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1.  Proximity to Natural Gas Wells and Reported Health Status: Results of a Household Survey in Washington County, Pennsylvania 
Background: Little is known about the environmental and public health impact of unconventional natural gas extraction activities, including hydraulic fracturing, that occur near residential areas.
Objectives: Our aim was to assess the relationship between household proximity to natural gas wells and reported health symptoms.
Methods: We conducted a hypothesis-generating health symptom survey of 492 persons in 180 randomly selected households with ground-fed wells in an area of active natural gas drilling. Gas well proximity for each household was compared with the prevalence and frequency of reported dermal, respiratory, gastrointestinal, cardiovascular, and neurological symptoms.
Results: The number of reported health symptoms per person was higher among residents living < 1 km (mean ± SD, 3.27 ± 3.72) compared with > 2 km from the nearest gas well (mean ± SD, 1.60 ± 2.14; p = 0.0002). In a model that adjusted for age, sex, household education, smoking, awareness of environmental risk, work type, and animals in house, reported skin conditions were more common in households < 1 km compared with > 2 km from the nearest gas well (odds ratio = 4.1; 95% CI: 1.4, 12.3; p = 0.01). Upper respiratory symptoms were also more frequently reported in persons living in households < 1 km from gas wells (39%) compared with households 1–2 km or > 2 km from the nearest well (31 and 18%, respectively) (p = 0.004). No equivalent correlation was found between well proximity and other reported groups of respiratory, neurological, cardiovascular, or gastrointestinal conditions.
Conclusion: Although these results should be viewed as hypothesis generating, and the population studied was limited to households with a ground-fed water supply, proximity of natural gas wells may be associated with the prevalence of health symptoms including dermal and respiratory conditions in residents living near natural gas extraction activities. Further study of these associations, including the role of specific air and water exposures, is warranted.
Citation: Rabinowitz PM, Slizovskiy IB, Lamers V, Trufan SJ, Holford TR, Dziura JD, Peduzzi PN, Kane MJ, Reif JS, Weiss TR, Stowe MH. 2015. Proximity to natural gas wells and reported health status: results of a household survey in Washington County, Pennsylvania. Environ Health Perspect 123:21–26; http://dx.doi.org/10.1289/ehp.1307732
doi:10.1289/ehp.1307732
PMCID: PMC4286272  PMID: 25204871
2.  Comparison of ARIMA and Random Forest time series models for prediction of avian influenza H5N1 outbreaks 
BMC Bioinformatics  2014;15(1):276.
Background
Time series models can play an important role in disease prediction. Incidence data can be used to predict the future occurrence of disease events. Developments in modeling approaches provide an opportunity to compare different time series models for predictive power.
Results
We applied ARIMA and Random Forest time series models to incidence data of outbreaks of highly pathogenic avian influenza (H5N1) in Egypt, available through the online EMPRES-I system. We found that the Random Forest model outperformed the ARIMA model in predictive ability. Furthermore, we found that the Random Forest model is effective for predicting outbreaks of H5N1 in Egypt.
Conclusions
Random Forest time series modeling provides enhanced predictive ability over existing time series models for the prediction of infectious disease outbreaks. This result, along with those showing the concordance between bird and human outbreaks (Rabinowitz et al. 2012), provides a new approach to predicting these dangerous outbreaks in bird populations based on existing, freely available data. Our analysis uncovers the time-series structure of outbreak severity for highly pathogenic avain influenza (H5N1) in Egypt.
