The systolic array genetic algorithm, an example of systolic arrays as a reconfigurable design methodology

We advocate the use of systolic design techniques to create custom hardware for Custom Computing Machines. We have developed a hardware genetic algorithm based on systolic arrays to illustrate the feasibility of the approach. The architecture is independent of the lengths of chromosomes used and can be scaled in size to accommodate different population sizes. An FPGA prototype design can process 16 million genes per second.

Time patterns in UK demand for alcohol and tobacco: an application of the EM algorithm

Capturing the pattern of structural change is a relevant task in applied demand analysis, as consumer preferences may vary significantly over time. Filtering and smoothing techniques have recently played an increasingly relevant role. A dynamic Almost Ideal Demand System with random walk parameters is estimated in order to detect modifications in consumer habits and preferences, as well as changes in the behavioural response to prices and income. Systemwise estimation, consistent with the underlying constraints from economic theory, is achieved through the EM algorithm. The proposed model is applied to UK aggregate consumption of alcohol and tobacco, using quarterly data from 1963 to 2003. Increased alcohol consumption is explained by a preference shift, addictive behaviour and a lower price elasticity. The dynamic and time-varying specification is consistent with the theoretical requirements imposed at each sample point. (c) 2005 Elsevier B.V. All rights reserved.

The effect of selective decontamination of the digestive tract on mortality in multiple trauma patients: a multicenter randomized controlled trial

Objective: Evaluation of selective decontamination of the digestive tract (SDD) on late mortality in ventilated trauma patients in an intensive care unit (ICU). Methods: A multicenter, randomized controlled trial was undertaken in 401 trauma patients with Hospital Trauma Index-Injury Severity Score of 16 or higher. Patients were randomized to control (n = 200) or SDD (n = 201), using polymyxin E, tobramycin, and amphotericin B in throat and gut throughout ICU treatment combined with cefotaxime for 4 days. Primary endpoint was late mortality excluding early death from hemorrhage or craniocerebral injury. Secondary endpoints were infection and organ dysfunction. Results: Mortality was 20.9% with SDD and 22.0% in controls. Overall late mortality was 15.3% (57/372) as 29 patients died from cerebral injury, 16 SDD and 13 control. The odds ratio (95% confidence intervals) of late mortality for SDD relative to control was 0.75 (0.40-1.37), corresponding to estimates of 13.4% SDD and 17.2% control. The overall infection rate was reduced in the test group (48.8% vs. 61.0%). SDD reduced lower airway infections (30.9% vs. 50.0%) and bloodstream infections due to aerobic Gram-negative bacilli (2.5% vs. 7.5%). No difference in organ dysfunction was found. Concluson: This study demonstrates that SDD significantly reduces infection in multiple trauma, although this RCT in 401 patients was underpowered to detect a mortality benefit.

The significance of "nonsignificance" in randomized controlled studies: a discussion inspired by a double-blinded study on St. John's Wort (Hypericum perforatum L.) for premenstrual symptoms

Objectives: This study aimed to investigate the efficacy of St. John's wort extract (SJW) as a treatment for premenstrual symptoms. Design: The study was a randomized, double-blinded, placebo-controlled trial, with two parallel treatment groups. After a no-treatment baseline cycle, volunteers were randomized to either SJW or placebo for a further two menstrual cycles. Settings/location: A postal trial conducted from The University of Reading, Berkshire, England. Subjects: One hundred and sixty-nine (169) normally menstruating women who experienced recurrent premenstrual symptoms were recruited onto the study. One hundred and twenty-five (125) completed the protocol and were included in the analysis. Interventions: Six hundred milligrams (600) mg of SJW (standardized to contain 1800 mug of hypericin) or placebo (containing lactose and cellulose). Outcome measure: A menstrual diary was used to assess changes in premenstrual symptoms. The anxiety-related subgroup of symptoms of this instrument was used as the primary outcome measure. Results: After averaging the effects of treatment over both treatment cycles it was found that there was a trend for SJW to be superior to placebo. However, this finding was not statistically significant. Conclusion: The possibility that this nonsignificant finding resulted from insufficient statistical power in the study, rather than a lack of efficacy of SJW, is discussed. Following this discussion the recommendation is made that, in future, similar studies should be powered to detect a minimum clinically relevant difference between treatments.

