Multivariate analyses for monitoring EDCs and PPCPs in a lake water.

The analysis of endocrine disrupting compounds (EDCs) and pharmaceutical and personal care products (PPCP), present at trace level in surface waters, is often expensive, time-consuming, and complex. Implementing effective monitoring strategies for these compounds is essential to determine the types of analytes, sampling locations, and sampling frequencies. Multivariate analyses were used to investigate the patterns of EDCs and PPCPs in Lake Mead, Nevada, for these purposes. The results of cluster analysis and principal component analysis to identify the patterns among compounds demonstrated that selected pharmaceuticals tended to be present together with each other, whereas hormones did not show patterns with other compounds. The results of cluster analysis and discriminant analysis to investigate the spatial variation of EDCs and PPCPs eliminated redundant sampling locations, verifying the current selection of sampling locations in Lake Mead. The results of autocorrelation provided optimal sampling frequencies for EDCs and PPCPs, suggesting either monthly or quarterly monitoring of these compounds in Lake Mead. The patterns of the compounds could be site specific; depending on weather and hydrological conditions of the water systems, but this study's approaches will facilitate effective assessment and monitoring of EDCs and PPCPs in surface water.

Comment on Murtaugh.

Murtaugh and I agree on an important point: abandon accept/reject declarations. That alone will go a long way to improving statistical practice. (2) Don't confuse P values or deltaAIC with binary declarations. An argument against one is not necessarily an argument against the other. (3) Be careful interpreting a P value or deltaAIC as strength of evidence. That interpretation cannot be made formal and the connection between P, deltaAIC, and evidence must be recalibrated for each new problem. (4) Plot. Check models. Plot. Check assumptions. Plot.

Hemlock woolly adelgid and elongate hemlock scale induce changes in foliar and twig volatiles of eastern hemlock.

Eastern hemlock (Tsuga canadensis) is in rapid decline because of infestation by the invasive hemlock woolly adelgid (Adelges tsugae; 'HWA') and, to a lesser extent, the invasive elongate hemlock scale (Fiorinia externa; 'EHS'). For many conifers, induced oleoresin-based defenses play a central role in their response to herbivorous insects; however, it is unknown whether eastern hemlock mobilizes these inducible defenses. We conducted a study to determine if feeding by HWA or EHS induced changes in the volatile resin compounds of eastern hemlock. Young trees were experimentally infested for 3 years with HWA, EHS, or neither insect. Twig and needle resin volatiles were identified and quantified by gas chromatography/mass spectrometry. We observed a suite of changes in eastern hemlock's volatile profile markedly different from the largely terpenoid-based defense response of similar conifers. Overall, both insects produced a similar effect: most twig volatiles decreased slightly, while most needle volatiles increased slightly. Only HWA feeding led to elevated levels of methyl salicylate, a signal for systemic acquired resistance in many plants, and benzyl alcohol, a strong antimicrobial and aphid deterrent. Green leaf volatiles, often induced in wounded plants, were increased by both insects, but more strongly by EHS. The array of phytochemical changes we observed may reflect manipulation of the tree's biochemistry by HWA, or simply the absence of functional defenses against piercing-sucking insects due to the lack of evolutionary contact with these species. Our findings verify that HWA and EHS both induce changes in eastern hemlock's resin chemistry, and represent the first important step toward understanding the effects of inducible chemical defenses on hemlock susceptibility to these exotic pests.

Dynamic linear model analysis of optical imaging data acquired from the human neocortex.

The amount of light absorbed and scattered by neocortical tissue is altered by neuronal activity. Imaging of intrinsic optical signals (ImIOS), a technique for mapping these activity-evoked optical changes with an imaging detector, has the potential to be useful for both clinical and experimental investigations of the human neocortex. However, its usefulness for human studies is currently limited because intraoperatively acquired ImIOS data is noisy. To improve the reliability and usefulness of ImIOS for human studies, it is desirable to find appropriate methods for the removal of noise artifacts and its statistical analysis. Here we develop a Bayesian, dynamic linear modeling approach that appears to address these problems. A dynamic linear model (DLM) was constructed that included cyclic components to model the heartbeat and respiration artifacts, and a local linear component to model the activity-evoked response. The robustness of the model was tested on a set of ImIOS data acquired from the exposed cortices of six human subjects illuminated with either 535nm or 660nm light. The DLM adequately reduced noise artifacts in these data while reliably preserving their activity-evoked optical responses. To demonstrate how these methods might be used for intraoperative neurosurgical mapping, optical data acquired from a single human subject during direct electrical stimulation of the cortex were quantitatively analyzed. This example showed that the DLM can be used to provide quantitative information about human ImIOS data that is not available through qualitative analysis alone.

