On the enhancement of creativity by alcohol: pharmacology or expectation?

Creative individuals may use psychoactive drugs to enhance their ability to produce creative works, but it is difficult to differentiate the pharmacological effects from other influences. Part of the problem is that creativity defies any simple definition, making it hard to determine when or how much creativity is evident. The other major obstacle is that life circumstances are confounded with the propensity to use drugs (including alcohol), so the causal relation of drugs to creativity is uncertain. We examined this question by an experiment in which subjects were asked to creatively combine pictures of wildflowers that were implicitly organized around a set of three dimensions: color, shape, and number. Pharmacological and expected effects of alcohol were dissociated in the experiment by using the balanced placebo design (BPD). The results showed no pharmacological effect of alcohol on the creative combinations that subjects produced. However, the novelty and structural recombination of the wildflower arrangements were enhanced when subjects thought they had consumed alcohol, whether or not they had actually done so. Implications for measuring creativity and the possible motivation to use drugs for creative effect are discussed.     

Genetic diversity among Mycobacterium avium complex strains recovered from children with and without human immunodeficiency virus infection

The genetic diversity and molecular epidemiology of Mycobacterium avium complex (MAC) infections in children with and without human immunodeficiency virus (HIV) infection were evaluated. Isolates recovered from 136 children were subtyped by sequence analysis of a 360-bp region of the gene (hsp65) encoding a 65-kDa heat-shock protein. Twenty-one distinct hsp65 alleles were identified. On the basis of hsp65 genotype, 6 isolates were not MAC organisms. Of the remaining 130 samples, 61% were M. avium, 37% were Mycobacterium intracellulare, and 2% were species nonspecific MAC. Eighty-eight percent of the isolates obtained from HIV-infected children were M. avium. In contrast, only 38% of the isolates obtained from children without HIV infection were M. avium (chi2 test, P < .001). M. avium isolates were further subtyped by Southern blot analysis with insertion element IS1245. Taken together, no evidence for a single clonal M. avium strain causing infection was detected.     

Biased suppression of hematopoiesis and multiple developmental defects in chimeric mice containing Shp-2 mutant cells

Shp-2 is a cytoplasmic tyrosine phosphatase that contains two Src homology 2 (SH2) domains at the N terminus. Biochemical data suggests that Shp-2 acts downstream of a variety of receptor and cytoplasmic tyrosine kinases. A targeted deletion mutation in the N-terminal SH2 (SH2-N) domain results in embryonic lethality of homozygous mutant mice at midgestation. In vitro embryonic stem (ES) cell differentiation assays suggest that Shp-2 might play an important role in hematopoiesis. By aggregating homozygous mutant (Shp-2(-/-)) ES cells and wild-type (WT) embryos, we created Shp-2(-/-)-WT chimeric animals. We report here an essential role of Shp-2 in the control of blood cell development. Despite the widespread contribution of mutant cells to various tissues, no Shp-2(-/-) progenitors for erythroid or myeloid cells were detected in the fetal liver and bone marrow of chimeric animals by using the in vitro CFU assay. Furthermore, hematopoiesis was defective in Shp-2(-/-) yolk sacs. In addition, the Shp-2 mutation caused multiple developmental defects in chimeric mice, characterized by short hind legs, aberrant limb features, split lumbar vertebrae, abnormal rib patterning, and pathological changes in the lungs, intestines, and skin. These results demonstrate a functional involvement of Shp-2 in the differentiation of multiple tissue-specific cells and in body organization. More importantly, the requirement for Shp-2 is more stringent in hematopoiesis than in other systems.     

