Publications

BACKGROUND

Although many probiotic products are currently available in yogurt or pill form in the United States (US), there is uncertainty surrounding the structure of regulation of these products. As more therapeutic probiotics are developed, changes to existing regulatory process in the United States may be required to meet the needs of patients and users in the population.

OBJECTIVE

This study examined how patients with chronic gastrointestinal (GI) diseases view the regulation of probiotics.

DESIGN

We conducted a multi-site qualitative study consisting of focus groups of patients with chronic gastrointestinal diseases at three tertiary hospitals: at [institutions removed for blinded review].

RESULTS

We conducted 22 focus groups with 136 patients with major gastrointestinal (GI) diseases between March and August 2009. Participants were not familiar with the existing regulation of probiotic products but wanted assurances of accurate labelling of strain as well as safety. Participants raised concerns that regulation of probiotics might be accompanied by greater costs, reduced access and increased involvement of pharmaceutical companies. Although participants voiced significant doubt of government regulators, they felt that products containing genetically modified probiotic strains should have oversight comparable to that of pharmaceutical drugs.

DISCUSSION AND CONCLUSION

If GI patient perspectives are indicative of public perceptions of therapeutic probiotics in the United States, consumers may expect more rigorous regulation in the future while simultaneously wanting low costs, easy access and low involvement of pharmaceutical companies. Manufacturers, translational scientists, clinicians and regulators should be sensitive to consumer attitudes when designing, testing and regulating new therapeutic probiotics.

PURPOSE

To develop and evaluate variable-density spiral first-pass perfusion pulse sequences for improved efficiency and off-resonance performance and to demonstrate the utility of an apodizing density compensation function (DCF) to improve signal-to-noise ratio (SNR) and reduce dark-rim artifact caused by cardiac motion and Gibbs Ringing.

METHODS

Three variable density spiral trajectories were designed, simulated, and evaluated in 18 normal subjects, and in eight patients with cardiac pathology on a 1.5T scanner.

RESULTS

By using a DCF, which intentionally apodizes the k-space data, the sidelobe amplitude of the theoretical point spread function (PSF) is reduced by 68%, with only a 13% increase in the full-width at half-maximum of the main-lobe when compared with the same data corrected with a conventional variable-density DCF, and has an 8% higher resolution than a uniform density spiral with the same number of interleaves and readout duration. Furthermore, this strategy results in a greater than 60% increase in measured SNR when compared with the same variable-density spiral data corrected with a conventional DCF (P < 0.01). Perfusion defects could be clearly visualized with minimal off-resonance and dark-rim artifacts.

CONCLUSION

Variable-density spiral pulse sequences using an apodized DCF produce high-quality first-pass perfusion images with minimal dark-rim and off-resonance artifacts, high SNR and contrast-to-noise ratio, and good delineation of resting perfusion abnormalities.

BACKGROUND

Malaria, malnutrition and anaemia are major causes of morbidity and mortality in African children. The interplay between these conditions is complex and limited data exist on factors associated with these conditions among infants born to HIV-uninfected and infected women.

METHODS

Two hundred HIV-exposed (HIV-uninfected infants born to HIV-infected mothers) and 400 HIV-unexposed infants were recruited from an area of high malaria transmission in rural Uganda. A cross-sectional survey was performed at enrolment to measure the prevalence of malaria parasitaemia, measures of malnutrition (z-scores <2 standard deviations below mean) and anaemia (haemoglobin <8 gm/dL). Multivariate logistic regression was used to measure associations between these conditions and risk factors of interest including household demographics, malaria prevention practices, breastfeeding practices, household structure and wealth index.

RESULTS

The prevalence of malaria parasitaemia was 20%. Factors protective against parasitaemia included female gender (OR = 0.66, p = 0.047), mother's age (OR = 0.81 per five-year increase, p = 0.01), reported bed net use (OR = 0.63, p = 0.03) and living in a well-constructed house (OR = 0.25, p = 0.01). Although HIV-unexposed infants had a higher risk of parasitaemia compared to HIV-exposed infants (24% vs 14%, p = 0.004), there was no significant association between HIV-exposure status and parasitaemia after controlling for the use of malaria preventative measures including bed net use and trimethoprim-sulphamethoxazole prophylaxis. The prevalence of stunting, underweight, and wasting were 10%, 7%, and 3%, respectively. HIV-exposed infants had a higher odds of stunting (OR = 2.23, p = 0.005), underweight (OR = 1.73, p = 0.09) and wasting (OR = 3.29, p = 0.02). The prevalence of anaemia was 12%. Risk factors for anaemia included older infant age (OR = 2.05 per one month increase, p = 0.003) and having malaria parasitaemia (OR = 5.74, p < 0.001).

CONCLUSIONS

Compared to HIV-unexposed infants, HIV-exposed infants had a higher use of malaria preventative measures and lower odds of malaria parasitaemia. Having a better constructed house was also protective against malaria parasitaemia. HIV-exposure was the primary risk factor for measures of malnutrition. The primary risk factor for anaemia was malaria parasitaemia. These findings suggest the need to better target existing interventions for malaria, malnutrition and anaemia as well as the need to explore further the mechanisms behind the observed associations.

Genome-scale RNAi libraries enable the systematic interrogation of gene function. However, the interpretation of RNAi screens is complicated by the observation that RNAi reagents designed to suppress the mRNA transcripts of the same gene often produce a spectrum of phenotypic outcomes due to differential on-target gene suppression or perturbation of off-target transcripts. Here we present a computational method, Analytic Technique for Assessment of RNAi by Similarity (ATARiS), that takes advantage of patterns in RNAi data across multiple samples in order to enrich for RNAi reagents whose phenotypic effects relate to suppression of their intended targets. By summarizing only such reagent effects for each gene, ATARiS produces quantitative, gene-level phenotype values, which provide an intuitive measure of the effect of gene suppression in each sample. This method is robust for data sets that contain as few as 10 samples and can be used to analyze screens of any number of targeted genes. We used this analytic approach to interrogate RNAi data derived from screening more than 100 human cancer cell lines and identified HNF1B as a transforming oncogene required for the survival of cancer cells that harbor HNF1B amplifications. ATARiS is publicly available at http://broadinstitute.org/ataris.