Naomi C. Brownstein

Preclinical episodes of orofacial pain symptoms and their association with health care behaviors in the OPPERA prospective cohort study

Summary One in 3 adults developed temporomandibular disorder symptoms over 2.3 years. Comorbid pain was common and recurrence was rapid, yet many did not seek health care or use analgesics. Abstract The course of preclinical pain symptoms sheds light on the etiology and prognosis of chronic pain. We aimed to quantify rates of developing initial and recurrent symptoms of painful temporomandibular disorder (TMD) and to evaluate associations with health behaviors. In the OPPERA prospective cohort study, 2,719 individuals aged 18 to 44 years with lifetime absence of TMD when enrolled completed 25,103 quarterly (3‐monthly) questionnaires during a median 2.3‐year follow‐up period. Questionnaires documented TMD symptom episodes, headache, other body pain, health care attendance, and analgesic use, and. Kaplan‐Meier methods for clustered data estimated symptom‐free survival time. Multivariable models assessed demographic variation in TMD symptom rates and evaluated associations with health care and analgesic use. One‐third of the study subjects developed TMD symptoms and for a quarter of symptomatic episodes, pain intensity was severe. Initial TMD symptoms developed at an annual rate of 18.8 episodes per 100 persons. The annual rate more than doubled for first‐recurrence and doubled again for second or subsequent recurrence such that, 1 year after first recurrence, 71% of study subjects experienced a second recurrence. The overall rate increased with age and was greater in African Americans and lower in Asians relative to those of white race/ethnicity. The probability of TMD symptoms was strongly associated with concurrent episodes of headache and body pain and with past episodes of TMD symptoms. Episodes of TMD symptoms, headache, and body pain were associated with increases of ∼10% in probability of analgesic use and health care attendance. Yet, even when TMD, headache, and body pain occurred concurrently, 27% of study subjects neither attended health care nor used analgesics.

Maternal residential exposure to agricultural pesticides and birth defects in a 2003 to 2005 North Carolina birth cohort

BACKGROUND Birth defects are responsible for a large proportion of disability and infant mortality. Exposure to a variety of pesticides have been linked to increased risk of birth defects. METHODS We conducted a case-control study to estimate the associations between a residence-based metric of agricultural pesticide exposure and birth defects. We linked singleton live birth records for 2003 to 2005 from the North Carolina (NC) State Center for Health Statistics to data from the NC Birth Defects Monitoring Program. Included women had residence at delivery inside NC and infants with gestational ages from 20 to 44 weeks (n = 304,906). Pesticide exposure was assigned using a previously constructed metric, estimating total chemical exposure (pounds of active ingredient) based on crops within 500 meters of maternal residence, specific dates of pregnancy, and chemical application dates based on the planting/harvesting dates of each crop. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals for four categories of exposure (<10(th) , 10-50(th) , 50-90(th) , and >90(th) percentiles) compared with unexposed. Models were adjusted for maternal race, age at delivery, education, marital status, and smoking status. RESULTS We observed elevated ORs for congenital heart defects and certain structural defects affecting the gastrointestinal, genitourinary and musculoskeletal systems (e.g., OR [95% confidence interval] [highest exposure vs. unexposed] for tracheal esophageal fistula/esophageal atresia = 1.98 [0.69, 5.66], and OR for atrial septal defects: 1.70 [1.34, 2.14]). CONCLUSION Our results provide some evidence of associations between residential exposure to agricultural pesticides and several birth defects phenotypes. Birth Defects Research (Part A) 106:240-249, 2016.