Use of a novel Hill-climbing genetic algorithm in protein folding simulations

We have developed a novel Hill-climbing genetic algorithm (GA) for simulation of protein folding. The program (written in C) builds a set of Cartesian points to represent an unfolded polypeptide's backbone. The dihedral angles determining the chain's configuration are stored in an array of chromosome structures that is copied and then mutated. The fitness of the mutated chain's configuration is determined by its radius of gyration. A four-helix bundle was used to optimise simulation conditions, and the program was compared with other, larger, genetic algorithms on a variety of structures. The program ran 50% faster than other GA programs. Overall, tests on 100 non-redundant structures gave comparable results to other genetic algorithms, with the Hill-climbing program running from between 20 and 50% faster. Examples including crambin, cytochrome c, cytochrome B and hemerythrin gave good secondary structure fits with overall alpha carbon atom rms deviations of between 5 and 5.6 Angstrom with an optimised hydrophobic term in the fitness function. (C) 2003 Elsevier Ltd. All rights reserved.

Chromatographic alignment of LC-MS and LC-MS/MS datasets by genetic algorithm feature extraction

Liquid chromatography-mass spectrometry (LC-MS) datasets can be compared or combined following chromatographic alignment. Here we describe a simple solution to the specific problem of aligning one LC-MS dataset and one LC-MS/MS dataset, acquired on separate instruments from an enzymatic digest of a protein mixture, using feature extraction and a genetic algorithm. First, the LC-MS dataset is searched within a few ppm of the calculated theoretical masses of peptides confidently identified by LC-MS/MS. A piecewise linear function is then fitted to these matched peptides using a genetic algorithm with a fitness function that is insensitive to incorrect matches but sufficiently flexible to adapt to the discrete shifts common when comparing LC datasets. We demonstrate the utility of this method by aligning ion trap LC-MS/MS data with accurate LC-MS data from an FTICR mass spectrometer and show how hybrid datasets can improve peptide and protein identification by combining the speed of the ion trap with the mass accuracy of the FTICR, similar to using a hybrid ion trap-FTICR instrument. We also show that the high resolving power of FTICR can improve precision and linear dynamic range in quantitative proteomics. The alignment software, msalign, is freely available as open source.

Flavonoids and cognitive function: a review of human randomized controlled trial studies and recommendations for future studies

Evidence in support of the neuroprotective effects of flavonoids has increased significantly in recent years, although to date much of this evidence has emerged from animal rather than human studies. Nonetheless, with a view to making recommendations for future good practice, we review 15 existing human dietary intervention studies that have examined the effects of particular types of flavonoid on cognitive performance. The studies employed a total of 55 different cognitive tests covering a broad range of cognitive domains. Most studies incorporated at least one measure of executive function/working memory, with nine reporting significant improvements in performance as a function of flavonoid supplementation compared to a control group. However, some domains were overlooked completely (e.g. implicit memory, prospective memory), and for the most part there was little consistency in terms of the particular cognitive tests used making across study comparisons difficult. Furthermore, there was some confusion concerning what aspects of cognitive function particular tests were actually measuring. Overall, while initial results are encouraging, future studies need to pay careful attention when selecting cognitive measures, especially in terms of ensuring that tasks are actually sensitive enough to detect treatment effects.

The significance of "nonsignificance" in randomized controlled studies: a discussion inspired by a double-blinded study on St. John's Wort (Hypericum perforatum L.) for premenstrual symptoms

Objectives: This study aimed to investigate the efficacy of St. John's wort extract (SJW) as a treatment for premenstrual symptoms. Design: The study was a randomized, double-blinded, placebo-controlled trial, with two parallel treatment groups. After a no-treatment baseline cycle, volunteers were randomized to either SJW or placebo for a further two menstrual cycles. Settings/location: A postal trial conducted from The University of Reading, Berkshire, England. Subjects: One hundred and sixty-nine (169) normally menstruating women who experienced recurrent premenstrual symptoms were recruited onto the study. One hundred and twenty-five (125) completed the protocol and were included in the analysis. Interventions: Six hundred milligrams (600) mg of SJW (standardized to contain 1800 mug of hypericin) or placebo (containing lactose and cellulose). Outcome measure: A menstrual diary was used to assess changes in premenstrual symptoms. The anxiety-related subgroup of symptoms of this instrument was used as the primary outcome measure. Results: After averaging the effects of treatment over both treatment cycles it was found that there was a trend for SJW to be superior to placebo. However, this finding was not statistically significant. Conclusion: The possibility that this nonsignificant finding resulted from insufficient statistical power in the study, rather than a lack of efficacy of SJW, is discussed. Following this discussion the recommendation is made that, in future, similar studies should be powered to detect a minimum clinically relevant difference between treatments.

