Mining of Consumer Product Ingredient and Purchasing Data to Identify Potential Chemical Coexposures

Background: Chemicals in consumer products are a major contributor to human chemical coexposures. Consumers purchase and use a wide variety of products containing potentially thousands of chemicals. There is a need to identify potential real-world chemical coexposures to prioritize in vitro toxicity screening. However, due to the vast number of potential chemical combinations, this identification has been a major challenge.Objectives: We aimed to develop and implement a data-driven procedure for identifying prevalent chemical combinations to which humans are exposed through purchase and use of consumer products.Methods: We applied frequent itemset mining to an integrated data set linking consumer product chemical ingredient data with product purchasing data from 60,000 households to identify chemical combinations resulting from co-use of consumer products.Results: We identified co-occurrence patterns of chemicals over all households as well as those specific to demographic groups based on race/ethnicity, income, education, and family composition. We also identified chemicals with the highest potential for aggregate exposure by identifying chemicals occurring in multiple products used by the same household. Last, a case study of chemicals active in estrogen and androgen receptor in silico models revealed priority chemical combinations co-targeting receptors involved in important biological signaling pathways.Discussion: Integration and comprehensive analysis of household purchasing data and product-chemical information provided a means to assess human near-field exposure and inform selection of chemical combinations for high-throughput screening in in vitro assays. https://doi.org/10.1289/EHP8610     

Electrophysiologic latency to the external obliques of the laryngeal cough expiration reflex in humans

OBJECTIVE: The purpose of this study was to trigger the laryngeal cough expiration reflex using inhaled tartaric acid aerosol and to record the latency between the time of initiation of the laryngeal cough expiration reflex component of the laryngeal cough reflex and the onset of electromyographically recorded responses in the external abdominal oblique in humans. DESIGN: Five male subjects were tested in the seated position, and four latencies were recorded for each subject. The latencies were recorded from laryngeal stimulation to an electromyogram in the muscle belly of the left external abdominal oblique. The time line was activated by a microswitch attached to a breath-activated nebulizer. Data were analyzed using SPSS for mean latency and standard deviation. RESULTS: The mean (standard deviation) latency to the external abdominal oblique muscle was 17.6 +/- 10.6 msec. No adverse events to inhalation were reported. CONCLUSION: SIn humans, nebulized tartaric acid stimulates primarily rapid adapting receptors in the supraglottic larynx rather than C-fiber receptors. This receptor location in humans evolved neurologically to protect the airway during speech and swallowing, making the laryngeal cough expiration reflex an inseparable component of the laryngeal cough reflex, thus making it clinically significant when assessing airway protection.     

A Randomized Comparison of Aripiprazole and Risperidone for the Acute Treatment of First-Episode Schizophrenia and Related Disorders: 3-Month Outcomes

Research findings are particularly important for medication choice for first-episode patients as individual prior medication response to guide treatment decisions is unavailable. We describe the first large-scale double-masked randomized comparison with first-episode patients of aripiprazole and risperidone, 2 commonly used first-episode treatment agents. One hundred ninety-eight participants aged 15–40 years with schizophrenia, schizophreniform disorder, schizoaffective disorder or psychotic disorder Not Otherwise Specified, and who had been treated in their lifetime with antipsychotics for 2 weeks or less were randomly assigned to double-masked aripiprazole (5–30mg/d) or risperidone (1–6mg/d) and followed for 12 weeks. Positive symptom response rates did not differ (62.8% vs 56.8%) nor did time to response. Aripiprazole-treated participants had better negative symptom outcomes but experienced more akathisia. Body mass index change did not differ between treatments but advantages were found for aripiprazole treatment for total and low-density lipoprotein cholesterol, fasting glucose, and prolactin levels. Post hoc analyses suggested advantages for aripiprazole on depressed mood. Overall, if the potential for akathisia is a concern, low-dose risperidone as used in this trial maybe a preferred choice over aripiprazole. Otherwise, aripiprazole would be the preferred choice over risperidone in most situations based upon metabolic outcome advantages and some symptom advantages within the context of similar positive symptom response between medications.Key words: clinical trial, treatment response, negative symptoms, akathisia, metabolic side effects     