doi:10.1186/1471-2105-15-276
PMCID: PMC4152592  PMID: 25123979
3.  Dispatching the wandering mind? Toward a laboratory method for cuing “spontaneous” off-task thought 
Cognitive psychologists and neuroscientists study most phenomena of attention by measuring subjects' overt responses to discrete environmental stimuli that can be manipulated to test competing theories. The mind wandering experience, however, cannot be locally instigated by cleverly engineered stimuli. Investigators must therefore rely on correlational and observational methods to understand subjects' flow of thought, which is only occasionally and indirectly monitored. In an effort toward changing this state of affairs, we present four experiments that develop a method for inducing mind wandering episodes—on demand—in response to task-embedded cues. In an initial laboratory session, subjects described their personal goals and concerns across several life domains (amid some filler questionnaires). In a second session, 48 h later, subjects completed a go/no-go task in which they responded to the perceptual features of words; unbeknownst to subjects, some stimulus words were presented in triplets to represent the personal concerns they had described in session 1. Thought probes appearing shortly after these personal-goal triplets indicated that, compared to control triplets, priming subjects' concerns increased mind wandering rate by about 3–4%. We argue that this small effect is, nonetheless, a promising development toward the pursuit of an experimentally informed, theory-driven science of mind wandering.
doi:10.3389/fpsyg.2013.00570
PMCID: PMC3760067  PMID: 24027542
mind wandering; consciousness; goal priming; attention; current concerns
4.  Mephedrone Does not Damage Dopamine Nerve Endings of the Striatum but Enhances the Neurotoxicity of Methamphetamine, Amphetamine and MDMA 
Journal of neurochemistry  2013;125(1):102-110.
Mephedrone (4-methylmethcathinone) is a β-ketoamphetamine stimulant drug of abuse with close structural and mechanistic similarities to methamphetamine. One of the most powerful actions associated with mephedrone is the ability to stimulate dopamine (DA) release and block its reuptake through its interaction with the dopamine transporter (DAT). Although mephedrone does not cause toxicity to DA nerve endings, its ability to serve as a DAT blocker could provide protection against methamphetamine-induced neurotoxicity like other DAT inhibitors. To test this possibility, mice were treated with mephedrone (10, 20 or 40 mg/kg) prior to each injection of a neurotoxic regimen of methamphetamine (4 injections of 2.5 or 5.0 mg/kg at 2 hr intervals). The integrity of DA nerve endings of the striatum was assessed through measures of DA, DAT and tyrosine hydroxylase levels. The moderate to severe DA toxicity associated with the different doses of methamphetamine was not prevented by any dose of mephedrone but was, in fact, significantly enhanced. The hyperthermia caused by combined treatment with mephedrone and methamphetamine was the same as seen after either drug alone. Mephedrone also enhanced the neurotoxic effects of amphetamine and MDMA on DA nerve endings. In contrast, nomifensine protected against methamphetamine-induced neurotoxicity. Because mephedrone increases methamphetamine neurotoxicity, the present results suggest that it interacts with the DAT in a manner unlike that of other typical DAT inhibitors. The relatively innocuous effects of mephedrone alone on DA nerve endings mask a potentially dangerous interaction with drugs that are often co-abused with it, leading to heightened neurotoxicity.
doi:10.1111/jnc.12114
PMCID: PMC3604033  PMID: 23205838
mephedrone; methamphetamine; MDMA; amphetamine; dopamine; neurotoxicity
5.  Why Does Working Memory Capacity Predict Variation in Reading Comprehension? On the Influence of Mind Wandering and Executive Attention 
Some people are better readers than others, and this variation in comprehension ability is predicted by measures of working memory capacity (WMC). The primary goal of this study was to investigate the mediating role of mind wandering experiences in the association between WMC and normal individual differences in reading comprehension, as predicted by the executive-attention theory of WMC (e.g., Engle & Kane, 2004). We used a latent-variable, structural-equation-model approach, testing skilled adult readers on three WMC span tasks, seven varied reading comprehension tasks, and three attention-control tasks. Mind wandering was assessed using experimenter-scheduled thought probes during four different tasks (two reading, two attention-control tasks). The results support the executive-attention theory of WMC. Mind wandering across the four tasks loaded onto a single latent factor, reflecting a stable individual difference. Most importantly, mind wandering was a significant mediator in the relationship between WMC and reading comprehension, suggesting that the WMC-comprehension correlation is driven, in part, by attention control over intruding thoughts. We discuss implications for theories of WMC, attention control, and reading comprehension.