Prebiotic evaluation of a novel galactooligosaccharide mixture produced by the enzymatic activity of Bifidobacterium bifidum NCIMB 41171, in healthy humans: a randomized, double-blind, crossover, placebo-controlled intervention study

Background: Galactooligosaccharides are selectively fermented by the beneficial member of the colonic microflora contributing to the health of the host. Objective: We assessed the prebiotic potential of a novel galactooligosaccharide produced through the action of beta-galactosidases, originating from a probiotic Bifidobacterium bifidum strain, against a galactooligosaccharide produced through the action of an industrial P-galactosidase and a placebo. Design: Fifty-nine healthy human volunteers participated in this study. Initially, the effect of the matrix on the prebiotic properties of a commercially available galactooligosaccharide (7 g/d) was assessed during 7-d treatment periods with a 7-d washout period in between. During the second phase, 30 volunteers were assigned to a sequence of treatments (7 d) differing in the amount of the novel galactooligosaccharide (0, 3.6, or 7 g/d). Stools were recovered before and after each intervention, and bacteria numbers were determined by fluorescent in situ hybridization. Results: Addition of the novel galactooligosaccharide mixture significantly increased the bifidobacterial population ratio compared with the placebo (P < 0.05), whereas 7 g/d of the novel galactooligosaccharide significantly increased the bifidobacterial ratio compared with the commercial galactooligosaccharide (P < 0.05). Moreover, a significant relation (P < 0.001) between the bifidobacteria proportion and the novel galactooligosaccharide dose (0, 3.6, and 7 g/d) was observed. This relation was similar to the effect of the novel galactooligosaccharide on the prebiotic index of each dose. Conclusions: This study showed that galactooligosaccharide mixtures produced with different beta-galactosidases show different prebiotic properties and that, by using enzymes originating from bifidobacterial species, an increase in the bifidogenic properties of the prebiotic product is achievable.

A double-blind, randomized, controlled crossover trial of glutamine supplementation in home parenteral nutrition

Objective: Studies suggest clinical benefit of glutamine-supplemented parenteral nutrition. The aim was to determine if the inclusion of 10 g of glutamine as part of the nitrogen source of home parenteral nutrition (HPN) reduces infectious complications. Subjects/Methods: Thirty-five patients on HPN were recruited and 22 completed the study. Patients were randomized to receive either standard HPN or glutamine-supplemented HPN. Patients were assessed at randomization, 3 and 6 months later then they were crossed over to the alternative HPN and reassessed at 3 and 6 months. Assessments included plasma amino acid concentrations, intestinal permeability and absorption, nutritional status, oral and parenteral intake, quality of life, routine biochemistry and haematology. Results: No difference was seen between the groups at randomization. No difference was detected between the treatment phases for infective complications (55% in the standard treatment phase and 36% in the glutamine-supplemented phase P 0.67). There were no differences in nutritional status, intestinal permeability, plasma glutamine concentrations or quality of life. Conclusion: Although limited by the sample size, the study has shown that glutamine as part of the nitrogen source of parenteral nutrition can be given to patients on HPN for 6 months without any adverse effects.

Artichoke leaf extract (Cynara scolymus) reduces plasma cholesterol in otherwise healthy hypercholesterolemic adults: A randomized, double blind placebo controlled trial

Cardiovascular diseases are the chief causes of death in the UK, and are associated with high circulating levels of total cholesterol in the plasma. Artichoke leaf extracts (ALEs) have been reported to reduce plasma lipids levels, including total cholesterol, although high quality data is lacking. The objective of this trial was to assess the effect of ALE on plasma lipid levels and general well-being in otherwise healthy adults with mild to moderate hypercholesterolemia. 131 adults were screened for total plasma cholesterol in the range 6.0-8.0 mmol/l, with 75 suitable volunteers randomised onto the trial. Volunteers consumed 1280 mg of a standardised ALE, or matched placebo, daily for 12 weeks. Plasma total cholesterol decreased in the treatment group by an average of 4.2% (from 7.16 (SD 0.62) mmol/l to 6.86 (SD 0.68) mmol/l) and increased in the control group by an average of 1.9% (6.90 (SD 0.49) mmol/l to 7.03 (0.61) mmol/l), the difference between groups being statistically significant (p = 0.025). No significant differences between groups were observed for LDL cholesterol, HDL cholesterol or triglyceride levels. General well-being improved significantly in both the treatment (11%) and control groups (9%) with no significant differences between groups. In conclusion, ALE consumption resulted in a modest but favourable statistically significant difference in total cholesterol after 12 weeks. In comparison with a previous trial, it is suggested that the apparent positive health status of the study population may have contributed to the modesty of the observed response. (C) 2008 Elsevier GmbH. All rights reserved.