Influence of timing on the dosimetric analysis of transperineal ultrasound-guided, prostatic conformal brachytherapy

Postoperative computed tomography (CT)-based dosimetric analysis of transperineal ultrasound-guided conformal prostate brachytherapy provides detailed information regarding the coverage and uniformity of the implant. However, there is no generally accepted standard for the optimal timing of the postoperative dosimetry. This report details dosimetric analysis and the effect of timing based upon CT and orthogonal film evaluation for ten unselected patients implanted with either iodine-125 (125I) or palladium-103 (103Pd). Within 2 hours after implantation, patients underwent a CT scan and the first of four sequential sets of orthogonal films. Subsequent orthogonal films were obtained on days 3, 14, and 28 postimplant. CT-based dosimetry revealed coverage of the prostate to the prescribed minimal peripheral dose (mPD) at 93.1 +/- 3.6% of the volume, the prostate volume receiving 150% of mPD was 38.2 +/- 8.7%, and the urethral and rectal doses were 114 +/- 12% and 78 +/- 19% of mPD, respectively. The implanted seeds seen on orthogonal films acted as markers for temporal changes in prostate dimensions, and the standard deviation of each dimension was used as input in an ellipsoidal volume calculation. Seed coordinates were self normalized to the center of gravity of each two-dimensional view and were measured relative to the linear regression line in the superior-inferior direction. The reproducibility of the anteroposterior (AP) film setup in terms of temporal variation in the angle of the regression line was markedly better than that of the lateral films, 1.8 degrees +/- 1.2 degrees vs. 4.3 degrees +/- 2.6 degrees, respectively. Dimensional contraction from day 0 to day 28 averaged 11.3% in the superior-inferior direction, 8.5% in the AP/PA (posteroanterior) direction, and 2.5% in the right-left lateral direction. This translated into a volume change of 20.9% (ranged 11.6-31.6%), which was determined by using the ellipsoid method. The half-life for edema resolution was 10.6 +/- 1.8 days (range 8.6-14.3 days). However, because of variability in the degree and extent of edema and its rate of resolution, we believe that it may be futile to define a single point in time as the most accurate indicator of the postoperative dose distribution. Rather, it may be preferable to accept universal standardization of timing and methodology for CT-based postoperative dosimetry, which would facilitate comparison of results between centers and maximize the information content of that single measurement. We conclude that day 0 represents the optimal time, because dosimetric evaluation at that time minimizes patient discomfort and inconvenience (a catheter is already in place), provides information about edema when it is near its maximum extent, and provides prompt closure of the learning loop and, as such, hopefully will result in improved implantation techniques and results.     

Lipid modification strategies in the production of nutritionally functional fats and oils

Rapid improvements in the understanding of the nutritional requirements of both infants and adults has led to new developments in the modification of fats and oils. Specific targets include the improvement in growth and development of infants, treatment of disease in adults, and disease prevention. Efforts have been focussed on the production of structured lipids using medium-chain acids and long-chain polyunsaturated fatty acids (PUFAs), as well as the concentration of long-chain PUFAs from new and existing sources. Short- and medium-chain fatty acids are metabolized differently than long-chain fatty acids and have been used as a source of rapid energy for preterm infants and patients with fat malabsorption-related diseases. Long-chain PUFAs, specifically docosahexaenoic acid and arachidonic acid, are important both in the growth and development of infants, while n-3 PUFAs have been associated with reduced risk of cardiovascular disease in adults. Based on the requirements for individual fat components by different segments of the population, including infants, adults, and patients, ideal fats can be formulated to meet their needs. By using specific novel fat sources and lipid modification techniques, the concentrations of medium-chain, long-chain saturated, and long-chain polyunsaturated fatty acids as well as cholesterol can be varied to meet the individual needs of each of these groups. While genetic modification of oilseeds and other novel sources of specific lipid components are still being developed, chemical and lipase-catalyzed interesterification reactions have moved to the forefront of lipid modification technology. Fractionation of fats and oils to provide fractions with different nutritional properties has potential, but little work has been performed on the nutritional applications of this method. The choice of suitable lipid modification technologies will depend on the target lipid structure, production costs, and consumer demand. A combination of some or all of the present lipid modification techniques may be required for this purpose.