doi:10.1037/a0025250
PMCID: PMC3387280  PMID: 21875246
working memory; executive control; mind wandering; individual differences; reading comprehension; attention control
6.  Drifting from Slow to “D’oh!” Working Memory Capacity and Mind Wandering Predict Extreme Reaction Times and Executive-Control Errors 
A combined experimental, individual-differences, and thought-sampling study tested the predictions of executive attention (e.g., Engle & Kane, 2004) and coordinative binding (e.g., Oberauer, Süß, Wilhelm, & Sander, 2007) theories of working memory capacity (WMC). We assessed 288 subjects’ WMC and their performance and mind-wandering rates during a sustained-attention task; subjects completed either a go/no-go version requiring executive control over habit, or a vigilance version that did not. We further combined the data with those from McVay and Kane (2009) to: (1) gauge the contributions of WMC and attentional lapses to the worst-performance rule and the tail, or τ parameter, of response time (RT) distributions; (2) assess which parameters from a quantitative evidence-accumulation RT model were predicted by WMC and mind-wandering reports, and (3) consider intra-subject RT patterns – particularly, speeding – as potential objective markers of mind wandering. We found that WMC predicted action and thought control in only some conditions, that attentional lapses (indicated by TUT reports and drift-rate variability in evidence accumulation) contributed to τ, performance accuracy, and WMC’s association with them, and that mind-wandering experiences were not predicted by trial-to-trial RT changes, and so they cannot always be inferred from objective performance measures.
doi:10.1037/a0025896
PMCID: PMC3395723  PMID: 22004270
working memory; executive control; mind wandering; individual differences; reaction time
7.  Aging Ebbs the Flow of Thought: Adult Age Differences in Mind Wandering, Executive Control, and Self-Evaluation 
Acta psychologica  2012;142(1):136-147.
Two experiments examined the relations among adult aging, mind wandering, and executive-task performance, following from surprising laboratory findings that older adults report fewer task-unrelated thoughts (TUTs) than do younger adults (e.g., Giambra, 1989; Jackson & Balota, 2011). Because older adults may experience more ability- and performance-related worry during cognitive tasks in the laboratory, and because these evaluative thoughts (known as task-related interference, “TRI”) might be sometimes misclassified by subjects as task-related, we asked subjects to distinguish task-related thoughts from TRI and TUTs when probed during ongoing tasks. In Experiment 1, younger and older adults completed either a go/no-go or a vigilance version of a sustained attention to response task (SART). Older adults reported more TRI and fewer TUTs than did younger adults while also performing more accurately. In Experiment 2, subjects completed either a 1- or 2-back version of the n-back task. Older adults again reported more TRI and fewer TUTs than younger adults in both versions, while performing better than younger adults in the 1-back and worse in the 2-back. Across experiments, older adults’ reduced TUT rates were independent of performance relative to younger adults. And, although older adults consistently reported more TRI and less mind wandering than did younger adults, overall they reported more on-task thoughts. TRI cannot, therefore, account completely for prior reports of decreasing TUTs with aging. We discuss the implications of these results for various theoretical approaches to mind-wandering.
doi:10.1016/j.actpsy.2012.11.006
PMCID: PMC3545047  PMID: 23261422
aging; mind wandering; executive control; consciousness; working memory
8.  Altered Gene Expression in Cultured Microglia in Response to Simulated Blast Overpressure: Possible Role of Pulse Duration 
Neuroscience Letters  2012;522(1):47-51.
Blast overpressure has long been known to cause barotrauma to air-filled organs such as lung and middle ear. However, experience in Iraq and Afghanistan is revealing that individuals exposed to explosive munitions can also suffer traumatic brain injury (TBI) even in the absence of obvious external injury. The interaction of a blast shock wave with the brain in the intact cranial vault is extremely complex making it difficult to conclude that a blast wave interacts in a direct manner with the brain to cause injury. In an attempt to “isolate” the shock wave and test its primary effects on cells, we exposed cultured microglia to simulated blast overpressure in a barochamber. Overpressures ranging from 15–45 psi did not change microglial Cox-2 levels or TNF-α secretion nor did they cause cell damage. Microarray analysis revealed increases in expression of a number of microglial genes relating to immune function and inflammatory responses to include Saa3, Irg1, Fas and CxCl10. All changes in gene expression were dependent on pulse duration and were independent of pressure. These results indicate that microglia are mildly activated by blast overpressure and uncover a heretofore undocumented role for pulse duration in this process.