Dilution of microbicide gels with vaginal fluid and semen simulants: effect on rheological properties and coating flow.

Microbicides are agents applied topically to the vagina to prevent HIV transmission. Microbicide products formulated as semi-solid dosage forms or "gels" coat vulnerable tissue to deliver active ingredients. Effective microbicide delivery vehicles must have appropriate rheological properties to ensure appropriate deployment in vivo. Microbicide products become diluted by fluids in the vagina after application; dilution affects vehicle rheological properties and mechanics of vaginal distribution, thus affecting efficacy. To simulate the changes that might occur after application, this study analyzed the effects of small dilutions (10-30%) with vaginal fluid and semen simulants on three semi-solid vaginal formulations: a cellulose lubricant (KY Jelly), a polyacrylic acid moisturizer (Replens), and a carrageenan prototype microbicide (Carraguard). Rheological behavior was characterized using cone-and-plate rheometry. Data were fitted to either the power-law, Carreau, or Herschel-Bulkley model. Rheological parameters from these fits were input to models of coating flow due squeezing, and the simulated area coated output from these models was used to compare the responses of the different formulations to the two diluents for varying degrees of dilution. There were differences in the responses of the three materials to dilution. Even small dilutions altered the rank order of vaginal coating rates compared to the undiluted formulations.

The evolutionary forest algorithm.

MOTIVATION: Gene genealogies offer a powerful context for inferences about the evolutionary process based on presently segregating DNA variation. In many cases, it is the distribution of population parameters, marginalized over the effectively infinite-dimensional tree space, that is of interest. Our evolutionary forest (EF) algorithm uses Monte Carlo methods to generate posterior distributions of population parameters. A novel feature is the updating of parameter values based on a probability measure defined on an ensemble of histories (a forest of genealogies), rather than a single tree. RESULTS: The EF algorithm generates samples from the correct marginal distribution of population parameters. Applied to actual data from closely related fruit fly species, it rapidly converged to posterior distributions that closely approximated the exact posteriors generated through massive computational effort. Applied to simulated data, it generated credible intervals that covered the actual parameter values in accordance with the nominal probabilities. AVAILABILITY: A C++ implementation of this method is freely accessible at http://www.isds.duke.edu/~scl13

Optical imaging and analysis of human vaginal coating by drug delivery gels.

OBJECTIVE: We used a new optical imaging technique to compare human intravaginal coating distributions of Conceptrol (Advanced Care Products, Brunswick, NJ) and Advantage (Columbia Laboratories, Aventuna, FL). These gels are surrogates for future microbicidal gels, differing in molecular structures and biophysical properties. METHODS: For each protocol, a 3-mL gel bolus was inserted to the posterior fornix while the woman was in the supine position. She then either (1) remained supine (10 min); or (2) sat up (1 min), stood up (1 min), sat down (1 min) and returned to supine for a net elapsed time of 10 min. The imaging device is sized/shaped like a phallus, and measurements while the device was inserted provide data that simulate peri-intromission coating. RESULTS: Coating by Advantage was more extensive and uniform than coating by Conceptrol, with smaller bare spots of uncoated epithelium. Change in posture tended to increase extent and uniformity of coating, details differing between gels. CONCLUSIONS: Results are consistent with predictions of mechanistic coating theory, using gel rheological data as inputs.

Ensembles of gustatory cortical neurons anticipate and discriminate between tastants in a single lick.

The gustatory cortex (GC) processes chemosensory and somatosensory information and is involved in learning and anticipation. Previously we found that a subpopulation of GC neurons responded to tastants in a single lick (Stapleton et al., 2006). Here we extend this investigation to determine if small ensembles of GC neurons, obtained while rats received blocks of tastants on a fixed ratio schedule (FR5), can discriminate between tastants and their concentrations after a single 50 muL delivery. In the FR5 schedule subjects received tastants every fifth (reinforced) lick and the intervening licks were unreinforced. The ensemble firing patterns were analyzed with a Bayesian generalized linear model whose parameters included the firing rates and temporal patterns of the spike trains. We found that when both the temporal and rate parameters were included, 12 of 13 ensembles correctly identified single tastant deliveries. We also found that the activity during the unreinforced licks contained signals regarding the identity of the upcoming tastant, which suggests that GC neurons contain anticipatory information about the next tastant delivery. To support this finding we performed experiments in which tastant delivery was randomized within each block and found that the neural activity following the unreinforced licks did not predict the upcoming tastant. Collectively, these results suggest that after a single lick ensembles of GC neurons can discriminate between tastants, that they may utilize both temporal and rate information, and when the tastant delivery is repetitive ensembles contain information about the identity of the upcoming tastant delivery.

