A sequential Cox approach for estimating the causal effect of treatment in the presence of time-dependent confounding applied to data from the Swiss HIV Cohort Study

When estimating the effect of treatment on HIV using data from observational studies, standard methods may produce biased estimates due to the presence of time-dependent confounders. Such confounding can be present when a covariate, affected by past exposure, is both a predictor of the future exposure and the outcome. One example is the CD4 cell count, being a marker for disease progression for HIV patients, but also a marker for treatment initiation and influenced by treatment. Fitting a marginal structural model (MSM) using inverse probability weights is one way to give appropriate adjustment for this type of confounding. In this paper we study a simple and intuitive approach to estimate similar treatment effects, using observational data to mimic several randomized controlled trials. Each 'trial' is constructed based on individuals starting treatment in a certain time interval. An overall effect estimate for all such trials is found using composite likelihood inference. The method offers an alternative to the use of inverse probability of treatment weights, which is unstable in certain situations. The estimated parameter is not identical to the one of an MSM, it is conditioned on covariate values at the start of each mimicked trial. This allows the study of questions that are not that easily addressed fitting an MSM. The analysis can be performed as a stratified weighted Cox analysis on the joint data set of all the constructed trials, where each trial is one stratum. The model is applied to data from the Swiss HIV cohort study.

Role of catechol in the radical reduction of B-alkylcatecholboranes in presence of methanol

Mechanistic investigations on the previously reported reduction of B-alkylcatecholboranes in the presence of methanol led to the disclosure of a new mechanism involving catechol as a reducing agent. More than just revising the mechanism of this reaction, we disclose here the surprising role of catechol, a chain breaking antioxidant, which becomes a source of hydrogen atoms in an efficient radical chain process

Mental reversal of imagined melodies: A role for the posterior parietal cortex

Two fMRI experiments explored the neural substrates of a musical imagery task that required manipulation of the imagined sounds: temporal reversal of a melody. Musicians were presented with the first few notes of a familiar tune (Experiment 1) or its title (Experiment 2), followed by a string of notes that was either an exact or an inexact reversal. The task was to judge whether the second string was correct or not by mentally reversing all its notes, thus requiring both maintenance and manipulation of the represented string. Both experiments showed considerable activation of the superior parietal lobe (intraparietal sulcus) during the reversal process. Ventrolateral and dorsolateral frontal cortices were also activated, consistent with the memory load required during the task. We also found weaker evidence for some activation of right auditory cortex in both studies, congruent with results from previous simpler music imagery tasks. We interpret these results in the context of other mental transformation tasks, such as mental rotation in the visual domain, which are known to recruit the intraparietal sulcus region, and we propose that this region subserves general computations that require transformations of a sensory input. Mental imagery tasks may thus have both task or modality-specific components as well as components that supersede any specific codes and instead represent amodal mental manipulation.

Perception of emotion in sounded and imagined music

WE STUDIED THE EMOTIONAL RESPONSES BY MUSICIANS to familiar classical music excerpts both when the music was sounded, and when it was imagined.We used continuous response methodology to record response profiles for the dimensions of valence and arousal simultaneously and then on the single dimension of emotionality. The response profiles were compared using cross-correlation analysis, and an analysis of responses to musical feature turning points, which isolate instances of change in musical features thought to influence valence and arousal responses. We found strong similarity between the use of an emotionality arousal scale across the stimuli, regardless of condition (imagined or sounded). A majority of participants were able to create emotional response profiles while imagining the music, which were similar in timing to the response profiles created while listening to the sounded music.We conclude that similar mechanisms may be involved in the processing of emotion in music when the music is sounded and when imagined.