Bromelain as an adjunctive treatment for moderate-to-severe osteoarthritis of the knee: a randomized placebo-controlled pilot study

Background: Osteoarthritis (OA) of the knee is the most prevalent joint disorder. Previous studies suggest that bromelain, a pineapple extract, may be a safer alternative/adjunctive treatment for knee OA than current conventional treatment. Aim: To assess the efficacy of bromelain in treating OA of the knee. Design: Randomized, double-blind placebo-controlled trial. Methods: Subjects (n=47) with a confirmed diagnosis of moderate to severe knee OA were randomized to 12 weeks of bromelain 800 mg/day or placebo, with a 4-week follow-up. Knee (pain, stiffness and function) and quality-of-life symptoms were reported monthly in the WOMAC and SF36 questionnaires, respectively. Adverse events were also recorded. The primary outcome measure was the change in total WOMAC score from baseline to the end of treatment at week 12. Longitudinal models were used to evaluate outcome. Results: Thirty-one patients completed the trial (14 bromelain, 17 placebo). No statistically significant differences were observed between groups for the primary outcome (coefficient 11.16, p=0.27, 95%CI-8.86 to 31.18), nor the WOMAC subscales or SF36. Both treatment groups showed clinically relevant improvement in the WOMAC disability subscale only. Adverse events were generally mild in nature. Discussion: This study suggests that bromelain is not efficacious as an adjunctive treatment of moderate to severe OA, but its limitations support the need for a follow-up study.

Can a short period of micronutrient supplementation in older institutionalized people improve response to influenza vaccine? A randomized, controlled trial

OBJECTIVES: To test the hypothesis that a micronutrient supplement can improve seroconversion after influenza immunization in older institutionalized people. DESIGN: Randomized, double-blind, placebo-controlled study. SETTING: Nursing and residential homes in Liverpool, United Kingdom. PARTICIPANTS: One hundred sixty-four residents aged 60 and older from 31 homes were initially randomized; of these, 119 (72.6%) completed the study. INTERVENTION: Participants were randomized to receive a micronutrient supplement providing the reference nutrient intake for all vitamins and trace elements or identical placebo. Tablets were taken over an 8-week period during September and October 2000; influenza vaccine was administered 4 weeks after their commencement. MEASUREMENTS: The hemagglutination-inhibiting antibody response as defined by a fourfold or greater titer rise over 4 weeks and assessed separately for each of the three antigens contained in the 2000/2001 influenza vaccine (A/New Caledonia/20/99 (H1N1), A/Moscow/10/99 (H3N2), B/Beijing/184/93 (B)). RESULTS: Despite a significant increase in serum concentrations of vitamins A, C, D-3, E, folate, and selenium in the supplemented group, there was no significant difference between groups (supplemented vs placebo, respectively) in the proportion of participants seroconverting to H1N1 (41% vs 49%, P=.374), H3N2 (49% vs 58%, P=.343), or B (41% vs 40%, P=.944). CONCLUSION: A micronutrient supplement providing the reference nutrient intake administered over 8 weeks had no beneficial effect on antibody response to influenza vaccine in older people living in long-term care.

Variable step LMS algorithm using the accumulated instantaneous error concept

The convergence speed of the standard Least Mean Square adaptive array may be degraded in mobile communication environments. Different conventional variable step size LMS algorithms were proposed to enhance the convergence speed while maintaining low steady state error. In this paper, a new variable step LMS algorithm, using the accumulated instantaneous error concept is proposed. In the proposed algorithm, the accumulated instantaneous error is used to update the step size parameter of standard LMS is varied. Simulation results show that the proposed algorithm is simpler and yields better performance than conventional variable step LMS.