Reliability of an fMRI paradigm for emotional processing in a multisite longitudinal study

Multisite neuroimaging studies can facilitate the investigation of brain‐related changes in many contexts, including patient groups that are relatively rare in the general population. Though multisite studies have characterized the reliability of brain activation during working memory and motor functional magnetic resonance imaging tasks, emotion processing tasks, pertinent to many clinical populations, remain less explored. A traveling participants study was conducted with eight healthy volunteers scanned twice on consecutive days at each of the eight North American Longitudinal Prodrome Study sites. Tests derived from generalizability theory showed excellent reliability in the amygdala ( = 0.82), inferior frontal gyrus (IFG; = 0.83), anterior cingulate cortex (ACC; = 0.76), insula ( = 0.85), and fusiform gyrus ( = 0.91) for maximum activation and fair to excellent reliability in the amygdala ( = 0.44), IFG ( = 0.48), ACC ( = 0.55), insula ( = 0.42), and fusiform gyrus ( = 0.83) for mean activation across sites and test days. For the amygdala, habituation ( = 0.71) was more stable than mean activation. In a second investigation, data from 111 healthy individuals across sites were aggregated in a voxelwise, quantitative meta‐analysis. When compared with a mixed effects model controlling for site, both approaches identified robust activation in regions consistent with expected results based on prior single‐site research. Overall, regions central to emotion processing showed strong reliability in the traveling participants study and robust activation in the aggregation study. These results support the reliability of blood oxygen level‐dependent signal in emotion processing areas across different sites and scanners and may inform future efforts to increase efficiency and enhance knowledge of rare conditions in the population through multisite neuroimaging paradigms. Hum Brain Mapp 36:2558–2579, 2015. © 2015 Wiley Periodicals, Inc .     

Teaching teamwork during the Neonatal Resuscitation Program: a randomized trial.

OBJECTIVE: To add a team training and human error curriculum to the Neonatal Resuscitation Program (NRP) and measure its effect on teamwork. We hypothesized that teams that received the new course would exhibit more teamwork behaviors than those in the standard NRP course. STUDY DESIGN: Interns were randomized to receive NRP with team training or standard NRP, then video recorded when they performed simulated resuscitations at the end of the day-long course. Outcomes were assessed by observers blinded to study arm allocation and included the frequency or duration of six team behaviors: inquiry, information sharing, assertion, evaluation of plans, workload management and vigilance. RESULT: The interns in the NRP with team training group exhibited more frequent team behaviors (number of episodes per minute (95% CI)) than interns in the control group: information sharing 1.06 (0.24, 1.17) vs 0.13 (0.00, 0.43); inquiry 0.35 (0.11, 0.42) vs 0.09 (0.00, 0.10); assertion 1.80 (1.21, 2.25) vs 0.64 (0.26, 0.91); and any team behavior 3.34 (2.26, 4.11) vs 1.03 (0.48, 1.30) (P-values <0.008 for all comparisons). Vigilance and workload management were practiced throughout the entire simulated code by nearly all the teams in the NRP with team training group (100% for vigilance and 88% for workload management) vs only 53 and 20% of the teams in the standard NRP. No difference was detected in the frequency of evaluation of plans. CONCLUSION: Compared with the standard NRP, NRP with a teamwork and human error curriculum led interns to exhibit more team behaviors during simulated resuscitations.     

Depression dexamethasone nonsuppression and negative symptoms in schizophrenia

This study compared three measures of depression in schizophrenia and their correlation with the Dexamethasone Suppression Test (DST). The degree of overlap of these three measures with negative symptoms was also examined. The Hamilton Depression Rating Scale (HDRS), the depressive syndrome score of the Present State Examination (PSE), and the Scale for the Assessment of Negative Symptoms (SANS) were administered to 50 acutely ill, hospitalized schizophrenics. Patients were diagnosed using DSM-III criteria for schizophrenia. DSM-III criteria were also used to assess the presence of a major depressive episode. Results were that DST nonsuppression was significantly associated with the presence of a major depressive episode, but not with depressive rating scale scores or with negative symptoms. It is concluded that the DST may be of value in differentiating a depressive syndrome from a negative symptom syndrome in schizophrenia.