Behavioral and neural correlates of perceived and imagined musical timbre

The generality of findings implicating secondary auditory areas in auditory imagery was tested by using a timbre imagery task with fMRI. Another aim was to test whether activity in supplementary motor area (SMA) seen in prior studies might have been related to subvocalization. Participants with moderate musical background were scanned while making similarity judgments about the timbre of heard or imagined musical instrument sounds. The critical control condition was a visual imagery task. The pattern of judgments in perceived and imagined conditions was similar, suggesting that perception and imagery access similar cognitive representations of timbre. As expected, judgments of heard timbres, relative to the visual imagery control, activated primary and secondary auditory areas with some right-sided asymmetry. Timbre imagery also activated secondary auditory areas relative to the visual imagery control, although less strongly, in accord with previous data. Significant overlap was observed in these regions between perceptual and imagery conditions. Because the visual control task resulted in deactivation of auditory areas relative to a silent baseline, we interpret the timbre imagery effect as a reversal of that deactivation. Despite the lack of an obvious subvocalization component to timbre imagery, some activity in SMA was observed, suggesting that SMA may have a more general role in imagery beyond any motor component.

Perceived and Imagined Tempos of Familiar Songs

Two studies investigated the similarity of metronome settings to perceived and imagined familiar songs by subjects unselected for musical ability. In Study 1, mean tempo settings in the two tasks were about 100 beats per minute. Songs with slower perceived tempos tended to be faster in the imagery task and vice versa. In Study 2, subjects set fastest and slowest acceptable tempos for the same set of songs in the imagery mode. These settings were positively correlated with the preferred tempo for the song. Most subjects thought that there were limits on how fast or slow a song could be imagined. These results suggest that tempo is explicitly represented in auditory imagery.

Can imagined whole-body rotations improve vestibular compensation?

Unilateral damage to the labyrinth and the vestibular nerve cause rotational vertigo, postural imbalance, oculomotor disorders and spatial disorientation. Electrophysiological investigations in animals revealed that such deficits are partly due to imbalanced spontaneous activity and sensitivity to motion in neurons located in the ipsilesional and contralesional vestibular nuclei. Neurophysiological reorganizations taking place in the vestibular nuclei are the basis of the decline of the symptoms over time, a phenomenon known as vestibular compensation. Vestibular compensation is facilitated by motor activity and sensory experience, and current rehabilitation programs favor physical activity during the acute stage of a unilateral vestibular loss. Unfortunately, vestibular-defective patients tend to develop strategies in order to avoid movements causing imbalance and nausea (in particular body movements towards the lesioned side), which impedes vestibular compensation. Neuroanatomical evidence suggests a cortical control of postural and oculomotor reflexes based on corticofugal projections to the vestibular nuclei and, therefore, the possibility to manipulate vestibular functions through top-down mechanisms. Based on evidence from neuroimaging studies showing that imagined whole-body movements can activate part of the vestibular cortex, we propose that mental imagery of whole-body rotations to the lesioned and to the healthy side will help rebalancing the activity in the ipsilesional and contralesional vestibular nuclei. Whether imagined whole-body rotations can improve vestibular compensation could be tested in a randomized controlled study in such patients beneficiating, or not, from a mental imagery training. If validated, this hypothesis will help developing a method contributing to reduce postural instability and falls in vestibular-defective patients. Imagined whole-body rotations thus could provide a simple, safe, home-based and self-administered therapeutic method with the potential to overcome the inconvenience related to physical movements.

Postoperative splanchnic blood flow redistribution in response to fluid challenges in the presence and absence of endotoxemia in a porcine model

