Treatment of Cryptococcal Meningitis with Combination Amphotericin B and Flucytosine for Four as Compared with Six Weeks

Abstract One hundred ninety-four patients with cryptococcal meningitis were enrolled in a multicenter, prospective, randomized clinical trial to compare the efficacy and toxicity of four as compared with six weeks of combination amphotericin B and flucytosine therapy. Among 91 patients who met preestablished criteria for randomization, cure or improvement was noted in 75 percent of those treated for four weeks and in 85 percent of those treated for six weeks. The estimated relapse rate for the four-week regimen was higher — 27 as compared with 16 percent — whereas the incidence of toxic effects for the two regimens was similar — 44 as compared with 43 percent. Among 23 transplant recipients, 4 of 5 treated for four weeks relapsed, leading to the decision to treat the rest of the group for six weeks. Only 3 of the 18 treated for six weeks relapsed. In a third group of 80 patients, the protocol was not followed during the initial four weeks, and these patients were not randomized. Thirty-eight died or relapsed. Multifactorial analysis of pretreatment factors for all 194 patients identified three significant predictors (P These and other findings in this study are consistent with the view that the four-week regimen should be reserved for patients who have meningitis without neurologic complications, underlying disease, or immunosuppressive therapy; a pretreatment cerebrospinal fluid white-cell count above 20 per cubic millimeter and a serum cryptococcal antigen titer below 1:32; and at four weeks of therapy, a negative cerebrospinal fluid India ink preparation and serum and cerebrospinal fluid cryptococcal-antigen titers below 1:8. Patients who do not meet these criteria should receive at least six weeks of therapy. (N Engl J Med 1987; 317:334–41.

The Molecular Genetic Architecture of Self-Employment

Economic variables such as income, education, and occupation are known to affect mortality and morbidity, such as cardiovascular disease, and have also been shown to be partly heritable. However, very little is known about which genes influence economic variables, although these genes may have both a direct and an indirect effect on health. We report results from the first large-scale collaboration that studies the molecular genetic architecture of an economic variable-entrepreneurship-that was operationalized using self-employment, a widely-available proxy. Our results suggest that common SNPs when considered jointly explain about half of the narrow-sense heritability of self-employment estimated in twin data (σg2/σP2= 25%, h2= 55%). However, a meta-analysis of genome-wide association studies across sixteen studies comprising 50,627 participants did not identify genome-wide significant SNPs. 58 SNPs with p<10-5were tested in a replication sample (n = 3,271), but none replicated. Furthermore, a gene-based test shows that none of the genes that were previously suggested in the literature to influence entrepreneurship reveal significant associations. Finally, SNP-based genetic scores that use results from the meta-analysis capture less than 0.2% of the variance in self-employment in an independent sample (p≥0.039). Our results are consistent with a highly polygenic molecular genetic architecture of self-employment, with many genetic variants of small effect. Although self-employment is a multi-faceted, heavily environmentally influenced, and biologically distal trait, our results are similar to those for other genetically complex and biologically more proximate outcomes, such as height, intelligence, personality, and several diseases

From Methods to Methodology: Reflection on Keeping the Philosophical Commitments of Interpretative Phenomenological Analysis

This paper details the transition of one researcher in his journey from attending to the methods of research to identifying and enacting the methodology of interpretative phenomenological analysis (IPA). In the backdrop of this paper is a larger qualitative study that is employing IPA to understand a rich picture of how engineering student become engineers, particularly by attending to the fuzzy boundaries between technical and social features of this identity. To ground the discussion of the paper, we draw on a transcript from a single interview in this study conducted with Kevin, a graduating mechanical engineer. We transparently share a reflexive account of conducting IPA research in order to introduce IPA as an excellent research tool for open areas of engineering education research. Further, our goals are to instill confidence in novice qualitative researchers as they embark on the arduous but rewarding path of conducting engineering education research using qualitative methods

Samarium(II) iodide mediated radical/polar crossover reactions of cyclobutenes. An efficient approach to the BCD ring system of the penitrems

(Matrix presented) Radical/polar crossover reactions of derivatives of 1-(2-cyclobutenyl)-2-(2-iodoaryl)ethanones with acetone promoted by samarium diiodide and HMPA provide 1-(1-hydroxy-1-methylethyl)-2,2a,4,8b-tetrahydro-1H-cyclobuta[a] naphthalen-3-one derivatives in about 50% isolated yield. This reaction shows promise for construction of the BCD ring fragment of the penitrems

VIBRATION EXPOSURE OF INDIVIDUALS USING WHEELCHAIRS OVER CONCRETE PAVER SURFACES

SUMMARY According to the International Standards Organization 2631-1 standard on human vibration, individuals in a seated position are at risk of injury due to whole-body vibrations when exposed for long periods of time. Wheelchair users fit this description perfectly, however little research has been conducted to evaluate the amount of vibration transmitted to a wheelchair user. The vibration exposure was produced by traversing nine pavement surfaces with 10 individuals without disabilities in a manual and powered wheelchair. The surfaces included poured, jointed concrete and concrete and clay pavers with chamfers from 0 to 8 mm wide and two herringbone laying patterns for selected surfaces. Power wheelchair results: The standard poured concrete surface was used as a norm and compared to the other surfaces. Two surfaces resulted in higher vibration exposure than the standard; an 8mm wide chamfer concrete paver in a 90 degree herringbone pattern and a 6mm wide chamfer pavers 90 degree herringbone pattern. Manual wheelchair results: Three surfaces resulted in higher vibration exposure than the standard surface; the 8mm wide chamfer surface in a 90 degree herringbone pattern, and the two 6mm wide chamfer surfaces placed in 90 and 45 degree patterns. Recommendations: Smaller chamfer widths on pavers exposes individuals using wheelchairs to less vibration. Also, pavers installed in a 90 degree herringbone pattern produced lower vibration exposures. It is recommended that only pavers of 6 mm wide chamfers or less be used with a 90 degree herringbone pattern