The observation that cyclosporine inhibits HCV replication in vitro has led some programs to use cyclosporine as the calcineurin inhibitor (CNI) of choice after orthotopic liver transplantation ...(OLT). Previous studies comparing outcomes with different CNIs used small HCV cohorts or had short-term follow-up. We examined patient survival and fibrosis progression in all HCV-infected adult primary OLT recipients from 1995 to 2004 at the Annette C. and Harold C. Simmons Transplant Institute (n = 516). Patients were categorized by their CNI on day 7 post-OLT, and they were excluded if they died before day 14. Patient and donor age, sex, race, and prevalence of cytomegalovirus infection post-OLT were similar in the tacrolimus and cyclosporine patients. As expected, acute cellular rejection and steroid-resistant rejection were less common in tacrolimus-treated patients. Although no difference in 1-year survival was seen, tacrolimus patients (n = 268) had superior 5-year survival compared to cyclosporine patients (n = 248) (75% vs. 67%; P = 0.02). Fibrosis progression was no different between the groups. In our retrospective analysis of 516 post-OLT patients, tacrolimus improved long-term survival compared to cyclosporine in HCV-infected patients, although it did not impact HCV fibrosis progression.
Different renal-sparing immunosuppressive protocols have been used in liver transplantation. At our institution, muromonab-CD3 (OKT3) is used in patients with acute renal failure (ARF), along with a ...delay in starting a calcineurin inhibitor. This study was conducted to compare outcomes in liver transplant patients with ARF who received OKT3 and those who did not. From 1988 to 2007, ARF was present in 1685 of 2587 patients (65%). OKT3 was used in 109 patients (OKT3 group). The control group (1416 patients) received a low-dose calcineurin inhibitor. The OKT3 group was more critically ill. In spite of this, the OKT3 group patients who were on renal replacement therapy (RRT) achieved long-term survival similar to that of the control group on RRT. Among the patients who were not on RRT, the OKT3 group had a higher complete recovery rate, but this did not translate into improved long-term survival. Bacterial and fungal infections were more common in the OKT3 group; however, there was no increased risk of malignancy or death from hepatitis C recurrence. The use of OKT3 in patients with ARF allowed more critically ill patients on RRT to achieve survival rates similar to those of patients who did not receive OKT3.
The Second Prospectus Development Team (PDT-2) of the U.S. Weather Research Program was charged with identifying research opportunities that are best matched to emerging operational and experimental ...measurement and modeling methods. The overarching recommendation of PDT-2 is that inputs for weather forecast models can best be obtained through the use of composite observing systems together with adaptive (or targeted) observing strategies employing both in situ and remote sensing. Optimal observing systems and strategies are best determined through a three-part process: observing system simulation experiments, pilot field measurement programs, and model-assisted data sensitivity experiments. Furthermore, the mesoscale research community needs easy and timely access to the new operational and research datasets in a form that can readily be reformatted into existing software packages for analysis and display. The value of these data is diminished to the extent that they remain inaccessible. The composite observing system of the future must combine synoptic observations, routine mobile observations, and targeted observations, as the current or forecast situation dictates. High costs demand fuller exploitation of commercial aircraft, meteorological and navigation Global Positioning System (GPS) satellites, and Doppler radar. Single observing systems must be assessed in the context of a composite system that provides complementary information. Maintenance of the current North American rawinsonde network is critical for progress in both research-oriented and operational weather forecasting. Adaptive sampling strategies are designed to improve large-scale and regional weather prediction but they will also improve diagnosis and prediction of flash flooding, air pollution, forest fire management, and other environmental emergencies. Adaptive measurements can be made by piloted or unpiloted aircraft. Rawinsondes can be launched and satellites can be programmed to make adaptive observations at special times or in specific regions. PDT-2 specifically recommends the following forms of data gathering: a pilot field and modeling study should be designed and executed to assess the benefit of adaptive observations over the eastern Pacific for mesoscale forecasts over the contiguous United