in this family, FAM3A...
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We report the identification and characterization of a novel cytokine-like gene family using structure-based methods to search for novel four-helix-bundle cytokines in genomics databases. There are four genes in this family, FAM3A, FAM3B, FAM3C, and FAM3D, each encoding a protein (224-235 amino acids) with a hydrophobic leader sequence. Northern analysis indicates that FAM3B is highly expressed in pancreas, FAM3D in placenta, and FAM3A and FAM3C in almost all tissues. Immunohistochemistry showed that FAM3A is expressed prominently in the vascular endothelium, particularly capillaries. We found that FAM3A and FAM3B protein were both localized to the islets of Langerhans of the endocrine pancreas. Recombinant FAM3B protein has delayed effects on beta-cell function, inhibiting basal insulin secretion from a beta-cell line in a dose-dependent manner.
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We have retrospectively evaluated the results of two cycles of mobilization and collection of peripheral blood progenitor cells (PBPC) from 46 healthy donors included in the Spanish National Donor Registry. Mobilization involved t...
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We have retrospectively evaluated the results of two cycles of mobilization and collection of peripheral blood progenitor cells (PBPC) from 46 healthy donors included in the Spanish National Donor Registry. Mobilization involved the administration of granulocyte colony-stimulating factor (G-CSF) at a median dose of 10 microg/kg per day, and apheresis was begun after the fourth dose of G-CSF in both cycles. The median interval between both mobilizations was 187 days (range, 7-1428 days). The incidence and types of side-effects were similar after both donations, with 25 and 26 donors developing some toxicity after the first and second donations, respectively. The median number of CD34(+) cells collected was higher after the first mobilization than after the second (5.15 versus 3.16 x 10(6)/kg, respectively; p = 0.05), and 29 donors yielded fewer CD34(+) cells after the second mobilization (p = 0.018). A lower proportion of donors yielded CD34(+) cell counts >4 x 10(6)/kg after the second cycle than after the first (52% versus 76%, respectively; p = 0.057). Our study shows that second rounds of PBPC collection from normal donors are well tolerated but are associated with a significantly reduced number of CD34(+) cells collected when the same mobilization scheme is used.
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Health-related quality of life (HRQL) was examined in relation to prevalent fractures in 4816 community-dwelling Canadian men and women 50 years and older participating in the Canadian Multicentre Osteoporosis Study (CaMos). Fract...
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Health-related quality of life (HRQL) was examined in relation to prevalent fractures in 4816 community-dwelling Canadian men and women 50 years and older participating in the Canadian Multicentre Osteoporosis Study (CaMos). Fractures were of three categories: clinically recognized main fractures, subclinical vertebral fractures and fractures at other sites. Main fractures were divided and analyzed at the hip, spine, wrist/forearm, pelvis and rib sites. Baseline assessments of anthropometric data, medical history, therapeutic drug use, spinal radiographs and prevalent fractures were obtained from all participants. The SF-36 instrument was used as a tool to measure HRQL. A total of 652 (13.5%) main fractures were reported. Results indicated that hip, spine, wrist/forearm, pelvis and rib fractures had occurred in 78 (1.6%), 40 (0.8%), 390 (8.1%), 19 (0.4%) and 125 (2.6%) individuals, respectively (subjects may have had more than one main fracture). Subjects who had experienced a main prevalent fracture had lower HRQL scores compared with non-fractured participants. The largest differences were observed in the physical functioning (-4.0; 95% confidence intervals (CI): -6.0, -2.0) and role-physical functioning domains (-5.8; 95% CI: -9.5, -2.2). In women, the physical functioning domain was most influenced by hip (-14.9%; 95% CI: -20.9, -9.0) and pelvis (-18.1; 95% CI: -27.6, -8.6) fractures. In men, the role-physical domain was most affected by hip fractures (-35.7; 95% CI: -60.4, -11.1). Subjects who experienced subclinical vertebral fractures had lower HRQL scores than those without prevalent fractures. In conclusion, HRQL was lower in the physical functioning domain in women and the role-physical domain in men who sustained main fractures at the hip. Subclinical vertebral fractures exerted a moderate effect on HRQL.
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Deleted in Malignant Brain Tumors 1 (DMBT1) at chromosome region 10q25.3-q26.1 has been proposed as a candidate tumor-suppressor gene for brain, digestive tract, and lung cancer. Recent studies on its expression in lung cancer hav...
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Deleted in Malignant Brain Tumors 1 (DMBT1) at chromosome region 10q25.3-q26.1 has been proposed as a candidate tumor-suppressor gene for brain, digestive tract, and lung cancer. Recent studies on its expression in lung cancer have led to divergent results and have raised a controversial discussion. Moreover, DMBT1 has been implicated with epithelial protection in the respiratory tract. We thus wondered how a loss of its expression could be related to carcinogenesis in the lung. To address these issues, we investigated the DMBT1 expression and location in the normal lung and lung cancer. By reverse-transcription PCR, a down-regulation of the DMBT1 expression in lung cancer cell lines is commonly detected. Immunohistochemical studies in situ demonstrate that there are also low steady-state levels of DMBT1 in the normal respiratory epithelium. However, an up-regulation takes place in the tumor-flanking epithelium and upon respiratory inflammation. Lung carcinomas show increased DMBT1 expression compared to that of undiseased lung tissue, but decreased DMBT1 levels compared to that of tumor-flanking and inflammatory tissue. A switch from a lumenal secretion to a secretion to the extracellular matrix takes place during lung carcinogenesis. Our data may resolve the controversial discussion on its expression in lung carcinomas. We hypothesize that the changes of the DMBT1 expression and location do reflect a time course that may point to possible mechanisms for its role in epithelial cancer.
