Foetal alcohol syndrome in Saskatchewan: unchanged incidence in a 20-year period

Ethers and thioethers of monosaccharides have been synthesised which show potent toxicity to mouse (LD50 > or = 4 g.kg-1 O.W. and 0.2 to 1.5 g.kg-1 I.P.W.). A study of calcium antagonist activity for the full series of compounds indicated that the activity was similar for both O- and S- ethers and maximum activities were observed for monoacetoneglucose ethers possessing carbon chain close to 8 carbons.     

Biochemical alterations of the tunica albuginea in impotence

PURPOSE: The objectives of this study were to quantify the immunohistochemical stainings of collagen types I, III and IV, and investigate the value of glycohistochemical staining with 3 lectin types specific to a particular glycan structure, Arachis hypogaea, Triticum vulgare and concanavalin A, as a method of defining possible changes in the collagen structure of the tunica albuginea in potent and impotent patients. MATERIALS AND METHODS: The study involved 4 normal men, 4 with pure venous leakage and 4 with pure arterial disease. Collagen types I, III and IV, and lectins Arachis hypogaea, Triticum vulgare and concanavalin A were studied using a cell image processor. The labeling index relates to the percentage of staining and mean optical density relates to the staining intensity. RESULTS: Mean labeling index values for the 3 types of collagen and lectins were similar (p > 0.05). Mean optical density value relating to collagen type I was significantly higher in the arteriogenic group than in the other groups (p < 0.05), while mean optical density value of collagen type IV was significantly higher in the venogenic group than in the 2 other groups (p < 0.05). Mean optical density values relating to the 3 lectin types were similar in the 3 clinical groups (p > 0.05). CONCLUSIONS: An alteration in the distribution and structure of the various collagen types and lectins in the tunica albuginea of impotent patients has been shown that may interfere with normal function and lead to impotence.     

Modeling Spin-Dependent Transport in InAs/GaSb/AlSb Resonant Tunneling Structures

The Rashba effect resonant tunneling diode is a candidate for achieving spin polarizing under zero magnetic field using only conventional non-magnetic III–V semiconductor heterostructures. We point out the challenges involved based on simple arguments, and offer strategies for overcoming these difficulties. We present modeling results that demonstrate the benefits of the InAs/GaSb/AlSb-based asymmetric resonant interband tunneling diode (a-RITD) for spin filtering applications.     

Intensive postremission chemotherapy in adults with acute myeloid leukemia. Cancer and Leukemia Group B

BACKGROUND: About 65 percent of previously untreated adults with primary acute myeloid leukemia (AML) enter complete remission when treated with cytarabine and an anthracycline. However, such responses are rarely durable when conventional postremission therapy is administered. Uncontrolled trials have suggested that intensive postremission therapy may prolong these complete remissions. METHODS: We treated 1088 adults with newly diagnosed AML with three days of daunorubicin and seven days of cytarabine and randomly assigned patients who had a complete remission to receive four courses of cytarabine at one of three doses: 100 mg per square meter of body-surface area per day for five days by continuous infusion, 400 mg per square meter per day for five days by continuous infusion, or 3 g per square meter in a 3-hour infusion every 12 hours (twice daily) on days 1, 3, and 5. All patients then received four courses of monthly maintenance treatment. RESULTS: Of the 693 patients who had a complete remission, 596 were randomly assigned to receive postremission cytarabine. After a median follow-up of 52 months, the disease-free survival rates in the three treatment groups were significantly different (P = 0.003). Relative to the 100-mg group, the hazard ratios were 0.67 for the 3-g group (95 percent confidence interval, 0.53 to 0.86) and 0.75 for the 400-mg group (95 percent confidence interval, 0.60 to 0.94). The probability of remaining in continuous complete remission after four years for patients 60 years of age or younger was 24 percent in the 100-mg group, 29 percent in the 400-mg group, and 44 percent in the 3-g group (P = 0.002). In contrast, for patients older than 60, the probability of remaining disease-free after four years was 16 percent or less in each of the three postremission cytarabine groups. CONCLUSIONS: These data support the concept of a dose-response effect for cytarabine in patients with AML who are 60 years of age or younger. The results with the high-dose schedule in this age group are comparable to those reported in similar patients who have undergone allogeneic bone marrow transplantation during a first remission.     