doi:10.1016/j.neulet.2012.06.012
PMCID: PMC3396767  PMID: 22698585
microglia; gene expression; blast; overpressure; barochamber; primary trauma
9.  Genetic depletion of brain 5HT reveals a common molecular pathway mediating compulsivity and impulsivity 
Journal of Neurochemistry  2012;121(6):974-984.
Neuropsychiatric disorders characterized by behavioral disinhibition, including disorders of compulsivity (e.g., obsessive-compulsive disorder; OCD) and impulse-control (e.g., impulsive aggression), are severe, highly prevalent and chronically disabling. Treatment options for these diseases are extremely limited. The pathophysiological bases of disorders of behavioral disinhibition are poorly understood but it has been suggested that serotonin dysfunction may play a role. Mice lacking the gene encoding brain tryptophan hydroxylase 2 (Tph2−/−), the initial and rate-limiting enzyme in the synthesis of serotonin, were tested in numerous behavioral assays that are well known for their utility in modeling human neuropsychiatric diseases. Mice lacking Tph2 (and brain 5HT) show intense compulsive and impulsive behaviors to include extreme aggression. The impulsivity is motor in form and not cognitive because Tph2−/− mice show normal acquisition and reversal learning on a spatial learning task. Restoration of 5HT levels by treatment of Tph2−/− mice with its immediate precursor 5-hydroxytryptophan attenuated compulsive and impulsive-aggressive behaviors. Surprisingly, in Tph2−/− mice, the lack of 5HT was not associated with anxiety-like behaviors. The results indicate that 5HT mediates behavioral disinhibition in the mammalian brain independent of anxiogenesis.
doi:10.1111/j.1471-4159.2012.07739.x
PMCID: PMC3371128  PMID: 22443164
brain serotonin; compulsivity; impulsivity; aggression; behavioral disinhibition
10.  Mephedrone, an Abused Psychoactive Component of “Bath Salts” and Methamphetamine Congener, Does not Cause Neurotoxicity to Dopamine Nerve Endings of the Striatum 
Journal of Neurochemistry  2012;120(6):1097-1107.
Mephedrone (4-methylmethcathinone) is a β-ketoamphetamine with close structural analogy to substituted amphetamines and cathinone derivatives. Abuse of mephedrone has increased dramatically in recent years and has become a significant public health problem in the US and Europe. Unfortunately, very little information is available on the pharmacological and neurochemical actions of mephedrone. In light of the proven abuse potential of mephedrone and considering its similarity to methamphetamine and methcathinone, it is particularly important to know if mephedrone shares with these agents an ability to cause damage to dopamine nerve endings of the striatum. Accordingly, we treated mice with a binge-like regimen of mephedrone (4X 20 or 40 mg/kg) and examined the striatum for evidence of neurotoxicity 2 or 7 days after treatment. While mephedrone caused hyperthermia and locomotor stimulation, it did not lower striatal levels of dopamine, tyrosine hydroxylase or the dopamine transporter under any of the treatment conditions used presently. Furthermore, mephedrone did not cause microglial activation in striatum nor did it increase glial fibrillary acidic protein levels. Taken together, these surprising results suggest that mephedrone, despite its numerous mechanistic overlaps with methamphetamine and the cathinone derivatives, does not cause neurotoxicity to dopamine nerve endings of the striatum.
doi:10.1111/j.1471-4159.2011.07632.x
PMCID: PMC3296829  PMID: 22191803
mephedrone; dopamine; neurotoxicity; β-ketoamphetamines; microglial activation; methamphetamine
11.  Does Mind Wandering Reflect Executive Function or Executive Failure? Comment on Smallwood and Schooler (2006) and Watkins (2008) 
Psychological bulletin  2010;136(2):188-207.