Rapid taste responses in the gustatory cortex during licking.

Rapid tastant detection is necessary to prevent the ingestion of potentially poisonous compounds. Behavioral studies have shown that rats can identify tastants in approximately 200 ms, although the electrophysiological correlates for fast tastant detection have not been identified. For this reason, we investigated whether neurons in the primary gustatory cortex (GC), a cortical area necessary for tastant identification and discrimination, contain sufficient information in a single lick cycle, or approximately 150 ms, to distinguish between tastants at different concentrations. This was achieved by recording neural activity in GC while rats licked four times without a liquid reward, and then, on the fifth lick, received a tastant (FR5 schedule). We found that 34% (61 of 178) of GC units were chemosensitive. The remaining neurons were activated during some phase of the licking cycle, discriminated between reinforced and unreinforced licks, or processed task-related information. Chemosensory neurons exhibited a latency of 70-120 ms depending on concentration, and a temporally precise phasic response that returned to baseline in tens of milliseconds. Tastant-responsive neurons were broadly tuned and responded to increasing tastant concentrations by either increasing or decreasing their firing rates. In addition, some responses were only evoked at intermediate tastant concentrations. In summary, these results suggest that the gustatory cortex is capable of processing multimodal information on a rapid timescale and provide the physiological basis by which animals may discriminate between tastants during a single lick cycle.

Long-lasting novelty-induced neuronal reverberation during slow-wave sleep in multiple forebrain areas.

The discovery of experience-dependent brain reactivation during both slow-wave (SW) and rapid eye-movement (REM) sleep led to the notion that the consolidation of recently acquired memory traces requires neural replay during sleep. To date, however, several observations continue to undermine this hypothesis. To address some of these objections, we investigated the effects of a transient novel experience on the long-term evolution of ongoing neuronal activity in the rat forebrain. We observed that spatiotemporal patterns of neuronal ensemble activity originally produced by the tactile exploration of novel objects recurred for up to 48 h in the cerebral cortex, hippocampus, putamen, and thalamus. This novelty-induced recurrence was characterized by low but significant correlations values. Nearly identical results were found for neuronal activity sampled when animals were moving between objects without touching them. In contrast, negligible recurrence was observed for neuronal patterns obtained when animals explored a familiar environment. While the reverberation of past patterns of neuronal activity was strongest during SW sleep, waking was correlated with a decrease of neuronal reverberation. REM sleep showed more variable results across animals. In contrast with data from hippocampal place cells, we found no evidence of time compression or expansion of neuronal reverberation in any of the sampled forebrain areas. Our results indicate that persistent experience-dependent neuronal reverberation is a general property of multiple forebrain structures. It does not consist of an exact replay of previous activity, but instead it defines a mild and consistent bias towards salient neural ensemble firing patterns. These results are compatible with a slow and progressive process of memory consolidation, reflecting novelty-related neuronal ensemble relationships that seem to be context- rather than stimulus-specific. Based on our current and previous results, we propose that the two major phases of sleep play distinct and complementary roles in memory consolidation: pretranscriptional recall during SW sleep and transcriptional storage during REM sleep.

Effect of temperature and pH on contraceptive gel viscosity.

The rheological properties of four commercially available spermicidal gels (two polyacrylic acid derivatives and two carboxymethylcellulose based) and their dilutions with a vaginal fluid simulant (pH 4.2) and a semen simulant (pH 7.7) were measured at 25 degrees C and 37 degrees C over a biologically relevant range of shear rates. All four gels were shear thinning with temperature-dependent rheological properties. The two types of gels responded differently to dilution. The rheological properties of the polyacrylic acid derivative gels were strongly dependent on the type of diluent used. Their viscosities after dilution with the semen simulant were 100 times greater than after comparable dilutions with the vaginal fluid simulant, this effect being due primarily to the higher pH. The cellulose gels did not exhibit such an effect. These results suggest that the polyacrylic acid and cellulose gels interact differently with the vaginal environment in vivo. Such differences could lead to differences in the extent and durability of epithelial coating.