Economic analysis of tirilazad mesylate for aneurysmal subarachnoid hemorrhage. Economic evaluation of a phase III clinical trial in Europe and Australia

This study used data from a multinational phase III randomized, double-blind, vehicle-controlled trial to evaluate the cost-effectiveness of tirilazad mesylate (Freedox) in the treatment of aneurysmal subarachnoid hemorrhage. In men, therapy with 6 mg/kg per day of tirilazad mesylate was associated with significantly increased survival, increased cost of care, and ratios of cost per death averted that compare favorably with the ratios of other life and death interventions. In women, it appeared to have no effects on costs or survival. Further clinical studies may provide additional information about the cost-effectiveness of this intervention.     

A randomized controlled trial of filgrastim during remission induction and consolidation chemotherapy for adults with acute lymphoblastic leukemia: CALGB study 9111

Recombinant human granulocyte colony-stimulating factor (G-CSF; filgrastim) shortens the time to neutrophil recovery after intensive chemotherapy, but its role in the treatment of adults with acute lymphoblastic leukemia (ALL) is uncertain. We randomly assigned 198 adults with untreated ALL (median age, 35 years; range, 16 to 83) to receive either placebo or G-CSF (5 microgram/kg/d) subcutaneously, beginning 4 days after starting intensive remission induction chemotherapy and continuing until the neutrophil count was >/=1, 000/microL for 2 days. The study assignment was unblinded as individual patients achieved a complete remission (CR). Patients initially assigned to G-CSF then continued to receive G-CSF through 2 monthly courses of consolidation therapy. Patients assigned to placebo received no further study drug. The median time to recover neutrophils >/=1,000/microL during the remission induction course was 16 days (interquartile range [IQR], 15 to 18 days) for the patients assigned to receive G-CSF and 22 days (IQR, 19 to 29 days) for the patients assigned to placebo (P < .001). Patients in the G-CSF group had significantly shorter durations of neutropenia (<1, 000/microL) and thrombocytopenia (<50,000/microL) and fewer days in the hospital (median, 22 days v 28 days; P = .02) compared with patients receiving placebo. The patients assigned to receive G-CSF had a higher CR rate and fewer deaths during remission induction than did those receiving placebo (P = .04 by the chi-square test for trend). During Courses IIA and IIB of consolidation treatment, patients in the G-CSF group had significantly more rapid recovery of neutrophils >/=1,000/microL than did the control group by approximately 6 to 9 days. However, the patients in the G-CSF group did not complete the planned first 3 months of chemotherapy any more rapidly than did the patients in the placebo group. Overall toxicity was not lessened by the use of G-CSF. After a median follow-up of 4. 7 years, there were no significant differences in either the disease-free survival (P = .53) or the overall survival (P = .25) for the patients assigned to G-CSF (medians, 2.3 years and 2.4 years, respectively) compared with those assigned to placebo (medians, 1.7 and 1.8 years, respectively). Adults who received intensive chemotherapy for ALL benefited from G-CSF treatment, but its use did not markedly affect the ultimate outcome.     

How crystals that sense and respond to their environments could evolve

An enduring mystery in biology is how a physical entity simple enough to have arisen spontaneously could have evolved into the complex life seen on Earth today. Cairns-Smith has proposed that life might have originated in clays which stored genomes consisting of an arrangement of crystal monomers that was replicated during growth. While a clay genome is simple enough to have conceivably arisen spontaneously, it is not obvious how it might have produced more complex forms as a result of evolution. Here, we examine this possibility in the tile assembly model, a generalized model of crystal growth that has been used to study the self-assembly of DNA tiles. We describe hypothetical crystals for which evolution of complex crystal sequences is driven by the scarceness of resources required for growth. We show how, under certain circumstances, crystal growth that performs computation can predict which resources are abundant. In such cases, crystals executing programs that make these predictions most accurately will grow fastest. Since crystals can perform universal computation, the complexity of computation that can be used to optimize growth is unbounded. To the extent that lessons derived from the tile assembly model might be applicable to mineral crystals, our results suggest that resource scarcity could conceivably have provided the evolutionary pressures necessary to produce complex clay genomes that sense and respond to changes in their environment.