In this Comment, we contrast different conceptions of mind wandering that were presented in two recent theoretical reviews: Smallwood and Schooler (2006) and Watkins (2008). We also introduce a new perspective on the role of executive control in mind wandering by integrating empirical evidence presented in Smallwood and Schooler (2006) with two theoretical frameworks: Watkins’s (2008) elaborated control theory and Klinger’s (1971; 2009) current concerns theory. In contrast to the Smallwood-Schooler claim that mind-wandering recruits executive resources, we argue that mind wandering represents a failure of executive control and that it is dually determined by the presence of automatically generated thoughts in response to environmental and mental cues and the ability of the executive-control system to deal with this interference. We present empirical support for this view from experimental, neuroimaging, and individual-differences research.
doi:10.1037/a0018298
PMCID: PMC2850105  PMID: 20192557
12.  A mouse model of human repetitive mild traumatic brain injury 
Journal of neuroscience methods  2011;203(1):41-49.
A novel method for the study of repetitive mild traumatic brain injury (rmTBI) that models the most common form of head injury in humans is presented. Existing animal models of TBI impart focal, severe damage unlike that seen in repeated and mild concussive injuries, and few are configured for repetitive application. Our model is a modification of the Marmarou weight drop method and allows repeated head impacts to lightly anesthetized mice. A key facet of this method is the delivery of an impact to the cranium of an unrestrained subject allowing rapid acceleration of the free-moving head and torso, an essential characteristic known to be important for concussive injury in humans, and a factor that is missing from existing animal models of TBI. Our method does not require scalp incision, emplacement of protective skull helmets or surgery and the procedure can be completed in 1-2 minutes. Mice spontaneously recover the righting reflex and show no evidence of seizures, paralysis or impaired behavior. Skull fractures and intracranial bleeding are very rare. Minor deficits in motor coordination and locomotor hyperactivity recover over time. Histological analyses reveal mild astrocytic reactivity (increased expression of GFAP) and increased phospho-tau but a lack of blood-brain-barrier disruption, edema and microglial activation. This new animal model is simple and cost-effective and will facilitate characterization of the neurobiological and behavioral consequences of rmTBI. It is also ideal for high throughput screening of potential new therapies for mild concussive injuries as experienced by athletes and military personnel.
doi:10.1016/j.jneumeth.2011.09.003
PMCID: PMC3221913  PMID: 21930157
traumatic brain injury; mild; repetitive; concussive; head acceleration; tauopathy
13.  Mice Genetically Depleted of Brain Serotonin Display Social Impairments, Communication Deficits and Repetitive Behaviors: Possible Relevance to Autism 
PLoS ONE  2012;7(11):e48975.
Autism is a complex neurodevelopmental disorder characterized by impaired reciprocal social interaction, communication deficits and repetitive behaviors. A very large number of genes have been linked to autism, many of which encode proteins involved in the development and function of synaptic circuitry. However, the manner in which these mutated genes might participate, either individually or together, to cause autism is not understood. One factor known to exert extremely broad influence on brain development and network formation, and which has been linked to autism, is the neurotransmitter serotonin. Unfortunately, very little is known about how alterations in serotonin neuronal function might contribute to autism. To test the hypothesis that serotonin dysfunction can contribute to the core symptoms of autism, we analyzed mice lacking brain serotonin (via a null mutation in the gene for tryptophan hydroxylase 2 (TPH2)) for behaviors that are relevant to this disorder. Mice lacking brain serotonin (TPH2−/−) showed substantial deficits in numerous validated tests of social interaction and communication. These mice also display highly repetitive and compulsive behaviors. Newborn TPH2−/− mutant mice show delays in the expression of key developmental milestones and their diminished preference for maternal scents over the scent of an unrelated female is a forerunner of more severe socialization deficits that emerge in weanlings and persist into adulthood. Taken together, these results indicate that a hypo-serotonin condition can lead to behavioral traits that are highly characteristic of autism. Our findings should stimulate new studies that focus on determining how brain hyposerotonemia during critical neurodevelopmental periods can alter the maturation of synaptic circuits known to be mis-wired in autism and how prevention of such deficits might prevent this disorder.
doi:10.1371/journal.pone.0048975
PMCID: PMC3490915  PMID: 23139830
14.  Tracking the train of thought from the laboratory into everyday life: An experience-sampling study of mind wandering across controlled and ecological contexts 
Psychonomic bulletin & review  2009;16(5):857-863.