Effect of zinc supplementation on neuronal precursor proliferation in the rat hippocampus after traumatic brain injury

There is great deal of debate about the possible role of adult-born hippocampal cells in the prevention of depression and related mood disorders. We first showed that zinc supplementation prevents the development of the depression-like behavior anhedonia associated with an animal model of traumatic brain injury (TBI). This work then examined the effect of zinc supplementation on the proliferation of new cells in the hippocampus that have the potential to participate in neurogenesis. Rats were fed a zinc adequate (ZA, 30ppm) or zinc supplemented (ZS, 180ppm) diet for 4wk followed by TBI using controlled cortical impact. Stereological counts of EdU-positive cells showed that TBI doubled the density of proliferating cells 24h post-injury (p<0.05), and supplemental zinc significantly increased this by an additional 2-fold (p<0.0001). While the survival of these proliferating cells decreased at the same rate in ZA and in ZS rats after injury, the total density of newly born cells was approximately 60% higher in supplemented rats 1wk after TBI. Furthermore, chronic zinc supplementation resulted in significant increases in the density of new doublecortin-positive neurons one week post-TBI that were maintained for 4wk after injury (p<0.01). While the effect of zinc supplementation on neuronal precursor cells in the hippocampus was robust, use of targeted irradiation to eliminate these cells after zinc supplementation and TBI revealed that these cells are not the sole mechanism through which zinc acts to prevent depression associated with brain injury, and suggest that other zinc dependent mechanisms are needed for the anti-depressant effect of zinc in this model of TBI.

Unavoidable Sets of Partial Words

The notion of an unavoidable set of words appears frequently in the fields of mathematics and theoretical computer science, in particular with its connection to the study of combinatorics on words. The theory of unavoidable sets has seen extensive study over the past twenty years. In this paper we extend the definition of unavoidable sets of words to unavoidable sets of partial words. Partial words, or finite sequences that may contain a number of “do not know” symbols or “holes,” appear naturally in several areas of current interest such as molecular biology, data communication, and DNA computing. We demonstrate the utility of the notion of unavoidability of sets of partial words by making use of it to identify several new classes of unavoidable sets of full words. Along the way we begin work on classifying the unavoidable sets of partial words of small cardinality. We pose a conjecture, and show that affirmative proof of this conjecture gives a sufficient condition for classifying all the unavoidable sets of partial words of size two. We give a result which makes the conjecture easy to verify for a significant number of cases. We characterize many forms of unavoidable sets of partial words of size three over a binary alphabet, and completely characterize such sets over a ternary alphabet. Finally, we extend our results to unavoidable sets of partial words of size k over a k-letter alphabet.

Paired single residue‐transposed Lys‐N and Lys‐C digestions for label‐free identification of N‐terminal and C‐terminal MS/MS peptide product ions: ultrahigh resolution Fourier transform ion cyclotron resonance mass spectrometry and tandem mass spectrometry for peptide de novo sequencing

RATIONALE Paired Lys-N and Lys-C proteases produce peptides of identical mass and similar retention time, but different tandem mass spectra. Data from these parallel experiments provide constraints that are applied before data analysis. With this approach, we can find matched spectra before analysis, distinguish ion type, and determine residue level confidence. METHODS Aliquots are digested separately by Lys-N and Lys-C peptidases, and analyzed by reversed-phase nano-flow liquid chromatography, collision-induced dissociation, and 14.5 T Fourier transform ion cyclotron resonance mass spectrometry. Matched pairs of fragmentation spectra with equal precursor mass and similar retention times from each digestion are compared, leveraging single-residue transposed information with independent interferences to confidently identify fragment ion type, residues, and peptides. The paired spectra are solved together as a single de novo sequencing problem. RESULTS Two pairs of spectra of a de novo sequenced 18-mer are presented. In one example, the 18-mer has coverage of all residues except the N- and C- terminal lysines and their adjacent residues. The confidence level is high due to six pairs of transposed ions. In the other example, the coverage is incomplete. Nonetheless, nine pairs of transposed ions facilitate identification of two trimer sequence tags with high confidence, one with medium confidence, and additional sequence information with residue-by-residue confidence, thus demonstrating the value of residue-by-residue confidence. CONCLUSIONS Sequence identity and variability, such as post-translational modifications (PTMs), are essential to understanding biological function and disease. The present method facilitates discovery of new peptides with multiple levels of confidence, promises potential characterization of PTMs, and validates peptides from databases. Independent validation may be of interest for a number of applications.

An evaluation of metrics for assessing maternal exposure to agricultural pesticides.