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Population pharmacokinetic-dynamic analysis was prospectively integrated in the clinical phase II programme of EO9 to determine the population pharmacokinetic profile in a larger population of patients, to estimate individual pati...
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Population pharmacokinetic-dynamic analysis was prospectively integrated in the clinical phase II programme of EO9 to determine the population pharmacokinetic profile in a larger population of patients, to estimate individual patient pharmacokinetic parameters, and to investigate relationships between drug exposure and clinical outcome. A sparse sampling method was developed, which involved three sampling times, and was implemented during course 1. A Bayesian algorithm was used to estimate individual pharmacokinetic parameters, in particular total plasma clearance (CL) of EO9 and area under the curve (AUC). In total, samples were collected of 85 (65%) of the patients. Pharmacokinetic evaluation was successful in 61 (72%) of the sampled patients. CL of EO9 showed substantial variability (median 5.08 l/min; range 2.67-6.42) and was of the same magnitude as in the phase I study where full pharmacokinetic profiles were used. No significant relationships were noticed between exposure parameters and safety, but overall limited toxicity was observed. No tumor responses were documented. Prospective implementation of large-scale population pharmacokinetic-dynamic analysis is feasible and may generate important findings, in particular when tumor responses and relevant toxicity are observed.
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OBJECTIVE: This document describes cyclophotocoagulation procedures for glaucoma and examines the evidence to answer key questions about patient selection, and efficacy of transscleral and endoscopic techniques. METHODS: A literat...
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OBJECTIVE: This document describes cyclophotocoagulation procedures for glaucoma and examines the evidence to answer key questions about patient selection, and efficacy of transscleral and endoscopic techniques. METHODS: A literature search conducted for the years 1968 to 2000 retrieved 130 citations. The author reviewed 34 of these articles and selected 19 for the panel methodologist to review and rate according to the strength of evidence. A Level I rating is assigned to properly conducted, well-designed, randomized clinical trials; a Level II rating is assigned to well-designed cohort and case-control studies; and a Level III rating is assigned to case series and poorly designed prospective and retrospective studies, including case-control studies. RESULTS: The predominant problem with all studies on cyclophotocoagulation is the lack of a uniform definition of success, which makes comparisons difficult. One randomized controlled trial (Level I evidence) compared the efficacy of transscleral cyclophotocoagulation with noncontact Nd:YAG and semiconductor diode laser. It found no significant difference between the two, although a significant problem was the variability allowed with laser parameters. Most of the literature consists of noncomparative case series that provide evidence that is limited and often not convincing. CONCLUSION: Cyclophotocoagulation is indicated for patients with refractory glaucoma who have failed trabeculectomy or tube shunt procedures, patients with minimal useful vision and elevated intraocular pressure, and patients who have no visual potential and need pain relief (based on Level III evidence). It may be useful for patients whose general medical condition precludes invasive surgery or who refuse more aggressive surgery (i.e., filter or tube). It is also useful in emergent situations, such as the acute onset of neovascular glaucoma. There is insufficient evidence to definitively compare the relative efficacy of the cyclophotocoagulation procedures for glaucoma. It is the panel's opinion, however, that semiconductor diode systems appear to possess the best combination of effectiveness (based on Level III evidence), portability, expense, and ease of use at this time.
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Our analysis of the ND2 sequences revealed six clades within winter wrens (Troglodytes troglodytes). These clades corresponded to six geographical regions: western Nearctic, eastern Nearctic, eastern Asia, Nepal, Caucasus and Euro...
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Our analysis of the ND2 sequences revealed six clades within winter wrens (Troglodytes troglodytes). These clades corresponded to six geographical regions: western Nearctic, eastern Nearctic, eastern Asia, Nepal, Caucasus and Europe, and differed by 3-8.8% of sequence divergence. Differences among regions explained 96% of the sequence variation in winter wren. Differences among individuals within localities explained 3% of the sequence variation, and differences among localities within regions explained 1%. Grouping sequences into subspecies instead of localities did not change these proportions. Proliferation of the six clades coincided with Early and Middle Pleistocene glaciations. The distribution of winter wren clades can be explained by a series of five consecutive vicariant events. Western Nearctic wrens diverged from the Holarctic ancestor 1.6 Myr before the present time (MYBP). Eastern Nearctic and Palaearctic wrens diverged 1 MYBP. Eastern and western Palaearctic birds diverged 0.83 MYBP. Nepalese and east Asian wrens diverged 0.67 MYBP, and Caucasian birds diverged from European wrens 0.54 MyBP. The winter wren has a much greater degree of inter- and intracontinental differentiation than the three other Holarctic birds studied to date-dunlin (Calidris alpina), common raven (Corvus corax) and three-toed woodpecker (Picoides trydactylus)-and represents an example of cryptic speciation that has been overlooked. [References: 28]
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