States; studies should be done over the western Atlantic and Caribbean–Gulf of Mexico regions, particularly during hurricane season; and enhanced observations should be implemented for the mountainous western states and for the Mississippi and Missouri River Valleys. Data sensitivity tests and observing system simulation experiments (OSSEs) are important tools for gauging the benefit of existing or proposed observing systems. OSSEs involve only model predictions and are essentially self-contained. Data sensitivity tests require the full consideration of modeling infrastructure, namely, observation ingest quality control, objective analysis, and numerical prediction. Sensitivity tests involving both wind and moisture profiles are particularly needed to determine their impact on improved precipitation forecasts. New variational analysis techniques are capable of assimilating so-called proxy observations. These techniques should be fully exploited. Diabatic initialization should be addressed through the assimilation of satellite cloud data and very high resolution WSR-88D radar measurements into very high resolution models with sophisticated cloud microphysics. Success in this area should improve quantitative precipitation forecasts in the first few (model) hours. There is a pressing need to better understand the interaction of moist convection with large-scale flow. One key is better characterization of the impact of precipitation formation and evaporation on the fluxes of mass, momentum, and heat in moist convection. Humidity measurement in precipitating downdrafts is a crucial measurement, which currently cannot be made reliably. The capabilities of polarization-diversity radar should be explored in a quasi-operational context to determine whether WSR-88D radars should be upgraded. Progress in quantitative precipitation forecasting is impeded by poorly resolved and inaccurate water vapor measurements. Further improvements in numerical weather prediction demand improved monitoring of Earth surface characteristics so that spatial and temporal variations in air–surface fluxes are realistically simulated. Over land, priority should be given to the coupling of mesoscale meteorological models with hydrological models and to routine assimilation of surface (soil, moisture, and plant) characteristics. Improved air–sea fluxes are essential to proper modeling of marine cyclogenesis. The most important, practical ocean measurements include sea surface temperature, thermocline depth, wave spectra, and ice coverage and thickness.
A linkage map was constructed for the honey bee based on the segregation of 365 random amplified polymorphic DNA (RAPD) markers in haploid male progeny of a single female bee. The X locus for sex ...determination and genes for black body color and malate dehydrogenase were mapped to separate linkage groups. RAPD markers were very efficient for mapping, with an average of about 2.8 loci mapped for each 10-nucleotide primer that was used in polymerase chain reactions. The mean interval size between markers on the map was 9.1 cM. The map covered 3110 cM of linked markers on 26 linkage groups. We estimate the total genome size to be approximately 3450 cM. The size of the map indicated a very high recombination rate for the honey bee. The relationship of physical to genetic distance was estimated at 52 kb/cM, suggesting that map-based cloning of genes will be feasible for this species
Rethinking child care research Besharov, Douglas J; Morrow, Jeffrey S; Layzer, Jean I ...
Evaluation review,
10/2006, Letnik:
30, Številka:
5
Journal Article
Recenzirano
This introduction summarizes the articles in this collection. It describes how the articles address one or more of the key elements of the child care research model: (a) selecting and measuring the ...independent variables to determine the characteristics (`qualities') of the child care environment (and, in some studies, the characteristics of parents and family), (b) selecting and measuring the dependent variables to determine the child's physical and developmental status after a period of time in a particular child care arrangement (usually a school year) compared with that of children in other arrangements (or simply the same child before spending time in the arrangement), (c) establishing causal links between the independent and dependent variables that are either assumed in randomized experiments or estimated through statistical controls in nonexperimental studies, and (d) assessing impacts across subgroups to see whether the program benefits one particular group more (or less) than others. The collection closes with a proposal to develop a systematic federal research program to pursue improvements in child care and early childhood education programs. Reprinted by permission of Sage Publications, Inc.