Quantitative trait Loci for health traits in Finnish Ayrshire cattle

A whole-genome scan was conducted to search for quantitative trait loci (QTL) affecting health traits in Finnish Ayrshire dairy cattle. The mapping population consisted of 12 bulls and their 491 sons in a granddaughter design. A total of 150 markers were typed covering all 29 autosomes. The traits under study were somatic cell score, mastitis, and a group of other veterinary treatments. Effects of the QTL and positions were estimated with the regression method. When carrying out interval mapping on each chromosome, cofactors were used to adjust for QTL identified at other chromosomes. Empirical P-values were obtained by permutation. Altogether 17 QTL were detected with genomewise significant P-values in the across family analysis. Quantitative trait loci affecting SCS were identified on chromosomes 1, 3, 11, 18, 21, 24, 27, 29, and QTL for mastitis on chromosomes 14, 18. Quantitative trait loci for other veterinary treatments were found on chromosomes 1, 2, 5, 8, 15, 22, and 23. The allele substitution effects were from 0.5 to 1.7 genetic standard deviations. The positions of these health QTL did not overlap with milk QTL detected in previous studies of the same population.     

Quantitative trait loci affecting milk production traits in Finnish Ayrshire dairy cattle

A whole genome scan of Finnish Ayrshire was conducted to map quantitative trait loci (QTL) affecting milk production. The analysis included 12 half-sib families containing a total of 494 bulls in a granddaughter design. The families were genotyped with 150 markers to construct a 2764 cM (Haldane) male linkage map. In this study interval mapping with multiple-marker regression approach was extended to analyse multiple chromosomes simultaneously. The method uses identified QTL on other chromosomes as cofactors to increase mapping power. The existence of multiple QTL on the same linkage group was also analyzed by fitting a two-QTL model to the analysis. Empirical values for chromosome-wise significance thresholds were determined using a permutation test. Two genome-wise significant QTL were identified when chromosomes were analyzed individually, one affecting fat percentage on chromosome (BTA) 14 and another affecting fat yield on BTA12. The cofactor analysis revealed in total 31 genome-wise significant QTL. The result of two-QTL analysis suggests the existence of two QTL for fat percentage on BTA3. In general, most of the identified QTL confirm results from previous studies of Holstein-Friesian cattle. A new QTL for all yield components was identified on BTA12 in Finnish Ayrshire.     

Simple evolution of complex crystal species

Cairns-Smith has proposed that life began as structural patterns in clays that self-replicated during cycles of crystal growth and fragmentation. Complex, evolved crystal forms could then have catalyzed the formation of a more advanced genetic material. A crucial weakness of this theory is that it is unclear how complex crystals might arise through Darwinian evolution and selection. Here we investigate whether complex crystal patterns could evolve using a model system for crystal growth, DNA tile crystals, that is amenable to both theoretical and experimental inquiry. It was previously shown that in principle, the evolution of crystals assembled from a set of thousands of DNA tile types under very specific environmental conditions could produce arbitrarily complex patterns. Here we show that evolution driven only by the dearth of one monomer type could produce complex crystals from just 12 monomer types. When a monomer type is rare, crystals that use few of this monomer type are selected for. We use explicit enumeration to show that there are situations in which crystal species that use a particular monomer type less frequently will grow faster, yet to do so requires that the information contained in the crystal become more complex. We show that this feature of crystal organization could allow more complex crystal morphologies to be selected for in the right environment, using both analysis in a simple model of self-assembly and stochastic kinetic simulations of crystal growth. The proposed mechanism of evolution is simple enough to test experimentally and is sufficiently general that it may apply to other DNA tile crystals or even to natural crystals, suggesting that complex crystals could evolve from simple starting materials because of relative differences in concentrations of the materials needed for growth.