We evaluate the use of three different exposure metrics to estimate maternal agricultural pesticide exposure during pregnancy. Using a geographic information system-based method of pesticide exposure estimation, we combine data on crop density and specific pesticide application amounts/dates to create the three exposure metrics. For illustration purposes, we create each metric for a North Carolina cohort of pregnant women, 2003–2005, and analyze the risk of congenital anomaly development with a focus on metric comparisons. Based on the results, and the need to balance data collection efforts/computational efficiency with accuracy, the metric which estimates total chemical exposure using application dates based on crop-specific earliest planting and latest harvesting information is preferred. Benefits and drawbacks of each metric are discussed and recommendations for extending the analysis to other states are provided.

Status of Tenure Among Black and Latino Faculty in Academic Medicine.

Tenure has been used for years to recruit, promote, and retain faculty in higher education and has been associated with job security and academic freedom. Absence of tenure and not being in tenure-earning tracks is grouped with the challenges faced by underrepresented minorities in academic medicine. Those challenges include being found at the assistant professor rank more often, having more clinical responsibilities, and not being in leadership positions as often as compared to non-minority faculty. The role of tenure and tenure tracks is unclear as it relates to the presence of minority faculty. This article presents a look at the status of tenure among black and Latino faculty in academic medicine at US medical schools.

Application of Transformations in Parametric Inference

The objective of the present paper is to provide a simple approach to statistical inference using the method of transformations of variables. We demonstrate performance of this powerful tool on examples of constructions of various estimation procedures, hypothesis testing, Bayes analysis and statistical inference for the stress-strength systems. We argue that the tool of transformations not only should be used more widely in statistical research but should become a routine part of calculus-based courses of statistics. Finally, we provide sample problems for such a course as well as possible undergraduate reserach projects which utilize transformations of variables.

Comprehensive Community-Based Intervention and Asthma Outcomes in African American Adolescents

A comprehensive family- and community-based intervention was used to improve health outcomes in African American adolescents who are at high risk for poor morbidity and mortality. BrightcoveDefaultPlayer10.1542/6138648673001PEDS-VA_2017-3737 Video Abstract BACKGROUND: African American adolescents appear to be the most at risk for asthma morbidity and mortality even compared with other minority groups, yet there are few successful interventions for this population that are used to target poorly controlled asthma. METHODS: African American adolescents (age 12–16 years) with moderate-to-severe persistent asthma and ≥1 inpatient hospitalization or ≥2 emergency department visits in 12 months were randomly assigned to Multisystemic Therapy–Health Care or an attention control group (N = 167). Multisystemic Therapy–Health Care is a 6-month home- and community-based treatment that has been shown to improve illness management and health outcomes in high-risk adolescents by addressing the unique barriers for each individual family with cognitive behavioral interventions. The attention control condition was weekly family supportive counseling, which was also provided for 6 months in the home. The primary outcome was lung function (forced expiratory volume in 1 second [FEV1]) measured over 12 months of follow-up. RESULTS: Linear mixed-effects models revealed that compared with adolescents in the comparison group, adolescents in the treatment group had significantly greater improvements in FEV1 secondary outcomes of adherence to controller medication, and the frequency of asthma symptoms. Adolescents in the treatment group had greater reductions in hospitalizations, but there were no differences in reductions in emergency department visits. CONCLUSIONS: A comprehensive family- and community-based treatment significantly improved FEV1, medication adherence, asthma symptom frequency, and inpatient hospitalizations in African American adolescents with poorly controlled asthma. Further evaluation in effectiveness and implementation trials is warranted.

To Cluster, or Not to Cluster: An Analysis of Clusterability Methods

Abstract Clustering is an essential data mining tool that aims to discover inherent cluster structure in data. For most applications, applying clustering is only appropriate when cluster structure is present. As such, the study of clusterability, which evaluates whether data possesses such structure, is an integral part of cluster analysis. However, methods for evaluating clusterability vary radically, making it challenging to select a suitable measure. In this paper, we perform an extensive comparison of measures of clusterability and provide guidelines that clustering users can reference to select suitable measures for their applications.