We hypothesized that fluid administration may increase regional splanchnic perfusion after abdominal surgery-even in the absence of a cardiac stroke volume (SV) increase and independent of accompanying endotoxemia. Sixteen anesthetized pigs underwent abdominal surgery with flow probe fitting around splanchnic vessels and carotid arteries. They were randomized to continuous placebo or endotoxin infusion, and when clinical signs of hypovolemia (mean arterial pressure, <60 mmHg; heart rate, >100 beats · min(-1); urine production, <0.5 mL · kg(-1) · h(-1); arterial lactate concentration, >2 mmol · L(-1)) and/or low pulmonary artery occlusion pressure (target 5-8 mmHg) were present, they received repeated boli of colloids (50 mL) as long as SV increased 10% or greater. Stroke volume and regional blood flows were monitored 2 min before and 30 min after fluid challenges. Of 132 fluid challenges, 45 (34%) resulted in an SV increase of 10% or greater, whereas 82 (62%) resulted in an increase of 10% or greater in one or more of the abdominal flows (P < 0.001). During blood flow redistribution, celiac trunk (19% of all measurements) and hepatic artery flow (15%) most often decreased, whereas portal vein (10%) and carotid artery (7%) flow decreased less frequently (P = 0.015, between regions). In control animals, celiac trunk (30% vs. 9%, P = 0.004) and hepatic artery (25% vs. 11%, P = 0.040) flow decreased more often than in endotoxin-infused pigs. Accordingly, blood flow redistribution is a common phenomenon in the postoperative period and is only marginally influenced by endotoxemia. Fluid management based on SV changes may not be useful for improving regional abdominal perfusion.

Does the Presence of a Learning Disability Elicit a Stigmatization?

Aims: To determine whether or not a Learning Disability(LD) label leads to stigmatization. Study Design: This research used a 2(sex of participant) x 2(LD label)x 2 (Sex of stimulus person) factorial design. Place and Duration of Study: Bucknell University, between October 2010 and April 2011. Methodology: Sample: We included 200 participants (137 women and 63 men, ranging in age from 18 – 75 years, M = 26.41. Participants rated the stimulus individual on 27 personality traits, 8 Life success measures, and the Big-5 personality dimensions. Also, participants completed a Social Desirability measure. Results: A MANOVA revealed a main effect for the Learning Disability description, F(6, 185) = 6.41 p< .0001, eta2 = .17,for the Big-5 personality dimensions, Emotional Stability, F(1, 185) = 13.39, p < .001, eta2 = .066, and Openness to Experiences F(1,185) = 7.12, p< .008, eta2 = .036.Stimulus individuals described as having a learning disability were perceived as being less emotionally stable and more open to experiences than those described as not having a learning disability. Another MANOVA revealed a main effect for having a disability or not, F(8, 183) = 4.29, p< .0001, eta2 = .158, for the Life Success items, Attractiveness, F(1, 198) = 16.63, p< .0001, eta2 = .080, and Future Success,F(1, 198) = 4.57, p< .034, eta2 = .023. Stimulus individuals described as having a learning disability were perceived as being less attractive and with less potential for success than those described as not having a learning disability. Conclusion: The results of this research provide evidence that a bias exists toward those who have learning disabilities. The mere presence of an LD label had the ability to cause a differential perception of those with LDs and those without LDs.

The presence of iodinated contrast agents amplifies DNA radiation damage in computed tomography

The purpose of this study was to determine the influence of iodinated contrast agents on the formation of DNA double-strand breaks in vitro in lymphocytes and to verify these results in patients undergoing diagnostic computed tomography examinations. Blood samples were irradiated in vitro in the presence of iodinated X-ray contrast agent. Controls were irradiated without contrast agent. Fourteen patients were investigated using contrast-enhanced computed tomography (CT), and 14 other patients with unenhanced CT. Blood samples were taken prior to and 5 min and 1, 2 and 24 h after the CT examination. In these blood samples the average number of γH2Ax-foci per lymphocyte was enumerated by fluorescence microscopy. Statistical differences between foci numbers developed in the presence and absence of contrast agent were tested using an independent sample t-test. In vitro foci numbers after irradiation were significantly higher when contrast agent was present during irradiation. In vivo, γH2Ax-foci levels were 58% higher in patients undergoing contrast-enhanced CT compared with those undergoing unenhanced CT. In the presence of iodinated contrast agents DNA, damage is increased and the radiation dose is not the only factor affecting the amount of DNA damage. Individual patient characteristics and biological dosimetry applications, e.g. the analysis of γH2Ax-foci, have to be considered.