The appropriate selection of lung transplant recipients is an important determinant of outcomes. This consensus document is an update of the recipient selection guidelines published in 2006. The ...Pulmonary Council of the International Society for Heart and Lung Transplantation (ISHLT) organized a Writing Committee of international experts to provide consensus opinion regarding the appropriate timing of referral and listing of candidates for lung transplantation. A comprehensive search of the medical literature was conducted with the assistance of a medical librarian. Writing Committee members were assigned specific topics to research and discuss. The Chairs of the Writing Committee were responsible for evaluating the completeness of the literature search, providing editorial support for the manuscript, and organizing group discussions regarding its content. The consensus document makes specific recommendations regarding the timing of referral and of listing for lung transplantation. These recommendations include discussions not present in previous ISHLT guidelines, including lung allocation scores, bridging to transplant with mechanical circulatory and ventilator support, and expanded indications for lung transplantation. In the absence of high-grade evidence to support decision making, these consensus guidelines remain part of a continuum of expert opinion based on available studies and personal experience. Some positions are immutable. Although transplant is rightly a treatment of last resort for end-stage lung disease, early referral allows proper evaluation and thorough patient education. Subsequent waiting list activation implies a tacit agreement that transplant offers a significant individual survival advantage. It is both the challenge and the responsibility of the transplant community globally to ensure organ allocation maximizes the potential benefits of a scarce resource, thereby achieving that advantage.
The purpose of this study was to elucidate the genetic origin of minor histocompatibility (H) antigens. Toward this end common inbred mouse strains, distinct subspecies, and species of the subgenus ...Mus were examined for expression of various minor H antigens. These antigens were encoded by the classical minor H loci H-3 and H-4 or by newly identified minor H antigens detected as a consequence of mutation. Both minor H antigens that stimulate MHC class I-restricted cytotoxic T cells (Tc) and antigens that stimulate MHC class II-restricted helper T cells (Th) were monitored. The results suggested that strains of distinct ancestry commonly express identical or cross-reactive antigens. Moreover, a correlation between the lack of expression of minor H antigens and ancestral heritage was observed. To address whether the antigens found on unrelated strains were allelic with the sensitizing minor H antigens or a consequence of antigen cross-reactivity, classical genetic segregation analysis was carried out. Even in distinct subspecies and species, the minor H antigens always mapped to the site of the appropriate minor H locus. Together the results suggest: 1) minor H antigen sequences are evolutionarily stable in that their pace of antigenic change is slow enough to predate subspeciation and speciation; 2) the minor H antigens originated in the inbred strains as a consequence of a rare polymorphism or loss mutation carried in a founder mouse stock that caused the mouse to perceive the wild-type protein as foreign; 3) there is a remarkable lack of antigenic cross-reactivity between the defined minor H antigens and other gene products.
Following administration to rats of a single ip dose (6.6 mg kg-1) of the investigational antitumor agent caracemide (N-acetyl-N,O-bismethylcarbamoylhydroxylamine), the mercapturic acid derivative ...N-acetyl-S-(N-methylcarbamoyl)cysteine (AMCC) was identified in urine by thermospray LC-MS. Quantification of this conjugate was carried out by stable isotope dilution thermospray LC-MS, which indicated that the fraction of the caracemide dose recovered as AMCC in 24-h urine collections was 54.0 +/- 5.5% (n = 4). Since AMCC is known to represent a major urinary metabolite of methyl isocyanate (MIC) in the rat, the results of this study support the contention that caracemide yields MIC as a toxic intermediate in vivo. Furthermore, with the aid of a specifically deuterium-labeled analog of caracemide (carbamoyloxy-C2H3caracemide), it was shown that the methylcarbamoyl group of AMCC derived from both the O-methylcarbamoyl (72%) and N-methylcarbamoyl (28%) side chains of the drug. In view of these findings, it is concluded that caracemide acts as a latent form of MIC in vivo and that this reactive isocyanate (or labile S-linked conjugates thereof) may contribute to the antitumor properties and/or adverse side-effects of caracemide.
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