In an experience-sampling study that bridged laboratory, ecological, and individual-differences approaches to mind-wandering research, 72 subjects completed an executive-control task with periodic thought probes (reported by McVay & Kane, 2009) and then carried PDAs for a week that signaled them 8 times daily to report immediately whether their thoughts were off-task. Subjects who reported more mind wandering during the laboratory task endorsed more mind-wandering experiences during everyday life (and were more likely to report worries as off-task thought content). We also conceptually replicated laboratory findings that mind wandering predicts task performance: subjects rated their daily-life performance to be impaired when they reported off-task thoughts, with greatest impairment when subjects’ mind wandering lacked meta-consciousness. The propensity to mind-wander appears to be a stable cognitive characteristic and seems to predict performance difficulties in daily life, just as it does in the laboratory.
doi:10.3758/PBR.16.5.857
PMCID: PMC2760023  PMID: 19815789
15.  Conducting the Train of Thought: Working Memory Capacity, Goal Neglect, and Mind Wandering in an Executive-Control Task 
Based on the executive-attention theory of working memory capacity (WMC; e.g., Kane, Conway, Hambrick, & Engle, 2007) we tested the relations among WMC, mind wandering, and goal neglect in a sustained-attention-to-response task (SART; a go/no-go task). In three SART versions, making conceptual versus perceptual processing demands, subjects periodically indicated their thought content when probed following rare no-go targets. SART processing demands did not affect mind-wandering rates, but mind-wandering rates varied with WMC and predicted goal-neglect errors in the task; furthermore, mind-wandering rates partially mediated the WMC-SART relation, indicating that WMC-related differences in goal neglect were due, in part, to variation in the control of conscious thought.
doi:10.1037/a0014104
PMCID: PMC2750806  PMID: 19210090
16.  Familial Clustering of Migraine, Episodic Vertigo, and Ménière’s Disease 
Objective
To evaluate the association between migraine, episodic vertigo, and Ménière’s disease in families.
Study Design
Clinical report.
Setting
University Neurotology Clinic.
Patients
Index patients identified with Ménière’s disease and migraine and their family members.
Intervention
Structured interview to assess a diagnosis of migraine, episodic vertigo, and Ménière’s disease in 6 families. Genotyping was performed on 3 sets of twins to analyze monozygosity or dizygosity.
Main Outcome Measures
Clinical history of migraine, episodic vertigo, and Ménière’s disease.
Results
Six index patients and 57 family members were interviewed either by a senior neurologist in person over the phone by a trained study coordinator. An additional 6 family members completed questionnaires by mail. All 6 index patients had Ménière’s disease and migraine. Twenty-six (41%) of the 63 relatives met International Classification of Headache Disorders II criteria for migraine headaches. Thirteen (50%) of these 26 experienced migraine with aura. Three others experienced typical aura without headache. Seventeen (27%) of 63 family members experienced recurrent spells of spontaneous episodic vertigo. There was one twin pair in each of 3 families; 2 pairs were monozygotic and one was dizygotic. In each twin pair, one twin had migraine and Ménière’s disease, whereas the other experienced migraine and episodic vertigo without auditory symptoms.
Conclusion
The frequent association of episodic vertigo, migraine, and Ménière’s disease in closely related individuals, including identical twins supports the heritability of a migraine-Ménière’s syndrome, with variable expression of the individual features of hearing loss, episodic vertigo, and migraine headaches.
doi:10.1097/mao.0b013e31815c2abb
PMCID: PMC2820370  PMID: 18046258
Episodic vertigo; Ménière’s disease; Migraine

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