Analysis of the Impact of Public Comment on Regulatory Decision Making: The Arsenic Standards

A method for the characterization and analysis of public comment on an EPA standard was proposed. The arsenic emissions standard was chosen since it was the most commented upon standard ever promulgated by the Agency. The proposed method worked well, as participating groups were clearly defined and the intent of each of the groups was reasonable in relation to their inferred environmental ideology. The effectiveness of each of the major groups of commenters was measured by relating the number of comments submitted versus the number of changes made. Comments received on the risk assessment constituted 89 percent of all comments submitted, over half were submitted by citizens not belonging to any particular special interest group. Few changes were made to the risk assessment as a result of the comments and the effectiveness of the comments for all groups was less than two percent. Comments submitted on the technical issues of the standard were more successful in causing change to the proposed standard. The effectiveness of each group varied widely, but the average effectiveness was 20 times greater than for comments submitted on risk issues. Many changes dealt with the submittal of new cost and emissions data by the affected industries. To allow for a discussion of the comment process, Godschalk's Exchange Model was altered and applied to the standard. The Exchange Model indicated that the comment process was successful except in the Agency's response to the public comment. A group theory model was used to analyze the Agency's response to the comment. This model indicated that the changes made to the proposed standards by the EPA could not be explained rationally on the basis of public comment. Other factors which influence EPA must be considered when explaining the Agency's decisions in light of the public intent.Master of Science in Public Healt

Pharmacokinetics and Dosing of Levofloxacin in Children Treated for Active or Latent Multidrug-resistant Tuberculosis, Federated States of Micronesia and Republic of the Marshall Islands

In the Federated States of Micronesia (FSM) and then the Republic of the Marshall Islands (RMI), levofloxacin pharmacokinetics (PK) were studied in children receiving directly observed once-daily regimens (10 mg/kg, age >5 years; 15–20 mg/kg, age ≤5 years) for either multidrug-resistant tuberculosis (MDR TB) disease or latent infection after MDR TB exposure, to inform future dosing strategies

A Distinct Translation Initiation Mechanism Generates Cryptic Peptides for Immune Surveillance

MHC class I molecules present a comprehensive mixture of peptides on the cell surface for immune surveillance. The peptides represent the intracellular protein milieu produced by translation of endogenous mRNAs. Unexpectedly, the peptides are encoded not only in conventional AUG initiated translational reading frames but also in alternative cryptic reading frames. Here, we analyzed how ribosomes recognize and use cryptic initiation codons in the mRNA. We find that translation initiation complexes assemble at non-AUG codons but differ from canonical AUG initiation in response to specific inhibitors acting within the peptidyl transferase and decoding centers of the ribosome. Thus, cryptic translation at non-AUG start codons can utilize a distinct initiation mechanism which could be differentially regulated to provide peptides for immune surveillance

Increasing Prevalence of Nontuberculous Mycobacteria in Respiratory Specimens from US-Affiliated Pacific Island Jurisdictions

Nontuberculous mycobacteria (NTM) respiratory infections represent a growing public health problem in many countries. However, there are limited published epidemiologic studies for the Western Pacific region. We reviewed respiratory specimens submitted to Diagnostic Laboratory Services in Hawaii, USA, for culture of Mycobacterium tuberculosis during August 2007–December 2011 to determine the NTM isolation rate. We observed a statistically significant increase in the rate of specimens with NTM isolated in respiratory culture (adjusted rate ratio per year 1.65, 95% CI 1.54–1.77; p<0.01). In contrast, the number of patients with respiratory cultures positive for M. tuberculosis showed no increase (adjusted rate ratio per year 0.98, 95% CI 0.94–1.01; p = 0.19). A 6-month subset of NTM isolates was identified by using a nucleic acid probe or 16S rRNA sequencing. M. avium complex and M. fortuitum were the most common NTM identified

Genomic analyses of the ancestral Manila family of <i>Mycobacterium tuberculosis</i>

<div><p>With its airborne transmission and prolonged latency period, <i>Mycobacterium tuberculosis</i> spreads worldwide as one of the most successful bacterial pathogens and continues to kill millions of people every year. <i>M</i>. <i>tuberculosis</i> lineage 1 is inferred to originate ancestrally based on the presence of the 52-bp TbD1 sequence and analysis of single nucleotide polymorphisms. Previously, we briefly reported the complete genome sequencing of <i>M</i>. <i>tuberculosis</i> strains 96121 and 96075, which belong to the ancient Manila family and modern Beijing family respectively. Here we present the comprehensive genomic analyses of the Manila family in lineage 1 compared to complete genomes in lineages 2–4. Principal component analysis of the presence and absence of CRISPR spacers suggests that Manila isolate 96121 is distinctly distant from lineages 2–4. We further identify a truncated <i>whiB5</i> gene and a putative operon consisting of genes encoding a putative serine/threonine kinase PknH and a putative ABC transporter, which are only found in the genomes of Manila family isolates. Six single nucleotide polymorphisms are uniquely conserved in 38 Manila strains. Moreover, when compared to <i>M</i>. <i>tuberculosis</i> H37Rv, 59 proteins are under positive selection in Manila family isolate 96121 but not in Beijing family isolate 96075. The unique features further serve as biomarkers for Manila strains and may shed light on the limited transmission of this ancestral lineage outside of its Filipino host population.</p></div

Introduction and evaluation of multidrug-resistant tuberculosis supplemental surveillance in the United States

The current tuberculosis (TB) case reporting system for the United States, the Report of Verified Case of TB (RVCT), has minimal capture of multidrug-resistant (MDR) TB treatment and adverse events. Data were abstracted in five states using the form for 13 MDR TB patients during 2012–2015. The Centers for Disease Control and Prevention Guidelines for Evaluating Public Health Surveillance Systems were used to evaluate attributes of the form. Unstructured interviews with pilot sites and stakeholders provided qualitative feedback. The form was acceptable, simple, stable, representative, and provided high-quality data but was not flexible or timely. For the 13 patients on whom data were collected, the median duration of treatment with an injectable medication was 216 days (IQR 203–252). Six (46%) patients reported a side effect requiring a medication change and eight (62%) had a side effect present at treatment completion. A standardized MDR TB supplemental surveillance form was well received by stakeholders whose feedback was critical to making modifications. The finalized form will be implemented nationally in 2020 and will provide MDR TB treatment and morbidity data in the United States to help ensure patients with MDR TB receive the most effective treatment regimens with the least toxic drugs. Keywords: Drug resistance, Surveillance, Tuberculosi